82_FR_6290 82 FR 6278 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins and Enhanced Biosafety Requirements

82 FR 6278 - Possession, Use, and Transfer of Select Agents and Toxins; Biennial Review of the List of Select Agents and Toxins and Enhanced Biosafety Requirements

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Federal Register Volume 82, Issue 12 (January 19, 2017)

Page Range6278-6294
FR Document2017-00726

In accordance with the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (the Bioterrorism Response Act), the Centers for Disease Control and Prevention (CDC) in the Department of Health and Human Services (HHS) has reviewed the list of biological agents and toxins that have the potential to pose a severe threat to public health and safety. Following the review, HHS has decided: Not to finalize the proposed changes to the list of select agents and toxins at this time; to finalize provisions to address toxin permissible limits and the inactivation of select agents; to finalize specific provisions to the section of the regulations addressing biosafety; and to clarify regulatory language concerning security, training, incident response, and records. In a companion document published in this issue of the Federal Register, the U.S. Department of Agriculture (USDA) has made parallel regulatory changes.

Federal Register, Volume 82 Issue 12 (Thursday, January 19, 2017)
[Federal Register Volume 82, Number 12 (Thursday, January 19, 2017)]
[Rules and Regulations]
[Pages 6278-6294]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-00726]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Docket No. CDC-2015-0006]

42 CFR Part 73

RIN 0920-AA59


Possession, Use, and Transfer of Select Agents and Toxins; 
Biennial Review of the List of Select Agents and Toxins and Enhanced 
Biosafety Requirements

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: In accordance with the Public Health Security and Bioterrorism 
Preparedness and Response Act of 2002 (the Bioterrorism Response Act), 
the Centers for Disease Control and Prevention (CDC) in the Department 
of Health and Human Services (HHS) has reviewed the list of biological 
agents and toxins that have the potential to pose a severe threat to 
public health and safety. Following the review, HHS has decided: Not to 
finalize the proposed changes to the list of select agents and toxins 
at this time; to finalize provisions to address toxin permissible 
limits and the inactivation of select agents; to finalize specific 
provisions to the section of the regulations addressing biosafety; and 
to clarify regulatory language concerning security, training, incident 
response, and records. In a companion document published in this issue 
of the Federal Register, the U.S. Department of Agriculture (USDA) has 
made parallel regulatory changes.

DATES: Effective February 21, 2017.

FOR FURTHER INFORMATION CONTACT: Dr. Samuel S. Edwin, Director, 
Division of Select Agents and Toxins, Centers for Disease Control and 
Prevention, 1600

[[Page 6279]]

Clifton Road NE., MS-A46, Atlanta, Georgia 30329. Telephone: (404) 718-
2000.

SUPPLEMENTARY INFORMATION: The preamble to this final rule is organized 
as follows:

I. Executive Summary
II. Changes to 42 CFR Part 73
    A. Modifications to the List of HHS and Overlap Select Agents 
and Toxins
    B. Responses to Other Proposed Changes
    i. Definitions
    ii. Inactivation of a Select Agent
    iii. Toxins
    iv. Exclusion Involving Patient Care
    v. Exemptions for Select Agents and Toxins
    vi. Registration
    vii. Responsible Official
    viii. Visitor Access to Select Agents and Toxins
    ix. Security, Biosafety, and Incident Response Plans
    x. Training
    xi. Records
III. Alternatives Considered
IV. Required Regulatory Analyses
    A. Executive Orders 12866 and 13563
    B. The Regulatory Flexibility Act
    C. Paperwork Reduction Act of 1995
    D. E.O. 12988: Civil Justice Reform
    E. E.O. 13132: Federalism
    F. Plain Language Act of 2010
V. References

I. Executive Summary

    On February 27, 2015 we published an Advance Notice of Proposed 
Rulemaking (ANPRM) (80 FR 10656) that initiated the required biennial 
review and republication of the HHS list of select agents and toxins. 
The ANPRM solicited public comments regarding whether any biological 
agents and toxins should be added or removed from the HHS list of 
select agents and toxins based on the following criteria:
    (1) The effect on human health of exposure to the agent or toxin;
    (2) The degree of contagiousness of the agent or toxin, and the 
methods by which the agent or toxin is transferred to humans;
    (3) The availability and effectiveness of pharmacotherapies and 
immunizations to treat and prevent any illness resulting from infection 
by the agent or exposure to the toxin; and
    (4) Any other criteria, including the needs of children and other 
vulnerable populations that the commenter considered appropriate.
    This notice also asked for public comment on whether HHS should 
remove the following agents from the HHS list of select agents and 
toxins: Coxiella burnetii, Rickettsia prowazekii, Bacillus anthracis 
Pasteur, Brucella abortus, B. melitensis, and B. suis.
    On January 19, 2016, we published a Notice of Proposed Rulemaking 
(NPRM) (81 FR 2805). The NPRM solicited public comments regarding 
whether any biological agents and toxins should be added or removed 
from the HHS list of select agents and toxins based on the same 
criteria used in ANPRM:
    We also invited comments on the following:
    (1) Methods that should be required to validate the rendering of a 
select agent non-viable or regulated nucleic acids that can produce 
infectious forms of any select agent virus as non-infectious;
    (2) Proposed changes to the aggregate amount of toxin excluded from 
the requirements of the select agent regulations;
    (3) Removal of Diacetoxyscirpenol (DAS) and T-2 from the list;
    (4) Whether seven calendar days provides a sufficient amount of 
time for the entity to destroy or transfer a select agent or toxin 
after identification;
    (5) Specific biosafety measures that should be required to prevent 
laboratory acquired infections (LAIs) or accidental release of the 
select agents and toxins from an entity into the community; and
    (6) Alternative regulatory requirements that could be constructed 
such that a registered entity would know whether it had a theft or loss 
of a select agent or toxin without that registered entity first having 
``an accurate, current inventory for each select agent . . . held in 
long term storage.''
    (7) Whether short, paralytic alpha-conotoxins containing the 
following amino acid sequence 
(X1CCX2PACGX3X4X5
X6CX7), C. burnetii, R. prowazekii, B. anthracis 
Pasteur, B. abortus, B. melitensis, and B. suis should be removed from 
the HHS list of select agents and toxins.
    We received 22 public comments to the ANPRM and 35 public comments 
to the NPRM that addressed the composition of the HHS list of select 
agents and toxins. After carefully considering the technical input of 
subject matter experts, both within the Federal government and from 
public comments, and recommendations from Federal advisory groups, we 
have decided not to finalize the proposed changes to the list of select 
agents and toxins at this time. Upon further consideration, we may 
decide to finalize changes to the list at a future time.
    This final rule makes the following changes to current regulations:
    1. New provisions regarding the inactivation of select agents, 
specific biosafety requirements, and toxin requirements;
    2. Other revisions to the regulations to clarify regulatory 
language concerning security, training, and records.
    3. In addition, when HHS added B. cereus Biovar anthracis to the 
list of HHS select agents and toxins on September 14, 2016 by an 
interim final rule (81 FR 63138), we neglected to add the name of the 
agent to the immediate notification list for Tier 1 agents in sections 
5 and 9 of the regulations. We are correcting that error in this final 
rule.
    Costs of the Rule: The entities affected by this final rule include 
research and diagnostic facilities; Federal, State, and university 
laboratories; and private commercial and non-profit enterprises. The 
current regulations require registering for the possession, use, and 
transfer of select agents or toxins. In addition, the entity is 
currently required to ensure that the facility where the agent or toxin 
is housed has adequate biosafety and containment measures; that the 
physical security of the premises is adequate to prevent unauthorized 
access; that all individuals with approved access to select agents or 
toxins have the appropriate education, training, and/or experience to 
handle such agents or toxins; and that complete records concerning 
activities related to the select agents or toxins are maintained.
    The HHS final rule will further reduce or minimize the risk of 
misuse of select agents and toxins that have the potential to pose a 
severe threat to human health. HHS recognizes that several of the 
required measures of the regulations may impose certain operational 
costs upon affected entities. Specifically, the rule will clarify that 
an entity must use a validated method to render a select agent non-
viable or a regulated infectious nucleic acid sample non-infectious for 
future use. This means the method must be scientifically sound and 
produce consistent results each time it is used. Appropriate reporting 
and record keeping is required in order to mitigate threats to human 
health. In many cases, however, the affected entities already employ 
some or all of the required measures. Compliance costs actually 
incurred will therefore vary from one entity to the next.
    While information on the specific changes that would need to occur 
at individual sites and the associated costs was not readily available 
during proposed rulemaking, some general observations regarding the 
potential costs were presented. These general cost observations can be 
found in the Regulatory Impact Analysis. Based on the current 
recordkeeping and reporting requirements, an additional 10 to 20 hours 
per year may be required by entities. At an imputed cost of $33.40 per 
hour, this additional time

[[Page 6280]]

requirement per entity will total between $334 and $668 per year, or in 
total for all registered entities between $80,000 and $160,000.
    Benefits: The objectives of the HHS final rule are to create a 
means of ensuring enhanced oversight in the transfer, storage, and use 
of select agents and toxins; clarify that an entity must use a 
validated method to render a select agent non-viable or a regulated 
infectious nucleic acid sample non-infectious for future use; and 
require that entities in possession of such agents and toxins develop 
and implement effective means of biosafety, information security, and 
physical security. The overall benefit of the amended regulatory 
provisions will be a reduced likelihood of the accidental or 
intentional release of a select agent or toxin; and the avoidance of 
human morbidity, mortality and the economic loss associated with such a 
release. The goal of the amended regulations is to enhance the 
protection of human health and safety.

II. Changes to 42 CFR Part 73

    The table below describes the changes to the current regulation.

------------------------------------------------------------------------
      Section No.             Section title               Change
------------------------------------------------------------------------
73.0...................  Applicability and        No changes.
                          related requirements.
73.1...................  Definitions............  Adds definitions:
                                                   Validated
                                                   inactivation
                                                   procedure and
                                                   viability testing
                                                   protocol.
73.2...................  Purpose and scope......  No changes.
73.3...................  HHS select agents and    Clarifies language to
                          toxins.                  include addition of
                                                   B. cereus Biovar
                                                   anthracis and adds
                                                   new paragraphs.
73.4...................  Overlap select agents    Clarifies language to
                          and toxins.              include addition of
                                                   B. cereus Biovar
                                                   anthracis and adds
                                                   new paragraphs.
73.5...................  Exemptions for HHS       Clarifies language;
                          select agents and        redesignates
                          toxins.                  paragraph; and adds
                                                   new paragraph.
73.6...................  Exemptions for overlap   Clarifies language;
                          select agents and        redesignates
                          toxins.                  paragraph; and adds
                                                   new paragraph.
73.7...................  Registration and         Redesignates
                          related security risk    paragraphs; adds new
                          assessments.             paragraph.
73.8...................  Denial, revocation, or   No changes.
                          suspension of
                          registration.
73.9...................  Responsible Official...  Clarifies language to
                                                   include addition of
                                                   B. cereus Biovar
                                                   anthracis and adds
                                                   new paragraphs.
73.10..................  Restricting access to    Clarifies language.
                          select agents and
                          toxins; security risk
                          assessments.
73.11..................  Security...............  Clarifies language and
                                                   adds new paragraph.
73.12..................  Biosafety..............  Clarifies language.
73.13..................  Restricted experiments.  No changes.
73.14..................  Incident response......  Clarifies language.
73.15..................  Training...............  Clarifies language and
                                                   adds new paragraph.
73.16..................  Transfers..............  Clarifies language.
73.17..................  Records................  Clarifies language and
                                                   adds new paragraph.
73.18..................  Inspections............  No changes.
73.19..................  Notification of theft,   No changes.
                          loss, or release.
73.20..................  Administrative review..  No changes.
73.21..................  Civil money penalties..  No changes.
------------------------------------------------------------------------

A. Modifications to the List of HHS and Overlap Select Agents and 
Toxins

    We received 22 public comments to the ANPRM and 35 public comments 
to the NPRM that addressed the composition of the HHS list of select 
agents and toxins. After carefully considering the technical input of 
subject matter experts, both within the Federal government and from 
public comments, and recommendations from Federal advisory groups, we 
have decided not to finalize the proposed changes to the list of select 
agents and toxins at this time.

B. Responses to Other Proposed Changes

i. Definitions
    It recently became clear that some inactivation protocols have 
failed to inactivate B. anthracis spores completely, as evidenced by 
inactivation failures that led to the inadvertent transfer of 
potentially live B. anthracis samples by the Department of Defense in 
2015. In response to this incident, new requirements were proposed to 
address the inactivation of select agents. We proposed adding 
definitions for the terms ``inactivation'' and ``kill curve'' to 
clarify the new inactivation provisions. As discussed below, we have 
removed the proposed requirement for a ``kill curve,'' and accordingly, 
we have also removed the proposed definition of ``kill curve.''
    To exclude a select agent or regulated nucleic acids that can 
produce infectious forms of any select agent virus from the 
requirements of the select agent regulations, an entity will need to 
subject the select agent or the nucleic acids to a validated 
inactivation procedure whose efficacy is confirmed through a viability 
testing protocol.
    Commenters stated that additional definitions should be provided 
for ``validated inactivation procedure,'' ``sterility testing 
protocol,'' and ``safety margin.'' We agree with the commenters and are 
defining the terms as described below. ``Validated inactivation 
procedure'' means ``a procedure, whose efficacy is confirmed by data 
generated from a viability testing protocol, to render a select agent 
non-viable but allows the select agent to retain characteristics of 
interest for future use; or to render any nucleic acids that can 
produce infectious forms of any select agent virus non-infectious for 
future use.''
    Further, we have not included a separate definition for 
``inactivation'' as it is now captured in the definition of ``validated 
inactivation procedure.''
    We have changed the proposed phrase ``sterility testing protocol'' 
to ``viability testing protocol'' and defined the latter as ``a 
protocol to confirm the validated inactivation procedure by 
demonstrating the material is free of all viable select agent.'' This 
change reflects the intent that the validated inactivation procedure, 
or the procedure for removal of viable select agents from material

[[Page 6281]]

containing select agents, must render the material non-viable (i.e., 
unable to replicate). In addition, any nucleic acids that can produce 
infectious forms of any select agent virus must be rendered non-
infectious for future use.
    We are choosing to not define the term ``safety margin'' and have 
incorporated the concept of a performance standard instead.
    The new definitions will help clarify the regulatory language found 
in 42 CFR 73.3, 73.4.
ii. Inactivation of a Select Agent
    Historical inactivation failures by registered entities required us 
to focus on ways to increase the certainty that inactivated select 
agents intended for further use do not contain live agent. This is 
particularly important when the inactivation methods are tempered in 
order to avoid disrupting some of the physical characteristics of the 
agent. We proposed adding specific requirements to the exclusion 
sections of the regulations (42 CFR 73.3(d), 73.4(d)) to address the 
requirements for rendering select agents, nucleic acids that can 
produce infectious forms of any select agent virus, or extracts from 
select agents non-viable.
    Sections 73.3(d)(2) (HHS select agents and toxins) and 73.4(d)(2) 
(Overlap select agents and toxins) both provide that a non-viable 
select agent is excluded from the requirements of the select agent 
regulations. We proposed that for a select agent to be non-viable or to 
render nucleic acids that can produce infectious forms of any select 
agent virus non-infectious for future use, an entity must use a 
validated inactivation procedure. Commenters stated there is some 
confusion between inactivation validation requirements for moving 
materials to a lower containment level and inactivation validation 
requirements for waste disposal. We are clarifying that these 
provisions apply to a select agent that is inactivated for future use 
as a non-select agent and is not intended for material for waste 
disposal.
    Many commenters stated that the focus on strengthening inactivation 
requirements was being driven by an incorrect public perception of 
recent procedural errors that occurred at federally run research 
laboratories. Without commenting on what is or might be the public's 
perception with regard to inactivation problems, we disagree with these 
comments because the focus on inactivation failures with select agents 
is based on the realization that past inactivation activities have 
proved to be inadequate.
    We proposed that an entity would be required to develop a site-
specific kill curve to identify conditions of inactivation for each 
select agent. Commenters stated that although the generation of kill 
curves is appropriate for inactivation procedures using heat, 
irradiation and filtration, it is not generally applicable to 
determining infectivity of nucleic acids. Commenters stated that for 
inactivation procedures where a ``kill curve is not applicable, 
inactivation conditions are selected and then replicated to obtain 100% 
inactivation within a statistical certainty.''
    We agree with the commenters and are withdrawing the proposal to 
require a kill curve and safety margin because these would not be 
applicable to all inactivation procedures. Further, the variety of 
agents and inactivation procedures makes it likely that prescriptive 
requirements would have unintended negative consequences on research. 
We are, nonetheless, finalizing requirements for a validated 
inactivation procedure and viability testing. We are requiring that for 
a select agent or regulated nucleic acid that can produce infectious 
forms of any select agent virus to be excluded from the requirements of 
the select agent regulations, an entity will be responsible for 
achieving a certain performance standard that is confirmed through a 
viability testing protocol. Surrogate strains that are known to possess 
equivalent properties with respect to inactivation can be used to 
validate an inactivation procedure. However, if there are known strain-
to-strain variations in the resistance of a select agent to an 
inactivation procedure, then an inactivation procedure validated on a 
lesser resistant strain must also be validated on the more resistant 
strains. Additional guidance regarding this performance standard has 
been developed and is available at www.selectagents.gov.
    Many commenters asked HHS to state clearly if the standard for 
select agent inactivation is complete sterility (i.e., not a single 
viable pathogen in the entire volume of an inactivated sample), a log 
reduction in viable pathogen titer, or the limit of detection of the 
assay. We agree that it is important to specify the intent of the 
performance standard. HHS recognizes the limits of detection of the 
viability testing procedures (related to the detection assay and the 
sampling of inactivated material) and expected run-to-run variation 
when following an inactivation procedure precisely precludes 
demonstrating full sterility of inactivated material. These sources of 
error must be considered when establishing performance parameters for 
inactivation procedures. While complete sterility is not a feasible 
goal for material that is intended for further use, HHS expects that 
the risk of live agent in inactivated materials will be as low as 
realistically possible from both a safety and security perspective.
    We proposed that entities subject representative samples of an 
inactivated select agent to a validated sterility testing protocol to 
ensure that the inactivation procedure has rendered the select agent 
non-viable. Commenters stated that it is not always practical to 
conduct validation on each sample that is inactivated. Often samples 
are in limited quantities and validation studies will leave very little 
or no sample for the experimental purpose. Commenters also stated that 
the requirement to subject representative samples to sterility testing 
using a validated protocol requires further clarification. Commenters 
stated that it is reasonable to require this type of testing when the 
inactivation procedure is first established and if any changes to the 
inactivation protocol are made. However, commenters stated that it 
cannot be reasonably done on each sample in laboratory research if the 
inactivation protocol has not changed. They stated that implementing 
such a requirement would waste specimens where limited volumes are 
available, would be costly in terms of technical time and resources, 
and is scientifically unjustified.
    We agree with the commenters that the varied needs and conditions 
for inactivation preclude setting a specific standard for viability 
testing at this time. We have removed the proposed sterility testing 
requirement for select agents and nucleic acids that can produce 
infectious forms of any select agent virus and have incorporated this 
concept into the performance standard. The requirement to develop a 
validated inactivation procedure and subsequent validation data derived 
from viability testing will determine the extent of sampling required. 
This activity will provide the associated measures of uncertainty with 
the sampling protocol chosen.
    We proposed adding exclusion requirements that extracts from a 
select agent could not be excluded from the requirements of the select 
agent regulations until an individual or entity met the following 
requirements: (1) Any extract is subjected to a process that removes 
all viable cells, spores, or virus particles; (2) any extract is 
subjected to a validated sterility testing protocol; (3) any viability 
of an extract that was subjected to a validated inactivation

[[Page 6282]]

protocol is reported to the Responsible Official (RO); and (4) any 
viability of a select agent or infectivity of regulated nucleic acids 
that can produce infectious forms of any select agent virus, previously 
assessed as inactive by their validated sterility testing protocol, is 
reported to APHIS or CDC.
    Some commenters expressed concern with having to subject every 
extract from a select agent, such as nucleic acids, to sterility 
testing. We agree with the commenters and are replacing the term 
``extract'' with ``material containing a select agent'' to clarify that 
the requirements apply to material containing a select agent such as 
serum or liquid culture where select agents are typically removed via 
filtration without a previous inactivation step. The term ``extract'' 
is commonly used in conjunction with nucleic acids extracted from a 
select agent. We are using the term ``extract'' in the final rule to 
reflect the application of two processing steps: An inactivation step 
to destroy the select agent (e.g., lysis of select agent) and then 
another step (such as filtration), to remove any remaining viable 
select agents. Extracts from a select agent (nucleic acids, antigens, 
lysates) would be subject to the performance standard for select agents 
in the new sections 3(d)(3) and 4(d)(3) of the select agent regulations 
that includes viability testing but does not necessarily require 
viability testing on every sample. The requirement to develop a 
validated inactivation procedure and subsequent validation data derived 
from viability testing will determine the extent of sampling required. 
However, material containing select agents, as opposed to extracts 
(e.g., nucleic acids, antigens, lysates), that is subjected to a 
process to remove all viable cells, spores, or virus particles would 
require viability testing on every sample prior to treating it as a 
non-select agent. The distinguishing feature between ``material 
containing a select agent'' and an extract from a select agent is that 
in the former the select agent will only be removed and in the latter 
the select agent will be destroyed before removal. The more stringent 
requirement for viability testing of all material containing a select 
agent where the select agent was removed is warranted because of the 
lack of select agent destruction which increases the risk of viable 
select agent remaining in the material.
    We proposed that if there are strain-to-strain variations in 
resistance of a select agent to the inactivation procedure, then a 
specific kill curve must be developed for each strain that undergoes 
the inactivation procedure. We received comments asking us to clarify 
language to specify under what circumstances strain-to-strain 
differences must be validated. Commenters also stated that this is an 
unnecessary use of resources especially when agents, based on their 
morphological characteristics, are susceptible to similar inactivating 
agents. Commenters suggested at a minimum the language should state 
that this requirement only applies when there are known strain-to-
strain variations in resistance of a select agent to the inactivation 
procedure.
    We agree with the commenters and added in the term ``known'' 
strain-to-strain variation and, as stated previously, have removed the 
kill curve requirement.
    Commenters also inquired whether surrogate strains can be used to 
develop inactivation procedures. We agree with the commenters that 
surrogate strains known to possess equivalent properties with respect 
to inactivation as a select agent can be used to develop inactivation 
procedures. We have revised the requirement to include the provision 
that ``Surrogate strains that are known to possess equivalent 
properties with respect to inactivation can be used to validate an 
inactivation procedure; however, if there are known strain-to-strain 
variations in the resistance of a select agent to an inactivation 
procedure, then an inactivation procedure validated on a lesser 
resistant strain must also be validated on the more resistant 
strains.''
    Commenters were concerned about performing viability testing on 
materials such as a single diagnostic sample that is determined to 
contain a select agent and where there is a limited amount of material 
with which to work. For example, consider an entity using a 
commercially available RNA extraction kit on a diagnostic sample to 
obtain RNA for sequencing, and the sample is identified to contain 
highly pathogenic avian influenza (HPAI). In this situation, the entire 
single sample would be used when trying to demonstrate that the 
inactivation procedure was effective. We agree with the commenters. As 
noted above, surrogate select agent strains that are known to possess 
equivalent properties with respect to inactivation as the select agent 
can be used to develop validated inactivation procedures. In this 
example, low pathogenic avian influenza (LPAI) could be used to 
validate the inactivation procedure for diagnostic samples that are 
identified as containing HPAI, if LPAI possesses equivalent properties 
with respect to inactivation as HPAI. In addition, we are clarifying 
that these provisions do not apply to diagnostic samples until they are 
identified to contain a select agent and are inactivated for future use 
as a non-select agent.
    Many commenters asked who would determine the validity of an 
inactivation protocol. The responsibility for this activity remains 
with the entity, which will allow for researchers to continue to 
develop new inactivation procedures. Entities retain the responsibility 
to evaluate their inactivation procedures, to include consideration of 
the biosafety and security risks posed by the inactivated material. The 
Federal Select Agent Program (FSAP) inspectors will verify that the 
entity has developed a validated inactivation procedure and may review 
validation data during an entity's inspection. We made no changes based 
on these comments.
    Many commenters stated that the intent behind the annual review 
provisions was not clear. We agree with the commenters and modified the 
provisions to state that an entity ``Review, and revise as necessary, 
each of the entity's validated inactivation procedures or viable agent 
removal method. The review must be conducted annually or after any 
change in Principal Investigator, change in the validated inactivation 
procedure or viable agent removal method, or failure of the validated 
inactivation procedure or viable agent removal method. The review must 
be documented and training must be conducted if there are any changes 
to the validated inactivation procedure, viable agent removal method, 
or viability testing protocol.'' We made these changes because the 
annual review of an entity's validated inactivation procedures or 
viable agent removal method is key to a successful inactivation 
program. The annual review requirement does not necessarily involve 
revalidating inactivation procedures. This review could simply be the 
evaluation of the site-specific standard operating procedures for 
validated inactivation of select agents to ensure the inactivating 
conditions used and upper agent concentration limits found in 
validation data are consistent, and that entity staff are following the 
site-specific standard operating procedures for validated inactivation 
of select agents.
    However, sometimes an entity will need to revalidate inactivation 
procedures during the annual review. For example, if the entity 
identifies that staff are not adhering to standard operating procedures 
for validated inactivation of select agents, or if the entity wants to 
deviate from the validated inactivation procedure, the

[[Page 6283]]

entity will need to revalidate the inactivation procedures during the 
annual review. Further, in this final rule, we have consolidated the 
review provisions into one provision, clarified that the reviews must 
be documented, and moved this provision into the requirements for the 
RO as they will be the individual responsible for these review 
activities.
    Many commenters stated that the intent of the inactivation failure 
reporting requirements was not clear and reporting every inactivation 
failure to CDC or APHIS was burdensome. We agree with the commenters 
and have modified reporting requirements to require the RO to 
``Investigate to determine the reason for any failure of a validated 
inactivation procedure or any failure to remove viable agent from 
material. If the Responsible Official is unable to determine the cause 
of a deviation from a validated inactivation procedure or a viable 
agent removal method; or receives a report of any inactivation failure 
after the movement of material to another location, the Responsible 
Official must report immediately by telephone or email the inactivation 
failure or viable agent removal method failure to CDC or APHIS.'' The 
intent of this modification is to create an environment at the entity 
where inactivation or select agent removal failures are investigated to 
determine the reason for the failure as opposed to merely re-subjecting 
the material to the inactivation or select agent removal method. It is 
the position of the FSAP that each failure represents either human 
error in conducting the validated procedure or an inadequate 
inactivation method or an inadequate select agent removal method if no 
human error can be discovered. Both situations demand careful attention 
by the entity to ensure training and/or reevaluation of the 
inactivation procedure in order to minimize the likelihood that the 
situation would reoccur in the future. The revised regulatory language 
only requires reporting of inactivation or select agent removal 
failures to FSAP when the RO cannot establish that the failure resulted 
from human error or when an entity receives a report of any 
inactivation failure after the movement of material to another 
location.
    We also proposed that written records be kept for select agents 
that have been subjected to a procedure to render them non-viable, or 
regulated nucleic acids that can produce infectious forms of any select 
agent virus that have been subjected to a procedure to render them 
incapable of producing infectious forms of any select agent virus. Some 
commenters stated that the proposal was not clear how long these 
records must be kept and who is responsible for keeping these records. 
We made no changes based on these comments as these records are subject 
to the records retention requirement in section 17 of the select agent 
regulations and must be kept for three years by a registered individual 
or entity.
    Some commenters asked about the conditions of submitting a waiver 
to the inactivation provisions of the select agent regulations. An 
entity may submit a request to FSAP to apply an alternative 
inactivation procedure. The entity is to provide justification 
regarding the alternative procedure including a description of what 
material is to be waived, the inactivation protocol and viability test 
to be used, validation data, and any other supporting information/
references, such as scientific references. Accordingly, we revised the 
provision found in sections 3(d)(6) and 4(d)(6) to include information 
on how to apply for a waiver that reads ``. . . To apply for such a 
determination a registered individual or entity must submit a written 
request and supporting scientific information to FSAP. A written 
decision granting or denying the request will be issued.'' Additional 
guidance has been developed and is available at: www.selectagents.gov.
iii. Toxins
    To ensure the language is consistent with the exclusion language 
found in 73.3(e) which describes the exclusion of toxins that have been 
modified to be less potent or toxic, we are making a technical change 
to the regulation and revising the terms ``nonfunctional'' toxin to 
``nontoxic'' toxin and ``functional form(s) of any of the toxins'' to 
``toxic form(s) of any of the toxins.'' This change is being made to 
clarify the intent of the regulations as the terms ``nonfunctional'' 
and ``functional'' are broad and have led to confusion. The intention 
behind the original provisions was to exclude toxins that can no longer 
exert their toxic effect and cause disease and regulate those that can. 
For example, Botulinum neurotoxin has three functional domains--binding 
domain, translocation domain and catalytic domain. Each functional 
domain solely can be manipulated such that the toxin is no longer toxic 
and does not cause diseases even though the other two domains may be 
functional.
Due Diligence
    We are adding a more specific documentation requirement to the 
toxin exclusion provision found in section 73.3(d)(3)(i) of the select 
agent regulations to require the transferor of an unregulated amount of 
a select toxin to document the identity of the recipient and the 
legitimate need (i.e., prophylactic, protective, bona fide research, or 
other peaceful purpose) claimed by the recipient. The name of the toxin 
and the total amount transferred must also be documented. Identity 
information of the person requesting and using the toxins must include 
the individual's name, institution name, address, telephone number, and 
email address. We received one comment requesting to include language 
for transfers of toxins within an institution. We made no changes based 
on this comment because intra-entity transfers, where the sender and 
the recipient are covered by the same certificate of registration, are 
already addressed in section 17(3)(viii) of the regulations.
Toxin Permissible Limits
    As proposed, we are increasing the toxin exclusion aggregate 
amounts. We received 10 comments supporting the increase in the toxin 
exclusion aggregate amounts. We received three general comments 
opposing the increase of the exclusion aggregate amounts and two 
additional comments opposing the increase of the ricin exclusion 
aggregate amount. One commenter stated that no changes were necessary. 
Another commenter had concerns regarding whether the risk assessment 
scenarios were relevant to the goal of reducing any significant harm 
able to be caused by illegitimate use of any lethal amounts of toxin. 
We are making no changes based on these comments.
    DHS developed toxin parameters and attack scenarios for potential 
inhalation and ingestion exposures to select toxins to protect the 
homeland against the potential release of weaponized biological toxins. 
The DHS group analyzed a range of release sizes (in mg) for each select 
toxin in order to estimate the number of people that would be exposed 
to each toxin amount by ingestion of milk (using published TD[50] or 
LD[50]) and/or indoor inhalation (using published LD[50]). Revised 
toxin exclusion aggregate amounts were proposed based on the data 
generated by the models to expose <10 or <100 people by inhalation or 
ingestion to the LD[50] or TD[50] levels of toxin. A commenter stated 
that (1) the scenarios proposed appear to consider a high-consequence 
event or exposure to a given toxin and that the interpretation of what 
constitutes a high-consequence event or exposure is impacted not only 
in the number of people affected but in

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the attention afforded by news media and the public and (2) a revision 
of these exclusion limits should also consider amounts that would be 
sufficient for research purposes. We are making no changes based on 
these comments because we do not believe the impact the news media may 
have if an exposure occurs is an appropriate consideration for the 
listing of a biological agent or toxin. Further, the consideration of 
amounts sufficient for research purposes is a subjective assessment as 
smaller academic laboratories have differing needs than an entity that 
is developing detection assays. The comments specific to ricin raised 
concerns that the increased exclusion aggregate amounts would increase 
the risk of (1) exposure to laboratory workers and (2) that individuals 
would have access to greater amounts of material to use for nefarious 
purposes. We are making no changes based on these comments. We do not 
agree that the increased permissible limits will increase the risk of 
laboratory worker exposure. The new proposed exclusion amount is less 
than an oral lethal dose for a single person weighing more than 50 kg, 
based on 20 mg/kg-body weight (Ref. 1), thus a single fatality would 
require consuming more than all of the ricin in the laboratory. Ricin 
does display a higher toxicity when administered intravenously or by 
inhalation, but these two routes of exposure require either injection 
or manipulation to generate particles capable of reaching the lower 
respiratory tract, respectively, two processes not likely to occur 
accidentally. Also, entities that produce ricin typically do so in 
liquid, as opposed to lyophilized powder formulations, thus decreasing 
the risk of ingestion or aerosol exposure. Additionally, the increased 
exclusion aggregate amounts would allow entities to more efficiently 
produce and store ricin preparations which are typically frozen in 
aliquots until the need to use the material arises. Finally, while 
increasing the permissible limits allows individuals with nefarious 
purposes access to greater amounts of toxin, we do not believe access 
to the revised amounts poses a severe threat to public health and 
safety based on the reasons stated above.
Toxins: Exclusion of an HHS Select Toxin Identified in an Original Food 
Samples and Clinical Samples
    As proposed, we are excluding from the requirements of the 
regulations a select toxin identified in an original food sample and 
clinical samples. Original food samples and clinical samples are those 
specimens that are submitted to laboratories for diagnosis or 
verification purposes to identify or verify a biological agent or 
toxin. For example, an original food sample could be a container of 
potato salad or juice. An original clinical sample could be serum or 
stool from a patient. Laboratories that test food and clinical samples 
for the presence of toxins generally do not know the level of toxin in 
a sample and do not extract and purify a toxin as part of their 
studies. Therefore, our proposal to exclude select toxin identified in 
an original food sample or clinical sample identified is consistent 
with the rationale for the current exclusion for animals exposed to 
toxins (42 CFR 73.3(d)(4)). This exclusion was based on recommendations 
by toxin subject matter experts. We received one comment that supported 
this exclusion.
Exclusion of Botulinum Neurotoxin Produced as a Byproduct
    In the NPRM, we proposed to exclude all toxins that are only 
produced as a byproduct of a study of the toxin producing host organism 
so long as the toxin had not been intentionally collected, purified, or 
otherwise extracted, and the material containing the toxin was 
inactivated and properly disposed of within 30 days of the initiation 
of the culture. Based on the input from subject matter experts, the 
final regulatory language narrows the exception to only Botulinum 
neurotoxin produced as a byproduct in the study of Botulinum neurotoxin 
producing species of Clostridium. Work with that organism is already 
regulated, thus providing regulatory oversight of the material during 
the 30 day time frame, as opposed to an agent like Staphylococcus 
aureus, the organism that produces Staphylococcal enterotoxins, which 
is not regulated. One commenter stated that clarification was needed in 
the ``exclusion of toxin produced as a by-product'' and inquired 
whether this provision applies to material held in long term storage or 
cell lysates or culture supernatants kept for diagnostic or research 
purposes other than toxin work. Since the situations described by the 
commenter referred to material held in long term storage (longer than 
30 days) this exclusion would not apply.
iv. Exclusion Involving Patient Care
    To clarify how the select agent regulations apply to activities 
associated with the diagnosis and care for individuals infected with a 
select agent, we proposed that waste generated during the delivery of 
patient care is not considered regulated under the select agent 
regulations. One commenter recommended that we define patient care as 
part of the diagnosis definition. Specifically, the commenter suggested 
we define diagnosis as ``the analysis of specimens for the purpose of 
identifying or confirming the presence or characteristics of a select 
agent or toxin provided that such analysis is associated with the 
determination or provision of patient treatment in a patient care 
setting, or directly related to protecting the public health or safety, 
animal health or animal products, or plant health or plant products. 
Clinical or diagnostic specimen retention times as required for patient 
treatment are included within the determination of the point in time 
when patient care has concluded.'' Another commenter stated ``the 
challenges of differentiating between patient care and experimental 
research when treating infectious diseases are complex and nuanced and 
any effort to introduce regulation of medical care involving select 
agents and toxins has the potential to introduce inconsistencies and 
confusion.'' The proposed exclusion language in the NPRM was ``Waste 
generated during the delivery of patient care from a patient infected 
with a select agent that is decontaminated with a validated method 
within seven calendar days of the conclusion of patient care.'' We 
revised the proposed language based on the two comments to state: 
``Waste generated during the delivery of patient care by health care 
professionals from a patient diagnosed with an illness or condition 
associated with a select agent, where such waste is, within seven days 
of the conclusion of patient care, decontaminated, or transferred for 
destruction in compliance with state and Federal regulations.''
    We revised the proposed exemption language in 42 CFR 73.5(a)(3), 
and 42 CFR 73.6(a)(3) to provide that, unless otherwise directed by the 
HHS Secretary or APHIS Administrator, as appropriate, ``the clinical or 
diagnostic specimens collected from a patient infected with a select 
agent are transferred in accordance with Sec.  73.16 or destroyed on-
site by a recognized sterilization or inactivation process within seven 
days after delivery of patient care by health care professionals has 
concluded.''
    For specimens generated from the patient, the specimens are not 
subject to the select agent regulations for only the period that they 
are directly associated with the diagnosis. In accordance with sections 
five and six of the select agent regulations, within seven calendar 
days after identification, a specimen is subject to the select agent 
regulations

[[Page 6285]]

and must be transferred in accordance with section 73.16 or destroyed 
on-site by a recognized sterilization or inactivation process. Since 
the material would be excluded from the regulations, there would be no 
requirement to document the transfer or destructions. A specimen must 
be secured against theft, loss, or release during the period between 
identification and transfer or destruction, and any theft, loss, or 
release of the specimen must be reported. All specimens generated from 
the patient and kept more than seven days after acute patient care 
concludes would be subject to the select agent regulations.
v. Exemptions for Select Agents and Toxins
Informing Specimen Provider
    Since a registered or reference laboratory typically confirms the 
identification of a select agent or toxin for public health and 
agriculture, we proposed to require that a registered or reference 
laboratory inform the specimen provider of the identification as a 
condition for a clinical or diagnostic laboratory to maintain their 
exemption under 42 CFR 73.5(a), and 42 CFR 73.6(a). Two commenters 
stated they did not believe basic good practices require regulations. 
We made no changes based on these comments because this provision will 
ensure that the reference laboratory notifies the specimen provider of 
the identification of the select agent or toxin. It is important that 
the specimen provider is aware that they are in possession of the agent 
or toxin and must meet the requirements outlined in 42 CFR 73.5, 73.6 
(e.g., cannot maintain possession of the select agent or toxin, must 
destroy or get approval for a transfer, and report a theft, loss, or 
release).
Identification of Toxin
    In the current select agent regulations, in order for clinical or 
diagnostic laboratories to maintain their exemption under 42 CFR 
73.5(a), and 42 CFR 73.6(a), the clinical or diagnostic laboratory 
must, either immediately or within seven calendar days, report the 
identification of a select agent or toxin to APHIS or CDC unless 
directed otherwise by HHS Secretary or APHIS Administrator. In the 
NPRM, we proposed to amend the language in 42 CFR 73.5(a), and 42 CFR 
73.6(a) to state: ``Unless directed otherwise by the Secretary, within 
seven calendar days after identification of the select agent or toxin 
(except for Botulinum neurotoxin (BoNT) and/or Staphylococcal 
enterotoxins (Subtypes A-E)), or within 30 calendar days after 
identification of Botulinum neurotoxin and/or Staphylococcal 
enterotoxin (Subtypes A-E), the select agent or toxin is transferred in 
accordance with Sec.  73.16 or destroyed on-site by a recognized 
sterilization or inactivation process.'' We sought comments concerning 
(1) the extension of the exemption time period to 30 days for BoNT and 
Staphylococcal enterotoxin (Subtypes A-E) to allow clinical and 
diagnostic laboratories sufficient time to complete their 
investigations without having to transfer or destroy the sample, and 
(2) whether seven calendar days provided sufficient amount of time for 
the entity to destroy or transfer other select agents or toxins after 
identification. We received one comment to extend the amount of time 
for other select agents or toxins to 10 calendar days since destruction 
may not occur on-site, therefore allowing the secure transport to the 
ultimate site of disposition. We made no changes to adjust the seven 
calendar day requirement for agents or toxins other than BoNT and 
Staphylococcal enterotoxin (Subtypes A-E) because the other agents or 
toxins do not involve the identification of both agent and toxin as 
part of diagnosis. Therefore, these situations are not as complicated 
and do not warrant additional time for reporting identification.
vi. Registration
    We are codifying in regulation the current FSAP policy that an 
entity is required to meet all of the regulatory requirements for those 
select agents and toxins listed on an entity's registration regardless 
of whether the select agent or toxin is in the actual possession of an 
entity, and without regard to the actual amounts of toxins in the 
possession of an entity. We received no comments regarding this 
proposal and have made no changes to the language in the proposed rule.
vii. Responsible Official
    Section 73.9(a)(6) of the select agent regulations currently states 
that the RO must ensure that an annual inspection is conducted for each 
laboratory where select agents and toxins are stored or used. This 
requirement also provides that the results of each inspection must be 
documented, and any deficiencies identified during an inspection must 
be corrected. We proposed adding a requirement that the RO must also 
document the corrective actions taken by the entity to address any 
identified deficiencies. We received one comment that supported this 
proposed requirement and are finalizing the requirement as proposed.
HHS or USDA Office of the Inspector General Hotline
    In its December 2014 report, the Federal Experts Security Advisory 
Panel (FESAP) recommended adding a specific regulatory requirement 
addressing how individuals are informed of the availability of 
procedures for accessing the HHS or USDA Office of Inspector General 
Hotlines to anonymously report a safety or security concern. In 
response to that recommendation, we proposed adding a requirement that 
the RO must ensure that individuals at their entity are provided the 
contact information of the HHS Office of Inspector General Hotline and 
USDA Office of Inspector General Hotline so that an individual is able 
to anonymously report a biosafety or security concern related to select 
agents and toxins. We received no comments regarding this proposed 
addition and are finalizing the requirement as proposed.
viii. Visitor Access to Select Agents and Toxins
    Section 73.10(e) of the select agent regulations currently provides 
that a person with a valid approval from the HHS Secretary or APHIS 
Administrator to have access to select agents and toxins may request, 
through his or her RO, that the HHS Secretary or APHIS Administrator 
provide their approved access status to another registered individual 
or entity for a specified period of time. This allows a person with 
approved access at a registered entity to have approved access to a 
select agent at another registered entity. To ensure that the RO of the 
entity hosting such a visitor is aware if a visiting individual loses 
access approval to select agents and toxins, we added a requirement 
that the RO at the home entity must immediately notify the RO of the 
visiting entity if a person's access to select agents or toxins has 
been terminated. We received one comment that supported this addition 
to the regulations and are finalizing the requirement as proposed.
ix. Security, Biosafety, and Incident Response Plans
    The select agent regulations require a registered entity to develop 
and implement a number of plans in order to ensure the safety and 
security of the select agents and toxins they handle. These are:
     A security plan that provides for measures sufficient to 
safeguard a select agent or toxin against unauthorized access, theft, 
loss, or release (42 CFR 73.11);

[[Page 6286]]

     A biosafety plan that provides for measures sufficient to 
contain a select agent or toxin (42 CFR 73.12); and
     An incident response plan that provides for measures that 
the registered entity will implement in the event of theft, loss, or 
release of a select agent or toxin; inventory discrepancies; security 
breaches (including information systems); severe weather and other 
natural disasters; workplace violence; bomb threats and suspicious 
packages; and emergencies such as fire, gas leak, explosion, power 
outage, or others. (42 CFR 73.14).
    The select agent regulations require that drills or exercises must 
be conducted at least annually to test and evaluate the effectiveness 
of the plans, and that the plans must be reviewed and revised, as 
necessary, after any drill or exercise, and after any incident. We 
proposed to require that these drills or exercises be documented to 
include how the drill or exercise tested and evaluated the plan, any 
problems identified and corrective actions that were taken, and the 
names of the individuals who participated in the drill or exercise. 
Three commenters stated that there was no need to codify the 
documentation of how a drill or exercise evaluated a plan and 
corrective actions in regulations because they believed this 
requirement is already being documented. We are making no changes based 
on the comments because this requirement will provide a more thorough 
accounting of required activities via testing and entity-directed 
improvements.
    Another commenter requested clarification regarding the recording 
of the names of individuals who participate in drills or exercises. The 
commenter believed the requirement should be limited to registered 
entity personnel and not include first responders or other non-entity 
participants, but list only the participating external agencies (e.g., 
emergency management, emergency medical services, or fire department). 
We agreed with the commenter and have amended the proposed regulatory 
language to clarify that an entity only needs to document the names of 
individuals at the registered entity. An entity may choose to list the 
external agencies who participated in the drill or exercise.
    Similar to the existing requirement for the security plan, we 
proposed to add a requirement that the biosafety and incident response 
plans be submitted for initial registration, renewal of registration, 
or when requested by FSAP. We received two comments regarding these 
proposals which supported this requirement. However, one commenter 
questioned the need for additional requirements as this is already done 
routinely. While we agreed with the commenter that some, or even most, 
entities already provide the plans routinely, we are making no changes 
to the proposed language so that all entities will be required to 
submit their biosafety and incidence response plans, consistent with 
the existing requirement for the security plan.
Security
    We proposed amending the requirement that a security plan contain a 
description of how the entity authorizes the means of entry into areas 
where select agents or toxins are stored or used, to add a requirement 
that the security plan must include a description of centralized access 
control management systems (e.g., keycards) and/or key management 
(e.g., mechanical keys). We proposed this requirement because during 
our inspections of registered entities we have observed that the 
central access control management system in some instances is 
controlled, either on- or off-site, by individuals who (1) have not 
received access approval from HHS Secretary or APHIS Administrator, and 
(2) have the ability to assign people access or override access 
controls without the knowledge of the entity's RO. Three commenters 
suggested that access management processes are sensitive and a greater 
security risk may result from having too detailed information available 
in a single document. One commenter recommended we include a definition 
of what an access control system is and what components need to be 
included in the security plan. After considering the comments and 
reconsidering the purpose of the proposed language, we are not 
finalizing the proposed revision. Our concerns about unauthorized 
persons either having access or granting access without the knowledge 
of the entity RO can be addressed by the current provisions found in 
subsections (c)(1) and (c)(2) of section 11 (security) of the select 
agent regulations, which make the RO responsible to ensure access 
controls, irrespective of the type of security system in place.
    Paragraphs (d)(7)(i) through (d)(7)(v) of section 11 (security) of 
the select agent regulations encompass a list of events that 
individuals with access approval from the HHS Secretary or the APHIS 
Administrator must immediately report to the RO. We proposed to add a 
new requirement that the RO must be notified of any loss of computer, 
hard drive, or other data storage device containing information that 
could be used to gain access to select agents or toxins. We received 
one comment requesting clarification on the time frame for 
notification. We made no changes based on the comment since the 
regulations under subsection (d) already provide that notification must 
be immediate. The notification will facilitate notification of the 
Federal Bureau of Investigation (FBI) if deemed necessary by the RO as 
the loss of such equipment may be criminal in nature.
Biosafety
    We proposed amending the regulatory language in section 73.12 of 
the select agent regulations to update the name change of the National 
Institutes of Health (NIH) ``Guidelines for Research Involving 
Recombinant or Synthetic Nucleic Acid Molecules'' (Ref. 2). We received 
no comments and are finalizing this change as proposed.
    The biosafety section of the select agent regulations contains a 
reference to the Occupational Safety and Health Administration (OSHA) 
regulations found in 29 CFR 1910.1200 and 1910.1450. These sections 
provide specific requirements for handling hazardous chemicals in the 
laboratories. These regulations also provide recommendations for safely 
working with chemicals including toxins and give non-mandatory 
recommendations for prudent practices in laboratories handling chemical 
hazards. Since the current edition of the CDC/NIH ``Biosafety in 
Microbiological and Biomedical Laboratories'' Appendix I (Ref. 3) now 
provides guidelines for work with toxins of biological origin, we 
proposed removal of the reference to these OSHA regulations. We note, 
however, that regulated entities are still required to meet the OSHA 
regulatory requirements where applicable. We received no comments and 
are finalizing this change as proposed.
    In the NPRM, we proposed adding the requirement that ``biosafety 
and containment procedures specific to each registered laboratory must 
be available to each individual working in that laboratory.'' We 
proposed adding this language to ensure that laboratory personnel 
working with select agents and toxins have access to relevant biosafety 
information and are therefore aware of the risks associated with these 
agents. One commenter requested clarification regarding the term 
``laboratory'' and whether the term referred to a single room or a 
building or to a group of rooms (e.g., laboratory, animal room, 
necropsy) used by a Principal Investigator for a research project. The 
commenter also requested

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clarification on the language ``must be available to each individual 
working in the laboratory'' and whether this implied that there must be 
a specific biosafety manual for each room. We also received three 
comments that questioned the need for a new requirement since the 
commenters believe a laboratory-specific biosafety manual was already 
accessible to individuals. We are not adding the proposed provision to 
the regulations because upon further reflection we agree with the 
commenters that individuals already have access to their biosafety 
plan.
    In the NPRM, we proposed adding specific provisions to the 
biosafety section that would require (1) a written risk assessment for 
each registered select agent or toxin; (2) written safety procedures to 
protect entity personnel, the public, and the environment from exposure 
to the select agent or toxin; (3) written decontamination procedures; 
and (4) written waste management procedures. We received 13 comments 
that stated that ``risk assessments'' should be defined and the 
proposed requirement of having these for each procedure involving a 
select agent or toxin that addresses the hazards associated with the 
agent or toxin must be clarified because risk assessments are completed 
through institutional review committees by collaborative processes with 
Principal Investigators and biosafety professionals. One commenter 
stated that a risk assessment was always a requirement. We agree with 
the commenters that ``risk assessment for each procedure'' should not 
be required and agreed that having a risk assessment was already 
addressed in the regulations as outlined in Section 12(a) that ``An 
individual or entity required to register under this part must develop 
and implement a written biosafety plan that is commensurate with the 
risk of the select agent or toxin, given its intended use.'' However, 
we have clarified in the final regulatory language found in section 
12(a)(1) of the select agent regulations that the biosafety plan 
include ``the hazardous characteristics of each agent or toxin listed 
on the entity's registration and the biosafety risk associated with 
laboratory procedures related to the select agent or toxin.''
    The majority of the commenters stated that the approach outlined in 
the NPRM discussion of section 12(a) would lead to decreased compliance 
and an increase in paperwork burden. One commenter stated that many 
biosafety plans are already upwards of 50 pages, and increasing the 
length further may greatly decrease the likelihood that researchers 
will continue to read these plans and use them as a resource. Another 
commenter stated that regulatory language should be omitted to prevent 
creating a redundant process such as those provisions already covered 
under training and incident response. We agree with commenters and have 
removed the training and incident response language that was noted in 
the NPRM because these provisions are already covered by other sections 
in the regulations (i.e., incident response and training sections). We 
combined other provisions to reduce the seven provisions listed in the 
NPRM to four provisions in the final rule.
    One commenter stated we should consider requiring the adoption of 
shared algorithms developed by the American Society for Microbiology 
(ASM) for use by clinical laboratories. These algorithms are presented 
as frequently asked questions (FAQs) from ASM to assist laboratories. 
We made no changes based on this comment because FSAP already provides 
FAQs to assist entities with meeting the biosafety requirements of the 
regulations.
    Another commenter recommended that we also offer the suggestion 
that entities consider implementing programs whereby personnel are 
required to work with another trained person (i.e., a ``buddy'' system 
or dual authentication) as an appropriate and effective proactive 
method for the prevention of laboratory acquired infections and 
accidental releases of select agents. We made no changes based on this 
comment as it is essential for entities to develop their own biosafety 
initiatives to meet their own needs. The commenter continued that many 
of these issues come down to the culture of safety in an entity, and 
adherence to established protocols and training. The commenters wanted 
the regulatory provisions to reflect an improved safety culture. Two 
commenters requested that we consider leaving the current provisions in 
place and develop guidance to assist entities that would include risk 
assessment, use of safety equipment, personal protective equipment, 
containment devices, and occupational health consideration. Another 
commenter stated that the new section appears redundant with the risk 
assessment(s) performed during review of work registrations by an 
Institutional Biosafety Committee. We agree with the commenters that 
the provisions focus on the hazards and risks associated with the 
select agents and toxins and the safety practices put in place by the 
entity to protect entity personnel, the public, and the environment. We 
have revised the proposed language to state that the biosafety plan 
must include the provisions found in section 12(a) of the select agent 
regulations (see Sec.  73.12(a)(1)-(4)). To address the commenters' 
suggestion that FSAP develop a guidance document regarding biosafety, 
additional guidance has been developed and is available at: http://www.selectagents.gov.
x. Training
    We proposed to amend section 15 of the select agent regulations to 
require that training be completed within 12 months of that 
individual's anniversary of receiving access approval from the HHS 
Secretary or the APHIS Administrator, or prior to his or her entry into 
an area where any select agents and toxins are used or stored, 
whichever occurs first. This change is necessary in order to ensure 
that individuals at registered entities receive timely training. We 
received no specific comments regarding this proposed change. However, 
seven commenters stated that we should include a description of the 
level of training necessary for personnel in varying positions with 
highly disparate job duties and responsibilities. The commenters 
requested that we clarify that the required training will be conducted 
at a level appropriate to the registered person's role and level of 
access to select agents. We made no changes based on this comment 
because the current regulatory language is clear that ``the training 
must address the particular needs of the individual, the work they will 
do, and the risks posed by the select agents or toxins.'' The training 
for the individuals should be determined by the entity based on at the 
level of which the individual will have access to select agents or 
toxins. The training that each person receives should be designed to 
ensure that they can carry out their responsibilities without causing 
harm to themselves, or to their fellow co[hyphen]workers, or to the 
public. We did clarify the regulatory language regarding training for 
an individual who must be escorted to specify that their training must 
be accomplished prior to the individual's entry into a registered area.
    One commenter also asked that we consider making ``training a pre-
requisite for access to select agents and toxins, and not a requirement 
for just being FSAP approved.'' The regulations in 42 CFR 73.15(a)(1) 
already requires that each approved individual receive information and 
training on biosafety, security (including security awareness), and 
incident response before that individual has access to any select 
agents and toxins. The same commenter

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asked that we clearly specify the requirements for both initial and 
annual training. While we made no changes to our regulatory language 
based on this comment, the document, ``Guidance for Meeting the 
Training Requirements of the Select Agent Regulations,'' found at 
http://www.selectagents.gov/guidance-training.html, has been amended to 
provide further detail and assistance regarding the content of initial 
and annual training. The same commenter stated that in two instances an 
employee's annual training deadline occurred in the middle of an 
extended medical leave during which it was not possible to complete the 
training, and the entity had to choose to either let the training 
become overdue, or to remove the individual from the registration and 
completely start over with the security risk assessment (SRA) approval 
process once the individual was back to work. The commenter stated that 
``SRA approved personnel could commonly be on other types of extended 
leave such as maternity leave, or on sabbatical doing research at 
another institution but still employed and SRA approved at their home 
institution.'' While we made no changes to our regulatory language 
based on this comment, we have updated our guidance, ``Guidance for 
Meeting the Training Requirements of the Select Agent Regulations,'' 
which is available at www.selectagents.gov, to include information on 
how to deal with situations regarding individuals that have extended 
absences from the laboratory.
xi. Records
    Based on our inspections of registered entities, we observed that 
not all entities maintain records of the final disposition of select 
agents when consumed or destroyed, and this impedes validation of 
inventory holdings. Section 73.17 of the select agent regulations 
currently does not include a requirement for documenting the final 
disposition of a select agent. To ensure the proper tracking of a 
select agent from acquisition to final disposition, we are adding a 
requirement for entity records to include the final disposition 
(including destruction) for each select agent that has been held in 
long-term storage. One commenter expressed concern that a requirement 
for a record of destruction of select agents would place an undue 
burden on investigators and recommended that this requirement be 
excluded from the final rule. However, the commenter did agree that an 
entity should be required to maintain a current and accurate inventory 
of all select agents in their possession and document when an agent is 
no longer in their possession. We agree with the commenter that final 
disposition needs to be part of the entity's recordkeeping requirement. 
We disagree with the commenter that this will place undue burden on 
investigators because this information can be included with an entity's 
existing recordkeeping system (e.g., inventory spreadsheet). Therefore, 
to clarify the regulatory language, we have revised the proposed 
regulatory language to provide that the record will need to include 
``the select agent used, purpose of use, and, when applicable, final 
disposition.''
    Section 73.17 of the select agent regulations currently states that 
records and databases need to be accurate. To ensure that the accuracy 
of handwritten records can be verified, we proposed to clarify that a 
handwritten record must be legible (i.e., capable of being read). We 
received one comment requesting that we define the term ``legible 
handwritten records.'' We made no changes based on this comment because 
we are using the term ``legible'' in its ordinary meaning.
    We proposed to expand the scope of records required to be 
maintained to include any records that contain information related to 
the requirements of the regulations. We received five comments that 
expressed concerns about the information being kept in laboratory 
notes. The commenters stated that the information is ``proprietary in 
nature,'' contains intellectual property information and should not be 
required to be provided to FSAP inspectors. We understand the concerns 
of the commenters and clarified the language to indicate that it is 
only information related to requirements of the select agent 
regulations that must be produced on request. Such information may be 
found in the biocontainment certifications, laboratory notebooks, 
institutional biosafety and/or animal use committee minutes and 
approved protocols, and records associated with occupational health and 
suitability programs. Accordingly, we will only review relevant 
portions of any laboratory notebooks or documents, and only if they 
contain information related to any requirements of the regulations 
under sections 73.5, 73.7, 73.9, 73.11, 73.12, 73.14, 73.15, 73.16, 
73.17, and 73.19 of the select agent regulations. Two commenters stated 
that certain records are ``protected under the HIPAA Privacy Rule.'' 
FSAP would expect any information provided to FSAP regarding an 
individual's health would be provided in accord with the HIPAA Privacy 
Rule, including the use and disclosure of protected health information 
to public health authorities authorized by law to collect or receive 
such information for preventing or controlling disease, injury, or 
disability.
Records for Long-Term Storage
    In the NPRM we also solicited information and ideas as to how a 
regulatory requirement could be constructed such that a registered 
entity would know whether a select agent or toxin had been lost or 
stolen, without that registered entity first having ``an accurate, 
current inventory for each select agent . . . held in long-term 
storage.'' In addition, we requested ideas as to how the current 
regulations could be amended to address the threat of the theft of a 
select agent from a container held in long-term storage. We received 
three comments that addressed this request. One commenter suggested 
that FSAP inspectors review the record of select agents held in long-
term storage and accept the attestation of the responsible 
investigators of their accuracy. Another commenter stated we should 
continue with FSAP's current select agent practices to allow for these 
stocks to be maintained in tamper-evident containers (e.g., security 
ties on freezer boxes) so that vials are not individually removed, 
thawed, and measured. The third commenter recommended dual 
authentication coupled with required entity inventory reviews. We 
appreciate the comments and will continue to consider how the 
recognition of theft and loss might be addressed through alternative 
approaches.

III. Alternatives Considered

    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 requires HHS and USDA to review and republish the 
list of select agents and toxins every two years. In drafting this 
final rule, we considered the action proposed in the NPRM of removing 
the six select agents and one toxin where its costs and benefits were 
discussed. If those policies were adopted, it would result in savings 
ranging from approximately $15,300 for a small commercial BSL-3 
laboratory to approximately $165,000 for a larger university with BSL-
2/3 laboratories for laboratories no longer regulated. Based on the 
review of FSAP database, approximately eleven small entities would no 
longer be regulated and would not be required to register with FSAP. If 
the entities withdrew their registration, it would result in an 
estimated saving of $168,300 annually. On the other hand, this policy 
could increase the likelihood of entities working with these removed 
select agents and toxin not having the

[[Page 6289]]

appropriate biosafety and security provisions in place to prevent an 
accidental or intentional release of a select agent or toxin. The 
intentional release could adversely affect the public health and 
safety. Recent events concerning the accidental transfer of select 
agents that had not been fully inactivated, leading to the inadvertent 
release of select agents, caused us to also look at provisions in this 
regulation. After carefully considering the technical input of subject 
matter experts, both within the Federal government and from public 
comments, and recommendations from Federal advisory groups, we have 
decided not to finalize the proposed changes to the list of select 
agents and toxins at this time.

IV. Required Regulatory Analyses

A. Executive Orders 12866 and 13563

    Under Executive Order (E.O.) 12866, Regulatory Planning and Review 
(58 FR 51735, October 4, 1993), CDC is required to determine whether 
this regulatory action would be ``significant'' and therefore subject 
to review by the Office of Management and Budget (OMB) and the 
requirements of the Executive Orders (E.O.). E.O. 12866 defines 
``significant regulatory action'' as any regulatory action that is 
likely to result in a rule that may:
     Have an annual effect on the economy of $100 million or 
more or adversely affect in a material way the economy, a sector of the 
economy, productivity, competition, jobs, the environment, public 
health or safety, or state, local, or tribal governments or 
communities;
     Create a serious inconsistency or otherwise interfere with 
an action taken or planned by another agency;
     Materially alter the budgetary impact of entitlements, 
grants, user fees, or loan programs or the rights and obligations of 
recipients; or,
     Raise novel legal or policy issues arising out of legal 
mandates, the President's priorities, or the principles set forth in 
E.O. 12866.
    E.O. 13563, Improving Regulation and Regulatory Review, (76 FR 
3821, January 21, 2011), updates some of the provisions of E.O. 12866 
in order to promote more streamlined regulatory actions. This E.O. 
charges, in part, that, while protecting ``public health, welfare, 
safety, and our environment'' that regulations must also ``promote 
predictability and reduce uncertainty'' in order to promote economic 
growth. Further, regulations must be written in plain language and be 
easy to understand.
    We have prepared an economic analysis for this rule. The economic 
analysis provides a cost-benefit analysis, as required by E.O. 12866, 
and a final regulatory flexibility analysis (See Section III.B. of this 
Preamble) that examines the potential economic effects of this rule on 
small entities, as required by the Regulatory Flexibility Act. The 
economic analysis is summarized below. Copies of the full analysis are 
available in the docket at www.regulations.gov or at www.select 
agents.gov.
    We have determined that this final rule is significant for the 
purposes of Executive Order 12866 and, therefore, this final rule has 
been reviewed by OMB.
Summary of the Regulatory Impact Analysis
    The Public Health Security and Bioterrorism Preparedness and 
Response Act of 2002 (Pub. L. 107-188) provides for the regulation of 
certain biological agents and toxins that have the potential to pose a 
severe threat to human, animal, or plant health, or to animal or plant 
products. APHIS and CDC have primary responsibility for implementing 
the provisions of the Act within the Department of Agriculture and the 
Department of Health and Human Services, respectively. Within APHIS, 
Veterinary Services (VS) select agents and toxins are those that have 
been determined to have the potential to pose a severe threat to animal 
health or animal products, and Plant Protection and Quarantine (PPQ) 
select agents and toxins are those that have been determined to have 
the potential to pose a severe threat to plant health or plant 
products. HHS select agents and toxins are those that have been 
determined to have the potential to pose a severe threat to human 
health. APHIS and CDC coordinate regulatory activities for overlap 
select agents and toxins that have been determined to pose a severe 
threat to human and animal health or products.
    Sections 201 and 212(a)(2) of the Act require a biennial review and 
republication of the select agent and toxin list, with revisions as 
appropriate in accordance with this law. These final rules will 
implement the recommendations of the fourth biennial review of select 
agent regulations and have finalized changes that will increase their 
usability as well as provide for enhanced program oversight. These 
amendments include new provisions regarding the inactivation of select 
agents, specific biosafety and toxin requirements and clarification of 
regulatory language concerning security, training, and records.
    The final rule will require that entities develop validated 
inactivation procedures for select agents or regulated infectious 
nucleic acid and maintain written records of having done so. Costs of 
complying with this amendment are expected to be modest.
    Currently, there are 286 entities registered with APHIS and CDC 
including 91 academic, 53 commercial, 81 State government, 45 Federal 
government, and 16 private (non-profit) institutions, most of which are 
considered to be small entities. Based on current record keeping and 
reporting requirements, an additional 10 to 20 hours per year may be 
required for maintaining records associated with select agents or 
material containing select agents or regulated nucleic acids that can 
produce infectious forms of any select agent virus that have been 
subjected to a validated inactivation procedure or a procedure for 
removal of viable select agents. At an imputed cost of $33.40 per hour 
(GS-12, step 2), this additional time requirement per entity will cost 
between $334 and $668 per year, or in total for all registered entities 
between $80,000 and $160,000. The final rule will not have a 
significant economic impact on a substantial number of small entities. 
Costs associated with this rule do not include costs related to 
training, overhead, updates to facilities, etc. We assume in this rule 
that all costs associated with such factors for entities performing 
inactivation procedures have already been incurred prior to rulemaking.
    The benefits of strengthened safeguards against the unintentional 
or deliberate release of a select agent or toxin greatly exceed 
compliance costs of the rules. As an example of losses that can occur, 
the October 2001 anthrax attacks caused five fatalities and 17 
illnesses, disrupted business and government activities (including $2 
billion in lost revenues for the Postal Service), and required more 
than $23 million to decontaminate one Senate office building and $3 
billion to decontaminate postal facilities and procure mail-sanitizing 
equipment. Deliberate introduction greatly increases the probability of 
a select agent becoming established and causing wide-ranging and 
devastating impacts to the economy, other disruptions to society, and 
diminished confidence in public and private institutions.
    The amended regulations will enhance the protection of human, 
animal, and plant health and safety. The final rules will reduce 
likelihood of the accidental or intentional release of a

[[Page 6290]]

select agent or toxin. Benefits of the rules will derive from the 
greater probability that a release will be prevented from occurring.

B. The Regulatory Flexibility Act (RFA), as Amended by the Small 
Business Regulatory Enforcement Fairness Act (SBREFA)

    We have examined the impacts of the proposed rule under RFA (5 
U.S.C. 601-612). Unless we certify that the proposed rule is not 
expected to have a significant economic impact on a substantial number 
of small entities, RFA, as amended by the Small Business Regulatory 
Enforcement Fairness Act (SBREFA), requires agencies to analyze 
regulatory options that would minimize any significant economic impact 
of a rule on small entities. We certify that this proposed rule will 
not have a significant economic impact on a substantial number of small 
entities within the meaning of the RFA because these registered 
entities are already required to comply with the select agent 
regulations. The small entities would only incur some costs if they are 
performing inactivation procedures and are not maintaining records. The 
additional costs that may be incurred are small in comparison to the 
long-term benefits of additional protection against the release of 
select agents and toxins that would result in devastating effects to 
the economy.
    This regulatory action is not a major rule as defined by Sec. 804 
of the Small Business Regulatory Enforcement Fairness Act of 1996. This 
proposed rule will not result in an annual effect on the economy of 
$100,000,000 or more; a major increase in cost or prices; or 
significant adverse effects on competition, employment, investment, 
productivity, innovation, or on the ability of United States-based 
companies to compete with foreign-based companies in domestic and 
export markets.

C. Paperwork Reduction Act of 1995

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), CDC has determined that the Paperwork 
Reduction Act does apply to information collection and recordkeeping 
requirements included in this rule. We note that the information 
collection and recordkeeping requirements are already approved by the 
Office of Management and Budget (OMB) under OMB Control Number 0920-
0576 (Possession, Use, and Transfer of Select Agents and Toxins (42 CFR 
73), Expiration 12/31/2018).

D. E.O. 12988: Civil Justice Reform

    This rule has been reviewed under E.O. 12988, Civil Justice Reform. 
Once the final rule is in effect, CDC notes that: (1) All State and 
local laws and regulations that are inconsistent with this rule will be 
preempted; (2) No retroactive effect will be given to this rule; and 
(3) Administrative proceedings will not be required before parties may 
file suit in court challenging this rule.

E. E.O. 13132: Federalism

    HHS/CDC has reviewed this final rule in accordance with E.O. 13132 
regarding Federalism, and has determined that it does not have 
``federalism implications.'' The rule does not ``have substantial 
direct effects on the States, on the relationship between the national 
government and the States, or on the distribution of power and 
responsibilities among the various levels of government.''

F. Plain Language Act of 2010

    Under the Plain Language Act of 2010 (Pub. L. 111-274, October 13, 
2010), executive Departments and Agencies are required to use plain 
language in documents that explain to the public how to comply with a 
requirement the Federal Government administers or enforces. HHS/CDC has 
attempted to use plain language in promulgating this rule consistent 
with the Federal Plain Writing Act guidelines.

V. References

1. D.R. Franz and N.K. Jaax (1997). Defense Against Toxin Weapons 
(Chapter 30). In Textbook of Military Medicine: Medical Aspects of 
Chemical and Biological Warfare, Borden Institute, Walter Reed Army 
Medical Center, Washington, DC. 631-642.
2. U.S. Department of Health and Human Services, National Institutes 
of Health. (2013). NIH Guidelines for Research Involving Recombinant 
Or Synthetic Nucleic Acid Molecules (NIH Guidelines). Retrieved from 
http://osp.od.nih.gov/sites/default/files/NIH_Guidelines.html.
3. U.S. Department of Health and Human Services, Centers for Disease 
Control and Prevention and National Institutes of Health. (2009). 
Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th 
Edition. Retrieved from http://www.cdc.gov/biosafety/publications/bmbl5/index.htm.

List of Subjects in 42 CFR Part 73

    Biologics, Packaging and containers, Penalties, Reporting and 
recordkeeping requirements, and Transportation.

    For the reasons discussed in the preamble, we amend 42 CFR part 73 
as follows:

PART 73--SELECT AGENTS AND TOXINS

0
1. The authority citation for part 73 continues to read as follows:

    Authority: 42 U.S.C. 262a; sections 201-2014, 221 and 231 of 
Title II of Public Law 107-188, 116 Stat 637 (42 U.S.C. 262a).


0
2. Section 73.1 is amended by adding in alphabetical order, definitions 
of validated inactivation procedure and viability testing protocol to 
read as set forth below.


Sec.  73.1  Definitions.

* * * * *
    Validated inactivation procedure means a procedure, whose efficacy 
is confirmed by data generated from a viability testing protocol, to 
render a select agent non-viable but allows the select agent to retain 
characteristics of interest for future use; or to render any nucleic 
acids that can produce infectious forms of any select agent virus non-
infectious for future use.
* * * * *
    Viability testing protocol means a protocol to confirm the 
validated inactivation procedure by demonstrating the material is free 
of all viable select agent.
* * * * *

0
3. Section 73.3 is amended as follows:
0
a. By revising paragraph (b).
0
b. By removing ``functional'' and adding in its place ``toxic'' in 
paragraph (c)(2).
0
c. By revising paragraph (d)(2).
0
d. By redesignating paragraph (d)(3) as (d)(7) and revising 
redesignated paragraphs (d)(7) introductory text and (d)(7)(i).
0
e. By redesignating paragraph (d)(4) as paragraph (d)(8).
0
f. By redesignating paragraph (d)(5) as paragraph (d)(12).
0
g. By adding new paragraphs (d)(3), (d)(4), (d)(5), (d)(6), (d)(9), 
(d)(10) and (d)(11).
0
h. By adding paragraph (e)(3).
0
i. By adding ``Bacillus cereus Biovar anthracis,'' before ``Botulinum 
neurotoxins'' in paragraph (f)(3)(i).
    The additions and revisions read as follows:


Sec.  73.3  HHS select agents and toxins.

* * * * *
    (b) HHS select agents and toxins:

Abrin
Bacillus cereus Biovar anthracis*
Botulinum neurotoxins*
Botulinum neurotoxin producing species of Clostridium*
Conotoxins (Short, paralytic alpha conotoxins containing the following

[[Page 6291]]

amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7) \1\
---------------------------------------------------------------------------

    \1\ C = Cysteine residues are all present as disulfides, with 
the 1st and 3rd Cysteine, and the 2nd and 4th Cysteine forming 
specific disulfide bridges; The consensus sequence includes known 
toxins [alpha]-MI and [alpha]-GI (shown above) as well as [alpha]-
GIA, Ac1.1a, [alpha]-CnIA, [alpha]-CnIB; X1 = any amino acid(s) or 
Des-X; X2 = Asparagine or Histidine; P = Proline; A = Alanine; G = 
Glycine; X3 = Arginine or Lysine; X4 = Asparagine, Histidine, 
Lysine, Arginine, Tyrosine, Phenylalanine or Tryptophan; X5 = 
Tyrosine, Phenylalanine, or Tryptophan; X6 = Serine, Threonine, 
Glutamate, Aspartate, Glutamine, or Asparagine; X7 = Any amino 
acid(s) or Des X and; ``Des X'' = ``an amino acid does not have to 
be present at this position.'' For example if a peptide sequence 
were XCCHPA then the related peptide CCHPA would be designated as 
Des-X.
---------------------------------------------------------------------------

Coxiella burnetii
Crimean-Congo hemorrhagic fever virus
Diacetoxyscirpenol
Eastern equine encephalitis virus
Ebola virus*
Francisella tularensis*
Lassa fever virus
Lujo virus
Marburg virus*
Monkeypox virus
Reconstructed replication competent forms of the 1918 pandemic 
influenza virus containing any portion of the coding regions of all 
eight gene segments (Reconstructed 1918 influenza virus)
Ricin
Rickettsia prowazekii
SARS coronavirus (SARS-CoV)
Saxitoxin
South American hemorrhagic fever viruses:
    Chapare
    Guanarito
    Junin
    Machupo
    Sabia
Staphylococcal enterotoxins (subtypes A-E)
T-2 toxin
Tetrodotoxin
Tick-borne encephalitis virus
    Far Eastern subtype
    Siberian subtype
Kyasanur Forest disease virus
Omsk haemorrhagic fever virus
Variola major virus (Smallpox virus)*
Variola minor virus (Alastrim)*
Yersinia pestis*
* * * * *
    (d) * * *
    (2) Non-viable HHS select agents or nontoxic HHS toxins.
    (3) A select agent or toxin that has been subjected to 
decontamination or a destruction procedure when intended for waste 
disposal.
    (4) A select agent or regulated nucleic acids that can produce 
infectious forms of any select agent virus that has been subjected to a 
validated inactivation procedure that is confirmed through a viability 
testing protocol. Surrogate strains that are known to possess 
equivalent properties with respect to inactivation can be used to 
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an 
inactivation procedure, then an inactivation procedure validated on a 
lesser resistant strain must also be validated on the more resistant 
strains.
    (5) Material containing a select agent that is subjected to a 
procedure that removes all viable select agent cells, spores, or virus 
particles if the material is subjected to a viability testing protocol 
to ensure that the removal method has rendered the material free of all 
viable select agent.
    (6) A select agent or regulated nucleic acids that can produce 
infectious forms of any select agent virus not subjected to a validated 
inactivation procedure or material containing a select agent not 
subjected to a procedure that removes all viable select agent cells, 
spores, or virus particles if the material is determined by the HHS 
Secretary to be effectively inactivated or effectively removed. To 
apply for a determination an individual or entity must submit a written 
request and supporting scientific information to CDC. A written 
decision granting or denying the request will be issued.
    (7) Except as required in Sec.  73.16(l), the aggregate amount of 
the toxin under the control of a principal investigator, treating 
physician or veterinarian, or commercial manufacturer or distributor 
does not, at any time, exceed the following amounts: 1000 mg of Abrin; 
1 mg of Botulinum neurotoxins; 100 mg of Conotoxins (Short, paralytic 
alpha conotoxins containing the following amino acid sequence 
X1CCX2PACGX3X4X5X
6CX7); 10,000 mg of Diacetoxyscirpenol; 1000 mg 
of Ricin; 500 mg of Saxitoxin; 100 mg of Staphylococcal enterotoxins 
(subtypes A-E); 10,000 mg of T-2 toxin; or 500 mg of Tetrodotoxin. 
Provided that,
    (i) The toxin is transferred only after the transferor uses due 
diligence and documents the identification of the recipient and the 
legitimate need (e.g., prophylactic, protective, bona fide research, or 
other peaceful purpose) claimed by the recipient to use such toxin. 
Information to be documented includes, but is not limited to, the 
recipient identity information, including the recipient's name, 
institution name, address, telephone number and email address; name of 
the toxin and the total amount transferred; and the legitimate need 
claimed by the recipient. Notwithstanding the provisions of paragraph 
(d) of this section, the HHS Secretary retains the authority to, 
without prior notification, inspect and copy or request the submission 
of the due diligence documentation to the CDC.
* * * * *
    (9) An HHS select toxin identified in an original food sample or 
clinical sample.
    (10) For those laboratories that are not exempt under Sec.  73.5(a) 
and Sec.  73.6(a), Botulinum neurotoxin that is produced as a byproduct 
in the study of Botulinum neurotoxin producing species of Clostridium 
so long as the toxin has not been intentionally cultivated, collected, 
purified, or otherwise extracted, and the material containing the toxin 
is rendered non-toxic and disposed of within 30 days of the initiation 
of the culture.
    (11) Waste generated during the delivery of patient care by health 
care professionals from a patient diagnosed with an illness or 
condition associated with a select agent, where that waste is 
decontaminated or transferred for destruction by complying with state 
and Federal regulations within seven calendar days of the conclusion of 
patient care.
    (e) * * *
    (3) An individual or entity may make a written request to the HHS 
Secretary for reconsideration of a decision denying an application for 
the exclusion of an attenuated strain of a select agent or a select 
toxin modified to be less potent or toxic. The written request for 
reconsideration must state the facts and reasoning upon which the 
individual or entity relies to show the decision was incorrect. The HHS 
Secretary will grant or deny the request for reconsideration as 
promptly as circumstances allow and will state, in writing, the reasons 
for the decision.
* * * * *

0
4. Section 73.4 is amended as follows:
0
a. By revising paragraph (b).
0
b. By removing ``functional'' and adding in its place ``toxic'' in 
paragraph (c)(2).
0
c. By revising paragraph (d)(2).
0
d. By redesignating paragraph (d)(3) as (d)(9).
0
e. By adding new paragraphs (d)(3), (d)(4), (d)(5), (d)(6), (d)(7) and 
(d)(8).
0
f. By adding paragraph (e)(3).
    The revision and additions read as follows:


Sec.  73.4  Overlap select agents and toxins.

* * * * *
    (b) Overlap select agents and toxins:

Bacillus anthracis *
Bacillus anthracis Pasteur strain

[[Page 6292]]

Brucella abortus
Brucella melitensis
Brucella suis
Burkholderia mallei *
Burkholderia pseudomallei *
Hendra virus
Nipah virus
Rift Valley fever virus
Venezuelan equine encephalitis virus
* * * * *
    (d) * * *
    (2) Non-viable overlap select agents or nontoxic overlap toxins.
    (3) A select agent or toxin that has been subjected to 
decontamination or a destruction procedure when intended for waste 
disposal.
    (4) A select agent or regulated nucleic acids that can produce 
infectious forms of any select agent virus that has been subjected to a 
validated inactivation procedure that is confirmed through a viability 
testing protocol. Surrogate strains that are known to possess 
equivalent properties with respect to inactivation can be used to 
validate an inactivation procedure; however, if there are known strain-
to-strain variations in the resistance of a select agent to an 
inactivation procedure, then an inactivation procedure validated on a 
lesser resistant strain must also be validated on the more resistant 
strains.
    (5) Material containing a select agent that is subjected to a 
procedure that removes all viable select agent cells, spores, or virus 
particles if the material is subjected to a viability testing protocol 
to ensure that the removal method has rendered the material free of all 
viable select agent.
    (6) A select agent or regulated nucleic acids that can produce 
infectious forms of any select agent virus not subjected to a validated 
inactivation procedure or material containing a select agent not 
subjected to a procedure that removes all viable select agent cells, 
spores, or virus particles if the material is determined by the HHS 
Secretary or Administrator to be effectively inactivated or effectively 
removed. To apply for a determination an individual or entity must 
submit a written request and supporting scientific information to CDC 
or APHIS. A written decision granting or denying the request will be 
issued.
    (7) An overlap select toxin identified in an original food sample 
or clinical sample.
    (8) Waste generated during the delivery of patient care by health 
care professionals from a patient diagnosed with an illness or 
condition associated with a select agent, where that waste is 
decontaminated or transferred for destruction by complying with state 
and Federal regulations within seven calendar days of the conclusion of 
patient care.
* * * * *
    (e) * * *
    (3) An individual or entity may make a written request to the HHS 
Secretary or Administrator for reconsideration of a decision denying an 
application for the exclusion of an attenuated strain of a select agent 
or a select toxin modified to be less potent or toxic. The written 
request for reconsideration must state the facts and reasoning upon 
which the individual or entity relies to show the decision was 
incorrect. The HHS Secretary or Administrator will grant or deny the 
request for reconsideration as promptly as circumstances allow and will 
state, in writing, the reasons for the decision.
* * * * *

0
5. Section 73.5 is amended as follows:
0
a. By revising paragraph (a)(1).
0
b. By redesignating paragraph (a)(3) as paragraph (a)(4) and revising 
newly redesignated paragraph (a)(4).
0
c. By adding new paragraph (a)(3).
0
d. By adding ``Bacillus cereus Biovar anthracis,'' before ``Botulinum 
neurotoxins'' in paragraph (a)(3)(i).
    The revisions and addition read as follows:


Sec.  73.5  Exemptions for HHS select agents and toxins.

    (a) * * *
    (1) Unless directed otherwise by the HHS Secretary, within seven 
calendar days after identification of the select agent or toxin (except 
for Botulinum neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-
E)), or within 30 calendar days after identification of Botulinum 
neurotoxin and/or Staphylococcal enterotoxin (Subtypes A-E), the select 
agent or toxin is transferred in accordance with Sec.  73.16 or 
destroyed on-site by a recognized sterilization or inactivation 
process,
* * * * *
    (3) Unless otherwise directed by the HHS Secretary, the clinical or 
diagnostic specimens collected from a patient infected with a select 
agent are transferred in accordance with Sec.  73.16 or destroyed on-
site by a recognized sterilization or inactivation process within seven 
calendar days after delivery of patient care by health care 
professionals has concluded, and
    (4) The identification of the agent or toxin is reported to CDC or 
APHIS, the specimen provider, and to other appropriate authorities when 
required by Federal, State, or local law by telephone, facsimile, or 
email. This report must be followed by submission of APHIS/CDC Form 4 
to APHIS or CDC within seven calendar days after identification.
* * * * *

0
6. Section 73.6 is amended as follows:
0
a. By redesignating paragraph (a)(3) as paragraph (a)(4) and revising 
newly redesignated paragraph (a)(4).
0
b. By adding new paragraph (a)(3).
    The revision and addition read as follows:


Sec.  73.6  Exemptions for overlap select agents and toxins.

    (a) * * *
    (3) Unless otherwise directed by the HHS Secretary or 
Administrator, the clinical or diagnostic specimens collected from a 
patient infected with a select agent are transferred in accordance with 
Sec.  73.16 or destroyed on-site by a recognized sterilization or 
inactivation process within seven calendar days after delivery of 
patient care by health care professionals has concluded, and
    (4) The identification of the agent or toxin is reported to CDC or 
APHIS, the specimen provider, and to other appropriate authorities when 
required by Federal, State, or local law by telephone, facsimile, or 
email. This report must be followed by submission of APHIS/CDC Form 4 
to APHIS or CDC within seven calendar days after identification.
* * * * *

0
7. Section 73.7 is amended as follows:
0
a. By redesignating paragraphs (b) through (k) as paragraphs (c) 
through (l), respectively.
0
b. By adding a new paragraph (b) to read as follows:


Sec.  73.7  Registration and related security risk assessments.

* * * * *
    (b) As a condition of registration, each entity is required to be 
in compliance with the requirements of this part for select agents and 
toxins listed on the registration regardless of whether the entity is 
in actual possession of the select agent or toxin. With regard to 
toxins, the entity registered for possession, use or transfer of a 
toxin must be in compliance with the requirements of this part 
regardless of the amount of toxin currently in its possession.
* * * * *

0
8. Section 73.9 is amended as follows:
0
a. In paragraph (a)(6) by removing ``laboratory'' and adding in its 
place ``registered space'' and adding ``and the corrections 
documented'' after ``corrected'' at the end of the sentence.
0
b. By adding paragraphs (a)(7), (a)(8) and (a)(9) to read as set forth 
below.

[[Page 6293]]

0
c. By adding ``Bacillus cereus Biovar anthracis,'' after ``Bacillus 
anthracis,'' in paragraph (c)(1).


Sec.  73.9  Responsible Official.

    (a) * * *
    (7) Ensure that individuals are provided the contact information 
for the HHS Office of Inspector General Hotline and the USDA Office of 
Inspector General Hotline so that they may anonymously report any 
biosafety or security concerns related to select agents and toxins.
    (8) Investigate to determine the reason for any failure of a 
validated inactivation procedure or any failure to remove viable select 
agent from material. If the Responsible Official is unable to determine 
the cause of a deviation from a validated inactivation procedure or a 
viable select agent removal method; or receives a report of any 
inactivation failure after the movement of material to another 
location, the Responsible Official must report immediately by telephone 
or email the inactivation or viable agent removal method failure to CDC 
or APHIS.
    (9) Review, and revise as necessary, each of the entity's validated 
inactivation procedures or viable select agent removal methods. The 
review must be conducted annually or after any change in Principal 
Investigator, change in the validated inactivation procedure or viable 
select agent removal method, or failure of the validated inactivation 
procedure or viable select agent removal method. The review must be 
documented and training must be conducted if there are any changes to 
the validated inactivation procedure, viable select agent removal 
method, or viability testing protocol.
* * * * *

0
9. Section 73.10 is amended as follows:
0
a. By a sentence to the end of paragraph (e) to read as follows:


Sec.  73.10  Restricting access to select agents and toxins; security 
risk assessments.

* * * * *
    (e) * * * A Responsible Official must immediately notify the 
Responsible Official of the visited entity if the person's access to 
select agents and toxins has been terminated.
* * * * *

0
10. Section 73.11 is amended as follows:
0
a. In paragraph (c)(5) by adding ``keycards,'' between ``keys,'' and 
``passwords'' and removing ``numbers'' and adding in its place 
``permissions''.
0
b. By adding paragraph (d)(7)(vi).
0
c. By adding a sentence to the end of paragraph (h).
    The additions read as follows:


Sec.  73.11  Security.

* * * * *
    (d) * * *
    (7) * * *
    (vi) Any loss of computer, hard drive or other data storage device 
containing information that could be used to gain access to select 
agents or toxins.
* * * * *
    (h) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and the names of registered 
entity personnel participants.

0
11. Section 73.12 is amended as follows:
0
a. By revising paragraph (a).
0
b. By removing paragraph (c)(2), redesignating paragraph (c)(3) as 
(c)(2), and in newly redesignated paragraph (c)(2), removing ``NIH 
Guidelines for Research Involving Recombinant DNA Molecules'' and 
adding in its place ``NIH Guidelines for Research Involving Recombinant 
or Synthetic Nucleic Acid Molecules''.
0
c. By adding a new sentence to the end of paragraph (e).
    The revision and addition read as follows:


Sec.  73.12  Biosafety.

    (a) An individual or entity required to register under this part 
must develop and implement a written biosafety plan that is 
commensurate with the risk of the select agent or toxin, given its 
intended use. The biosafety plan must contain sufficient information 
and documentation to describe the biosafety and containment procedures 
for the select agent or toxin, including any animals (including 
arthropods) or plants intentionally or accidentally exposed to or 
infected with a select agent. The current biosafety plan must be 
submitted for initial registration, renewal of registration, or when 
requested. The biosafety plan must include the following provisions:
    (1) The hazardous characteristics of each agent or toxin listed on 
the entity's registration and the biosafety risk associated with 
laboratory procedures related to the select agent or toxin;
    (2) Safeguards in place with associated work practices to protect 
entity personnel, the public, and the environment from exposure to the 
select agent or toxin including, but not limited to: Personal 
protective equipment and other safety equipment; containment equipment 
including, but not limited to, biological safety cabinets, animal 
caging systems, and centrifuge safety containers; and engineering 
controls and other facility safeguards;
    (3) Written procedures for each validated method used for 
disinfection, decontamination or destruction, as appropriate, of all 
contaminated or presumptively contaminated materials including, but not 
limited to: Cultures and other materials related to the propagation of 
select agents or toxins, items related to the analysis of select agents 
and toxins, personal protective equipment, animal caging systems and 
bedding (if applicable), animal carcasses or extracted tissues and 
fluids (if applicable), laboratory surfaces and equipment, and effluent 
material; and
    (4) Procedures for the handling of select agents and toxins in the 
same spaces with non-select agents and toxins to prevent unintentional 
contamination.
* * * * *
    (e) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and the names of registered 
entity personnel participants.

0
12. Section 73.14 is amended as follows:
0
a. By adding a new sentence to the end of paragraph (a).
0
b. By adding a new sentence to the end of paragraph (f).
    The additions read as follows:


Sec.  73.14  Incident response.

    (a) * * * The current incident response plan must be submitted for 
initial registration, renewal of registration, or when requested.
* * * * *
    (f) * * * Drills or exercises must be documented to include how the 
drill or exercise tested and evaluated the plan, any problems that were 
identified and corrective action(s) taken, and the names of registered 
entity personnel participants.

0
13. Section 73.15 is amended as follows:
0
a. Revising paragraph (a) to read as set forth below.
0
b. By adding paragraph (e) to read as set forth below.


Sec.  73.15  Training.

    (a) An individual or entity required to register under this part 
must provide information and training on biocontainment, biosafety, 
security (including security awareness), and incident response to:
    (1) Each individual with access approval from the HHS Secretary or

[[Page 6294]]

Administrator. The training must address the particular needs of the 
individual, the work they will do, and the risks posed by the select 
agents or toxins. The training must be accomplished prior to the 
individual's entry into an area where a select agent is handled or 
stored, or within 12 months of the date the individual was approved by 
the HHS Secretary or the Administrator for access, whichever is 
earlier.
    (2) Each individual not approved for access to select agents and 
toxins by the HHS Secretary or Administrator before that individual 
enters areas under escort where select agents or toxins are handled or 
stored (e.g., laboratories, growth chambers, animal rooms, greenhouses, 
storage areas, shipping/receiving areas, production facilities, etc.). 
Training for escorted personnel must be based on the risk associated 
with accessing areas where select agents and toxins are used and/or 
stored. The training must be accomplished prior to the individual's 
entry into where select agents or toxins are handled or stored (e.g., 
laboratories, growth chambers, animal rooms, greenhouses, storage 
areas, shipping/receiving areas, production facilities, etc.).
* * * * *
    (e) The Responsible Official must ensure and document that 
individuals are provided the contact information of the HHS Office of 
Inspector General Hotline and the USDA Office of Inspector General 
Hotline so that they may anonymously report any safety or security 
concerns related to select agents and toxins.

0
14. Section 73.16 is amended by revising paragraph (l)(1) to read as 
follows:


Sec.  73.16  Transfers.

* * * * *
    (l) * * *
    (1) Transfer the amounts only after the transferor uses due 
diligence and documents that the recipient has a legitimate need (e.g., 
prophylactic, protective, bona fide research, or other peaceful 
purpose) to handle or use such toxins. Information to be documented 
includes, but is not limited, to the recipient information, toxin and 
amount transferred, and declaration that the recipient has legitimate 
purpose to store and use such toxins.
* * * * *

0
15. Section 73.17 is amended as follows:
0
a. In paragraphs (a)(1)(iii) and (a)(3)(v) by adding ``or other storage 
container'' after ``freezer''.
0
b. By revising paragraph (a)(1)(v).
0
c. By adding paragraph (a)(8).
0
d . By revising paragraph (b).
0
e. By revising paragraph (c).
    The revision and additions read as follows:


Sec.  73.17  Records.

    (a) * * *
    (1) * * *
    (v) The select agent used, purpose of use, and, when applicable, 
final disposition,
* * * * *
    (8) For select agents or material containing select agents or 
regulated nucleic acids that can produce infectious forms of any select 
agent virus that have been subjected to a validated inactivation 
procedure or a procedure for removal of viable select agent:
    (i) A written description of the validated inactivation procedure 
or viable select agent removal method used, including validation data;
    (ii) A written description of the viability testing protocol used;
    (iii) A written description of the investigation conducted by the 
entity Responsible Official involving an inactivation or viable select 
agent removal failure and the corrective actions taken;
    (iv) The name of each individual performing the validated 
inactivation or viable select agent removal method;
    (v) The date(s) the validated inactivation or viable select agent 
removal method was completed;
    (vi) The location where the validated inactivation or viable select 
agent removal method was performed; and
    (vii) A certificate, signed by the Principal Investigator, that 
includes the date of inactivation or viable select agent removal, the 
validated inactivation or viable select agent removal method used, and 
the name of the Principal Investigator. A copy of the certificate must 
accompany any transfer of inactivated or select agent removed material.
* * * * *
    (b) The individual or entity must implement a system to ensure that 
all records and data bases created under this part are accurate and 
legible, have controlled access, and authenticity may be verified.
    (c) The individual or entity must promptly produce upon request any 
information that is related to the requirements of this part but is not 
otherwise contained in a record required to be kept by this section. 
The location of such information may include, but is not limited to, 
biocontainment certifications, laboratory notebooks, institutional 
biosafety and/or animal use committee minutes and approved protocols, 
and records associated with occupational health and suitability 
programs. All records created under this part must be maintained for 3 
years.

    Dated: January 9, 2017.
Sylvia M. Burwell,
Secretary.
[FR Doc. 2017-00726 Filed 1-18-17; 8:45 am]
 BILLING CODE 4163-18-P



                                                  6278             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  Docket Center (EPA/DC), West William                    Federal Register of July 27, 1989 (54 FR               ‘‘Significant New Uses of Chemical
                                                  Jefferson Clinton Bldg., Rm. 3334, 1301                 31314).                                                Substances,’’ remove the entries for
                                                  Constitution Ave. NW., Washington,                                                                             §§ 721.10927 and 721.10942.
                                                                                                          III. Statutory and Executive Order
                                                  DC. The Public Reading Room is open
                                                                                                          Reviews                                                PART 721—[AMENDED]
                                                  from 8:30 a.m. to 4:30 p.m., Monday
                                                  through Friday, excluding legal                            This action withdraws regulatory
                                                  holidays. The telephone number for the                  requirements that have not gone into                   ■ 3. The authority citation for part 721
                                                  Public Reading Room is (202) 566–1744,                  effect and which contain no new or                     continues to read as follows:
                                                  and the telephone number for the OPPT                   amended requirements. As such, the                       Authority: 15 U.S.C. 2604, 2607, and
                                                  Docket is (202) 566–0280. Please review                 Agency has determined that this action                 2625(c).
                                                  the visitor instructions and additional                 will not have any adverse impacts,
                                                                                                                                                                 § 721.10927      [Removed]
                                                  information about the docket available                  economic or otherwise. The statutory
                                                  at http://www.epa.gov/dockets.                          and Executive Order review                             ■   4. Remove § 721.10927.
                                                                                                          requirements applicable to the direct
                                                  FOR FURTHER INFORMATION CONTACT: For                                                                           § 721.10942      [Removed]
                                                                                                          final rule were discussed in the Federal
                                                  technical information contact: Kenneth                                                                         ■   5. Remove § 721.10942.
                                                                                                          Register of November 17, 2015 (81 FR
                                                  Moss, Chemical Control Division
                                                                                                          1250) (FRL–9953–41). Those review                      [FR Doc. 2017–00938 Filed 1–18–17; 8:45 am]
                                                  (7405M) Office of Pollution Prevention
                                                                                                          requirements do not apply to this action               BILLING CODE 6560–50–P
                                                  and Toxics, Environmental Protection
                                                                                                          because it is a withdrawal and does not
                                                  Agency, 1200 Pennsylvania Ave. NW.,
                                                                                                          contain any new or amended
                                                  Washington, DC 20460–0001; telephone
                                                                                                          requirements.                                          DEPARTMENT OF HEALTH AND
                                                  number: (202) 564–9232; email address:
                                                  moss.kenneth@epa.gov.                                   IV. Congressional Review Act (CRA)                     HUMAN SERVICES
                                                     For general information contact: The                   Pursuant to the Congressional Review                 [Docket No. CDC–2015–0006]
                                                  TSCA-Hotline, ABVI-Goodwill, 422                        Act (5 U.S.C. 801 et seq.), EPA will
                                                  South Clinton Ave. Rochester, NY                        submit a report containing this rule and               42 CFR Part 73
                                                  14620; telephone number: (202) 554–                     other required information to the U.S.                 RIN 0920–AA59
                                                  1404; email address: TSCA-Hotline@                      Senate, the U.S. House of
                                                  epa.gov.                                                Representatives, and the Comptroller                   Possession, Use, and Transfer of
                                                                                                          General of the United States prior to                  Select Agents and Toxins; Biennial
                                                  SUPPLEMENTARY INFORMATION:
                                                                                                          publication of the rule in the Federal                 Review of the List of Select Agents and
                                                  I. Does this action apply to me?                        Register. This action is not a ‘‘major                 Toxins and Enhanced Biosafety
                                                                                                          rule’’ as defined by 5 U.S.C. 804(2).                  Requirements
                                                    A list of potentially affected entities is
                                                  provided in the Federal Register of                     List of Subjects                                       AGENCY:  Centers for Disease Control and
                                                  November 17, 2015 (81 FR 1250) (FRL–                                                                           Prevention (CDC), Department of Health
                                                  9953–41). If you have questions                         40 CFR Part 9                                          and Human Services (HHS).
                                                  regarding the applicability of this action                Environmental protection, Reporting                  ACTION: Final rule.
                                                  to a particular entity, consult the                     and recordkeeping requirements.
                                                  technical person listed under FOR                                                                              SUMMARY:   In accordance with the Public
                                                                                                          40 CFR Part 721                                        Health Security and Bioterrorism
                                                  FURTHER INFORMATION CONTACT.
                                                                                                            Environmental protection, Chemicals,                 Preparedness and Response Act of 2002
                                                  II. What direct final SNURs are being                   Hazardous substances, Reporting and                    (the Bioterrorism Response Act), the
                                                  withdrawn?                                              recordkeeping requirements.                            Centers for Disease Control and
                                                     In the Federal Register of November                     Dated: January 9, 2017.                             Prevention (CDC) in the Department of
                                                  17, 2015 (81 FR 1250), EPA issued                       Maria J. Doa,                                          Health and Human Services (HHS) has
                                                  direct final SNURs for the chemical                     Director, Chemical Control Division, Office
                                                                                                                                                                 reviewed the list of biological agents
                                                  substances that are identified in this                  of Pollution Prevention and Toxics.                    and toxins that have the potential to
                                                  document. These direct final SNURs                                                                             pose a severe threat to public health and
                                                                                                            Therefore, 40 CFR chapter I is
                                                  were issued under the procedures in 40                                                                         safety. Following the review, HHS has
                                                                                                          amended as follows:
                                                  CFR part 721, subpart D. Because the                                                                           decided: Not to finalize the proposed
                                                  Agency received notices of intent to                    PART 9—[AMENDED]                                       changes to the list of select agents and
                                                  submit adverse comments, in                                                                                    toxins at this time; to finalize provisions
                                                  accordance with § 721.160(c)(3)(ii), EPA                ■ 1. The authority citation for part 9                 to address toxin permissible limits and
                                                  is withdrawing the direct final SNURs                   continues to read as follows:                          the inactivation of select agents; to
                                                  issued for the following chemical                          Authority: 7 U.S.C. 135 et seq., 136–               finalize specific provisions to the
                                                  substances, which were the subject of                   136y;15 U.S.C. 2001, 2003, 2005, 2006, 2601–           section of the regulations addressing
                                                  PMNs: bimodal mixture consisting of                     2671; 21 U.S.C. 331j, 346a, 348; 31 U.S.C.             biosafety; and to clarify regulatory
                                                  multi-walled carbon nanotubes and                       9701; 33 U.S.C. 1251 et seq., 1311, 1313d,             language concerning security, training,
                                                  other classes of carbon nanotubes                       1314, 1318, 1321, 1326, 1330, 1342, 1344,              incident response, and records. In a
                                                  (generic), (PMN No. P–11–482); and                      1345 (d) and (e), 1361; E.O. 11735, 38 FR              companion document published in this
                                                                                                          21243, 3 CFR, 1971–1975 Comp. p. 973; 42
asabaliauskas on DSK3SPTVN1PROD with RULES




                                                  carbon nanotubes (generic), (PMN No.                                                                           issue of the Federal Register, the U.S.
                                                                                                          U.S.C. 241, 242b, 243, 246, 300f, 300g, 300g–          Department of Agriculture (USDA) has
                                                  P–15–54). EPA intends to publish                        1, 300g–2, 300j–2, 300j–3, 300j–4, 300j–9,
                                                  proposed SNURs for the chemical                                                                                made parallel regulatory changes.
                                                                                                          1857 et seq., 6901–6992k, 7401–7671q, 7542,
                                                  substances identified in this document.                 9601–9657, 11023, 11048.                               DATES: Effective February 21, 2017.
                                                     For further information regarding                                                                           FOR FURTHER INFORMATION CONTACT: Dr.
                                                  EPA’s direct final rulemaking                           § 9.1   [Amended]                                      Samuel S. Edwin, Director, Division of
                                                  procedures for issuing SNURs, see 40                    ■ 2. In the table in § 9.1, under the                  Select Agents and Toxins, Centers for
                                                  CFR part 721, subpart D, and the                        undesignated center heading                            Disease Control and Prevention, 1600


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                           6279

                                                  Clifton Road NE., MS–A46, Atlanta,                      (81 FR 2805). The NPRM solicited                          3. In addition, when HHS added B.
                                                  Georgia 30329. Telephone: (404) 718–                    public comments regarding whether any                  cereus Biovar anthracis to the list of
                                                  2000.                                                   biological agents and toxins should be                 HHS select agents and toxins on
                                                  SUPPLEMENTARY INFORMATION: The                          added or removed from the HHS list of                  September 14, 2016 by an interim final
                                                  preamble to this final rule is organized                select agents and toxins based on the                  rule (81 FR 63138), we neglected to add
                                                  as follows:                                             same criteria used in ANPRM:                           the name of the agent to the immediate
                                                                                                             We also invited comments on the                     notification list for Tier 1 agents in
                                                  I. Executive Summary                                    following:                                             sections 5 and 9 of the regulations. We
                                                  II. Changes to 42 CFR Part 73                              (1) Methods that should be required to              are correcting that error in this final
                                                     A. Modifications to the List of HHS and
                                                        Overlap Select Agents and Toxins
                                                                                                          validate the rendering of a select agent               rule.
                                                     B. Responses to Other Proposed Changes               non-viable or regulated nucleic acids                     Costs of the Rule: The entities affected
                                                     i. Definitions                                       that can produce infectious forms of any               by this final rule include research and
                                                     ii. Inactivation of a Select Agent                   select agent virus as non-infectious;                  diagnostic facilities; Federal, State, and
                                                     iii. Toxins                                             (2) Proposed changes to the aggregate               university laboratories; and private
                                                     iv. Exclusion Involving Patient Care                 amount of toxin excluded from the                      commercial and non-profit enterprises.
                                                     v. Exemptions for Select Agents and                  requirements of the select agent                       The current regulations require
                                                        Toxins                                            regulations;                                           registering for the possession, use, and
                                                     vi. Registration                                        (3) Removal of Diacetoxyscirpenol                   transfer of select agents or toxins. In
                                                     vii. Responsible Official                            (DAS) and T–2 from the list;                           addition, the entity is currently required
                                                     viii. Visitor Access to Select Agents and               (4) Whether seven calendar days
                                                        Toxins
                                                                                                                                                                 to ensure that the facility where the
                                                     ix. Security, Biosafety, and Incident
                                                                                                          provides a sufficient amount of time for               agent or toxin is housed has adequate
                                                        Response Plans                                    the entity to destroy or transfer a select             biosafety and containment measures;
                                                     x. Training                                          agent or toxin after identification;                   that the physical security of the
                                                     xi. Records                                             (5) Specific biosafety measures that                premises is adequate to prevent
                                                  III. Alternatives Considered                            should be required to prevent laboratory               unauthorized access; that all individuals
                                                  IV. Required Regulatory Analyses                        acquired infections (LAIs) or accidental               with approved access to select agents or
                                                     A. Executive Orders 12866 and 13563                  release of the select agents and toxins                toxins have the appropriate education,
                                                     B. The Regulatory Flexibility Act                    from an entity into the community; and                 training, and/or experience to handle
                                                     C. Paperwork Reduction Act of 1995                      (6) Alternative regulatory                          such agents or toxins; and that complete
                                                     D. E.O. 12988: Civil Justice Reform                  requirements that could be constructed
                                                     E. E.O. 13132: Federalism
                                                                                                                                                                 records concerning activities related to
                                                                                                          such that a registered entity would                    the select agents or toxins are
                                                     F. Plain Language Act of 2010
                                                  V. References                                           know whether it had a theft or loss of                 maintained.
                                                                                                          a select agent or toxin without that                      The HHS final rule will further reduce
                                                  I. Executive Summary                                    registered entity first having ‘‘an                    or minimize the risk of misuse of select
                                                     On February 27, 2015 we published                    accurate, current inventory for each                   agents and toxins that have the potential
                                                  an Advance Notice of Proposed                           select agent . . . held in long term                   to pose a severe threat to human health.
                                                  Rulemaking (ANPRM) (80 FR 10656)                        storage.’’                                             HHS recognizes that several of the
                                                  that initiated the required biennial                       (7) Whether short, paralytic alpha-                 required measures of the regulations
                                                  review and republication of the HHS list                conotoxins containing the following                    may impose certain operational costs
                                                  of select agents and toxins. The ANPRM                  amino acid sequence                                    upon affected entities. Specifically, the
                                                  solicited public comments regarding                     (X1CCX2PACGX3X4X5X6CX7), C.                            rule will clarify that an entity must use
                                                  whether any biological agents and                       burnetii, R. prowazekii, B. anthracis                  a validated method to render a select
                                                  toxins should be added or removed from                  Pasteur, B. abortus, B. melitensis, and B.             agent non-viable or a regulated
                                                  the HHS list of select agents and toxins                suis should be removed from the HHS                    infectious nucleic acid sample non-
                                                  based on the following criteria:                        list of select agents and toxins.                      infectious for future use. This means the
                                                     (1) The effect on human health of                       We received 22 public comments to                   method must be scientifically sound
                                                  exposure to the agent or toxin;                         the ANPRM and 35 public comments to                    and produce consistent results each
                                                     (2) The degree of contagiousness of                  the NPRM that addressed the                            time it is used. Appropriate reporting
                                                  the agent or toxin, and the methods by                  composition of the HHS list of select                  and record keeping is required in order
                                                  which the agent or toxin is transferred                 agents and toxins. After carefully                     to mitigate threats to human health. In
                                                  to humans;                                              considering the technical input of                     many cases, however, the affected
                                                     (3) The availability and effectiveness               subject matter experts, both within the                entities already employ some or all of
                                                  of pharmacotherapies and                                Federal government and from public                     the required measures. Compliance
                                                  immunizations to treat and prevent any                  comments, and recommendations from                     costs actually incurred will therefore
                                                  illness resulting from infection by the                 Federal advisory groups, we have                       vary from one entity to the next.
                                                  agent or exposure to the toxin; and                     decided not to finalize the proposed                      While information on the specific
                                                     (4) Any other criteria, including the                changes to the list of select agents and               changes that would need to occur at
                                                  needs of children and other vulnerable                  toxins at this time. Upon further                      individual sites and the associated costs
                                                  populations that the commenter                          consideration, we may decide to finalize               was not readily available during
                                                  considered appropriate.                                 changes to the list at a future time.                  proposed rulemaking, some general
                                                     This notice also asked for public                       This final rule makes the following                 observations regarding the potential
asabaliauskas on DSK3SPTVN1PROD with RULES




                                                  comment on whether HHS should                           changes to current regulations:                        costs were presented. These general cost
                                                  remove the following agents from the                       1. New provisions regarding the                     observations can be found in the
                                                  HHS list of select agents and toxins:                   inactivation of select agents, specific                Regulatory Impact Analysis. Based on
                                                  Coxiella burnetii, Rickettsia prowazekii,               biosafety requirements, and toxin                      the current recordkeeping and reporting
                                                  Bacillus anthracis Pasteur, Brucella                    requirements;                                          requirements, an additional 10 to 20
                                                  abortus, B. melitensis, and B. suis.                       2. Other revisions to the regulations to            hours per year may be required by
                                                     On January 19, 2016, we published a                  clarify regulatory language concerning                 entities. At an imputed cost of $33.40
                                                  Notice of Proposed Rulemaking (NPRM)                    security, training, and records.                       per hour, this additional time


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                                                  6280                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  requirement per entity will total                                        infectious nucleic acid sample non-                                toxin; and the avoidance of human
                                                  between $334 and $668 per year, or in                                    infectious for future use; and require                             morbidity, mortality and the economic
                                                  total for all registered entities between                                that entities in possession of such agents                         loss associated with such a release. The
                                                  $80,000 and $160,000.                                                    and toxins develop and implement                                   goal of the amended regulations is to
                                                     Benefits: The objectives of the HHS                                   effective means of biosafety, information                          enhance the protection of human health
                                                  final rule are to create a means of                                      security, and physical security. The                               and safety.
                                                  ensuring enhanced oversight in the                                       overall benefit of the amended
                                                  transfer, storage, and use of select agents                                                                                                 II. Changes to 42 CFR Part 73
                                                                                                                           regulatory provisions will be a reduced
                                                  and toxins; clarify that an entity must
                                                                                                                           likelihood of the accidental or                                      The table below describes the changes
                                                  use a validated method to render a
                                                                                                                           intentional release of a select agent or                           to the current regulation.
                                                  select agent non-viable or a regulated

                                                      Section No.                                                    Section title                                                                         Change

                                                  73.0 ....................     Applicability and related requirements .....................................                    No changes.
                                                  73.1 ....................     Definitions .................................................................................   Adds definitions: Validated inactivation procedure and viabil-
                                                                                                                                                                                  ity testing protocol.
                                                  73.2 ....................     Purpose and scope ..................................................................            No changes.
                                                  73.3 ....................     HHS select agents and toxins .................................................                  Clarifies language to include addition of B. cereus Biovar
                                                                                                                                                                                  anthracis and adds new paragraphs.
                                                  73.4 ....................     Overlap select agents and toxins ............................................                   Clarifies language to include addition of B. cereus Biovar
                                                                                                                                                                                  anthracis and adds new paragraphs.
                                                  73.5 ....................     Exemptions for HHS select agents and toxins ........................                            Clarifies language; redesignates paragraph; and adds new
                                                                                                                                                                                  paragraph.
                                                  73.6 ....................     Exemptions for overlap select agents and toxins ....................                            Clarifies language; redesignates paragraph; and adds new
                                                                                                                                                                                  paragraph.
                                                  73.7 ....................     Registration and related security risk assessments ................                             Redesignates paragraphs; adds new paragraph.
                                                  73.8 ....................     Denial, revocation, or suspension of registration ....................                          No changes.
                                                  73.9 ....................     Responsible Official .................................................................          Clarifies language to include addition of B. cereus Biovar
                                                                                                                                                                                  anthracis and adds new paragraphs.
                                                  73.10 ..................      Restricting access to select agents and toxins; security risk                                   Clarifies language.
                                                                                  assessments.
                                                  73.11    ..................   Security ....................................................................................   Clarifies language and adds new paragraph.
                                                  73.12    ..................   Biosafety ...................................................................................   Clarifies language.
                                                  73.13    ..................   Restricted experiments ............................................................             No changes.
                                                  73.14    ..................   Incident response .....................................................................         Clarifies language.
                                                  73.15    ..................   Training ....................................................................................   Clarifies language and adds new paragraph.
                                                  73.16    ..................   Transfers ..................................................................................    Clarifies language.
                                                  73.17    ..................   Records ....................................................................................    Clarifies language and adds new paragraph.
                                                  73.18    ..................   Inspections ...............................................................................     No changes.
                                                  73.19    ..................   Notification of theft, loss, or release ........................................                No changes.
                                                  73.20    ..................   Administrative review ...............................................................           No changes.
                                                  73.21    ..................   Civil money penalties ...............................................................           No changes.



                                                  A. Modifications to the List of HHS and                                  B. anthracis samples by the Department                             and are defining the terms as described
                                                  Overlap Select Agents and Toxins                                         of Defense in 2015. In response to this                            below. ‘‘Validated inactivation
                                                                                                                           incident, new requirements were                                    procedure’’ means ‘‘a procedure, whose
                                                    We received 22 public comments to                                      proposed to address the inactivation of                            efficacy is confirmed by data generated
                                                  the ANPRM and 35 public comments to                                      select agents. We proposed adding                                  from a viability testing protocol, to
                                                  the NPRM that addressed the                                              definitions for the terms ‘‘inactivation’’                         render a select agent non-viable but
                                                  composition of the HHS list of select                                    and ‘‘kill curve’’ to clarify the new                              allows the select agent to retain
                                                  agents and toxins. After carefully                                       inactivation provisions. As discussed                              characteristics of interest for future use;
                                                  considering the technical input of                                       below, we have removed the proposed                                or to render any nucleic acids that can
                                                  subject matter experts, both within the                                  requirement for a ‘‘kill curve,’’ and                              produce infectious forms of any select
                                                  Federal government and from public                                       accordingly, we have also removed the                              agent virus non-infectious for future
                                                  comments, and recommendations from                                       proposed definition of ‘‘kill curve.’’                             use.’’
                                                  Federal advisory groups, we have
                                                                                                                              To exclude a select agent or regulated                             Further, we have not included a
                                                  decided not to finalize the proposed
                                                                                                                           nucleic acids that can produce                                     separate definition for ‘‘inactivation’’ as
                                                  changes to the list of select agents and
                                                                                                                           infectious forms of any select agent                               it is now captured in the definition of
                                                  toxins at this time.
                                                                                                                           virus from the requirements of the select                          ‘‘validated inactivation procedure.’’
                                                  B. Responses to Other Proposed                                           agent regulations, an entity will need to                             We have changed the proposed phrase
                                                  Changes                                                                  subject the select agent or the nucleic                            ‘‘sterility testing protocol’’ to ‘‘viability
asabaliauskas on DSK3SPTVN1PROD with RULES




                                                                                                                           acids to a validated inactivation                                  testing protocol’’ and defined the latter
                                                  i. Definitions
                                                                                                                           procedure whose efficacy is confirmed                              as ‘‘a protocol to confirm the validated
                                                    It recently became clear that some                                     through a viability testing protocol.                              inactivation procedure by
                                                  inactivation protocols have failed to                                       Commenters stated that additional                               demonstrating the material is free of all
                                                  inactivate B. anthracis spores                                           definitions should be provided for                                 viable select agent.’’ This change reflects
                                                  completely, as evidenced by                                              ‘‘validated inactivation procedure,’’                              the intent that the validated inactivation
                                                  inactivation failures that led to the                                    ‘‘sterility testing protocol,’’ and ‘‘safety                       procedure, or the procedure for removal
                                                  inadvertent transfer of potentially live                                 margin.’’ We agree with the commenters                             of viable select agents from material


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                           6281

                                                  containing select agents, must render                      We proposed that an entity would be                 establishing performance parameters for
                                                  the material non-viable (i.e., unable to                required to develop a site-specific kill               inactivation procedures. While
                                                  replicate). In addition, any nucleic acids              curve to identify conditions of                        complete sterility is not a feasible goal
                                                  that can produce infectious forms of any                inactivation for each select agent.                    for material that is intended for further
                                                  select agent virus must be rendered non-                Commenters stated that although the                    use, HHS expects that the risk of live
                                                  infectious for future use.                              generation of kill curves is appropriate               agent in inactivated materials will be as
                                                    We are choosing to not define the                     for inactivation procedures using heat,                low as realistically possible from both a
                                                  term ‘‘safety margin’’ and have                         irradiation and filtration, it is not                  safety and security perspective.
                                                  incorporated the concept of a                           generally applicable to determining                       We proposed that entities subject
                                                  performance standard instead.                           infectivity of nucleic acids. Commenters               representative samples of an inactivated
                                                    The new definitions will help clarify                 stated that for inactivation procedures                select agent to a validated sterility
                                                  the regulatory language found in 42 CFR                 where a ‘‘kill curve is not applicable,                testing protocol to ensure that the
                                                  73.3, 73.4.                                             inactivation conditions are selected and               inactivation procedure has rendered the
                                                                                                          then replicated to obtain 100%                         select agent non-viable. Commenters
                                                  ii. Inactivation of a Select Agent                      inactivation within a statistical                      stated that it is not always practical to
                                                    Historical inactivation failures by                   certainty.’’                                           conduct validation on each sample that
                                                  registered entities required us to focus                   We agree with the commenters and                    is inactivated. Often samples are in
                                                  on ways to increase the certainty that                  are withdrawing the proposal to require                limited quantities and validation studies
                                                  inactivated select agents intended for                  a kill curve and safety margin because                 will leave very little or no sample for
                                                  further use do not contain live agent.                  these would not be applicable to all                   the experimental purpose. Commenters
                                                  This is particularly important when the                 inactivation procedures. Further, the                  also stated that the requirement to
                                                  inactivation methods are tempered in                    variety of agents and inactivation                     subject representative samples to
                                                  order to avoid disrupting some of the                   procedures makes it likely that                        sterility testing using a validated
                                                  physical characteristics of the agent. We               prescriptive requirements would have                   protocol requires further clarification.
                                                  proposed adding specific requirements                   unintended negative consequences on                    Commenters stated that it is reasonable
                                                  to the exclusion sections of the                        research. We are, nonetheless, finalizing              to require this type of testing when the
                                                  regulations (42 CFR 73.3(d), 73.4(d)) to                requirements for a validated                           inactivation procedure is first
                                                  address the requirements for rendering                  inactivation procedure and viability                   established and if any changes to the
                                                  select agents, nucleic acids that can                   testing. We are requiring that for a select            inactivation protocol are made.
                                                  produce infectious forms of any select                  agent or regulated nucleic acid that can               However, commenters stated that it
                                                                                                          produce infectious forms of any select                 cannot be reasonably done on each
                                                  agent virus, or extracts from select
                                                                                                          agent virus to be excluded from the                    sample in laboratory research if the
                                                  agents non-viable.
                                                                                                          requirements of the select agent                       inactivation protocol has not changed.
                                                    Sections 73.3(d)(2) (HHS select agents
                                                                                                          regulations, an entity will be                         They stated that implementing such a
                                                  and toxins) and 73.4(d)(2) (Overlap                     responsible for achieving a certain                    requirement would waste specimens
                                                  select agents and toxins) both provide                  performance standard that is confirmed                 where limited volumes are available,
                                                  that a non-viable select agent is                       through a viability testing protocol.                  would be costly in terms of technical
                                                  excluded from the requirements of the                   Surrogate strains that are known to                    time and resources, and is scientifically
                                                  select agent regulations. We proposed                   possess equivalent properties with                     unjustified.
                                                  that for a select agent to be non-viable                respect to inactivation can be used to                    We agree with the commenters that
                                                  or to render nucleic acids that can                     validate an inactivation procedure.                    the varied needs and conditions for
                                                  produce infectious forms of any select                  However, if there are known strain-to-                 inactivation preclude setting a specific
                                                  agent virus non-infectious for future                   strain variations in the resistance of a               standard for viability testing at this
                                                  use, an entity must use a validated                     select agent to an inactivation                        time. We have removed the proposed
                                                  inactivation procedure. Commenters                      procedure, then an inactivation                        sterility testing requirement for select
                                                  stated there is some confusion between                  procedure validated on a lesser resistant              agents and nucleic acids that can
                                                  inactivation validation requirements for                strain must also be validated on the                   produce infectious forms of any select
                                                  moving materials to a lower                             more resistant strains. Additional                     agent virus and have incorporated this
                                                  containment level and inactivation                      guidance regarding this performance                    concept into the performance standard.
                                                  validation requirements for waste                       standard has been developed and is                     The requirement to develop a validated
                                                  disposal. We are clarifying that these                  available at www.selectagents.gov.                     inactivation procedure and subsequent
                                                  provisions apply to a select agent that is                 Many commenters asked HHS to state                  validation data derived from viability
                                                  inactivated for future use as a non-select              clearly if the standard for select agent               testing will determine the extent of
                                                  agent and is not intended for material                  inactivation is complete sterility (i.e.,              sampling required. This activity will
                                                  for waste disposal.                                     not a single viable pathogen in the                    provide the associated measures of
                                                    Many commenters stated that the                       entire volume of an inactivated sample),               uncertainty with the sampling protocol
                                                  focus on strengthening inactivation                     a log reduction in viable pathogen titer,              chosen.
                                                  requirements was being driven by an                     or the limit of detection of the assay. We                We proposed adding exclusion
                                                  incorrect public perception of recent                   agree that it is important to specify the              requirements that extracts from a select
                                                  procedural errors that occurred at                      intent of the performance standard. HHS                agent could not be excluded from the
                                                  federally run research laboratories.                    recognizes the limits of detection of the              requirements of the select agent
asabaliauskas on DSK3SPTVN1PROD with RULES




                                                  Without commenting on what is or                        viability testing procedures (related to               regulations until an individual or entity
                                                  might be the public’s perception with                   the detection assay and the sampling of                met the following requirements: (1) Any
                                                  regard to inactivation problems, we                     inactivated material) and expected run-                extract is subjected to a process that
                                                  disagree with these comments because                    to-run variation when following an                     removes all viable cells, spores, or virus
                                                  the focus on inactivation failures with                 inactivation procedure precisely                       particles; (2) any extract is subjected to
                                                  select agents is based on the realization               precludes demonstrating full sterility of              a validated sterility testing protocol; (3)
                                                  that past inactivation activities have                  inactivated material. These sources of                 any viability of an extract that was
                                                  proved to be inadequate.                                error must be considered when                          subjected to a validated inactivation


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                                                  6282             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  protocol is reported to the Responsible                 We received comments asking us to                      provisions do not apply to diagnostic
                                                  Official (RO); and (4) any viability of a               clarify language to specify under what                 samples until they are identified to
                                                  select agent or infectivity of regulated                circumstances strain-to-strain                         contain a select agent and are
                                                  nucleic acids that can produce                          differences must be validated.                         inactivated for future use as a non-select
                                                  infectious forms of any select agent                    Commenters also stated that this is an                 agent.
                                                  virus, previously assessed as inactive by               unnecessary use of resources especially                   Many commenters asked who would
                                                  their validated sterility testing protocol,             when agents, based on their                            determine the validity of an inactivation
                                                  is reported to APHIS or CDC.                            morphological characteristics, are                     protocol. The responsibility for this
                                                     Some commenters expressed concern                    susceptible to similar inactivating                    activity remains with the entity, which
                                                  with having to subject every extract                    agents. Commenters suggested at a                      will allow for researchers to continue to
                                                  from a select agent, such as nucleic                    minimum the language should state that                 develop new inactivation procedures.
                                                  acids, to sterility testing. We agree with              this requirement only applies when                     Entities retain the responsibility to
                                                  the commenters and are replacing the                    there are known strain-to-strain                       evaluate their inactivation procedures,
                                                  term ‘‘extract’’ with ‘‘material                        variations in resistance of a select agent             to include consideration of the biosafety
                                                  containing a select agent’’ to clarify that             to the inactivation procedure.                         and security risks posed by the
                                                  the requirements apply to material                         We agree with the commenters and                    inactivated material. The Federal Select
                                                  containing a select agent such as serum                 added in the term ‘‘known’’ strain-to-                 Agent Program (FSAP) inspectors will
                                                  or liquid culture where select agents are               strain variation and, as stated                        verify that the entity has developed a
                                                  typically removed via filtration without                previously, have removed the kill curve                validated inactivation procedure and
                                                  a previous inactivation step. The term                  requirement.                                           may review validation data during an
                                                  ‘‘extract’’ is commonly used in                            Commenters also inquired whether                    entity’s inspection. We made no
                                                  conjunction with nucleic acids                          surrogate strains can be used to develop               changes based on these comments.
                                                  extracted from a select agent. We are                   inactivation procedures. We agree with                    Many commenters stated that the
                                                  using the term ‘‘extract’’ in the final rule            the commenters that surrogate strains                  intent behind the annual review
                                                  to reflect the application of two                       known to possess equivalent properties                 provisions was not clear. We agree with
                                                  processing steps: An inactivation step to               with respect to inactivation as a select               the commenters and modified the
                                                  destroy the select agent (e.g., lysis of                agent can be used to develop                           provisions to state that an entity
                                                  select agent) and then another step                     inactivation procedures. We have                       ‘‘Review, and revise as necessary, each
                                                  (such as filtration), to remove any                     revised the requirement to include the                 of the entity’s validated inactivation
                                                  remaining viable select agents. Extracts                provision that ‘‘Surrogate strains that                procedures or viable agent removal
                                                  from a select agent (nucleic acids,                     are known to possess equivalent                        method. The review must be conducted
                                                  antigens, lysates) would be subject to                  properties with respect to inactivation                annually or after any change in
                                                  the performance standard for select                     can be used to validate an inactivation                Principal Investigator, change in the
                                                  agents in the new sections 3(d)(3) and                  procedure; however, if there are known                 validated inactivation procedure or
                                                  4(d)(3) of the select agent regulations                 strain-to-strain variations in the                     viable agent removal method, or failure
                                                  that includes viability testing but does                resistance of a select agent to an                     of the validated inactivation procedure
                                                  not necessarily require viability testing               inactivation procedure, then an                        or viable agent removal method. The
                                                  on every sample. The requirement to                     inactivation procedure validated on a                  review must be documented and
                                                  develop a validated inactivation                        lesser resistant strain must also be                   training must be conducted if there are
                                                  procedure and subsequent validation                     validated on the more resistant strains.’’             any changes to the validated
                                                  data derived from viability testing will                   Commenters were concerned about                     inactivation procedure, viable agent
                                                  determine the extent of sampling                        performing viability testing on materials              removal method, or viability testing
                                                  required. However, material containing                  such as a single diagnostic sample that                protocol.’’ We made these changes
                                                  select agents, as opposed to extracts                   is determined to contain a select agent                because the annual review of an entity’s
                                                  (e.g., nucleic acids, antigens, lysates),               and where there is a limited amount of                 validated inactivation procedures or
                                                  that is subjected to a process to remove                material with which to work. For                       viable agent removal method is key to
                                                  all viable cells, spores, or virus particles            example, consider an entity using a                    a successful inactivation program. The
                                                  would require viability testing on every                commercially available RNA extraction                  annual review requirement does not
                                                  sample prior to treating it as a non-                   kit on a diagnostic sample to obtain                   necessarily involve revalidating
                                                  select agent. The distinguishing feature                RNA for sequencing, and the sample is                  inactivation procedures. This review
                                                  between ‘‘material containing a select                  identified to contain highly pathogenic                could simply be the evaluation of the
                                                  agent’’ and an extract from a select agent              avian influenza (HPAI). In this situation,             site-specific standard operating
                                                  is that in the former the select agent will             the entire single sample would be used                 procedures for validated inactivation of
                                                  only be removed and in the latter the                   when trying to demonstrate that the                    select agents to ensure the inactivating
                                                  select agent will be destroyed before                   inactivation procedure was effective.                  conditions used and upper agent
                                                  removal. The more stringent                             We agree with the commenters. As                       concentration limits found in validation
                                                  requirement for viability testing of all                noted above, surrogate select agent                    data are consistent, and that entity staff
                                                  material containing a select agent where                strains that are known to possess                      are following the site-specific standard
                                                  the select agent was removed is                         equivalent properties with respect to                  operating procedures for validated
                                                  warranted because of the lack of select                 inactivation as the select agent can be                inactivation of select agents.
                                                  agent destruction which increases the                   used to develop validated inactivation                    However, sometimes an entity will
asabaliauskas on DSK3SPTVN1PROD with RULES




                                                  risk of viable select agent remaining in                procedures. In this example, low                       need to revalidate inactivation
                                                  the material.                                           pathogenic avian influenza (LPAI) could                procedures during the annual review.
                                                     We proposed that if there are strain-                be used to validate the inactivation                   For example, if the entity identifies that
                                                  to-strain variations in resistance of a                 procedure for diagnostic samples that                  staff are not adhering to standard
                                                  select agent to the inactivation                        are identified as containing HPAI, if                  operating procedures for validated
                                                  procedure, then a specific kill curve                   LPAI possesses equivalent properties                   inactivation of select agents, or if the
                                                  must be developed for each strain that                  with respect to inactivation as HPAI. In               entity wants to deviate from the
                                                  undergoes the inactivation procedure.                   addition, we are clarifying that these                 validated inactivation procedure, the


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                          6283

                                                  entity will need to revalidate the                      commenters stated that the proposal                    73.3(d)(3)(i) of the select agent
                                                  inactivation procedures during the                      was not clear how long these records                   regulations to require the transferor of
                                                  annual review. Further, in this final                   must be kept and who is responsible for                an unregulated amount of a select toxin
                                                  rule, we have consolidated the review                   keeping these records. We made no                      to document the identity of the recipient
                                                  provisions into one provision, clarified                changes based on these comments as                     and the legitimate need (i.e.,
                                                  that the reviews must be documented,                    these records are subject to the records               prophylactic, protective, bona fide
                                                  and moved this provision into the                       retention requirement in section 17 of                 research, or other peaceful purpose)
                                                  requirements for the RO as they will be                 the select agent regulations and must be               claimed by the recipient. The name of
                                                  the individual responsible for these                    kept for three years by a registered                   the toxin and the total amount
                                                  review activities.                                      individual or entity.                                  transferred must also be documented.
                                                     Many commenters stated that the                         Some commenters asked about the                     Identity information of the person
                                                  intent of the inactivation failure                      conditions of submitting a waiver to the               requesting and using the toxins must
                                                  reporting requirements was not clear                    inactivation provisions of the select                  include the individual’s name,
                                                  and reporting every inactivation failure                agent regulations. An entity may submit                institution name, address, telephone
                                                  to CDC or APHIS was burdensome. We                      a request to FSAP to apply an                          number, and email address. We received
                                                  agree with the commenters and have                      alternative inactivation procedure. The                one comment requesting to include
                                                  modified reporting requirements to                      entity is to provide justification                     language for transfers of toxins within
                                                  require the RO to ‘‘Investigate to                      regarding the alternative procedure                    an institution. We made no changes
                                                  determine the reason for any failure of                 including a description of what material               based on this comment because intra-
                                                  a validated inactivation procedure or                   is to be waived, the inactivation                      entity transfers, where the sender and
                                                  any failure to remove viable agent from                 protocol and viability test to be used,                the recipient are covered by the same
                                                  material. If the Responsible Official is                validation data, and any other                         certificate of registration, are already
                                                  unable to determine the cause of a                      supporting information/references, such                addressed in section 17(3)(viii) of the
                                                  deviation from a validated inactivation                 as scientific references. Accordingly, we              regulations.
                                                  procedure or a viable agent removal                     revised the provision found in sections
                                                  method; or receives a report of any                     3(d)(6) and 4(d)(6) to include              Toxin Permissible Limits
                                                  inactivation failure after the movement                 information on how to apply for a              As proposed, we are increasing the
                                                  of material to another location, the                    waiver that reads ‘‘. . . To apply for      toxin exclusion aggregate amounts. We
                                                  Responsible Official must report                        such a determination a registered           received 10 comments supporting the
                                                  immediately by telephone or email the                   individual or entity must submit a          increase in the toxin exclusion aggregate
                                                  inactivation failure or viable agent                    written request and supporting              amounts. We received three general
                                                  removal method failure to CDC or                        scientific information to FSAP. A           comments opposing the increase of the
                                                  APHIS.’’ The intent of this modification                written decision granting or denying the    exclusion aggregate amounts and two
                                                  is to create an environment at the entity               request will be issued.’’ Additional        additional comments opposing the
                                                  where inactivation or select agent                      guidance has been developed and is          increase of the ricin exclusion aggregate
                                                  removal failures are investigated to                    available at: www.selectagents.gov.         amount. One commenter stated that no
                                                  determine the reason for the failure as                                                             changes were necessary. Another
                                                                                                          iii. Toxins                                 commenter had concerns regarding
                                                  opposed to merely re-subjecting the
                                                  material to the inactivation or select                     To ensure the language is consistent     whether the risk assessment scenarios
                                                  agent removal method. It is the position                with the exclusion language found in        were relevant to the goal of reducing
                                                  of the FSAP that each failure represents                73.3(e) which describes the exclusion of any significant harm able to be caused
                                                  either human error in conducting the                    toxins that have been modified to be less by illegitimate use of any lethal amounts
                                                  validated procedure or an inadequate                    potent or toxic, we are making a            of toxin. We are making no changes
                                                  inactivation method or an inadequate                    technical change to the regulation and      based on these comments.
                                                  select agent removal method if no                       revising the terms ‘‘nonfunctional’’           DHS developed toxin parameters and
                                                  human error can be discovered. Both                     toxin to ‘‘nontoxic’’ toxin and             attack scenarios for potential inhalation
                                                  situations demand careful attention by                  ‘‘functional form(s) of any of the toxins’’ and ingestion exposures to select toxins
                                                  the entity to ensure training and/or                    to ‘‘toxic form(s) of any of the toxins.’’  to protect the homeland against the
                                                  reevaluation of the inactivation                        This change is being made to clarify the potential release of weaponized
                                                  procedure in order to minimize the                      intent of the regulations as the terms      biological toxins. The DHS group
                                                  likelihood that the situation would                     ‘‘nonfunctional’’ and ‘‘functional’’ are    analyzed a range of release sizes (in mg)
                                                  reoccur in the future. The revised                      broad and have led to confusion. The        for each select toxin in order to estimate
                                                  regulatory language only requires                       intention behind the original provisions the number of people that would be
                                                  reporting of inactivation or select agent               was to exclude toxins that can no longer exposed to each toxin amount by
                                                  removal failures to FSAP when the RO                    exert their toxic effect and cause disease ingestion of milk (using published
                                                  cannot establish that the failure resulted              and regulate those that can. For            TD[50] or LD[50]) and/or indoor
                                                  from human error or when an entity                      example, Botulinum neurotoxin has           inhalation (using published LD[50]).
                                                  receives a report of any inactivation                   three functional domains—binding            Revised toxin exclusion aggregate
                                                  failure after the movement of material to               domain, translocation domain and            amounts were proposed based on the
                                                  another location.                                       catalytic domain. Each functional           data generated by the models to expose
                                                     We also proposed that written records                domain solely can be manipulated such <10 or <100 people by inhalation or
asabaliauskas on DSK3SPTVN1PROD with RULES




                                                  be kept for select agents that have been                that the toxin is no longer toxic and       ingestion to the LD[50] or TD[50] levels
                                                  subjected to a procedure to render them                 does not cause diseases even though the of toxin. A commenter stated that (1) the
                                                  non-viable, or regulated nucleic acids                  other two domains may be functional.        scenarios proposed appear to consider a
                                                  that can produce infectious forms of any                                                            high-consequence event or exposure to
                                                  select agent virus that have been                       Due Diligence                               a given toxin and that the interpretation
                                                  subjected to a procedure to render them                    We are adding a more specific            of what constitutes a high-consequence
                                                  incapable of producing infectious forms                 documentation requirement to the toxin event or exposure is impacted not only
                                                  of any select agent virus. Some                         exclusion provision found in section        in the number of people affected but in


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                                                  6284             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  the attention afforded by news media                    samples are those specimens that are                   considered regulated under the select
                                                  and the public and (2) a revision of                    submitted to laboratories for diagnosis                agent regulations. One commenter
                                                  these exclusion limits should also                      or verification purposes to identify or                recommended that we define patient
                                                  consider amounts that would be                          verify a biological agent or toxin. For                care as part of the diagnosis definition.
                                                  sufficient for research purposes. We are                example, an original food sample could                 Specifically, the commenter suggested
                                                  making no changes based on these                        be a container of potato salad or juice.               we define diagnosis as ‘‘the analysis of
                                                  comments because we do not believe                      An original clinical sample could be                   specimens for the purpose of identifying
                                                  the impact the news media may have if                   serum or stool from a patient.                         or confirming the presence or
                                                  an exposure occurs is an appropriate                    Laboratories that test food and clinical               characteristics of a select agent or toxin
                                                  consideration for the listing of a                      samples for the presence of toxins                     provided that such analysis is
                                                  biological agent or toxin. Further, the                 generally do not know the level of toxin               associated with the determination or
                                                  consideration of amounts sufficient for                 in a sample and do not extract and                     provision of patient treatment in a
                                                  research purposes is a subjective                       purify a toxin as part of their studies.               patient care setting, or directly related to
                                                  assessment as smaller academic                          Therefore, our proposal to exclude                     protecting the public health or safety,
                                                  laboratories have differing needs than                  select toxin identified in an original                 animal health or animal products, or
                                                  an entity that is developing detection                  food sample or clinical sample                         plant health or plant products. Clinical
                                                  assays. The comments specific to ricin                  identified is consistent with the                      or diagnostic specimen retention times
                                                  raised concerns that the increased                      rationale for the current exclusion for                as required for patient treatment are
                                                  exclusion aggregate amounts would                       animals exposed to toxins (42 CFR                      included within the determination of
                                                  increase the risk of (1) exposure to                    73.3(d)(4)). This exclusion was based on               the point in time when patient care has
                                                  laboratory workers and (2) that                         recommendations by toxin subject                       concluded.’’ Another commenter stated
                                                  individuals would have access to greater                matter experts. We received one                        ‘‘the challenges of differentiating
                                                  amounts of material to use for nefarious                comment that supported this exclusion.                 between patient care and experimental
                                                  purposes. We are making no changes                                                                             research when treating infectious
                                                                                                          Exclusion of Botulinum Neurotoxin
                                                  based on these comments. We do not                                                                             diseases are complex and nuanced and
                                                                                                          Produced as a Byproduct
                                                  agree that the increased permissible                                                                           any effort to introduce regulation of
                                                  limits will increase the risk of laboratory                In the NPRM, we proposed to exclude                 medical care involving select agents and
                                                  worker exposure. The new proposed                       all toxins that are only produced as a                 toxins has the potential to introduce
                                                  exclusion amount is less than an oral                   byproduct of a study of the toxin                      inconsistencies and confusion.’’ The
                                                  lethal dose for a single person weighing                producing host organism so long as the                 proposed exclusion language in the
                                                  more than 50 kg, based on 20 mg/kg-                     toxin had not been intentionally                       NPRM was ‘‘Waste generated during the
                                                  body weight (Ref. 1), thus a single                     collected, purified, or otherwise                      delivery of patient care from a patient
                                                  fatality would require consuming more                   extracted, and the material containing                 infected with a select agent that is
                                                  than all of the ricin in the laboratory.                the toxin was inactivated and properly                 decontaminated with a validated
                                                  Ricin does display a higher toxicity                    disposed of within 30 days of the                      method within seven calendar days of
                                                  when administered intravenously or by                   initiation of the culture. Based on the                the conclusion of patient care.’’ We
                                                  inhalation, but these two routes of                     input from subject matter experts, the                 revised the proposed language based on
                                                  exposure require either injection or                    final regulatory language narrows the                  the two comments to state: ‘‘Waste
                                                  manipulation to generate particles                      exception to only Botulinum neurotoxin                 generated during the delivery of patient
                                                  capable of reaching the lower                           produced as a byproduct in the study of                care by health care professionals from a
                                                  respiratory tract, respectively, two                    Botulinum neurotoxin producing                         patient diagnosed with an illness or
                                                  processes not likely to occur                           species of Clostridium. Work with that                 condition associated with a select agent,
                                                  accidentally. Also, entities that produce               organism is already regulated, thus                    where such waste is, within seven days
                                                  ricin typically do so in liquid, as                     providing regulatory oversight of the                  of the conclusion of patient care,
                                                  opposed to lyophilized powder                           material during the 30 day time frame,                 decontaminated, or transferred for
                                                  formulations, thus decreasing the risk of               as opposed to an agent like                            destruction in compliance with state
                                                  ingestion or aerosol exposure.                          Staphylococcus aureus, the organism                    and Federal regulations.’’
                                                  Additionally, the increased exclusion                   that produces Staphylococcal                              We revised the proposed exemption
                                                  aggregate amounts would allow entities                  enterotoxins, which is not regulated.                  language in 42 CFR 73.5(a)(3), and 42
                                                  to more efficiently produce and store                   One commenter stated that clarification                CFR 73.6(a)(3) to provide that, unless
                                                  ricin preparations which are typically                  was needed in the ‘‘exclusion of toxin                 otherwise directed by the HHS Secretary
                                                  frozen in aliquots until the need to use                produced as a by-product’’ and inquired                or APHIS Administrator, as appropriate,
                                                  the material arises. Finally, while                     whether this provision applies to                      ‘‘the clinical or diagnostic specimens
                                                  increasing the permissible limits allows                material held in long term storage or cell             collected from a patient infected with a
                                                  individuals with nefarious purposes                     lysates or culture supernatants kept for               select agent are transferred in
                                                  access to greater amounts of toxin, we                  diagnostic or research purposes other                  accordance with § 73.16 or destroyed
                                                  do not believe access to the revised                    than toxin work. Since the situations                  on-site by a recognized sterilization or
                                                  amounts poses a severe threat to public                 described by the commenter referred to                 inactivation process within seven days
                                                  health and safety based on the reasons                  material held in long term storage                     after delivery of patient care by health
                                                  stated above.                                           (longer than 30 days) this exclusion                   care professionals has concluded.’’
                                                                                                          would not apply.                                          For specimens generated from the
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                                                  Toxins: Exclusion of an HHS Select                                                                             patient, the specimens are not subject to
                                                  Toxin Identified in an Original Food                    iv. Exclusion Involving Patient Care                   the select agent regulations for only the
                                                  Samples and Clinical Samples                              To clarify how the select agent                      period that they are directly associated
                                                    As proposed, we are excluding from                    regulations apply to activities associated             with the diagnosis. In accordance with
                                                  the requirements of the regulations a                   with the diagnosis and care for                        sections five and six of the select agent
                                                  select toxin identified in an original                  individuals infected with a select agent,              regulations, within seven calendar days
                                                  food sample and clinical samples.                       we proposed that waste generated                       after identification, a specimen is
                                                  Original food samples and clinical                      during the delivery of patient care is not             subject to the select agent regulations


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                           6285

                                                  and must be transferred in accordance                   30 calendar days after identification of               HHS or USDA Office of the Inspector
                                                  with section 73.16 or destroyed on-site                 Botulinum neurotoxin and/or                            General Hotline
                                                  by a recognized sterilization or                        Staphylococcal enterotoxin (Subtypes                     In its December 2014 report, the
                                                  inactivation process. Since the material                A–E), the select agent or toxin is                     Federal Experts Security Advisory Panel
                                                  would be excluded from the regulations,                 transferred in accordance with § 73.16                 (FESAP) recommended adding a
                                                  there would be no requirement to                        or destroyed on-site by a recognized                   specific regulatory requirement
                                                  document the transfer or destructions. A                sterilization or inactivation process.’’
                                                                                                                                                                 addressing how individuals are
                                                  specimen must be secured against theft,                 We sought comments concerning (1) the
                                                                                                                                                                 informed of the availability of
                                                  loss, or release during the period                      extension of the exemption time period
                                                                                                                                                                 procedures for accessing the HHS or
                                                  between identification and transfer or                  to 30 days for BoNT and Staphylococcal
                                                                                                                                                                 USDA Office of Inspector General
                                                  destruction, and any theft, loss, or                    enterotoxin (Subtypes A–E) to allow
                                                                                                                                                                 Hotlines to anonymously report a safety
                                                  release of the specimen must be                         clinical and diagnostic laboratories
                                                                                                                                                                 or security concern. In response to that
                                                  reported. All specimens generated from                  sufficient time to complete their
                                                                                                                                                                 recommendation, we proposed adding a
                                                  the patient and kept more than seven                    investigations without having to transfer
                                                                                                                                                                 requirement that the RO must ensure
                                                  days after acute patient care concludes                 or destroy the sample, and (2) whether
                                                                                                                                                                 that individuals at their entity are
                                                  would be subject to the select agent                    seven calendar days provided sufficient
                                                                                                          amount of time for the entity to destroy               provided the contact information of the
                                                  regulations.                                                                                                   HHS Office of Inspector General Hotline
                                                                                                          or transfer other select agents or toxins
                                                  v. Exemptions for Select Agents and                     after identification. We received one                  and USDA Office of Inspector General
                                                  Toxins                                                  comment to extend the amount of time                   Hotline so that an individual is able to
                                                                                                          for other select agents or toxins to 10                anonymously report a biosafety or
                                                  Informing Specimen Provider
                                                                                                          calendar days since destruction may not                security concern related to select agents
                                                     Since a registered or reference                                                                             and toxins. We received no comments
                                                                                                          occur on-site, therefore allowing the
                                                  laboratory typically confirms the                                                                              regarding this proposed addition and
                                                                                                          secure transport to the ultimate site of
                                                  identification of a select agent or toxin                                                                      are finalizing the requirement as
                                                                                                          disposition. We made no changes to
                                                  for public health and agriculture, we                   adjust the seven calendar day                          proposed.
                                                  proposed to require that a registered or                requirement for agents or toxins other
                                                  reference laboratory inform the                                                                                viii. Visitor Access to Select Agents and
                                                                                                          than BoNT and Staphylococcal                           Toxins
                                                  specimen provider of the identification                 enterotoxin (Subtypes A–E) because the
                                                  as a condition for a clinical or                        other agents or toxins do not involve the                Section 73.10(e) of the select agent
                                                  diagnostic laboratory to maintain their                 identification of both agent and toxin as              regulations currently provides that a
                                                  exemption under 42 CFR 73.5(a), and 42                  part of diagnosis. Therefore, these                    person with a valid approval from the
                                                  CFR 73.6(a). Two commenters stated                      situations are not as complicated and do               HHS Secretary or APHIS Administrator
                                                  they did not believe basic good practices               not warrant additional time for                        to have access to select agents and
                                                  require regulations. We made no                         reporting identification.                              toxins may request, through his or her
                                                  changes based on these comments                                                                                RO, that the HHS Secretary or APHIS
                                                  because this provision will ensure that                 vi. Registration                                       Administrator provide their approved
                                                  the reference laboratory notifies the                     We are codifying in regulation the                   access status to another registered
                                                  specimen provider of the identification                 current FSAP policy that an entity is                  individual or entity for a specified
                                                  of the select agent or toxin. It is                     required to meet all of the regulatory                 period of time. This allows a person
                                                  important that the specimen provider is                 requirements for those select agents and               with approved access at a registered
                                                  aware that they are in possession of the                toxins listed on an entity’s registration              entity to have approved access to a
                                                  agent or toxin and must meet the                        regardless of whether the select agent or              select agent at another registered entity.
                                                  requirements outlined in 42 CFR 73.5,                   toxin is in the actual possession of an                To ensure that the RO of the entity
                                                  73.6 (e.g., cannot maintain possession of               entity, and without regard to the actual               hosting such a visitor is aware if a
                                                  the select agent or toxin, must destroy                 amounts of toxins in the possession of                 visiting individual loses access approval
                                                  or get approval for a transfer, and report              an entity. We received no comments                     to select agents and toxins, we added a
                                                  a theft, loss, or release).                             regarding this proposal and have made                  requirement that the RO at the home
                                                                                                          no changes to the language in the                      entity must immediately notify the RO
                                                  Identification of Toxin
                                                                                                          proposed rule.                                         of the visiting entity if a person’s access
                                                     In the current select agent regulations,                                                                    to select agents or toxins has been
                                                  in order for clinical or diagnostic                     vii. Responsible Official                              terminated. We received one comment
                                                  laboratories to maintain their exemption                   Section 73.9(a)(6) of the select agent              that supported this addition to the
                                                  under 42 CFR 73.5(a), and 42 CFR                        regulations currently states that the RO               regulations and are finalizing the
                                                  73.6(a), the clinical or diagnostic                     must ensure that an annual inspection                  requirement as proposed.
                                                  laboratory must, either immediately or                  is conducted for each laboratory where
                                                  within seven calendar days, report the                  select agents and toxins are stored or                 ix. Security, Biosafety, and Incident
                                                  identification of a select agent or toxin               used. This requirement also provides                   Response Plans
                                                  to APHIS or CDC unless directed                         that the results of each inspection must                 The select agent regulations require a
                                                  otherwise by HHS Secretary or APHIS                     be documented, and any deficiencies                    registered entity to develop and
                                                  Administrator. In the NPRM, we                          identified during an inspection must be                implement a number of plans in order
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                                                  proposed to amend the language in 42                    corrected. We proposed adding a                        to ensure the safety and security of the
                                                  CFR 73.5(a), and 42 CFR 73.6(a) to state:               requirement that the RO must also                      select agents and toxins they handle.
                                                  ‘‘Unless directed otherwise by the                      document the corrective actions taken                  These are:
                                                  Secretary, within seven calendar days                   by the entity to address any identified                  • A security plan that provides for
                                                  after identification of the select agent or             deficiencies. We received one comment                  measures sufficient to safeguard a select
                                                  toxin (except for Botulinum neurotoxin                  that supported this proposed                           agent or toxin against unauthorized
                                                  (BoNT) and/or Staphylococcal                            requirement and are finalizing the                     access, theft, loss, or release (42 CFR
                                                  enterotoxins (Subtypes A–E)), or within                 requirement as proposed.                               73.11);


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                                                  6286             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                    • A biosafety plan that provides for                  supported this requirement. However,                   containing information that could be
                                                  measures sufficient to contain a select                 one commenter questioned the need for                  used to gain access to select agents or
                                                  agent or toxin (42 CFR 73.12); and                      additional requirements as this is                     toxins. We received one comment
                                                    • An incident response plan that                      already done routinely. While we agreed                requesting clarification on the time
                                                  provides for measures that the registered               with the commenter that some, or even                  frame for notification. We made no
                                                  entity will implement in the event of                   most, entities already provide the plans               changes based on the comment since the
                                                  theft, loss, or release of a select agent or            routinely, we are making no changes to                 regulations under subsection (d) already
                                                  toxin; inventory discrepancies; security                the proposed language so that all                      provide that notification must be
                                                  breaches (including information                         entities will be required to submit their              immediate. The notification will
                                                  systems); severe weather and other                      biosafety and incidence response plans,                facilitate notification of the Federal
                                                  natural disasters; workplace violence;                  consistent with the existing requirement               Bureau of Investigation (FBI) if deemed
                                                  bomb threats and suspicious packages;                   for the security plan.                                 necessary by the RO as the loss of such
                                                  and emergencies such as fire, gas leak,                                                                        equipment may be criminal in nature.
                                                  explosion, power outage, or others. (42                 Security
                                                  CFR 73.14).                                                We proposed amending the                            Biosafety
                                                    The select agent regulations require                  requirement that a security plan contain                  We proposed amending the regulatory
                                                  that drills or exercises must be                        a description of how the entity                        language in section 73.12 of the select
                                                  conducted at least annually to test and                 authorizes the means of entry into areas               agent regulations to update the name
                                                  evaluate the effectiveness of the plans,                where select agents or toxins are stored               change of the National Institutes of
                                                  and that the plans must be reviewed and                 or used, to add a requirement that the                 Health (NIH) ‘‘Guidelines for Research
                                                  revised, as necessary, after any drill or               security plan must include a description               Involving Recombinant or Synthetic
                                                  exercise, and after any incident. We                    of centralized access control                          Nucleic Acid Molecules’’ (Ref. 2). We
                                                  proposed to require that these drills or                management systems (e.g., keycards)                    received no comments and are finalizing
                                                  exercises be documented to include                      and/or key management (e.g.,                           this change as proposed.
                                                  how the drill or exercise tested and                    mechanical keys). We proposed this                        The biosafety section of the select
                                                  evaluated the plan, any problems                        requirement because during our                         agent regulations contains a reference to
                                                  identified and corrective actions that                  inspections of registered entities we                  the Occupational Safety and Health
                                                  were taken, and the names of the                        have observed that the central access                  Administration (OSHA) regulations
                                                  individuals who participated in the drill               control management system in some                      found in 29 CFR 1910.1200 and
                                                  or exercise. Three commenters stated                    instances is controlled, either on- or off-            1910.1450. These sections provide
                                                  that there was no need to codify the                    site, by individuals who (1) have not                  specific requirements for handling
                                                  documentation of how a drill or exercise                received access approval from HHS                      hazardous chemicals in the laboratories.
                                                  evaluated a plan and corrective actions                 Secretary or APHIS Administrator, and                  These regulations also provide
                                                  in regulations because they believed this               (2) have the ability to assign people                  recommendations for safely working
                                                  requirement is already being                            access or override access controls                     with chemicals including toxins and
                                                  documented. We are making no changes                    without the knowledge of the entity’s                  give non-mandatory recommendations
                                                  based on the comments because this                      RO. Three commenters suggested that                    for prudent practices in laboratories
                                                  requirement will provide a more                         access management processes are                        handling chemical hazards. Since the
                                                  thorough accounting of required                         sensitive and a greater security risk may              current edition of the CDC/NIH
                                                  activities via testing and entity-directed              result from having too detailed                        ‘‘Biosafety in Microbiological and
                                                  improvements.                                           information available in a single                      Biomedical Laboratories’’ Appendix I
                                                    Another commenter requested                           document. One commenter                                (Ref. 3) now provides guidelines for
                                                  clarification regarding the recording of                recommended we include a definition                    work with toxins of biological origin, we
                                                  the names of individuals who                            of what an access control system is and                proposed removal of the reference to
                                                  participate in drills or exercises. The                 what components need to be included                    these OSHA regulations. We note,
                                                  commenter believed the requirement                      in the security plan. After considering                however, that regulated entities are still
                                                  should be limited to registered entity                  the comments and reconsidering the                     required to meet the OSHA regulatory
                                                  personnel and not include first                         purpose of the proposed language, we                   requirements where applicable. We
                                                  responders or other non-entity                          are not finalizing the proposed revision.              received no comments and are finalizing
                                                  participants, but list only the                         Our concerns about unauthorized                        this change as proposed.
                                                  participating external agencies (e.g.,                  persons either having access or granting                  In the NPRM, we proposed adding the
                                                  emergency management, emergency                         access without the knowledge of the                    requirement that ‘‘biosafety and
                                                  medical services, or fire department).                  entity RO can be addressed by the                      containment procedures specific to each
                                                  We agreed with the commenter and                        current provisions found in subsections                registered laboratory must be available
                                                  have amended the proposed regulatory                    (c)(1) and (c)(2) of section 11 (security)             to each individual working in that
                                                  language to clarify that an entity only                 of the select agent regulations, which                 laboratory.’’ We proposed adding this
                                                  needs to document the names of                          make the RO responsible to ensure                      language to ensure that laboratory
                                                  individuals at the registered entity. An                access controls, irrespective of the type              personnel working with select agents
                                                  entity may choose to list the external                  of security system in place.                           and toxins have access to relevant
                                                  agencies who participated in the drill or                  Paragraphs (d)(7)(i) through (d)(7)(v)              biosafety information and are therefore
                                                  exercise.                                               of section 11 (security) of the select                 aware of the risks associated with these
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                                                    Similar to the existing requirement for               agent regulations encompass a list of                  agents. One commenter requested
                                                  the security plan, we proposed to add a                 events that individuals with access                    clarification regarding the term
                                                  requirement that the biosafety and                      approval from the HHS Secretary or the                 ‘‘laboratory’’ and whether the term
                                                  incident response plans be submitted                    APHIS Administrator must immediately                   referred to a single room or a building
                                                  for initial registration, renewal of                    report to the RO. We proposed to add                   or to a group of rooms (e.g., laboratory,
                                                  registration, or when requested by                      a new requirement that the RO must be                  animal room, necropsy) used by a
                                                  FSAP. We received two comments                          notified of any loss of computer, hard                 Principal Investigator for a research
                                                  regarding these proposals which                         drive, or other data storage device                    project. The commenter also requested


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                           6287

                                                  clarification on the language ‘‘must be                 researchers will continue to read these                that the biosafety plan must include the
                                                  available to each individual working in                 plans and use them as a resource.                      provisions found in section 12(a) of the
                                                  the laboratory’’ and whether this                       Another commenter stated that                          select agent regulations (see
                                                  implied that there must be a specific                   regulatory language should be omitted                  § 73.12(a)(1)–(4)). To address the
                                                  biosafety manual for each room. We also                 to prevent creating a redundant process                commenters’ suggestion that FSAP
                                                  received three comments that                            such as those provisions already                       develop a guidance document regarding
                                                  questioned the need for a new                           covered under training and incident                    biosafety, additional guidance has been
                                                  requirement since the commenters                        response. We agree with commenters                     developed and is available at: http://
                                                  believe a laboratory-specific biosafety                 and have removed the training and                      www.selectagents.gov.
                                                  manual was already accessible to                        incident response language that was
                                                                                                                                                                 x. Training
                                                  individuals. We are not adding the                      noted in the NPRM because these
                                                  proposed provision to the regulations                   provisions are already covered by other                   We proposed to amend section 15 of
                                                  because upon further reflection we agree                sections in the regulations (i.e., incident            the select agent regulations to require
                                                  with the commenters that individuals                    response and training sections). We                    that training be completed within 12
                                                  already have access to their biosafety                  combined other provisions to reduce the                months of that individual’s anniversary
                                                  plan.                                                   seven provisions listed in the NPRM to                 of receiving access approval from the
                                                     In the NPRM, we proposed adding                      four provisions in the final rule.                     HHS Secretary or the APHIS
                                                  specific provisions to the biosafety                       One commenter stated we should                      Administrator, or prior to his or her
                                                  section that would require (1) a written                consider requiring the adoption of                     entry into an area where any select
                                                  risk assessment for each registered                     shared algorithms developed by the                     agents and toxins are used or stored,
                                                  select agent or toxin; (2) written safety               American Society for Microbiology                      whichever occurs first. This change is
                                                  procedures to protect entity personnel,                 (ASM) for use by clinical laboratories.                necessary in order to ensure that
                                                  the public, and the environment from                    These algorithms are presented as                      individuals at registered entities receive
                                                  exposure to the select agent or toxin; (3)              frequently asked questions (FAQs) from                 timely training. We received no specific
                                                  written decontamination procedures;                     ASM to assist laboratories. We made no                 comments regarding this proposed
                                                  and (4) written waste management                        changes based on this comment because                  change. However, seven commenters
                                                  procedures. We received 13 comments                     FSAP already provides FAQs to assist                   stated that we should include a
                                                  that stated that ‘‘risk assessments’’                   entities with meeting the biosafety                    description of the level of training
                                                  should be defined and the proposed                      requirements of the regulations.                       necessary for personnel in varying
                                                  requirement of having these for each                       Another commenter recommended                       positions with highly disparate job
                                                  procedure involving a select agent or                   that we also offer the suggestion that                 duties and responsibilities. The
                                                  toxin that addresses the hazards                        entities consider implementing                         commenters requested that we clarify
                                                  associated with the agent or toxin must                 programs whereby personnel are                         that the required training will be
                                                  be clarified because risk assessments are               required to work with another trained                  conducted at a level appropriate to the
                                                  completed through institutional review                  person (i.e., a ‘‘buddy’’ system or dual               registered person’s role and level of
                                                  committees by collaborative processes                   authentication) as an appropriate and                  access to select agents. We made no
                                                  with Principal Investigators and                        effective proactive method for the                     changes based on this comment because
                                                  biosafety professionals. One commenter                  prevention of laboratory acquired                      the current regulatory language is clear
                                                  stated that a risk assessment was always                infections and accidental releases of                  that ‘‘the training must address the
                                                  a requirement. We agree with the                        select agents. We made no changes                      particular needs of the individual, the
                                                  commenters that ‘‘risk assessment for                   based on this comment as it is essential               work they will do, and the risks posed
                                                  each procedure’’ should not be required                 for entities to develop their own                      by the select agents or toxins.’’ The
                                                  and agreed that having a risk assessment                biosafety initiatives to meet their own                training for the individuals should be
                                                  was already addressed in the regulations                needs. The commenter continued that                    determined by the entity based on at the
                                                  as outlined in Section 12(a) that ‘‘An                  many of these issues come down to the                  level of which the individual will have
                                                  individual or entity required to register               culture of safety in an entity, and                    access to select agents or toxins. The
                                                  under this part must develop and                        adherence to established protocols and                 training that each person receives
                                                  implement a written biosafety plan that                 training. The commenters wanted the                    should be designed to ensure that they
                                                  is commensurate with the risk of the                    regulatory provisions to reflect an                    can carry out their responsibilities
                                                  select agent or toxin, given its intended               improved safety culture. Two                           without causing harm to themselves, or
                                                  use.’’ However, we have clarified in the                commenters requested that we consider                  to their fellow co-workers, or to the
                                                  final regulatory language found in                      leaving the current provisions in place                public. We did clarify the regulatory
                                                  section 12(a)(1) of the select agent                    and develop guidance to assist entities                language regarding training for an
                                                  regulations that the biosafety plan                     that would include risk assessment, use                individual who must be escorted to
                                                  include ‘‘the hazardous characteristics                 of safety equipment, personal protective               specify that their training must be
                                                  of each agent or toxin listed on the                    equipment, containment devices, and                    accomplished prior to the individual’s
                                                  entity’s registration and the biosafety                 occupational health consideration.                     entry into a registered area.
                                                  risk associated with laboratory                         Another commenter stated that the new                     One commenter also asked that we
                                                  procedures related to the select agent or               section appears redundant with the risk                consider making ‘‘training a pre-
                                                  toxin.’’                                                assessment(s) performed during review                  requisite for access to select agents and
                                                     The majority of the commenters stated                of work registrations by an Institutional              toxins, and not a requirement for just
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                                                  that the approach outlined in the NPRM                  Biosafety Committee. We agree with the                 being FSAP approved.’’ The regulations
                                                  discussion of section 12(a) would lead                  commenters that the provisions focus on                in 42 CFR 73.15(a)(1) already requires
                                                  to decreased compliance and an                          the hazards and risks associated with                  that each approved individual receive
                                                  increase in paperwork burden. One                       the select agents and toxins and the                   information and training on biosafety,
                                                  commenter stated that many biosafety                    safety practices put in place by the                   security (including security awareness),
                                                  plans are already upwards of 50 pages,                  entity to protect entity personnel, the                and incident response before that
                                                  and increasing the length further may                   public, and the environment. We have                   individual has access to any select
                                                  greatly decrease the likelihood that                    revised the proposed language to state                 agents and toxins. The same commenter


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                                                  6288             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  asked that we clearly specify the                       their possession. We agree with the                    authorized by law to collect or receive
                                                  requirements for both initial and annual                commenter that final disposition needs                 such information for preventing or
                                                  training. While we made no changes to                   to be part of the entity’s recordkeeping               controlling disease, injury, or disability.
                                                  our regulatory language based on this                   requirement. We disagree with the
                                                                                                                                                                 Records for Long-Term Storage
                                                  comment, the document, ‘‘Guidance for                   commenter that this will place undue
                                                  Meeting the Training Requirements of                    burden on investigators because this                      In the NPRM we also solicited
                                                  the Select Agent Regulations,’’ found at                information can be included with an                    information and ideas as to how a
                                                  http://www.selectagents.gov/guidance-                   entity’s existing recordkeeping system                 regulatory requirement could be
                                                  training.html, has been amended to                      (e.g., inventory spreadsheet). Therefore,              constructed such that a registered entity
                                                  provide further detail and assistance                   to clarify the regulatory language, we                 would know whether a select agent or
                                                  regarding the content of initial and                    have revised the proposed regulatory                   toxin had been lost or stolen, without
                                                  annual training. The same commenter                     language to provide that the record will               that registered entity first having ‘‘an
                                                  stated that in two instances an                         need to include ‘‘the select agent used,               accurate, current inventory for each
                                                  employee’s annual training deadline                     purpose of use, and, when applicable,                  select agent . . . held in long-term
                                                  occurred in the middle of an extended                   final disposition.’’                                   storage.’’ In addition, we requested
                                                  medical leave during which it was not                      Section 73.17 of the select agent                   ideas as to how the current regulations
                                                  possible to complete the training, and                  regulations currently states that records              could be amended to address the threat
                                                  the entity had to choose to either let the              and databases need to be accurate. To                  of the theft of a select agent from a
                                                  training become overdue, or to remove                   ensure that the accuracy of handwritten                container held in long-term storage. We
                                                  the individual from the registration and                records can be verified, we proposed to                received three comments that addressed
                                                  completely start over with the security                 clarify that a handwritten record must                 this request. One commenter suggested
                                                  risk assessment (SRA) approval process                  be legible (i.e., capable of being read).              that FSAP inspectors review the record
                                                  once the individual was back to work.                   We received one comment requesting                     of select agents held in long-term
                                                  The commenter stated that ‘‘SRA                         that we define the term ‘‘legible                      storage and accept the attestation of the
                                                  approved personnel could commonly be                    handwritten records.’’ We made no                      responsible investigators of their
                                                  on other types of extended leave such as                changes based on this comment because                  accuracy. Another commenter stated we
                                                  maternity leave, or on sabbatical doing                 we are using the term ‘‘legible’’ in its               should continue with FSAP’s current
                                                  research at another institution but still               ordinary meaning.                                      select agent practices to allow for these
                                                  employed and SRA approved at their                         We proposed to expand the scope of                  stocks to be maintained in tamper-
                                                  home institution.’’ While we made no                    records required to be maintained to                   evident containers (e.g., security ties on
                                                  changes to our regulatory language                      include any records that contain                       freezer boxes) so that vials are not
                                                  based on this comment, we have                          information related to the requirements                individually removed, thawed, and
                                                  updated our guidance, ‘‘Guidance for                    of the regulations. We received five                   measured. The third commenter
                                                  Meeting the Training Requirements of                    comments that expressed concerns                       recommended dual authentication
                                                  the Select Agent Regulations,’’ which is                about the information being kept in                    coupled with required entity inventory
                                                  available at www.selectagents.gov, to                   laboratory notes. The commenters stated                reviews. We appreciate the comments
                                                  include information on how to deal                      that the information is ‘‘proprietary in               and will continue to consider how the
                                                  with situations regarding individuals                   nature,’’ contains intellectual property               recognition of theft and loss might be
                                                  that have extended absences from the                    information and should not be required                 addressed through alternative
                                                  laboratory.                                             to be provided to FSAP inspectors. We                  approaches.
                                                                                                          understand the concerns of the
                                                  xi. Records                                                                                                    III. Alternatives Considered
                                                                                                          commenters and clarified the language
                                                     Based on our inspections of registered               to indicate that it is only information                   The Public Health Security and
                                                  entities, we observed that not all entities             related to requirements of the select                  Bioterrorism Preparedness and
                                                  maintain records of the final disposition               agent regulations that must be produced                Response Act of 2002 requires HHS and
                                                  of select agents when consumed or                       on request. Such information may be                    USDA to review and republish the list
                                                  destroyed, and this impedes validation                  found in the biocontainment                            of select agents and toxins every two
                                                  of inventory holdings. Section 73.17 of                 certifications, laboratory notebooks,                  years. In drafting this final rule, we
                                                  the select agent regulations currently                  institutional biosafety and/or animal use              considered the action proposed in the
                                                  does not include a requirement for                      committee minutes and approved                         NPRM of removing the six select agents
                                                  documenting the final disposition of a                  protocols, and records associated with                 and one toxin where its costs and
                                                  select agent. To ensure the proper                      occupational health and suitability                    benefits were discussed. If those
                                                  tracking of a select agent from                         programs. Accordingly, we will only                    policies were adopted, it would result in
                                                  acquisition to final disposition, we are                review relevant portions of any                        savings ranging from approximately
                                                  adding a requirement for entity records                 laboratory notebooks or documents, and                 $15,300 for a small commercial BSL–3
                                                  to include the final disposition                        only if they contain information related               laboratory to approximately $165,000
                                                  (including destruction) for each select                 to any requirements of the regulations                 for a larger university with BSL–2/3
                                                  agent that has been held in long-term                   under sections 73.5, 73.7, 73.9, 73.11,                laboratories for laboratories no longer
                                                  storage. One commenter expressed                        73.12, 73.14, 73.15, 73.16, 73.17, and                 regulated. Based on the review of FSAP
                                                  concern that a requirement for a record                 73.19 of the select agent regulations.                 database, approximately eleven small
                                                  of destruction of select agents would                   Two commenters stated that certain                     entities would no longer be regulated
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                                                  place an undue burden on investigators                  records are ‘‘protected under the HIPAA                and would not be required to register
                                                  and recommended that this requirement                   Privacy Rule.’’ FSAP would expect any                  with FSAP. If the entities withdrew
                                                  be excluded from the final rule.                        information provided to FSAP regarding                 their registration, it would result in an
                                                  However, the commenter did agree that                   an individual’s health would be                        estimated saving of $168,300 annually.
                                                  an entity should be required to maintain                provided in accord with the HIPAA                      On the other hand, this policy could
                                                  a current and accurate inventory of all                 Privacy Rule, including the use and                    increase the likelihood of entities
                                                  select agents in their possession and                   disclosure of protected health                         working with these removed select
                                                  document when an agent is no longer in                  information to public health authorities               agents and toxin not having the


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                             6289

                                                  appropriate biosafety and security                        We have prepared an economic                         regulatory language concerning security,
                                                  provisions in place to prevent an                       analysis for this rule. The economic                   training, and records.
                                                  accidental or intentional release of a                  analysis provides a cost-benefit analysis,                The final rule will require that entities
                                                  select agent or toxin. The intentional                  as required by E.O. 12866, and a final                 develop validated inactivation
                                                  release could adversely affect the public               regulatory flexibility analysis (See                   procedures for select agents or regulated
                                                  health and safety. Recent events                        Section III.B. of this Preamble) that                  infectious nucleic acid and maintain
                                                  concerning the accidental transfer of                   examines the potential economic effects                written records of having done so. Costs
                                                  select agents that had not been fully                   of this rule on small entities, as required            of complying with this amendment are
                                                  inactivated, leading to the inadvertent                 by the Regulatory Flexibility Act. The                 expected to be modest.
                                                  release of select agents, caused us to                  economic analysis is summarized                           Currently, there are 286 entities
                                                  also look at provisions in this                         below. Copies of the full analysis are                 registered with APHIS and CDC
                                                  regulation. After carefully considering                 available in the docket at                             including 91 academic, 53 commercial,
                                                  the technical input of subject matter                   www.regulations.gov or at www.select                   81 State government, 45 Federal
                                                  experts, both within the Federal                        agents.gov.                                            government, and 16 private (non-profit)
                                                  government and from public comments,                      We have determined that this final                   institutions, most of which are
                                                  and recommendations from Federal                        rule is significant for the purposes of                considered to be small entities. Based
                                                  advisory groups, we have decided not to                 Executive Order 12866 and, therefore,                  on current record keeping and reporting
                                                  finalize the proposed changes to the list               this final rule has been reviewed by                   requirements, an additional 10 to 20
                                                  of select agents and toxins at this time.               OMB.                                                   hours per year may be required for
                                                                                                                                                                 maintaining records associated with
                                                  IV. Required Regulatory Analyses                        Summary of the Regulatory Impact                       select agents or material containing
                                                  A. Executive Orders 12866 and 13563                     Analysis                                               select agents or regulated nucleic acids
                                                                                                                                                                 that can produce infectious forms of any
                                                    Under Executive Order (E.O.) 12866,                      The Public Health Security and
                                                                                                                                                                 select agent virus that have been
                                                  Regulatory Planning and Review (58 FR                   Bioterrorism Preparedness and
                                                                                                                                                                 subjected to a validated inactivation
                                                  51735, October 4, 1993), CDC is                         Response Act of 2002 (Pub. L. 107–188)
                                                                                                                                                                 procedure or a procedure for removal of
                                                  required to determine whether this                      provides for the regulation of certain
                                                                                                                                                                 viable select agents. At an imputed cost
                                                  regulatory action would be ‘‘significant’’              biological agents and toxins that have
                                                                                                                                                                 of $33.40 per hour (GS–12, step 2), this
                                                  and therefore subject to review by the                  the potential to pose a severe threat to
                                                                                                                                                                 additional time requirement per entity
                                                  Office of Management and Budget                         human, animal, or plant health, or to
                                                                                                                                                                 will cost between $334 and $668 per
                                                  (OMB) and the requirements of the                       animal or plant products. APHIS and
                                                                                                                                                                 year, or in total for all registered entities
                                                  Executive Orders (E.O.). E.O. 12866                     CDC have primary responsibility for                    between $80,000 and $160,000. The
                                                  defines ‘‘significant regulatory action’’               implementing the provisions of the Act                 final rule will not have a significant
                                                  as any regulatory action that is likely to              within the Department of Agriculture                   economic impact on a substantial
                                                  result in a rule that may:                              and the Department of Health and                       number of small entities. Costs
                                                                                                          Human Services, respectively. Within
                                                    • Have an annual effect on the                        APHIS, Veterinary Services (VS) select
                                                                                                                                                                 associated with this rule do not include
                                                  economy of $100 million or more or                                                                             costs related to training, overhead,
                                                                                                          agents and toxins are those that have                  updates to facilities, etc. We assume in
                                                  adversely affect in a material way the                  been determined to have the potential to
                                                  economy, a sector of the economy,                                                                              this rule that all costs associated with
                                                                                                          pose a severe threat to animal health or               such factors for entities performing
                                                  productivity, competition, jobs, the                    animal products, and Plant Protection
                                                  environment, public health or safety, or                                                                       inactivation procedures have already
                                                                                                          and Quarantine (PPQ) select agents and                 been incurred prior to rulemaking.
                                                  state, local, or tribal governments or                  toxins are those that have been
                                                  communities;                                                                                                      The benefits of strengthened
                                                                                                          determined to have the potential to pose               safeguards against the unintentional or
                                                    • Create a serious inconsistency or                   a severe threat to plant health or plant               deliberate release of a select agent or
                                                  otherwise interfere with an action taken                products. HHS select agents and toxins                 toxin greatly exceed compliance costs of
                                                  or planned by another agency;                           are those that have been determined to                 the rules. As an example of losses that
                                                    • Materially alter the budgetary                      have the potential to pose a severe                    can occur, the October 2001 anthrax
                                                  impact of entitlements, grants, user fees,              threat to human health. APHIS and CDC                  attacks caused five fatalities and 17
                                                  or loan programs or the rights and                      coordinate regulatory activities for                   illnesses, disrupted business and
                                                  obligations of recipients; or,                          overlap select agents and toxins that                  government activities (including $2
                                                    • Raise novel legal or policy issues                  have been determined to pose a severe                  billion in lost revenues for the Postal
                                                  arising out of legal mandates, the                      threat to human and animal health or                   Service), and required more than $23
                                                  President’s priorities, or the principles               products.                                              million to decontaminate one Senate
                                                  set forth in E.O. 12866.                                   Sections 201 and 212(a)(2) of the Act               office building and $3 billion to
                                                    E.O. 13563, Improving Regulation and                  require a biennial review and                          decontaminate postal facilities and
                                                  Regulatory Review, (76 FR 3821,                         republication of the select agent and                  procure mail-sanitizing equipment.
                                                  January 21, 2011), updates some of the                  toxin list, with revisions as appropriate              Deliberate introduction greatly increases
                                                  provisions of E.O. 12866 in order to                    in accordance with this law. These final               the probability of a select agent
                                                  promote more streamlined regulatory                     rules will implement the                               becoming established and causing wide-
                                                  actions. This E.O. charges, in part, that,              recommendations of the fourth biennial                 ranging and devastating impacts to the
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                                                  while protecting ‘‘public health,                       review of select agent regulations and                 economy, other disruptions to society,
                                                  welfare, safety, and our environment’’                  have finalized changes that will increase              and diminished confidence in public
                                                  that regulations must also ‘‘promote                    their usability as well as provide for                 and private institutions.
                                                  predictability and reduce uncertainty’’                 enhanced program oversight. These                         The amended regulations will
                                                  in order to promote economic growth.                    amendments include new provisions                      enhance the protection of human,
                                                  Further, regulations must be written in                 regarding the inactivation of select                   animal, and plant health and safety. The
                                                  plain language and be easy to                           agents, specific biosafety and toxin                   final rules will reduce likelihood of the
                                                  understand.                                             requirements and clarification of                      accidental or intentional release of a


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                                                  6290             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  select agent or toxin. Benefits of the                  D. E.O. 12988: Civil Justice Reform                    PART 73—SELECT AGENTS AND
                                                  rules will derive from the greater                         This rule has been reviewed under                   TOXINS
                                                  probability that a release will be                      E.O. 12988, Civil Justice Reform. Once
                                                  prevented from occurring.                                                                                      ■ 1. The authority citation for part 73
                                                                                                          the final rule is in effect, CDC notes that:
                                                                                                                                                                 continues to read as follows:
                                                  B. The Regulatory Flexibility Act (RFA),                (1) All State and local laws and
                                                  as Amended by the Small Business                        regulations that are inconsistent with                   Authority: 42 U.S.C. 262a; sections 201–
                                                  Regulatory Enforcement Fairness Act                     this rule will be preempted; (2) No                    2014, 221 and 231 of Title II of Public Law
                                                                                                                                                                 107–188, 116 Stat 637 (42 U.S.C. 262a).
                                                  (SBREFA)                                                retroactive effect will be given to this
                                                                                                          rule; and (3) Administrative proceedings               ■ 2. Section 73.1 is amended by adding
                                                    We have examined the impacts of the                   will not be required before parties may                in alphabetical order, definitions of
                                                  proposed rule under RFA (5 U.S.C. 601–                  file suit in court challenging this rule.              validated inactivation procedure and
                                                  612). Unless we certify that the                                                                               viability testing protocol to read as set
                                                  proposed rule is not expected to have a                 E. E.O. 13132: Federalism
                                                                                                                                                                 forth below.
                                                  significant economic impact on a                          HHS/CDC has reviewed this final rule
                                                  substantial number of small entities,                   in accordance with E.O. 13132 regarding                § 73.1    Definitions.
                                                  RFA, as amended by the Small Business                   Federalism, and has determined that it                 *      *     *      *     *
                                                  Regulatory Enforcement Fairness Act                     does not have ‘‘federalism                                Validated inactivation procedure
                                                  (SBREFA), requires agencies to analyze                  implications.’’ The rule does not ‘‘have               means a procedure, whose efficacy is
                                                  regulatory options that would minimize                  substantial direct effects on the States,              confirmed by data generated from a
                                                  any significant economic impact of a                    on the relationship between the national               viability testing protocol, to render a
                                                  rule on small entities. We certify that                 government and the States, or on the                   select agent non-viable but allows the
                                                  this proposed rule will not have a                      distribution of power and                              select agent to retain characteristics of
                                                  significant economic impact on a                        responsibilities among the various                     interest for future use; or to render any
                                                  substantial number of small entities                    levels of government.’’                                nucleic acids that can produce
                                                  within the meaning of the RFA because                                                                          infectious forms of any select agent
                                                  these registered entities are already                   F. Plain Language Act of 2010                          virus non-infectious for future use.
                                                  required to comply with the select agent                  Under the Plain Language Act of 2010                 *      *     *      *     *
                                                  regulations. The small entities would                   (Pub. L. 111–274, October 13, 2010),                      Viability testing protocol means a
                                                  only incur some costs if they are                       executive Departments and Agencies are                 protocol to confirm the validated
                                                  performing inactivation procedures and                  required to use plain language in                      inactivation procedure by
                                                  are not maintaining records. The                        documents that explain to the public                   demonstrating the material is free of all
                                                  additional costs that may be incurred                   how to comply with a requirement the                   viable select agent.
                                                  are small in comparison to the long-term                Federal Government administers or
                                                  benefits of additional protection against                                                                      *      *     *      *     *
                                                                                                          enforces. HHS/CDC has attempted to
                                                  the release of select agents and toxins                                                                        ■ 3. Section 73.3 is amended as follows:
                                                                                                          use plain language in promulgating this
                                                  that would result in devastating effects                                                                       ■ a. By revising paragraph (b).
                                                                                                          rule consistent with the Federal Plain
                                                  to the economy.                                                                                                ■ b. By removing ‘‘functional’’ and
                                                                                                          Writing Act guidelines.
                                                    This regulatory action is not a major                                                                        adding in its place ‘‘toxic’’ in paragraph
                                                  rule as defined by Sec. 804 of the Small                V. References                                          (c)(2).
                                                  Business Regulatory Enforcement                         1. D.R. Franz and N.K. Jaax (1997). Defense            ■ c. By revising paragraph (d)(2).
                                                  Fairness Act of 1996. This proposed rule                     Against Toxin Weapons (Chapter 30). In            ■ d. By redesignating paragraph (d)(3) as
                                                  will not result in an annual effect on the                   Textbook of Military Medicine: Medical            (d)(7) and revising redesignated
                                                  economy of $100,000,000 or more; a                           Aspects of Chemical and Biological                paragraphs (d)(7) introductory text and
                                                  major increase in cost or prices; or                         Warfare, Borden Institute, Walter Reed            (d)(7)(i).
                                                                                                               Army Medical Center, Washington, DC.              ■ e. By redesignating paragraph (d)(4) as
                                                  significant adverse effects on
                                                                                                               631–642.                                          paragraph (d)(8).
                                                  competition, employment, investment,                    2. U.S. Department of Health and Human
                                                  productivity, innovation, or on the                                                                            ■ f. By redesignating paragraph (d)(5) as
                                                                                                               Services, National Institutes of Health.
                                                  ability of United States-based                               (2013). NIH Guidelines for Research
                                                                                                                                                                 paragraph (d)(12).
                                                  companies to compete with foreign-                           Involving Recombinant Or Synthetic                ■ g. By adding new paragraphs (d)(3),
                                                  based companies in domestic and                              Nucleic Acid Molecules (NIH                       (d)(4), (d)(5), (d)(6), (d)(9), (d)(10) and
                                                  export markets.                                              Guidelines). Retrieved from http://               (d)(11).
                                                                                                               osp.od.nih.gov/sites/default/files/NIH_           ■ h. By adding paragraph (e)(3).
                                                  C. Paperwork Reduction Act of 1995                           Guidelines.html.                                  ■ i. By adding ‘‘Bacillus cereus Biovar
                                                                                                          3. U.S. Department of Health and Human                 anthracis,’’ before ‘‘Botulinum
                                                    In accordance with section 3507(d) of                      Services, Centers for Disease Control and
                                                  the Paperwork Reduction Act of 1995                                                                            neurotoxins’’ in paragraph (f)(3)(i).
                                                                                                               Prevention and National Institutes of
                                                  (44 U.S.C. 3501 et seq.), CDC has                                                                                 The additions and revisions read as
                                                                                                               Health. (2009). Biosafety in
                                                  determined that the Paperwork                                Microbiological and Biomedical                    follows:
                                                  Reduction Act does apply to                                  Laboratories (BMBL) 5th Edition.                  § 73.3    HHS select agents and toxins.
                                                  information collection and                                   Retrieved from http://www.cdc.gov/
                                                  recordkeeping requirements included in                       biosafety/publications/bmbl5/index.htm.           *     *    *     *     *
                                                                                                                                                                   (b) HHS select agents and toxins:
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                                                  this rule. We note that the information                 List of Subjects in 42 CFR Part 73
                                                  collection and recordkeeping                                                                                   Abrin
                                                  requirements are already approved by                      Biologics, Packaging and containers,                 Bacillus cereus Biovar anthracis*
                                                  the Office of Management and Budget                     Penalties, Reporting and recordkeeping                 Botulinum neurotoxins*
                                                  (OMB) under OMB Control Number                          requirements, and Transportation.                      Botulinum neurotoxin producing
                                                  0920–0576 (Possession, Use, and                           For the reasons discussed in the                       species of Clostridium*
                                                  Transfer of Select Agents and Toxins (42                preamble, we amend 42 CFR part 73 as                   Conotoxins (Short, paralytic alpha
                                                  CFR 73), Expiration 12/31/2018).                        follows:                                                 conotoxins containing the following


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                              6291

                                                    amino acid sequence                                   procedure that is confirmed through a                  provisions of paragraph (d) of this
                                                    X1CCX2PACGX3X4X5X6CX7) 1                              viability testing protocol. Surrogate                  section, the HHS Secretary retains the
                                                  Coxiella burnetii                                       strains that are known to possess                      authority to, without prior notification,
                                                  Crimean-Congo hemorrhagic fever virus                   equivalent properties with respect to                  inspect and copy or request the
                                                  Diacetoxyscirpenol                                      inactivation can be used to validate an                submission of the due diligence
                                                  Eastern equine encephalitis virus                       inactivation procedure; however, if                    documentation to the CDC.
                                                  Ebola virus*                                            there are known strain-to-strain                       *      *     *      *     *
                                                  Francisella tularensis*                                 variations in the resistance of a select                  (9) An HHS select toxin identified in
                                                  Lassa fever virus                                       agent to an inactivation procedure, then               an original food sample or clinical
                                                  Lujo virus                                              an inactivation procedure validated on                 sample.
                                                  Marburg virus*                                          a lesser resistant strain must also be                    (10) For those laboratories that are not
                                                  Monkeypox virus                                         validated on the more resistant strains.               exempt under § 73.5(a) and § 73.6(a),
                                                  Reconstructed replication competent                        (5) Material containing a select agent              Botulinum neurotoxin that is produced
                                                    forms of the 1918 pandemic influenza                  that is subjected to a procedure that                  as a byproduct in the study of
                                                    virus containing any portion of the                   removes all viable select agent cells,                 Botulinum neurotoxin producing
                                                    coding regions of all eight gene                      spores, or virus particles if the material             species of Clostridium so long as the
                                                    segments (Reconstructed 1918                          is subjected to a viability testing                    toxin has not been intentionally
                                                    influenza virus)                                      protocol to ensure that the removal                    cultivated, collected, purified, or
                                                  Ricin                                                   method has rendered the material free of               otherwise extracted, and the material
                                                  Rickettsia prowazekii                                   all viable select agent.                               containing the toxin is rendered non-
                                                  SARS coronavirus (SARS-CoV)                                (6) A select agent or regulated nucleic
                                                                                                                                                                 toxic and disposed of within 30 days of
                                                  Saxitoxin                                               acids that can produce infectious forms
                                                                                                                                                                 the initiation of the culture.
                                                  South American hemorrhagic fever                        of any select agent virus not subjected
                                                                                                                                                                    (11) Waste generated during the
                                                    viruses:                                              to a validated inactivation procedure or
                                                                                                                                                                 delivery of patient care by health care
                                                    Chapare                                               material containing a select agent not
                                                                                                                                                                 professionals from a patient diagnosed
                                                    Guanarito                                             subjected to a procedure that removes
                                                                                                                                                                 with an illness or condition associated
                                                    Junin                                                 all viable select agent cells, spores, or
                                                                                                                                                                 with a select agent, where that waste is
                                                    Machupo                                               virus particles if the material is
                                                                                                                                                                 decontaminated or transferred for
                                                    Sabia                                                 determined by the HHS Secretary to be
                                                                                                                                                                 destruction by complying with state and
                                                  Staphylococcal enterotoxins (subtypes                   effectively inactivated or effectively
                                                                                                                                                                 Federal regulations within seven
                                                       A–E)                                               removed. To apply for a determination
                                                                                                          an individual or entity must submit a                  calendar days of the conclusion of
                                                  T–2 toxin
                                                                                                          written request and supporting                         patient care.
                                                  Tetrodotoxin
                                                                                                                                                                    (e) * * *
                                                  Tick-borne encephalitis virus                           scientific information to CDC. A written
                                                                                                                                                                    (3) An individual or entity may make
                                                    Far Eastern subtype                                   decision granting or denying the request
                                                                                                                                                                 a written request to the HHS Secretary
                                                    Siberian subtype                                      will be issued.
                                                                                                             (7) Except as required in § 73.16(l),               for reconsideration of a decision
                                                  Kyasanur Forest disease virus
                                                                                                          the aggregate amount of the toxin under                denying an application for the exclusion
                                                  Omsk haemorrhagic fever virus
                                                                                                          the control of a principal investigator,               of an attenuated strain of a select agent
                                                  Variola major virus (Smallpox virus)*
                                                                                                          treating physician or veterinarian, or                 or a select toxin modified to be less
                                                  Variola minor virus (Alastrim)*
                                                  Yersinia pestis*                                        commercial manufacturer or distributor                 potent or toxic. The written request for
                                                                                                          does not, at any time, exceed the                      reconsideration must state the facts and
                                                  *     *     *    *     *                                                                                       reasoning upon which the individual or
                                                    (d) * * *                                             following amounts: 1000 mg of Abrin; 1
                                                                                                          mg of Botulinum neurotoxins; 100 mg of                 entity relies to show the decision was
                                                    (2) Non-viable HHS select agents or                                                                          incorrect. The HHS Secretary will grant
                                                  nontoxic HHS toxins.                                    Conotoxins (Short, paralytic alpha
                                                                                                          conotoxins containing the following                    or deny the request for reconsideration
                                                    (3) A select agent or toxin that has                                                                         as promptly as circumstances allow and
                                                  been subjected to decontamination or a                  amino acid sequence
                                                                                                          X1CCX2PACGX3X4X5X6CX7); 10,000 mg                      will state, in writing, the reasons for the
                                                  destruction procedure when intended                                                                            decision.
                                                  for waste disposal.                                     of Diacetoxyscirpenol; 1000 mg of Ricin;
                                                    (4) A select agent or regulated nucleic               500 mg of Saxitoxin; 100 mg of                         *      *     *      *     *
                                                  acids that can produce infectious forms                 Staphylococcal enterotoxins (subtypes                  ■ 4. Section 73.4 is amended as follows:
                                                  of any select agent virus that has been                 A–E); 10,000 mg of T–2 toxin; or 500 mg                ■ a. By revising paragraph (b).
                                                  subjected to a validated inactivation                   of Tetrodotoxin. Provided that,                        ■ b. By removing ‘‘functional’’ and
                                                                                                             (i) The toxin is transferred only after             adding in its place ‘‘toxic’’ in paragraph
                                                     1 C = Cysteine residues are all present as           the transferor uses due diligence and                  (c)(2).
                                                  disulfides, with the 1st and 3rd Cysteine, and the      documents the identification of the                    ■ c. By revising paragraph (d)(2).
                                                  2nd and 4th Cysteine forming specific disulfide         recipient and the legitimate need (e.g.,               ■ d. By redesignating paragraph (d)(3) as
                                                  bridges; The consensus sequence includes known          prophylactic, protective, bona fide                    (d)(9).
                                                  toxins a-MI and a-GI (shown above) as well as a-
                                                  GIA, Ac1.1a, a-CnIA, a-CnIB; X1 = any amino
                                                                                                          research, or other peaceful purpose)                   ■ e. By adding new paragraphs (d)(3),
                                                  acid(s) or Des-X; X2 = Asparagine or Histidine; P       claimed by the recipient to use such                   (d)(4), (d)(5), (d)(6), (d)(7) and (d)(8).
                                                  = Proline; A = Alanine; G = Glycine; X3 = Arginine      toxin. Information to be documented                    ■ f. By adding paragraph (e)(3).
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                                                  or Lysine; X4 = Asparagine, Histidine, Lysine,          includes, but is not limited to, the                      The revision and additions read as
                                                  Arginine, Tyrosine, Phenylalanine or Tryptophan;
                                                  X5 = Tyrosine, Phenylalanine, or Tryptophan; X6
                                                                                                          recipient identity information,                        follows:
                                                  = Serine, Threonine, Glutamate, Aspartate,              including the recipient’s name,
                                                  Glutamine, or Asparagine; X7 = Any amino acid(s)        institution name, address, telephone                   § 73.4    Overlap select agents and toxins.
                                                  or Des X and; ‘‘Des X’’ = ‘‘an amino acid does not      number and email address; name of the                  *     *    *     *     *
                                                  have to be present at this position.’’ For example                                                               (b) Overlap select agents and toxins:
                                                  if a peptide sequence were XCCHPA then the
                                                                                                          toxin and the total amount transferred;
                                                  related peptide CCHPA would be designated as Des-       and the legitimate need claimed by the                 Bacillus anthracis *
                                                  X.                                                      recipient. Notwithstanding the                         Bacillus anthracis Pasteur strain


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                                                  6292             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  Brucella abortus                                        Federal regulations within seven                       of APHIS/CDC Form 4 to APHIS or CDC
                                                  Brucella melitensis                                     calendar days of the conclusion of                     within seven calendar days after
                                                  Brucella suis                                           patient care.                                          identification.
                                                  Burkholderia mallei *                                   *      *     *    *      *                             *     *     *    *     *
                                                  Burkholderia pseudomallei *                                (e) * * *                                           ■ 6. Section 73.6 is amended as follows:
                                                  Hendra virus                                               (3) An individual or entity may make                ■ a. By redesignating paragraph (a)(3) as
                                                  Nipah virus                                             a written request to the HHS Secretary                 paragraph (a)(4) and revising newly
                                                  Rift Valley fever virus                                 or Administrator for reconsideration of                redesignated paragraph (a)(4).
                                                  Venezuelan equine encephalitis virus                    a decision denying an application for                  ■ b. By adding new paragraph (a)(3).
                                                  *      *    *     *      *                              the exclusion of an attenuated strain of                 The revision and addition read as
                                                     (d) * * *                                            a select agent or a select toxin modified              follows:
                                                     (2) Non-viable overlap select agents or              to be less potent or toxic. The written
                                                                                                                                                                 § 73.6 Exemptions for overlap select
                                                  nontoxic overlap toxins.                                request for reconsideration must state                 agents and toxins.
                                                     (3) A select agent or toxin that has                 the facts and reasoning upon which the
                                                                                                                                                                    (a) * * *
                                                  been subjected to decontamination or a                  individual or entity relies to show the                   (3) Unless otherwise directed by the
                                                  destruction procedure when intended                     decision was incorrect. The HHS                        HHS Secretary or Administrator, the
                                                  for waste disposal.                                     Secretary or Administrator will grant or               clinical or diagnostic specimens
                                                     (4) A select agent or regulated nucleic              deny the request for reconsideration as                collected from a patient infected with a
                                                  acids that can produce infectious forms                 promptly as circumstances allow and                    select agent are transferred in
                                                  of any select agent virus that has been                 will state, in writing, the reasons for the            accordance with § 73.16 or destroyed
                                                  subjected to a validated inactivation                   decision.                                              on-site by a recognized sterilization or
                                                  procedure that is confirmed through a                   *      *     *    *      *                             inactivation process within seven
                                                  viability testing protocol. Surrogate                   ■ 5. Section 73.5 is amended as follows:               calendar days after delivery of patient
                                                  strains that are known to possess                       ■ a. By revising paragraph (a)(1).                     care by health care professionals has
                                                  equivalent properties with respect to                   ■ b. By redesignating paragraph (a)(3) as              concluded, and
                                                  inactivation can be used to validate an                 paragraph (a)(4) and revising newly                       (4) The identification of the agent or
                                                  inactivation procedure; however, if                     redesignated paragraph (a)(4).                         toxin is reported to CDC or APHIS, the
                                                  there are known strain-to-strain                        ■ c. By adding new paragraph (a)(3).                   specimen provider, and to other
                                                  variations in the resistance of a select                ■ d. By adding ‘‘Bacillus cereus Biovar                appropriate authorities when required
                                                  agent to an inactivation procedure, then                anthracis,’’ before ‘‘Botulinum                        by Federal, State, or local law by
                                                  an inactivation procedure validated on                  neurotoxins’’ in paragraph (a)(3)(i).                  telephone, facsimile, or email. This
                                                  a lesser resistant strain must also be                     The revisions and addition read as                  report must be followed by submission
                                                  validated on the more resistant strains.                follows:                                               of APHIS/CDC Form 4 to APHIS or CDC
                                                     (5) Material containing a select agent                                                                      within seven calendar days after
                                                  that is subjected to a procedure that                   § 73.5 Exemptions for HHS select agents                identification.
                                                  removes all viable select agent cells,                  and toxins.
                                                                                                                                                                 *      *    *     *     *
                                                  spores, or virus particles if the material                 (a) * * *
                                                                                                                                                                 ■ 7. Section 73.7 is amended as follows:
                                                  is subjected to a viability testing                        (1) Unless directed otherwise by the
                                                                                                                                                                 ■ a. By redesignating paragraphs (b)
                                                  protocol to ensure that the removal                     HHS Secretary, within seven calendar
                                                                                                                                                                 through (k) as paragraphs (c) through (l),
                                                  method has rendered the material free of                days after identification of the select
                                                                                                                                                                 respectively.
                                                  all viable select agent.                                agent or toxin (except for Botulinum                   ■ b. By adding a new paragraph (b) to
                                                     (6) A select agent or regulated nucleic              neurotoxin and/or Staphylococcal                       read as follows:
                                                  acids that can produce infectious forms                 enterotoxin (Subtypes A–E)), or within
                                                  of any select agent virus not subjected                 30 calendar days after identification of               § 73.7 Registration and related security
                                                  to a validated inactivation procedure or                Botulinum neurotoxin and/or                            risk assessments.
                                                  material containing a select agent not                  Staphylococcal enterotoxin (Subtypes                   *      *     *     *    *
                                                  subjected to a procedure that removes                   A–E), the select agent or toxin is                        (b) As a condition of registration, each
                                                  all viable select agent cells, spores, or               transferred in accordance with § 73.16                 entity is required to be in compliance
                                                  virus particles if the material is                      or destroyed on-site by a recognized                   with the requirements of this part for
                                                  determined by the HHS Secretary or                      sterilization or inactivation process,                 select agents and toxins listed on the
                                                  Administrator to be effectively                         *      *    *     *     *                              registration regardless of whether the
                                                  inactivated or effectively removed. To                     (3) Unless otherwise directed by the                entity is in actual possession of the
                                                  apply for a determination an individual                 HHS Secretary, the clinical or diagnostic              select agent or toxin. With regard to
                                                  or entity must submit a written request                 specimens collected from a patient                     toxins, the entity registered for
                                                  and supporting scientific information to                infected with a select agent are                       possession, use or transfer of a toxin
                                                  CDC or APHIS. A written decision                        transferred in accordance with § 73.16                 must be in compliance with the
                                                  granting or denying the request will be                 or destroyed on-site by a recognized                   requirements of this part regardless of
                                                  issued.                                                 sterilization or inactivation process                  the amount of toxin currently in its
                                                     (7) An overlap select toxin identified               within seven calendar days after                       possession.
                                                  in an original food sample or clinical                  delivery of patient care by health care                *      *     *     *    *
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                                                  sample.                                                 professionals has concluded, and                       ■ 8. Section 73.9 is amended as follows:
                                                     (8) Waste generated during the                          (4) The identification of the agent or              ■ a. In paragraph (a)(6) by removing
                                                  delivery of patient care by health care                 toxin is reported to CDC or APHIS, the                 ‘‘laboratory’’ and adding in its place
                                                  professionals from a patient diagnosed                  specimen provider, and to other                        ‘‘registered space’’ and adding ‘‘and the
                                                  with an illness or condition associated                 appropriate authorities when required                  corrections documented’’ after
                                                  with a select agent, where that waste is                by Federal, State, or local law by                     ‘‘corrected’’ at the end of the sentence.
                                                  decontaminated or transferred for                       telephone, facsimile, or email. This                   ■ b. By adding paragraphs (a)(7), (a)(8)
                                                  destruction by complying with state and                 report must be followed by submission                  and (a)(9) to read as set forth below.


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                                                                   Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations                                           6293

                                                  ■ c. By adding ‘‘Bacillus cereus Biovar                 ■ c. By adding a sentence to the end of                biological safety cabinets, animal caging
                                                  anthracis,’’ after ‘‘Bacillus anthracis,’’ in           paragraph (h).                                         systems, and centrifuge safety
                                                  paragraph (c)(1).                                         The additions read as follows:                       containers; and engineering controls
                                                                                                                                                                 and other facility safeguards;
                                                  § 73.9   Responsible Official.                          § 73.11    Security.
                                                                                                                                                                    (3) Written procedures for each
                                                    (a) * * *                                             *      *    *     *     *                              validated method used for disinfection,
                                                    (7) Ensure that individuals are                          (d) * * *                                           decontamination or destruction, as
                                                  provided the contact information for the                   (7) * * *                                           appropriate, of all contaminated or
                                                  HHS Office of Inspector General Hotline                    (vi) Any loss of computer, hard drive               presumptively contaminated materials
                                                  and the USDA Office of Inspector                        or other data storage device containing                including, but not limited to: Cultures
                                                  General Hotline so that they may                        information that could be used to gain                 and other materials related to the
                                                  anonymously report any biosafety or                     access to select agents or toxins.                     propagation of select agents or toxins,
                                                  security concerns related to select                     *      *    *     *     *                              items related to the analysis of select
                                                  agents and toxins.                                         (h) * * * Drills or exercises must be               agents and toxins, personal protective
                                                    (8) Investigate to determine the reason               documented to include how the drill or                 equipment, animal caging systems and
                                                  for any failure of a validated                          exercise tested and evaluated the plan,                bedding (if applicable), animal carcasses
                                                  inactivation procedure or any failure to                any problems that were identified and                  or extracted tissues and fluids (if
                                                  remove viable select agent from                         corrective action(s) taken, and the                    applicable), laboratory surfaces and
                                                  material. If the Responsible Official is                names of registered entity personnel                   equipment, and effluent material; and
                                                  unable to determine the cause of a                      participants.                                             (4) Procedures for the handling of
                                                  deviation from a validated inactivation                 ■ 11. Section 73.12 is amended as                      select agents and toxins in the same
                                                  procedure or a viable select agent                      follows:                                               spaces with non-select agents and toxins
                                                  removal method; or receives a report of                 ■ a. By revising paragraph (a).                        to prevent unintentional contamination.
                                                  any inactivation failure after the                      ■ b. By removing paragraph (c)(2),
                                                                                                                                                                 *      *    *     *     *
                                                  movement of material to another                         redesignating paragraph (c)(3) as (c)(2),                 (e) * * * Drills or exercises must be
                                                  location, the Responsible Official must                 and in newly redesignated paragraph                    documented to include how the drill or
                                                  report immediately by telephone or                      (c)(2), removing ‘‘NIH Guidelines for                  exercise tested and evaluated the plan,
                                                  email the inactivation or viable agent                  Research Involving Recombinant DNA                     any problems that were identified and
                                                  removal method failure to CDC or                        Molecules’’ and adding in its place                    corrective action(s) taken, and the
                                                  APHIS.                                                  ‘‘NIH Guidelines for Research Involving                names of registered entity personnel
                                                    (9) Review, and revise as necessary,                  Recombinant or Synthetic Nucleic Acid                  participants.
                                                  each of the entity’s validated                          Molecules’’.
                                                                                                          ■ c. By adding a new sentence to the                   ■ 12. Section 73.14 is amended as
                                                  inactivation procedures or viable select
                                                  agent removal methods. The review                       end of paragraph (e).                                  follows:
                                                                                                             The revision and addition read as                   ■ a. By adding a new sentence to the
                                                  must be conducted annually or after any
                                                                                                          follows:                                               end of paragraph (a).
                                                  change in Principal Investigator, change
                                                                                                                                                                 ■ b. By adding a new sentence to the
                                                  in the validated inactivation procedure                 § 73.12    Biosafety.                                  end of paragraph (f).
                                                  or viable select agent removal method,
                                                                                                            (a) An individual or entity required to                 The additions read as follows:
                                                  or failure of the validated inactivation
                                                  procedure or viable select agent removal                register under this part must develop
                                                                                                                                                                 § 73.14   Incident response.
                                                  method. The review must be                              and implement a written biosafety plan
                                                                                                          that is commensurate with the risk of                    (a) * * * The current incident
                                                  documented and training must be                                                                                response plan must be submitted for
                                                  conducted if there are any changes to                   the select agent or toxin, given its
                                                                                                          intended use. The biosafety plan must                  initial registration, renewal of
                                                  the validated inactivation procedure,                                                                          registration, or when requested.
                                                  viable select agent removal method, or                  contain sufficient information and
                                                                                                          documentation to describe the biosafety                *     *      *     *     *
                                                  viability testing protocol.
                                                                                                          and containment procedures for the                       (f) * * * Drills or exercises must be
                                                  *     *     *     *     *                               select agent or toxin, including any                   documented to include how the drill or
                                                  ■ 9. Section 73.10 is amended as                        animals (including arthropods) or plants               exercise tested and evaluated the plan,
                                                  follows:                                                intentionally or accidentally exposed to               any problems that were identified and
                                                  ■ a. By a sentence to the end of                        or infected with a select agent. The                   corrective action(s) taken, and the
                                                  paragraph (e) to read as follows:                       current biosafety plan must be                         names of registered entity personnel
                                                                                                          submitted for initial registration,                    participants.
                                                  § 73.10 Restricting access to select agents
                                                  and toxins; security risk assessments.                  renewal of registration, or when                       ■ 13. Section 73.15 is amended as
                                                                                                          requested. The biosafety plan must                     follows:
                                                  *      *     *    *     *
                                                                                                          include the following provisions:                      ■ a. Revising paragraph (a) to read as set
                                                     (e) * * * A Responsible Official must                  (1) The hazardous characteristics of
                                                  immediately notify the Responsible                                                                             forth below.
                                                                                                          each agent or toxin listed on the entity’s             ■ b. By adding paragraph (e) to read as
                                                  Official of the visited entity if the                   registration and the biosafety risk
                                                  person’s access to select agents and                                                                           set forth below.
                                                                                                          associated with laboratory procedures
                                                  toxins has been terminated.                             related to the select agent or toxin;                  § 73.15   Training.
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                                                  *      *     *    *     *                                 (2) Safeguards in place with                            (a) An individual or entity required to
                                                  ■ 10. Section 73.11 is amended as                       associated work practices to protect                   register under this part must provide
                                                  follows:                                                entity personnel, the public, and the                  information and training on
                                                  ■ a. In paragraph (c)(5) by adding                      environment from exposure to the select                biocontainment, biosafety, security
                                                  ‘‘keycards,’’ between ‘‘keys,’’ and                     agent or toxin including, but not limited              (including security awareness), and
                                                  ‘‘passwords’’ and removing ‘‘numbers’’                  to: Personal protective equipment and                  incident response to:
                                                  and adding in its place ‘‘permissions’’.                other safety equipment; containment                       (1) Each individual with access
                                                  ■ b. By adding paragraph (d)(7)(vi).                    equipment including, but not limited to,               approval from the HHS Secretary or


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                                                  6294             Federal Register / Vol. 82, No. 12 / Thursday, January 19, 2017 / Rules and Regulations

                                                  Administrator. The training must                        ■ c. By adding paragraph (a)(8).                       laboratory notebooks, institutional
                                                  address the particular needs of the                     ■ d . By revising paragraph (b).                       biosafety and/or animal use committee
                                                  individual, the work they will do, and                  ■ e. By revising paragraph (c).                        minutes and approved protocols, and
                                                  the risks posed by the select agents or                   The revision and additions read as                   records associated with occupational
                                                  toxins. The training must be                            follows:                                               health and suitability programs. All
                                                  accomplished prior to the individual’s                                                                         records created under this part must be
                                                  entry into an area where a select agent                 § 73.17    Records.                                    maintained for 3 years.
                                                  is handled or stored, or within 12                        (a) * * *
                                                                                                                                                                   Dated: January 9, 2017.
                                                  months of the date the individual was                     (1) * * *
                                                                                                                                                                 Sylvia M. Burwell,
                                                  approved by the HHS Secretary or the                      (v) The select agent used, purpose of
                                                                                                          use, and, when applicable, final                       Secretary.
                                                  Administrator for access, whichever is
                                                                                                          disposition,                                           [FR Doc. 2017–00726 Filed 1–18–17; 8:45 am]
                                                  earlier.
                                                     (2) Each individual not approved for                                                                        BILLING CODE 4163–18–P
                                                                                                          *      *    *     *      *
                                                  access to select agents and toxins by the                 (8) For select agents or material
                                                  HHS Secretary or Administrator before                   containing select agents or regulated
                                                                                                                                                                 DEPARTMENT OF HEALTH AND
                                                  that individual enters areas under escort               nucleic acids that can produce
                                                                                                                                                                 HUMAN SERVICES
                                                  where select agents or toxins are                       infectious forms of any select agent
                                                  handled or stored (e.g., laboratories,                  virus that have been subjected to a                    42 CFR Part 100
                                                  growth chambers, animal rooms,                          validated inactivation procedure or a
                                                  greenhouses, storage areas, shipping/                   procedure for removal of viable select                 RIN 0906–AB01
                                                  receiving areas, production facilities,                 agent:
                                                  etc.). Training for escorted personnel                                                                         National Vaccine Injury Compensation
                                                                                                            (i) A written description of the
                                                  must be based on the risk associated                                                                           Program: Revisions to the Vaccine
                                                                                                          validated inactivation procedure or
                                                  with accessing areas where select agents                                                                       Injury Table
                                                                                                          viable select agent removal method
                                                  and toxins are used and/or stored. The                  used, including validation data;                       AGENCY:  Health Resources and Services
                                                  training must be accomplished prior to                    (ii) A written description of the                    Administration (HRSA), HHS.
                                                  the individual’s entry into where select                viability testing protocol used;                       ACTION: Final rule.
                                                  agents or toxins are handled or stored                    (iii) A written description of the
                                                  (e.g., laboratories, growth chambers,                   investigation conducted by the entity                  SUMMARY:    On July 29, 2015, the
                                                  animal rooms, greenhouses, storage                      Responsible Official involving an                      Secretary of Health and Human Services
                                                  areas, shipping/receiving areas,                        inactivation or viable select agent                    (the Secretary) published in the Federal
                                                  production facilities, etc.).                           removal failure and the corrective                     Register a Notice of Proposed
                                                  *      *     *     *    *                               actions taken;                                         Rulemaking (NPRM) to amend the
                                                     (e) The Responsible Official must                      (iv) The name of each individual                     regulations governing the National
                                                  ensure and document that individuals                    performing the validated inactivation or               Vaccine Injury Compensation Program
                                                  are provided the contact information of                 viable select agent removal method;                    (VICP or program) by proposing
                                                  the HHS Office of Inspector General                       (v) The date(s) the validated                        revisions to the Vaccine Injury Table
                                                  Hotline and the USDA Office of                          inactivation or viable select agent                    (Table). The Secretary based the Table
                                                  Inspector General Hotline so that they                  removal method was completed;                          revisions primarily on the 2012 Institute
                                                  may anonymously report any safety or                      (vi) The location where the validated                of Medicine (IOM) report, ‘‘Adverse
                                                  security concerns related to select                     inactivation or viable select agent                    Effects of Vaccines: Evidence and
                                                  agents and toxins.                                      removal method was performed; and                      Causality,’’ the work of nine HHS
                                                  ■ 14. Section 73.16 is amended by                         (vii) A certificate, signed by the                   workgroups who reviewed the IOM
                                                  revising paragraph (l)(1) to read as                    Principal Investigator, that includes the              findings, and consideration of the
                                                  follows:                                                date of inactivation or viable select                  Advisory Commission on Childhood
                                                                                                          agent removal, the validated                           Vaccines’ (ACCV) recommendations.
                                                  § 73.16   Transfers.                                    inactivation or viable select agent                    The Secretary amends the Table through
                                                  *      *     *     *    *                               removal method used, and the name of                   the changes in this final rule. These
                                                     (l) * * *                                            the Principal Investigator. A copy of the              changes will apply only to petitions for
                                                     (1) Transfer the amounts only after the              certificate must accompany any transfer                compensation under the VICP filed after
                                                  transferor uses due diligence and                       of inactivated or select agent removed                 this final rule becomes effective.
                                                  documents that the recipient has a                      material.                                              DATE: This rule is effective February 21,
                                                  legitimate need (e.g., prophylactic,                    *      *    *     *      *                             2017.
                                                  protective, bona fide research, or other                  (b) The individual or entity must                    FOR FURTHER INFORMATION CONTACT: Dr.
                                                  peaceful purpose) to handle or use such                 implement a system to ensure that all                  Narayan Nair, Acting Director, Division
                                                  toxins. Information to be documented                    records and data bases created under                   of Injury Compensation Programs,
                                                  includes, but is not limited, to the                    this part are accurate and legible, have               Healthcare Systems Bureau, HRSA,
                                                  recipient information, toxin and amount                 controlled access, and authenticity may                5600 Fishers Lane, Room 8N146B,
                                                  transferred, and declaration that the                   be verified.                                           Rockville, MD 20857, or by telephone
                                                  recipient has legitimate purpose to store                 (c) The individual or entity must                    (855) 266–2427. This is a toll-free
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                                                  and use such toxins.                                    promptly produce upon request any                      number.
                                                  *      *     *     *    *                               information that is related to the                     SUPPLEMENTARY INFORMATION:
                                                  ■ 15. Section 73.17 is amended as                       requirements of this part but is not
                                                  follows:                                                otherwise contained in a record                        I. Background
                                                  ■ a. In paragraphs (a)(1)(iii) and (a)(3)(v)            required to be kept by this section. The                  The National Childhood Vaccine
                                                  by adding ‘‘or other storage container’’                location of such information may                       Injury Act of 1986, title III of Public Law
                                                  after ‘‘freezer’’.                                      include, but is not limited to,                        99–660 (42 U.S.C. 300aa–10 et seq.),
                                                  ■ b. By revising paragraph (a)(1)(v).                   biocontainment certifications,                         established the VICP, a Federal


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Document Created: 2018-02-01 15:15:20
Document Modified: 2018-02-01 15:15:20
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionRules and Regulations
ActionFinal rule.
DatesEffective February 21, 2017.
ContactDr. Samuel S. Edwin, Director, Division of Select Agents and Toxins, Centers for Disease Control and Prevention, 1600 Clifton Road NE., MS-A46, Atlanta, Georgia 30329. Telephone: (404) 718- 2000.
FR Citation82 FR 6278 
RIN Number0920-AA59
CFR AssociatedBiologics; Packaging and Containers; Penalties; Reporting and Recordkeeping Requirements and Transportation

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