81 FR 22286 - National Institutes of Health (NIH) Office of Science Policy (OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health

Federal Register Volume 81, Issue 73 (April 15, 2016)

Page Range		22286-22289
FR Document		2016-08810

The NIH OSP is amending portions of the NIH Guidelines in order to provide investigators with biosafety guidance regarding the standards for containment of non-human primates (NHPs) in biosafety level (BL) 4 laboratories and to make such guidance consistent with the expectations articulated in the Centers for Disease Control and Prevention (CDC)/NIH Biosafety in Microbiological and Biomedical Laboratories 5th edition (BMBL). Specifically, the NIH Guidelines will allow for housing of NHPs in open caging in a dedicated animal holding room provided there are two physical barriers between that animal holding room and non-containment space within the laboratory, the animal holding room has negative air pressure with respect to any adjacent non-containment corridors, and there are specific decontamination protocols in place before the door to the animal holding room is opened to allow for the periodic transfer of new animals into the room. These amendments do not change the current containment requirements in the NIH Guidelines but rather offer an alternative for achieving primary containment without compromising safety. In addition, the recertification requirement for biosafety cabinets in BL4 laboratories is updated in recognition of the technological standards for modern biosafety cabinets. The NIH OSP also is updating the validation requirements for equipment responsible for centralized heat decontamination of liquid effluents in laboratories working with large animals. These amendments to the NIH Guidelines will be implemented immediately upon publication in the Federal Register. These changes were developed after extensive consultation with biosafety experts, directors of and principal investigators in BL4 facilities working with NHPs, and CDC's Division of Select Agent and Toxins (DSAT) leadership at a public workshop and discussion at a public Recombinant DNA Advisory Committee (RAC) meeting. Publication in the Federal Register will inform the scientific and biosafety communities.

Federal Register, Volume 81 Issue 73 (Friday, April 15, 2016)

[Federal Register Volume 81, Number 73 (Friday, April 15, 2016)]
[Notices]
[Pages 22286-22289]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-08810]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


National Institutes of Health (NIH) Office of Science Policy 
(OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the 
NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic 
Acid Molecules (NIH Guidelines)

SUMMARY: The NIH OSP is amending portions of the NIH Guidelines in 
order to provide investigators with biosafety guidance regarding the 
standards for containment of non-human primates (NHPs) in biosafety 
level (BL) 4 laboratories and to make such guidance consistent with the 
expectations articulated in the Centers for Disease Control and 
Prevention (CDC)/NIH Biosafety in Microbiological and Biomedical 
Laboratories 5th edition (BMBL). Specifically, the NIH Guidelines will 
allow for housing of NHPs in open caging in a dedicated animal holding 
room provided there are two physical barriers between that animal 
holding room and non-containment space within the laboratory, the 
animal holding room has negative air pressure with respect to any 
adjacent non-containment corridors, and there are specific 
decontamination protocols in place before the door to the animal 
holding room is opened to allow for the periodic transfer of new 
animals into the room. These amendments do not change the current 
containment requirements in the NIH Guidelines but rather offer an 
alternative for achieving primary containment without compromising 
safety.
    In addition, the recertification requirement for biosafety cabinets 
in BL4 laboratories is updated in recognition of the technological 
standards for modern biosafety cabinets. The NIH OSP also is updating 
the validation requirements for equipment responsible for centralized 
heat decontamination of liquid effluents in laboratories working with 
large animals.
    These amendments to the NIH Guidelines will be implemented 
immediately upon publication in the Federal Register. These changes 
were developed after extensive consultation with biosafety experts, 
directors of and principal investigators in BL4 facilities working with 
NHPs, and CDC's Division of Select Agent and Toxins (DSAT) leadership 
at a public workshop and discussion at a public Recombinant DNA 
Advisory Committee (RAC) meeting. Publication in the Federal Register 
will inform the scientific and biosafety communities.

FOR FURTHER INFORMATION CONTACT: If you have questions, or require 
additional information about these changes, please contact the NIH OSP 
by email at [email protected], or telephone at 301-496-9838.

SUPPLEMENTARY INFORMATION: The first three editions of the BMBL and the 
NIH Guidelines were consistent in their approach to requiring primary 
containment for animal work in BL4 containment laboratories. However, 
in the early 1990s, the BMBL was amended and the fourth edition stated 
that animals housed in BL4 suit laboratories (i.e., laboratories in 
which Class III cabinets are not used but instead personnel wear 
positive pressure protective suits) should be housed in a primary 
containment system (such as open cages covered with filtered bonnets 
and opened in laminar flow hoods or other equivalent containment 
systems). This language remains in the current BMBL (5th edition). With 
the change in the BMBL, primary containment caging was arguably 
preferred but no longer required under BL4 containment. In contrast, 
the NIH Guidelines have always required primary containment caging for 
all animals in BL4 laboratories.
    Non-human primates are social animals and require environmental 
enrichment. Researchers in several U.S. BL4 laboratories engaged in NHP 
research approached the NIH OSP with concerns that primary containment 
caging in BL4 laboratories hindered the creation of an environment that 
allowed animals to benefit from adequate social interaction. Also based 
on risk assessments and experiences comparing several primary 
containment caging systems, the researchers concluded that primary 
containment caging may actually create new hazards for laboratory 
workers. These findings included interference with observation of the 
animals from outside the room leading to more frequent entries into the 
BL4 animal room to monitor the animals, and exacerbation of cramped 
working conditions created by the additional barriers required by some 
containment systems, which increases the difficulty of working in 
inflated pressure suits as well as the potential for damage to the 
pressure suit. In addition, investigators stated that current BL4 
laboratory designs incorporate sophisticated engineering systems, which 
provide biosafety protection in a dedicated animal room equivalent to 
the primary containment caging required under the NIH

[[Page 22287]]

Guidelines. On March 28, 2014, the NIH OSP, together with the CDC 
Division of Select Agents (DSAT), held a meeting with investigators and 
biosafety personnel from nine BL4 laboratories in the U.S. and five 
international laboratories (agenda and roster available at http://osp.od.nih.gov/office-biotechnology-activities/event/2014-03-28-120000-2014-03-28-211500/primary-containment-non-human-primates-biosafety-level-4-laboratories-challenges-and-best-practices). That meeting was 
followed by a discussion at the June 11, 2014, meeting of the NIH RAC 
regarding housing of NHPs in BL4 laboratories (a webcast of that 
discussion is available at http://videocast.nih.gov/summary.asp?Live=14300&bhcp=1.)
    As a result of these discussions and after consultation with CDC 
DSAT, the NIH OSP is amending the NIH Guidelines to allow the housing 
of NHP in open cages in a dedicated animal room provided certain 
conditions as articulated below are met.
    In addition, OSP is updating the requirement for testing and 
certification of Class I and II biosafety cabinets at BL4 from every 
six months to annually, recognizing the technological advances in 
biosafety cabinet design and engineering that have occurred over the 
period since this performance measure was originally implemented.
    Finally, Appendix Q of the NIH Guidelines currently requires that 
the centralized heat treatment catch tank system in BL4 large animal 
laboratories be validated every 30 days. To carry out this testing 
effectively, the system should be near capacity (i.e. ``under load''). 
Some laboratories do not use their catch tank systems on a regular 
basis; therefore, a mandatory 30 day validation would require them to 
demonstrate that the equipment is functioning when it is not in use or 
is not at capacity. This will not serve the intended purpose of 
demonstrating that the equipment is functioning as intended. Therefore, 
validation intervals will need to be set based on the utilization of 
the system provided it is done at least once a year.
    To implement these changes, the following sections of the NIH 
Guidelines are to be amended:
    Appendix G-II-D-2-l. currently states:

    Appendix G-II-D-2-l. Laboratory animals involved in experiments 
requiring BL4 level physical containment shall be housed either in 
cages contained in Class III cabinets or in partial containment 
caging systems, such as Horsfall units (see Appendix G-III-K, 
Footnotes and References of Appendix G), open cages placed in 
ventilated enclosures, or solid-wall and -bottom cages placed on 
holding racks equipped with ultraviolet irradiation lamps and 
reflectors that are located in a specially designed area in which 
all personnel are required to wear one-piece positive pressure 
suits.

    Appendix G-II-D-2-1 is amended as follows with the addition of a 
new Appendix G-II-D-2-1-(2) that will address housing of NHPs:

Appendix G-II-D-2-l. Containment for Animal Research

    Appendix G-II-D-2-l-(1). Laboratory animals involved in experiments 
requiring BL4 level physical containment shall be housed either in 
cages contained in Class III cabinets or in partial containment caging 
systems, such as Horsfall units (see Appendix G-III-K, Footnotes and 
References of Appendix G), open cages placed in ventilated enclosures, 
or solid-wall and -bottom cages placed on holding racks equipped with 
ultraviolet irradiation lamps and reflectors that are located in a 
specially designed area in which all personnel are required to wear 
one-piece positive pressure suits.
    Appendix G-II-D-2-l-(2). Non-human primates (NHP) may be housed (1) 
under the containment conditions described in Appendix G-II-D-2-l-(1) 
above, or (2) in open cages within a dedicated animal holding room that 
serves as the primary barrier and in which all personnel are required 
to wear one-piece positive pressure suits. A room serving as a primary 
barrier must be air-tight and capable of being decontaminated using 
fumigation. If NHPs are to be contained in a dedicated animal holding 
room serving as the primary barrier, the following conditions shall be 
met:
    (i) Access to the animal holding room from service corridors 
outside of the BL4 containment space shall require passage through two 
sets of doors, and the inner most door must be an air pressure 
resistant (APR) door;
    (ii) For any animal holding room considered to be a primary 
barrier, APR door(s) providing direct ingress from the exterior service 
corridor shall be fitted with appropriate and redundant lock-out 
mechanisms to prevent access when the animal holding room is 
contaminated and in use. There should be more than one mechanism to 
ensure that this primary barrier door cannot be opened when the animal 
room is contaminated and the APR door shall not serve as an emergency 
exit from the BL4 laboratory. The APR door shall be appropriately 
tested to demonstrate that in the closed, locked-out mode, the door 
provides an air-tight barrier proven by pressure decay testing or other 
equivalent method;
    (iii) Any door(s) allowing access into a corridor from which there 
is direct ingress to an animal holding room must be fitted with either 
(1) an APR door or (2) a non-APR door, providing directional airflow is 
maintained from the laboratory corridor space into the animal room. For 
the purpose of fumigation, animal rooms equipped with non-APR doors 
opening into the adjacent interior corridors shall be considered one 
space (i.e., areas between air-tight doors shall be fumigated 
together).
    (iv) Any door(s) used for access to the service corridor (the 
secondary barrier) shall be self-closing and of solid construction, 
designed not to corrode, split or warp;
    (v) Access to the service corridor inside the secondary barrier 
shall be restricted and strictly controlled when animal rooms are in 
use. Whenever possible, the secondary barrier door(s) should be fitted 
with safety interlock switches designed to prevent it from opening when 
an animal holding room door (the primary barrier) is opened following 
room decontamination; if interlock devices cannot be used, specific 
administrative procedures shall be implemented to control access to the 
service corridor;
    (vi) The service corridor shall maintain a negative pressure 
(inward directional airflow) relative to adjoining traffic corridors;
    (vii) Prior to fumigation of the animal holding room, cages should 
be removed for autoclaving or chemical decontamination.
    (viii) Caging should be chosen to reduce the amount of animal 
detritus that can be thrown out of the cage and onto the floor of the 
animal holding room;
    (ix) The flow of personnel, material and equipment should be 
directed in order to minimize the spread of contamination from the 
animal holding room into adjacent areas of the laboratory.
    (x) Following animal room decontamination, safeguards involving the 
use of personal protective equipment and appropriate administrative 
controls shall be implemented for the safe retrieval of biological 
indicators in order to prevent the spread of infectious agents in the 
event of a decontamination failure.
    With regard to the frequency of class II biosafety cabinet 
recertification and testing, the NIH Guidelines require 
recertification/testing of biosafety cabinets at six-month intervals. 
However, modern biosafety cabinet

[[Page 22288]]

design specifications incorporate continuous electronic and physical 
monitoring systems that track multiple operational parameters such as 
pressure differential, air flow velocity and plenum pressure with added 
capabilities for remote control and monitoring. Continuous performance 
monitoring and redundant safety features obviate the need for frequent 
testing of modern biosafety cabinets under normal conditions of use. 
Also the testing of biosafety cabinets in biomedical high containment 
(BL4) laboratories entails a complete shutdown of the laboratory for 
decontamination with appropriate sterilants to allow technicians to 
access the equipment safely. This procedure increases risks to 
laboratory staff working with the sterilants (often in the form of 
toxic gasses) and requires a halt to all research activities for an 
extended period of time depending on the number of cabinets to be 
tested or recertified. The NIH is in agreement with the recommendation 
of the BMBL that class II biosafety cabinets be tested and certified at 
least annually, with the understanding that retesting may have to be 
performed as needed at the discretion of the Institutional Biosafety 
Committee (IBC), if for example, equipment is moved or subject to 
unusual conditions of use.
    Appendix G-II-D-4-p currently states:

    Appendix G-II-D-4-p. The treated exhaust air from Class I and II 
biological safety cabinets may be discharged into the laboratory 
room environment or the outside through the facility air exhaust 
system. If exhaust air from Class I or II biological safety cabinets 
is discharged into the laboratory the cabinets are tested and 
certified at six-month intervals. The exhaust air from Class III 
biological safety cabinets is discharged, without recirculation 
through two sets of high efficiency particulate air/HEPA filters in 
series, via the facility exhaust air system. If the treated exhaust 
air from any of these cabinets is discharged to the outside through 
the facility exhaust air system, it is connected to this system in a 
manner (e.g., thimble unit connection (see Appendix G-III-L, 
Footnotes and References of Appendix G)) that avoids any 
interference with the air balance of the cabinets or the facility 
exhaust air system.

    Appendix G-II-D-4-p is amended as follows:
    Appendix G-II-D-4-p. The treated exhaust air from Class I and II 
biological safety cabinets may be discharged into the laboratory room 
environment or the outside through the facility air exhaust system. If 
exhaust air from Class I or II biological safety cabinets is discharged 
into the laboratory the cabinets are tested and certified at minimum on 
a yearly basis. More frequent testing and certification, based on the 
amount of use or other safety factors, shall be left to the discretion 
of the IBC. The exhaust air from Class III biological safety cabinets 
is discharged, without recirculation through two sets of high 
efficiency particulate air/HEPA filters in series, via the facility 
exhaust air system. If the treated exhaust air from any of these 
cabinets is discharged to the outside through the facility exhaust air 
system, it is connected to this system in a manner (e.g., thimble unit 
connection (see Appendix G-III-L, Footnotes and References of Appendix 
G)) that avoids any interference with the air balance of the cabinets 
or the facility exhaust air system.
    With regard to the periodic biologic validation of the centralized 
heat treatment process for all BL3 and BL4 facilities, the NIH 
Guidelines requires that this process be performed every 30 days while 
the BMBL recommends at least an annual biological validation. Similar 
to biosafety cabinets, modern catch tank systems for heat treatment of 
all laboratory effluents have also become more sophisticated and now 
incorporate redundant monitoring systems to track temperature and 
pressure parameters during each heat treatment cycle. In addition it 
should be noted that proper validation of the heat treatment catch tank 
system requires that testing be performed when the system is at or near 
capacity (i.e. ``under load'')--more frequent validation of a heat 
treatment system that is below capacity may not serve the intended 
purpose of demonstrating that the equipment is functioning as intended. 
An additional margin of safety is achieved by monitoring sterilization 
cycle parameters on a routine basis. We are, therefore, in agreement 
with the recommendation of the BMBL that validation be performed as 
frequently as necessary at the discretion of the IBC and at least once 
annually to ensure that the centralized effluent heat treatment system 
is performing as intended under the established process parameters. 
This amendment shall apply to heat treatment systems used in both large 
animal BL3 and BL4 facilities.
    For large animal BL3 laboratories, the requirement for 
decontamination and inactivation (BL3-N) found at Appendix Q-II-C-1-b-
(5) currently states:

    Appendix Q-II-C-1-b-(5). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by 
heat treatment before being released into the sanitary system. The 
procedure used for heat decontamination of liquid wastes shall be 
monitored with a recording thermometer. The effectiveness of the 
heat decontamination process system shall be revalidated every 30 
days with an indicator organism.

    Appendix Q-II-C-1-b-(5) is amended as follows:
    Appendix Q-II-C-1-b-(5). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. The procedure 
used for heat decontamination of liquid wastes shall be monitored with 
a recording thermometer. The effectiveness of the heat decontamination 
process system shall be revalidated at minimum on a yearly basis with 
an indicator organism. More frequent validation, based on the amount of 
use or other safety factors, shall be left to the discretion of the 
IBC.
    For large animal BL3 laboratories, the requirement for animal 
facilities (BL3-N) found at Appendix Q-II-C-2-h currently states:

    Appendix Q-II-C-2-h. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. The 
procedure used for heat decontamination of liquid wastes shall be 
monitored with a recording thermometer. The effectiveness of the 
heat decontamination process system shall be revalidated every 30 
days with an indicator organism.

    Appendix Q-II-C-2-h is amended as follows:
    Appendix Q-II-C-2-h. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat treatment 
before being released into the sanitary system. The procedure used for 
heat decontamination of liquid wastes shall be monitored with a 
recording thermometer. The effectiveness of the heat decontamination 
process system shall be revalidated at minimum on a yearly basis with 
an indicator organism. More frequent validation, based on the amount of 
use or other safety factors, shall be left to the discretion of the 
IBC.
    For large animal BL4 laboratories, the requirement for 
decontamination and inactivation (BL4-N) found at Appendix Q-II-D-1-b-
(9) currently states:

    Appendix Q-II-D-1-b-(9). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by 
heat treatment before being released into the sanitary

[[Page 22289]]

system. Liquid wastes from shower rooms and toilets shall be 
decontaminated with chemical disinfectants or heat by methods 
demonstrated to be effective. The procedure used for heat 
decontamination of liquid wastes shall be monitored with a recording 
thermometer. The effectiveness of the heat decontamination process 
system shall be revalidated every 30 days with an indicator 
organism. Liquid wastes from the shower shall be chemically 
decontaminated using an Environmental Protection Agency-approved 
germicide. The efficacy of the chemical treatment process shall be 
validated with an indicator organism. Chemical disinfectants shall 
be neutralized or diluted before release into general effluent waste 
systems.

    Appendix Q-II-D-1-b-(9) is amended as follows:
    Appendix Q-II-D-1-b-(9). Liquid effluent from containment 
equipment, sinks, biological safety cabinets, animal rooms, primary 
barriers, floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. If required 
by design, regulation, local ordinance or policy, liquid wastes from 
shower rooms and toilets shall be decontaminated with chemical 
disinfectants or heat by methods demonstrated to be effective. The 
procedure used for heat decontamination of liquid wastes shall be 
monitored with a recording thermometer. The effectiveness of the heat 
decontamination process system shall be revalidated at minimum on a 
yearly basis with an indicator organism. More frequent validation, 
based on the amount of use or other safety factors, shall be left to 
the discretion of the IBC. If required by design, regulation, local 
ordinance or policy, liquid wastes from the shower shall be chemically 
decontaminated using an Environmental Protection Agency-approved 
germicide. The efficacy of the chemical treatment process shall be 
validated with an indicator organism. Chemical disinfectants shall be 
neutralized or diluted before release into general effluent waste 
systems.
    For large animal BL4 laboratories, the requirement for animal 
facilities (BL4-N) found at Appendix Q-II-D-2-i currently states:

    Appendix Q-II-D-2-i. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat 
treatment before being released into the sanitary system. Liquid 
wastes from shower rooms and toilets shall be decontaminated with 
chemical disinfectants or heat by methods demonstrated to be 
effective. The procedure used for heat decontamination of liquid 
wastes shall be monitored with a recording thermometer. The 
effectiveness of the heat decontamination process system shall be 
revalidated every 30 days with an indicator organism. Liquid wastes 
from the shower shall be chemically decontaminated using an 
Environmental Protection Agency-approved germicide. The efficacy of 
the chemical treatment process shall be validated with an indicator 
organism. Chemical disinfectants shall be neutralized or diluted 
before release into general effluent waste systems.

    Appendix Q-II-D-2-i is amended as follows:
    Appendix Q-II-D-2-i. Liquid effluent from containment equipment, 
sinks, biological safety cabinets, animal rooms, primary barriers, 
floor drains, and sterilizers shall be decontaminated by heat treatment 
before being released into the sanitary system. If required by design, 
regulation, local ordinance or policy, liquid wastes from shower rooms 
and toilets shall be decontaminated with chemical disinfectants or heat 
by methods demonstrated to be effective. The procedure used for heat 
decontamination of liquid wastes shall be monitored with a recording 
thermometer. The effectiveness of the heat decontamination process 
system shall be revalidated at minimum on a yearly basis with an 
indicator organism. More frequent validation, based on the amount of 
use or other safety factors, shall be left to the discretion of the 
IBC. If required by design, regulation, local ordinance or policy, 
liquid wastes from the shower shall be chemically decontaminated using 
an Environmental Protection Agency-approved germicide. The efficacy of 
the chemical treatment process shall be validated with an indicator 
organism. Chemical disinfectants shall be neutralized or diluted before 
release into general effluent waste systems.

     Dated: April 9, 2016.
Lawrence A. Tabak,
Deputy Director, National Institutes of Health.
[FR Doc. 2016-08810 Filed 4-14-16; 8:45 am]
 BILLING CODE 4140-01-P

Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices 22287

Guidelines. On March 28, 2014, the NIH or solid-wall and -bottom cages placed on pressure decay testing or other
OSP, together with the CDC Division of holding racks equipped with ultraviolet equivalent method;
Select Agents (DSAT), held a meeting irradiation lamps and reflectors that are (iii) Any door(s) allowing access into
with investigators and biosafety located in a specially designed area in which a corridor from which there is direct
all personnel are required to wear one-piece ingress to an animal holding room must
personnel from nine BL4 laboratories in positive pressure suits.
the U.S. and five international be fitted with either (1) an APR door or
laboratories (agenda and roster available Appendix G–II–D–2–1 is amended as (2) a non-APR door, providing
at http://osp.od.nih.gov/office- follows with the addition of a new directional airflow is maintained from
biotechnology-activities/event/2014-03- Appendix G–II–D–2–1–(2) that will the laboratory corridor space into the
28-120000-2014-03-28-211500/primary- address housing of NHPs: animal room. For the purpose of
containment-non-human-primates- fumigation, animal rooms equipped
Appendix G–II–D–2–l. Containment for with non-APR doors opening into the
biosafety-level-4-laboratories- Animal Research
challenges-and-best-practices). That adjacent interior corridors shall be
meeting was followed by a discussion at Appendix G–II–D–2–l–(1). Laboratory considered one space (i.e., areas
the June 11, 2014, meeting of the NIH animals involved in experiments between air-tight doors shall be
RAC regarding housing of NHPs in BL4 requiring BL4 level physical fumigated together).
laboratories (a webcast of that containment shall be housed either in (iv) Any door(s) used for access to the
discussion is available at http:// cages contained in Class III cabinets or service corridor (the secondary barrier)
videocast.nih.gov/ in partial containment caging systems, shall be self-closing and of solid
summary.asp?Live=14300&bhcp=1.) such as Horsfall units (see Appendix G– construction, designed not to corrode,
As a result of these discussions and III–K, Footnotes and References of split or warp;
after consultation with CDC DSAT, the Appendix G), open cages placed in (v) Access to the service corridor
NIH OSP is amending the NIH ventilated enclosures, or solid-wall and inside the secondary barrier shall be
Guidelines to allow the housing of NHP -bottom cages placed on holding racks restricted and strictly controlled when
in open cages in a dedicated animal equipped with ultraviolet irradiation animal rooms are in use. Whenever
room provided certain conditions as lamps and reflectors that are located in possible, the secondary barrier door(s)
articulated below are met. a specially designed area in which all should be fitted with safety interlock
In addition, OSP is updating the personnel are required to wear one- switches designed to prevent it from
requirement for testing and certification piece positive pressure suits. opening when an animal holding room
of Class I and II biosafety cabinets at Appendix G–II–D–2–l–(2). Non- door (the primary barrier) is opened
BL4 from every six months to annually, human primates (NHP) may be housed following room decontamination; if
recognizing the technological advances (1) under the containment conditions interlock devices cannot be used,
in biosafety cabinet design and described in Appendix G–II–D–2–l–(1) specific administrative procedures shall
engineering that have occurred over the above, or (2) in open cages within a be implemented to control access to the
period since this performance measure dedicated animal holding room that service corridor;
was originally implemented. serves as the primary barrier and in (vi) The service corridor shall
Finally, Appendix Q of the NIH which all personnel are required to wear maintain a negative pressure (inward
Guidelines currently requires that the one-piece positive pressure suits. A directional airflow) relative to adjoining
centralized heat treatment catch tank room serving as a primary barrier must traffic corridors;
system in BL4 large animal laboratories (vii) Prior to fumigation of the animal
be air-tight and capable of being
be validated every 30 days. To carry out holding room, cages should be removed
decontaminated using fumigation. If
this testing effectively, the system for autoclaving or chemical
NHPs are to be contained in a dedicated
should be near capacity (i.e. ‘‘under decontamination.
animal holding room serving as the (viii) Caging should be chosen to
load’’). Some laboratories do not use primary barrier, the following
their catch tank systems on a regular reduce the amount of animal detritus
conditions shall be met: that can be thrown out of the cage and
basis; therefore, a mandatory 30 day (i) Access to the animal holding room
validation would require them to onto the floor of the animal holding
from service corridors outside of the room;
demonstrate that the equipment is BL4 containment space shall require
functioning when it is not in use or is (ix) The flow of personnel, material
passage through two sets of doors, and and equipment should be directed in
not at capacity. This will not serve the the inner most door must be an air
intended purpose of demonstrating that order to minimize the spread of
pressure resistant (APR) door; contamination from the animal holding
the equipment is functioning as (ii) For any animal holding room
intended. Therefore, validation intervals room into adjacent areas of the
considered to be a primary barrier, APR laboratory.
will need to be set based on the door(s) providing direct ingress from the (x) Following animal room
utilization of the system provided it is exterior service corridor shall be fitted decontamination, safeguards involving
done at least once a year. with appropriate and redundant lock-
To implement these changes, the the use of personal protective
out mechanisms to prevent access when equipment and appropriate
following sections of the NIH Guidelines
the animal holding room is administrative controls shall be
are to be amended:
Appendix G–II–D–2–l. currently contaminated and in use. There should implemented for the safe retrieval of
be more than one mechanism to ensure biological indicators in order to prevent
asabaliauskas on DSK3SPTVN1PROD with NOTICES

states:
that this primary barrier door cannot be the spread of infectious agents in the
Appendix G–II–D–2–l. Laboratory animals opened when the animal room is event of a decontamination failure.
involved in experiments requiring BL4 level contaminated and the APR door shall With regard to the frequency of class
physical containment shall be housed either
in cages contained in Class III cabinets or in
not serve as an emergency exit from the II biosafety cabinet recertification and
partial containment caging systems, such as BL4 laboratory. The APR door shall be testing, the NIH Guidelines require
Horsfall units (see Appendix G–III–K, appropriately tested to demonstrate that recertification/testing of biosafety
Footnotes and References of Appendix G), in the closed, locked-out mode, the door cabinets at six-month intervals.
open cages placed in ventilated enclosures, provides an air-tight barrier proven by However, modern biosafety cabinet

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22288 Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices

design specifications incorporate certification, based on the amount of use The effectiveness of the heat
continuous electronic and physical or other safety factors, shall be left to the decontamination process system shall be
monitoring systems that track multiple discretion of the IBC. The exhaust air revalidated every 30 days with an indicator
from Class III biological safety cabinets organism.
operational parameters such as pressure
differential, air flow velocity and is discharged, without recirculation Appendix Q–II–C–1–b–(5) is amended
plenum pressure with added through two sets of high efficiency as follows:
capabilities for remote control and particulate air/HEPA filters in series, via Appendix Q–II–C–1–b–(5). Liquid
monitoring. Continuous performance the facility exhaust air system. If the effluent from containment equipment,
monitoring and redundant safety treated exhaust air from any of these sinks, biological safety cabinets, animal
features obviate the need for frequent cabinets is discharged to the outside rooms, primary barriers, floor drains,
testing of modern biosafety cabinets through the facility exhaust air system, and sterilizers shall be decontaminated
under normal conditions of use. Also it is connected to this system in a by heat treatment before being released
the testing of biosafety cabinets in manner (e.g., thimble unit connection into the sanitary system. The procedure
biomedical high containment (BL4) (see Appendix G–III–L, Footnotes and used for heat decontamination of liquid
laboratories entails a complete References of Appendix G)) that avoids wastes shall be monitored with a
shutdown of the laboratory for any interference with the air balance of recording thermometer. The
decontamination with appropriate the cabinets or the facility exhaust air effectiveness of the heat
sterilants to allow technicians to access system. decontamination process system shall
the equipment safely. This procedure With regard to the periodic biologic be revalidated at minimum on a yearly
increases risks to laboratory staff validation of the centralized heat basis with an indicator organism. More
working with the sterilants (often in the treatment process for all BL3 and BL4 frequent validation, based on the
form of toxic gasses) and requires a halt facilities, the NIH Guidelines requires amount of use or other safety factors,
to all research activities for an extended that this process be performed every 30 shall be left to the discretion of the IBC.
period of time depending on the number days while the BMBL recommends at For large animal BL3 laboratories, the
of cabinets to be tested or recertified. least an annual biological validation. requirement for animal facilities (BL3–
The NIH is in agreement with the Similar to biosafety cabinets, modern N) found at Appendix Q–II–C–2–h
recommendation of the BMBL that class catch tank systems for heat treatment of currently states:
II biosafety cabinets be tested and all laboratory effluents have also Appendix Q–II–C–2–h. Liquid effluent
certified at least annually, with the become more sophisticated and now from containment equipment, sinks,
understanding that retesting may have incorporate redundant monitoring biological safety cabinets, animal rooms,
to be performed as needed at the systems to track temperature and primary barriers, floor drains, and sterilizers
discretion of the Institutional Biosafety pressure parameters during each heat shall be decontaminated by heat treatment
Committee (IBC), if for example, treatment cycle. In addition it should be before being released into the sanitary
equipment is moved or subject to noted that proper validation of the heat system. The procedure used for heat
treatment catch tank system requires decontamination of liquid wastes shall be
unusual conditions of use. monitored with a recording thermometer.
Appendix G–II–D–4–p currently that testing be performed when the The effectiveness of the heat
states: system is at or near capacity (i.e. ‘‘under decontamination process system shall be
Appendix G–II–D–4–p. The treated exhaust load’’)—more frequent validation of a revalidated every 30 days with an indicator
air from Class I and II biological safety heat treatment system that is below organism.
cabinets may be discharged into the capacity may not serve the intended
laboratory room environment or the outside
Appendix Q–II–C–2–h is amended as
purpose of demonstrating that the
through the facility air exhaust system. If follows:
equipment is functioning as intended.
exhaust air from Class I or II biological safety Appendix Q–II–C–2–h. Liquid
An additional margin of safety is
cabinets is discharged into the laboratory the effluent from containment equipment,
achieved by monitoring sterilization
cabinets are tested and certified at six-month sinks, biological safety cabinets, animal
intervals. The exhaust air from Class III cycle parameters on a routine basis. We
rooms, primary barriers, floor drains,
biological safety cabinets is discharged, are, therefore, in agreement with the
and sterilizers shall be decontaminated
without recirculation through two sets of recommendation of the BMBL that
by heat treatment before being released
high efficiency particulate air/HEPA filters in validation be performed as frequently as
series, via the facility exhaust air system. If
into the sanitary system. The procedure
necessary at the discretion of the IBC
the treated exhaust air from any of these used for heat decontamination of liquid
and at least once annually to ensure that
cabinets is discharged to the outside through wastes shall be monitored with a
the centralized effluent heat treatment
the facility exhaust air system, it is connected recording thermometer. The
system is performing as intended under
to this system in a manner (e.g., thimble unit effectiveness of the heat
connection (see Appendix G–III–L, Footnotes the established process parameters. This
decontamination process system shall
and References of Appendix G)) that avoids amendment shall apply to heat
be revalidated at minimum on a yearly
any interference with the air balance of the treatment systems used in both large
basis with an indicator organism. More
cabinets or the facility exhaust air system. animal BL3 and BL4 facilities.
For large animal BL3 laboratories, the frequent validation, based on the
Appendix G–II–D–4–p is amended as amount of use or other safety factors,
follows: requirement for decontamination and
inactivation (BL3–N) found at Appendix shall be left to the discretion of the IBC.
Appendix G–II–D–4–p. The treated For large animal BL4 laboratories, the
exhaust air from Class I and II biological Q–II–C–1–b–(5) currently states:
asabaliauskas on DSK3SPTVN1PROD with NOTICES

requirement for decontamination and
safety cabinets may be discharged into Appendix Q–II–C–1–b–(5). Liquid effluent inactivation (BL4–N) found at Appendix
the laboratory room environment or the from containment equipment, sinks, Q–II–D–1–b–(9) currently states:
outside through the facility air exhaust biological safety cabinets, animal rooms,
primary barriers, floor drains, and sterilizers Appendix Q–II–D–1–b–(9). Liquid effluent
system. If exhaust air from Class I or II shall be decontaminated by heat treatment from containment equipment, sinks,
biological safety cabinets is discharged before being released into the sanitary biological safety cabinets, animal rooms,
into the laboratory the cabinets are system. The procedure used for heat primary barriers, floor drains, and sterilizers
tested and certified at minimum on a decontamination of liquid wastes shall be shall be decontaminated by heat treatment
yearly basis. More frequent testing and monitored with a recording thermometer. before being released into the sanitary

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Federal Register / Vol. 81, No. 73 / Friday, April 15, 2016 / Notices 22289

system. Liquid wastes from shower rooms revalidated every 30 days with an indicator projects to be submitted to the Office of
and toilets shall be decontaminated with organism. Liquid wastes from the shower Management and Budget (OMB) for
chemical disinfectants or heat by methods shall be chemically decontaminated using an review and approval.
demonstrated to be effective. The procedure Environmental Protection Agency-approved Written comments and/or suggestions
used for heat decontamination of liquid germicide. The efficacy of the chemical from the public and affected agencies
wastes shall be monitored with a recording treatment process shall be validated with an
thermometer. The effectiveness of the heat indicator organism. Chemical disinfectants
are invited on one or more of the
decontamination process system shall be shall be neutralized or diluted before release following points: (1) Whether the
revalidated every 30 days with an indicator into general effluent waste systems. proposed collection of information is
organism. Liquid wastes from the shower necessary for the proper performance of
shall be chemically decontaminated using an Appendix Q–II–D–2–i is amended as the function of the agency, including
Environmental Protection Agency-approved follows: whether the information will have
germicide. The efficacy of the chemical Appendix Q–II–D–2–i. Liquid effluent practical utility; (2) The accuracy of the
treatment process shall be validated with an from containment equipment, sinks, agency’s estimate of the burden of the
indicator organism. Chemical disinfectants biological safety cabinets, animal rooms,
shall be neutralized or diluted before release
proposed collection of information,
primary barriers, floor drains, and including the validity of the
into general effluent waste systems. sterilizers shall be decontaminated by methodology and assumptions used; (3)
Appendix Q–II–D–1–b–(9) is heat treatment before being released into Ways to enhance the quality, utility, and
amended as follows: the sanitary system. If required by clarity of the information to be
Appendix Q–II–D–1–b–(9). Liquid design, regulation, local ordinance or collected; and (4) Ways to minimize the
effluent from containment equipment, policy, liquid wastes from shower burden of the collection of information
sinks, biological safety cabinets, animal rooms and toilets shall be on those who are to respond, including
rooms, primary barriers, floor drains, decontaminated with chemical the use of appropriate automated,
and sterilizers shall be decontaminated disinfectants or heat by methods electronic, mechanical, or other
by heat treatment before being released demonstrated to be effective. The technological collection techniques or
into the sanitary system. If required by procedure used for heat other forms of information technology.
design, regulation, local ordinance or decontamination of liquid wastes shall To Submit Comments and For Further
policy, liquid wastes from shower be monitored with a recording Information: To obtain a copy of the
rooms and toilets shall be thermometer. The effectiveness of the data collection plans and instruments,
decontaminated with chemical heat decontamination process system submit comments in writing, or request
disinfectants or heat by methods shall be revalidated at minimum on a more information on the proposed
demonstrated to be effective. The yearly basis with an indicator organism. project, contact: David Sharlip, NLM
procedure used for heat More frequent validation, based on the Project Clearance Liaison, Office of
decontamination of liquid wastes shall amount of use or other safety factors, Administrative and Management
be monitored with a recording shall be left to the discretion of the IBC. Analysis Services, OAMAS, NLM, NIH,
thermometer. The effectiveness of the If required by design, regulation, local Building 38A, Room B2N12, 8600
heat decontamination process system ordinance or policy, liquid wastes from Rockville Pike, Bethesda, MD 20894, or
shall be revalidated at minimum on a the shower shall be chemically call non-toll-free number (301) 496–
yearly basis with an indicator organism. decontaminated using an Environmental 5441, or Email your request, including
More frequent validation, based on the Protection Agency-approved germicide. your address to: sharlipd@mail.nih.gov.
amount of use or other safety factors, The efficacy of the chemical treatment Formal requests for additional plans and
shall be left to the discretion of the IBC. process shall be validated with an instruments must be requested in
If required by design, regulation, local indicator organism. Chemical writing.
ordinance or policy, liquid wastes from disinfectants shall be neutralized or Comment Due Date: Comments
the shower shall be chemically diluted before release into general regarding this information collection are
decontaminated using an Environmental effluent waste systems. best assured of having their full effect if
Protection Agency-approved germicide. Dated: April 9, 2016.
received within 60 days of the date of
The efficacy of the chemical treatment this publication.
Lawrence A. Tabak, Proposed Collection: NLM People
process shall be validated with an
indicator organism. Chemical Deputy Director, National Institutes of Health. Locator System 0925–0612, Expiration
disinfectants shall be neutralized or [FR Doc. 2016–08810 Filed 4–14–16; 8:45 am] Date: 07/31/2016, EXTENSION,
diluted before release into general BILLING CODE 4140–01–P National Library of Medicine (NLM),
effluent waste systems. National Institutes of Health (NIH).
For large animal BL4 laboratories, the Need and Use of Information
requirement for animal facilities (BL4– DEPARTMENT OF HEALTH AND Collection: This collection of data is
N) found at Appendix Q–II–D–2–i HUMAN SERVICES intended to assist in the reunification of
currently states: family members and friends who are
National Institutes of Health separated during a disaster. Experience
Appendix Q–II–D–2–i. Liquid effluent
from containment equipment, sinks, Proposed Collection; 60-Day Comment in operational drills and during real-
biological safety cabinets, animal rooms, Request; NLM PEOPLE LOCATOR® world disasters such as the January 2010
primary barriers, floor drains, and sterilizers System earthquakes in Haiti demonstrates that
shall be decontaminated by heat treatment family members and loved ones are
asabaliauskas on DSK3SPTVN1PROD with NOTICES

before being released into the sanitary Summary: In compliance with the often separated during disasters and
system. Liquid wastes from shower rooms requirement of Section 3506(c)(2)(A) of have significant difficulty determining
and toilets shall be decontaminated with the Paperwork Reduction Act of 1995, each other’s safety, condition, and
chemical disinfectants or heat by methods
demonstrated to be effective. The procedure for opportunity for public comment on location. Reunification can not only
used for heat decontamination of liquid proposed data collection projects, the improve their emotional well-being
wastes shall be monitored with a recording National Library of Medicine (NLM), during the recovery period, but also
thermometer. The effectiveness of the heat National Institutes of Health (NIH), will improve the chances that injured
decontamination process system shall be publish periodic summaries of proposed victims will be cared for once they are

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Document Created: 2016-04-15 00:55:43
Document Modified: 2016-04-15 00:55:43

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Contact		If you have questions, or require additional information about these changes, please contact the NIH OSP by email at [email protected], or telephone at 301-496-9838.
FR Citation		81 FR 22286

81 FR 22286 - National Institutes of Health (NIH) Office of Science Policy (OSP) Recombinant or Synthetic Nucleic Acid Research: Action Under the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines)

DEPARTMENT OF HEALTH AND HUMAN SERVICESNational Institutes of Health

Federal Register Volume 81, Issue 73 (April 15, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health