83_FR_22928 83 FR 22832 - VSTA Records and Reports Specific to International Standards for Pharmacovigilance

83 FR 22832 - VSTA Records and Reports Specific to International Standards for Pharmacovigilance

DEPARTMENT OF AGRICULTURE
Animal and Plant Health Inspection Service

Federal Register Volume 83, Issue 96 (May 17, 2018)

Page Range22832-22836
FR Document2018-10540

We are amending the Virus-Serum-Toxin Act regulations concerning records and reports. This change requires veterinary biologics licensees and permittees to record and submit reports concerning adverse events associated with the use of biological products they produce or distribute. The information that must be included in the adverse event reports submitted to the Animal and Plant Health Inspection Service (APHIS) will be provided in separate guidance documents. These records and reports will help ensure that APHIS can provide complete and accurate information to consumers regarding adverse reactions or other problems associated with the use of licensed biological products.

Federal Register, Volume 83 Issue 96 (Thursday, May 17, 2018)
[Federal Register Volume 83, Number 96 (Thursday, May 17, 2018)]
[Rules and Regulations]
[Pages 22832-22836]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2018-10540]


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DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Parts 101 and 116

[Docket No. APHIS-2014-0063]
RIN 0579-AE11


VSTA Records and Reports Specific to International Standards for 
Pharmacovigilance

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: We are amending the Virus-Serum-Toxin Act regulations 
concerning records and reports. This change requires veterinary 
biologics licensees and permittees to record and submit reports 
concerning adverse events associated with the use of biological 
products they produce or distribute. The information that must be 
included in the adverse event reports submitted to the Animal and Plant 
Health Inspection Service (APHIS) will be provided in separate guidance 
documents. These records and reports will help ensure that APHIS can 
provide complete and accurate information to consumers regarding 
adverse reactions or other problems associated with the use of licensed 
biological products.

DATES: Effective June 18, 2018.

FOR FURTHER INFORMATION CONTACT: Dr. Donna L. Malloy, Section Leader, 
Operational Support, Center for Veterinary Biologics Policy, 
Evaluation, and Licensing, VS, APHIS, 4700 River Road Unit 148, 
Riverdale, MD 20737-1231; (301) 851-3426.

SUPPLEMENTARY INFORMATION: 

Background

    The Virus-Serum-Toxin Act regulations in 9 CFR part 116 (referred 
to below as the regulations) contain requirements for maintaining 
detailed records of information necessary to give a complete accounting 
of all the activities within a veterinary biologics establishment. 
These records include records and reports for unfavorable or unintended 
events that occur in animals after the use of a biological product.
    On September 4, 2015, we published in the Federal Register (80 FR 
53475-53478, Docket No. APHIS-2014-0063) a proposal \1\ to amend the 
regulations by establishing definitions for the terms adverse event and 
adverse event report and by providing requirements for adverse event 
records and reports. The changes we proposed are consistent with 
guidelines set out by the International Cooperation on Harmonization of 
Technical Requirements for Registration of Veterinary Medicinal 
Products (VICH). VICH is a unique project conducted under the World 
Organization for Animal Health that brings together the regulatory 
authorities of the European Union, Japan, and the United States and 
representatives from the animal health industry in the three regions. 
Regulatory authorities and industry experts from Australia, Canada, and 
New Zealand participate as observers.
---------------------------------------------------------------------------

    \1\ To view the proposed rule, supporting document, and the 
comments we received, go to http://www.regulations.gov/#!docketDetail;D=APHIS-2014-0063.
---------------------------------------------------------------------------

    The purpose of VICH is to harmonize technical requirements for 
veterinary medicinal products (both pharmaceuticals and biologics). As 
a VICH member, the Animal and Plant Health Inspection Service (APHIS) 
provides expertise on veterinary biological products and participates 
in efforts to enhance harmonization. Both APHIS and the animal health 
industry are committed to seek scientifically based harmonized 
technical requirements for the development and use of veterinary 
biological products. VICH Guideline GL42: Pharmacovigilance: Data 
Elements for Submission of Adverse Events Reports specifically 
addresses the information that should be included when submitting 
adverse event reports.\2\
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    \2\ The VICH pharmacovigilance guidelines can be accessed at 
http://www.vichsec.org/guidelines/pharmacovigilance.html.
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    We solicited comments concerning our proposal for 60 days ending 
November 3, 2015. We received four comments by that date. They were 
from industry associations, a manufacturer of veterinary biologics, and 
a private citizen. The commenters were generally supportive of the 
proposed rule but asked some questions and raised some concerns about 
the provisions. These comments are discussed below by topic.

General Comments

    One commenter stated that the current system for detecting safety 
issues with products has historically worked well. The commenter did 
not believe there have been significant safety issues that have not 
been detected in a timely fashion.
    APHIS agrees with the commenter that the existing system has worked 
well. However, we believe that this rule will significantly improve the 
existing system by enhancing our ability to monitor the observed 
performance of veterinary biologics. For example, currently each 
veterinary biologics manufacturer makes an independent determination 
concerning whether an adverse event report raises questions regarding 
purity, safety, potency, efficacy, preparation, testing, or 
distribution, and when and in what manner such a report of the adverse 
event will be provided to APHIS. Thus, without explicit reporting 
requirements concerning adverse events, reports that may signal 
problems concerning the use of veterinary biological products may not 
all be submitted to APHIS or may not be submitted in a timely manner.

[[Page 22833]]

Another objective of this rule is to implement VICH guidelines 
pertaining to international standards specific for pharmacovigilance, 
which may enhance the ability of the biologics industry to export their 
products.
    One commenter noted that the only VICH guideline specifically 
referenced in the proposed rule is VICH GL42. The commenter stated that 
where the final rule, guidance documents, or APHIS practice touches 
upon the subject matter in the VICH guidelines, APHIS should look to 
all the VICH guidelines to harmonize definitions and practices to the 
furthest extent possible. The commenter specifically mentioned VICH 
GL24, Pharmacovigilance of Veterinary Medicinal Products: Management of 
Adverse Event Reports as one which APHIS should consider when 
establishing future regulations or guidelines.
    APHIS agrees that consistency with all relevant VICH guidelines is 
important. In the proposed rule, we referenced GL42 because we were 
proposing to add definitions to 9 CFR part 101 which are consistent 
with definitions found in this guideline. In future actions, however, 
we will reference all VICH guidelines regarding pharmacovigilance. We 
will also review all VICH guidelines associated with pharmacovigilance 
and consider them when developing future guidance documents, and will 
provide an opportunity for the industry to review and comment on any 
such documents.
    One commenter stated that this rule should not be implemented until 
APHIS has the capability to receive submissions electronically. The 
commenter further stated that in establishing this capability APHIS 
should utilize the VICH Guidelines for the Electronic Standards for 
Transfer of Data, and Data Elements for Submission of Adverse Event 
Reports (VICH GL42, 30, and 35).
    APHIS agrees on the importance of electronic submission and we will 
prioritize the development of an electronic submission portal. However 
we do not agree that this rule should not be implemented until we have 
the capacity to receive electronic submissions. As noted above by 
another commenter, the current system for detecting safety signals with 
products has historically worked well. APHIS has, and will continue to 
have, the capability to receive adverse event information by phone, 
fax, email, etc. It is important to implement this rule in order to 
clarify specific reporting requirements and to harmonize with 
international standards. Since we already receive adverse event 
reports, we do not believe it is necessary to wait for the development 
of an electronic submission portal.
    One commenter stated that the same adverse event may be reported 
separately by two or more parties, such as the veterinarian and animal 
owner. The commenter stated that APHIS should ensure that it has the 
capability to detect any duplicate reports.
    We agree with the commenter and will work to develop internal 
systems to detect duplicate reports.
    One commenter recommended that APHIS engage the industry in 
substantial discussion relative to the method and process it will use 
for signal detection and trend analysis and signal assessment and 
management. The commenter stated that government and industry have the 
same goal of marketing pure, potent, safe, and effective products and 
industry is open to maintaining a partnership in signal detection, 
trend analysis, and risk management.
    APHIS agrees with the commenter and will continue to engage with 
industry as future guidance is developed.
    One commenter asked for clarification of APHIS expectations on the 
maintenance of pharmacovigilance data and practices when a facility is 
inspected.
    Proposed Sec.  116.9(a) provides that records must be maintained 
for 3 years after the date that the adverse event report is received.
    One commenter asked for clarification on the aspects of the adverse 
event data that will be subject to the Freedom of Information Act 
(FOIA) and/or routinely made available on the APHIS website. The 
commenter stated that they expected that FOIA requests for this data 
will be received and that this data has tremendous potential for 
misuse. The commenter strongly suggested that if the data is made 
available on the APHIS website, information should also be provided 
about the limitations on interpreting the data.
    In general, if APHIS receives a FOIA request for publicly available 
information, we do not need to supply the information to the requester. 
Instead, we provide guidance on where the information is available and 
how often it is updated. If the FOIA request is for specific data that 
is not available publicly, then we are mandated to supply the 
information in its entirety without redaction. If it is information 
owned by a biologics manufacturer, then APHIS will send the FOIA 
request and responsive records to the manufacturer for review and 
redaction, if the responsive records contain confidential business 
information or trade secrets.
    Because the adverse event reports we receive are voluntary, APHIS 
has not yet made summary reports available to the public. We are aware 
that the number of adverse event reports received are a very small 
percentage of what is occurring in the field. After mandatory adverse 
event reporting is implemented, APHIS will make summary reports 
publicly available on the APHIS website. APHIS is working to determine 
the specifics on how often those reports are published and what 
explanatory information is included.
    Though we have not finalized a process to manage this data 
publicly, we do agree with the commenter about the limitations on 
interpreting the data when made public. For example, comparing products 
by the prevalence of adverse event cases reported can be misleading if 
one does not consider the number of animals exposed for each respective 
product. Prior to implementing the process for public disclosure of the 
data, we will explore the method that best serves all veterinary 
biologics stakeholders. Included in this will be the review and 
consideration of how the Food and Drug Administration handles their 
pharmacovigilance data.
    One commenter recommended that APHIS remove the adverse event 
reporting restrictions on the licenses for conditionally licensed 
products. The commenter also recommended that APHIS engage with State 
veterinarians and inform them that adverse events will be made public 
and that the industry should not be required by the State to provide 
additional reports.
    APHIS intends to engage with State veterinarians and other public 
groups to advise them of the availability of adverse event reports on 
the APHIS website. However, we will not remove adverse reporting 
restrictions on licenses because there may be specific issues 
associated with a product that require clarification on the license.
    One commenter noted that the definition of an adverse event for 
diagnostic products includes ``failure in product performance.'' The 
commenter stated that most customer reports of problems can either be 
traced to technical errors, or cannot be replicated with the product 
itself. The commenter further stated that unverified reports should not 
be the basis of adverse event reports to APHIS. The commenter stated 
that it is fairly straightforward to verify a problem with kit 
performance, and it seems appropriate that this be part of the 
determination that an adverse event has occurred.

[[Page 22834]]

    The commenter is correct that for diagnostic kits a ``failure in 
product performance'' refers to a verified failure of the product 
itself, and would not include reports associated with equipment failure 
or technical errors. We will clarify this in guidance documents.
    In the proposed rule, we estimated that each report would require 
0.33 hours to generate and submit. One commenter stated that this 
estimate is too low. The commenter stated that any formal communication 
with a regulatory agency requires fact-checking and review, which add 
to the time required to generate the report. The commenter stated that 
they believe that a minimum of two full-time equivalent hours would be 
required for a simple report, with 4 to 6 hours being a likely average 
for all reports.
    APHIS recognizes the variability in the time that it will take to 
gather, review, assess, and report adverse event cases to the agency. 
For example, the type of product (vaccine, diagnostic test kits, etc.) 
can have a significant influence in the respective time required to 
process a case. The reporting time would also vary depending on whether 
a licensee/permittee submits cases individually or batches multiple 
ones in a single submission. Therefore, considering the variability of 
processing adverse event reports for licensees/permittees, we would 
agree that a more accurate estimate of burden would be a range of 1 to 
3 hours.

Definitions

    One commenter stated that the proposed definition of adverse event 
should align with the definition in VICH GL24.
    VICH GL24, which refers to all veterinary medicinal products (VMP), 
defines an adverse event as ``any observation in animals, whether or 
not considered to be product-related, that is unfavorable and 
unintended and that occurs after any use of VMP (off-label and on-label 
uses). Included are events related to a suspected lack of expected 
efficacy according to approved labeling or noxious reactions in humans 
after being exposed to VMP(s).''
    We proposed to define an adverse event as any observation in 
animals, whether or not the cause of the event is known, that is 
unfavorable and unintended, and that occurs after any use (as indicated 
on the label or any off-label use) of a biological product, including 
events related to a suspected lack of expected efficacy. For products 
intended to diagnose disease, adverse events refer to a failure in 
product performance that hinders an expected discovery of the correct 
diagnosis. APHIS believes that the two definitions are generally 
consistent and that the APHIS definition is appropriate for the 
regulation of veterinary biological products as compared to the 
regulation of all other veterinary medicinal products.
    One commenter stated that the definition of adverse event report in 
VICH GL24 requires a ``direct communication'' while the proposed APHIS 
definition referred to ``any communication.'' The commenter stated 
APHIS should use the words ``direct communication'' because this 
language would trigger reporting based upon reliable information; and 
specifically would not trigger reporting simply because the licensee 
became aware of, for example, an unsubstantiated blog post or 
anti[hyphen]product activity on the internet.
    APHIS agrees with the commenter. We have amended the definition of 
adverse event report to read ``direct communication'' instead of ``any 
communication''.
    One commenter noted that an adverse event report is defined as a 
communication received by a firm regarding an adverse event and which 
includes several pieces of information, including an ``identifiable 
animal.'' The commenter stated that test kits for diseases of livestock 
and poultry are most often used in laboratories, not at the location of 
the animals. The commenter further stated that laboratories would only 
rarely have access to individual animal identification devices in the 
normal course of their work. The commenter stated that if the intent of 
the rule is that all information listed must be available before a 
report to APHIS is required, that could greatly limit the number of 
reports. The commenter asked for clarification of the intent of the 
rule in this regard.
    APHIS agrees that this could be clearer. In cases where specific 
information regarding an animal identity is not readily available, we 
consider the species for which the product was used to be the minimum 
information for an ``identifiable animal.''

Frequency of Reporting

    One commenter noted that the terms serious adverse event and 
unexpected adverse event, which appear in VICH GL24, were not defined 
in the proposed rule. The commenter stated that those terms should not 
be considered factors that determine frequency of reporting.
    APHIS intends to define these terms in guidance documents that will 
be made available for review and comment by the industry and public 
before they are finalized. APHIS will work with the industry to develop 
guidance on these topics as the need arises.
    One commenter asked for clarification that APHIS is seeking 
spontaneous reports of adverse events, and not the results that could 
occur in clinical trials or other studies that would already be 
reported to APHIS in a study report, or adverse events that may be 
reported in the literature.
    The commenter is correct. Adverse event reports should address 
events that occur in field use of the product, not the results of 
clinical trials.
    One commenter stated that, in Sec.  116.9(b)(1), ``immediate'' 
should be interpreted to mean ``within 3 business days'' to be 
consistent with Veterinary Services Memorandum 800.57 ``Market 
Suspensions.'' The commenter stated that this would allow time for 
preliminary investigation. The commenter also stated that APHIS should 
replace the term ``immediate'' with ``3 business days'' in this 
section, as well as in Sec.  116.5(b).
    APHIS agrees that it is practical to interpret ``immediately'' as 
``within 3 business days'' and will clarify this in guidance documents, 
which will be needed to establish a consistent application to the 
interpretation of a serious event. The requirement in Sec.  116.9(b)(1) 
is consistent with the established requirement in Sec.  116.5(b), so we 
are making no changes to either paragraph.
    One commenter recommended that APHIS eliminate the 15 business day 
reporting requirement and any use of the concepts of 
``product[hyphen]related'', ``serious'', and ``expected'' for case 
management timelines. The commenter stated that even if these are 
eliminated, APHIS would still receive those adverse event reports that 
impact the purity, potency, safety, or efficacy of the product on a 3 
business day basis, and its ability to react very quickly to the most 
urgent situations would not be compromised. The commenter suggested 
that all other reports be submitted on the 90 calendar day requirement, 
which would provide sufficient time for a thorough investigation. A 
second commenter stated that a 90 day reporting period is too brief a 
period of time to submit reports; many of which will have nothing to 
report. The commenter suggested changes in the length of the reporting 
period over time
    APHIS agrees with the first commenter that serious and unexpected 
adverse events will be reported immediately within 3 business days and

[[Page 22835]]

as such the requirement of 15 business days is not necessary. We have 
amended Sec.  116.9(b)(2) to remove the 15 day reporting requirement. 
Adverse event reports will continue to be received immediately or 
within 90 calendar days. We have also amended Sec.  116.9(b) to require 
that adverse event reports determined to be product[hyphen]related, 
serious, and unexpected will be reported immediately and that other 
reports will be received within 90 days. We will also clarify that 
``immediately'' means ``within 3 business days'' in guidance documents. 
We do not agree with the second commenter regarding the need for the 90 
day reporting period, with changes in the length of the reporting 
period changing over time. Since we have removed the 15 day reporting 
period, the 90 day period will need to remain as a standard time. 
However, as pharmacovigilance data is accumulated APHIS will consider 
exemptions and will clarify in future guidance documents.
    Therefore, for the reasons given in the proposed rule and in this 
document, we are adopting the proposed rule as a final rule, with the 
changes discussed in this document.

Executive Orders 12866 and 13771 and Regulatory Flexibility Act

    This final rule has been determined to be not significant for the 
purposes of Executive Order 12866 and, therefore, has not been reviewed 
by the Office of Management and Budget. This rule is not an Executive 
Order 13771 regulatory action because this rule is not significant 
under Executive Order 12866.
    In accordance with 5 U.S.C. 604, we have performed a final 
regulatory flexibility analysis, which is summarized below, regarding 
the economic effects of this rule on small entities. Copies of the full 
analysis are available on the Regulations.gov website (see footnote 1 
in this document for a link to Regulations.gov) or by contacting the 
person listed under FOR FURTHER INFORMATION CONTACT.
    We are amending the Virus-Serum-Toxin Act regulations concerning 
records and reports. This change would require veterinary biologics 
licensees and permittees to record and submit reports concerning 
adverse events associated with the use of biological products they 
produce or distribute. The type of information that must be included in 
the adverse event reports submitted to APHIS would be provided in 
separate guidance documents.
    We are taking this action in order to limit the harm to animals due 
to adverse events related to a product's purity, safety, potency, 
efficacy, preparation, testing, or distribution. Current regulations 
may hinder APHIS from taking expeditious action in cases where 
veterinary biologics are unsatisfactory.
    For animal owners, the monetary benefits of the proposal are 
difficult to estimate because they would depend on unknowable factors--
the significance or gravity of the harm that would be avoided with the 
rule in effect, and the number and value of animals thereby protected. 
Manufacturer costs to comply with the proposed rule are expected be 
minimal; most establishments that would be affected already maintain 
recordkeeping systems for adverse event reports that capture most if 
not all of the information that would be required. Most of the 
establishments that would be affected by the proposed rule are small 
entities.

Executive Order 12372

    This program/activity is listed in the Catalog of Federal Domestic 
Assistance under No. 10.025 and is subject to Executive Order 12372, 
which requires intergovernmental consultation with State and local 
officials. (See 2 CFR chapter IV.)

Executive Order 12988

    This final rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule will not preempt any State or local laws, regulations, or 
policies where they are necessary to address local disease conditions 
or eradication programs. However, where safety, efficacy, purity, and 
potency of biological products are concerned, it is the Agency's intent 
to occupy the field. This includes, but is not limited to, the 
regulation of labeling. Under the Act, Congress clearly intended that 
there be national uniformity in the regulation of these products. There 
are no administrative proceedings which must be exhausted prior to a 
judicial challenge to the regulations under this rule.

Executive Order 13175

    This rule does not significantly or uniquely affect the communities 
of Indian Tribal governments. The rule does not impose any mandate on 
Tribal governments or impose any duties on these entities. Thus, no 
further action is required under Executive Order 13175.

Paperwork Reduction Act

    In accordance with section 3507(d) of the Paperwork Reduction Act 
of 1995 (44 U.S.C. 3501 et seq.), the information collection or 
recordkeeping requirements included in this final rule, which were 
filed under 0579-0209, have been submitted for approval to the Office 
of Management and Budget (OMB). When OMB notifies us of its decision, 
if approval is denied, we will publish a document in the Federal 
Register providing notice of what action we plan to take.

E-Government Act Compliance

    The Animal and Plant Health Inspection Service is committed to 
compliance with the E-Government Act to promote the use of the internet 
and other information technologies, to provide increased opportunities 
for citizen access to Government information and services, and for 
other purposes. For information pertinent to E-Government Act 
compliance related to this rule, please contact Ms. Kimberly Hardy, 
APHIS' Information Collection Coordinator, at (301) 851-2483.

Lists of Subjects

9 CFR Part 101

    Animal biologics.

9 CFR Part 116

    Animal biologics, Reporting and recordkeeping requirements.

    Accordingly, we are amending 9 CFR parts 101 and 116 as follows:

PART 101--DEFINITIONS

0
1. The authority citation for part 101 continues to read as follows:

    Authority:  21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.4.


0
2. Section 101.2 is amended by adding definitions for Adverse event and 
Adverse event report in alphabetical order to read as follows:


Sec.  101.2  Administrative terminology.

* * * * *
    Adverse event. Any observation in animals, whether or not the cause 
of the event is known, that is unfavorable and unintended, and that 
occurs after any use (as indicated on the label or any off-label use) 
of a biological product, including events related to a suspected lack 
of expected efficacy. For products intended to diagnose disease, 
adverse events refer to a failure in product performance that hinders 
an expected discovery of the correct diagnosis.
    Adverse event report. Direct communication concerning the 
occurrence of an adverse event from an identifiable first-hand reporter 
which includes the following information:
    (1) An identifiable reporter;
    (2) An identifiable animal;
    (3) An identifiable biologic product; and

[[Page 22836]]

    (4) One or more adverse events.
* * * * *

PART 116--RECORDS AND REPORTS

0
3. The authority citation for part 116 continues to read as follows:

     Authority:  21 U.S.C. 151-159; 7 CFR 2.22, 2.80, and 371.4.

0
4. In Sec.  116.1, paragraph (a)(3) is revised to read as follows:


Sec.  116.1  Applicability and general considerations.

    (a) * * *
    (3) Records (other than disposition records and adverse event 
records) required by this part must be completed by the licensee, 
permittee, or foreign manufacturer, as the case may be, before any 
portion of a serial of any product may be marketed in the United States 
or exported.
* * * * *

0
5. Section 116.8 is revised to read as follows:


Sec.  116.8  Completion and retention of records.

    All records (other than disposition records and adverse event 
records) required by this part must be completed by the licensee, 
permittee, or foreign manufacturer before any portion of a serial of 
any product may be marketed in the United States or exported. All 
records must be retained at the licensed or foreign establishment or 
permittee's place of business for a period of 2 years after the 
expiration date of a product or longer as may be required by the 
Administrator.

(Approved by the Office of Management and Budget under control 
number 0579-0013)

0
6. Section 116.9 is added to read as follows:


Sec.  116.9  Recording and reporting adverse events.

    (a) Licensees and permittees must maintain a detailed record for 
every adverse event report the licensee or permittee receives for any 
biological product it produces or distributes. These records shall be 
maintained for a period of 3 years after the date the adverse event 
report is received. The adverse event report form and guidance on how 
to complete it, including guidance specific to the various information 
blocks on the form, is available on the APHIS website at https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics or 
by writing to APHIS Center for Veterinary Biologics, 1920 Dayton 
Avenue, P.O. Box 844, Ames, Iowa 50010.
    (b) A report of all adverse events reports received by a licensee 
or permittee must be compiled and submitted to the Animal and Plant 
Health Inspection Service. The frequency of report submission is as 
follows:
    (1) Immediate notification is required if at any time there are 
indications that raise questions regarding the purity, safety, potency, 
or efficacy of a product, or if it appears that there may be a problem 
regarding the preparation, testing, or distribution of a product.
    (2) Adverse event reports determined by the licensee or permittee 
to be product-related, serious, and unexpected must also be reported 
immediately.
    (3) All other adverse event reports must be reported within 90 
calendar days of the date the report was first received.

(Approved by the Office of Management and Budget under control 
number 0579-0209)

    Done in Washington, DC, this 11th day of May 2018.
 Kevin Shea,
Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 2018-10540 Filed 5-16-18; 8:45 am]
 BILLING CODE 3410-34-P



                                           22832               Federal Register / Vol. 83, No. 96 / Thursday, May 17, 2018 / Rules and Regulations

                                           the FOR FURTHER INFORMATION CONTACT                     ACTION:   Final rule.                                 authorities and industry experts from
                                           section.                                                                                                      Australia, Canada, and New Zealand
                                                                                                   SUMMARY:   We are amending the Virus-                 participate as observers.
                                           List of Subjects in 7 CFR Part 900                      Serum-Toxin Act regulations                              The purpose of VICH is to harmonize
                                             Administrative practice and                           concerning records and reports. This                  technical requirements for veterinary
                                           procedure, Freedom of information,                      change requires veterinary biologics                  medicinal products (both
                                           Marketing agreements, Reporting and                     licensees and permittees to record and                pharmaceuticals and biologics). As a
                                           recordkeeping requirements.                             submit reports concerning adverse                     VICH member, the Animal and Plant
                                             For the reasons set forth above, 7 CFR                events associated with the use of                     Health Inspection Service (APHIS)
                                           part 900 is amended as follows:                         biological products they produce or                   provides expertise on veterinary
                                                                                                   distribute. The information that must be              biological products and participates in
                                           PART 900—GENERAL REGULATIONS                            included in the adverse event reports                 efforts to enhance harmonization. Both
                                                                                                   submitted to the Animal and Plant                     APHIS and the animal health industry
                                           ■ 1. The authority citation for part 900                Health Inspection Service (APHIS) will                are committed to seek scientifically
                                           continues to read as follows:                           be provided in separate guidance                      based harmonized technical
                                             Authority: 7 U.S.C. 601–674 and 7 U.S.C.              documents. These records and reports                  requirements for the development and
                                           7401.                                                   will help ensure that APHIS can provide               use of veterinary biological products.
                                           ■ 2. Add § 900.83 to subpart E read as                  complete and accurate information to                  VICH Guideline GL42:
                                           follows:                                                consumers regarding adverse reactions                 Pharmacovigilance: Data Elements for
                                                                                                   or other problems associated with the                 Submission of Adverse Events Reports
                                           § 900.83 Conducting Meetings via                        use of licensed biological products.                  specifically addresses the information
                                           Electronic Communication or Otherwise.                  DATES: Effective June 18, 2018.                       that should be included when
                                             Notwithstanding any other provisions                  FOR FURTHER INFORMATION CONTACT: Dr.                  submitting adverse event reports.2
                                           of a marketing order in this part,                      Donna L. Malloy, Section Leader,                         We solicited comments concerning
                                           administrative bodies of fruit, vegetable,              Operational Support, Center for                       our proposal for 60 days ending
                                           and specialty crop marketing orders,                    Veterinary Biologics Policy, Evaluation,              November 3, 2015. We received four
                                           and their committees/subcommittees                      and Licensing, VS, APHIS, 4700 River                  comments by that date. They were from
                                           may, upon due notice to all members                     Road Unit 148, Riverdale, MD 20737–                   industry associations, a manufacturer of
                                           and the public:                                         1231; (301) 851–3426.                                 veterinary biologics, and a private
                                             (a) Conduct meetings by any means of                                                                        citizen. The commenters were generally
                                                                                                   SUPPLEMENTARY INFORMATION:
                                           communication available, electronic or                                                                        supportive of the proposed rule but
                                           otherwise, that effectively assembles                   Background                                            asked some questions and raised some
                                           members and the public, and facilitates                    The Virus-Serum-Toxin Act                          concerns about the provisions. These
                                           open communication.                                     regulations in 9 CFR part 116 (referred               comments are discussed below by topic.
                                             (b) Vote by any means of                              to below as the regulations) contain
                                           communication available, electronic or                                                                        General Comments
                                                                                                   requirements for maintaining detailed
                                           otherwise; Provided, That votes cast are                records of information necessary to give                 One commenter stated that the
                                           verifiable and that quorum and other                    a complete accounting of all the                      current system for detecting safety
                                           procedural requirements of each                         activities within a veterinary biologics              issues with products has historically
                                           respective marketing order are met.                     establishment. These records include                  worked well. The commenter did not
                                             (c) With the approval of the Secretary,               records and reports for unfavorable or                believe there have been significant
                                           each administrative body may prescribe                  unintended events that occur in animals               safety issues that have not been detected
                                           any additional procedures necessary to                  after the use of a biological product.                in a timely fashion.
                                           carry out the objectives of paragraphs (a)                 On September 4, 2015, we published                    APHIS agrees with the commenter
                                           and (b) of this section.                                in the Federal Register (80 FR 53475–                 that the existing system has worked
                                             Dated: May 11, 2018.                                  53478, Docket No. APHIS–2014–0063) a                  well. However, we believe that this rule
                                           Bruce Summers,                                          proposal 1 to amend the regulations by                will significantly improve the existing
                                           Acting Administrator, Agricultural Marketing            establishing definitions for the terms                system by enhancing our ability to
                                           Service.                                                adverse event and adverse event report                monitor the observed performance of
                                           [FR Doc. 2018–10487 Filed 5–16–18; 8:45 am]             and by providing requirements for                     veterinary biologics. For example,
                                           BILLING CODE 3410–02–P                                  adverse event records and reports. The                currently each veterinary biologics
                                                                                                   changes we proposed are consistent                    manufacturer makes an independent
                                                                                                   with guidelines set out by the                        determination concerning whether an
                                                                                                   International Cooperation on                          adverse event report raises questions
                                           DEPARTMENT OF AGRICULTURE
                                                                                                   Harmonization of Technical                            regarding purity, safety, potency,
                                           Animal and Plant Health Inspection                      Requirements for Registration of                      efficacy, preparation, testing, or
                                           Service                                                 Veterinary Medicinal Products (VICH).                 distribution, and when and in what
                                                                                                   VICH is a unique project conducted                    manner such a report of the adverse
                                           9 CFR Parts 101 and 116                                 under the World Organization for                      event will be provided to APHIS. Thus,
                                                                                                   Animal Health that brings together the                without explicit reporting requirements
                                           [Docket No. APHIS–2014–0063]                                                                                  concerning adverse events, reports that
                                                                                                   regulatory authorities of the European
                                           RIN 0579–AE11                                           Union, Japan, and the United States and               may signal problems concerning the use
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                                                                                                   representatives from the animal health                of veterinary biological products may
                                           VSTA Records and Reports Specific to                    industry in the three regions. Regulatory             not all be submitted to APHIS or may
                                           International Standards for                                                                                   not be submitted in a timely manner.
                                           Pharmacovigilance                                         1 To view the proposed rule, supporting

                                                                                                   document, and the comments we received, go to           2 The VICH pharmacovigilance guidelines can be
                                           AGENCY:  Animal and Plant Health                        http://www.regulations.gov/#!docketDetail;D           accessed at http://www.vichsec.org/guidelines/
                                           Inspection Service, USDA.                               =APHIS-2014-0063.                                     pharmacovigilance.html.



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                                                               Federal Register / Vol. 83, No. 96 / Thursday, May 17, 2018 / Rules and Regulations                                          22833

                                           Another objective of this rule is to                    we do not believe it is necessary to wait             confidential business information or
                                           implement VICH guidelines pertaining                    for the development of an electronic                  trade secrets.
                                           to international standards specific for                 submission portal.                                       Because the adverse event reports we
                                           pharmacovigilance, which may enhance                       One commenter stated that the same                 receive are voluntary, APHIS has not yet
                                           the ability of the biologics industry to                adverse event may be reported                         made summary reports available to the
                                           export their products.                                  separately by two or more parties, such               public. We are aware that the number of
                                              One commenter noted that the only                    as the veterinarian and animal owner.                 adverse event reports received are a very
                                           VICH guideline specifically referenced                  The commenter stated that APHIS                       small percentage of what is occurring in
                                           in the proposed rule is VICH GL42. The                  should ensure that it has the capability              the field. After mandatory adverse event
                                           commenter stated that where the final                   to detect any duplicate reports.                      reporting is implemented, APHIS will
                                           rule, guidance documents, or APHIS                         We agree with the commenter and                    make summary reports publicly
                                           practice touches upon the subject matter                will work to develop internal systems to              available on the APHIS website. APHIS
                                           in the VICH guidelines, APHIS should                    detect duplicate reports.                             is working to determine the specifics on
                                           look to all the VICH guidelines to                         One commenter recommended that                     how often those reports are published
                                           harmonize definitions and practices to                  APHIS engage the industry in                          and what explanatory information is
                                           the furthest extent possible. The                       substantial discussion relative to the                included.
                                           commenter specifically mentioned                        method and process it will use for signal                Though we have not finalized a
                                           VICH GL24, Pharmacovigilance of                         detection and trend analysis and signal               process to manage this data publicly, we
                                           Veterinary Medicinal Products:                          assessment and management. The                        do agree with the commenter about the
                                           Management of Adverse Event Reports                     commenter stated that government and                  limitations on interpreting the data
                                           as one which APHIS should consider                      industry have the same goal of                        when made public. For example,
                                           when establishing future regulations or                 marketing pure, potent, safe, and                     comparing products by the prevalence
                                           guidelines.                                             effective products and industry is open               of adverse event cases reported can be
                                              APHIS agrees that consistency with                   to maintaining a partnership in signal                misleading if one does not consider the
                                           all relevant VICH guidelines is                         detection, trend analysis, and risk                   number of animals exposed for each
                                           important. In the proposed rule, we                     management.                                           respective product. Prior to
                                           referenced GL42 because we were                            APHIS agrees with the commenter                    implementing the process for public
                                           proposing to add definitions to 9 CFR                   and will continue to engage with                      disclosure of the data, we will explore
                                           part 101 which are consistent with                      industry as future guidance is                        the method that best serves all
                                           definitions found in this guideline. In                 developed.                                            veterinary biologics stakeholders.
                                           future actions, however, we will                           One commenter asked for clarification              Included in this will be the review and
                                           reference all VICH guidelines regarding                 of APHIS expectations on the                          consideration of how the Food and Drug
                                           pharmacovigilance. We will also review                  maintenance of pharmacovigilance data                 Administration handles their
                                           all VICH guidelines associated with                     and practices when a facility is                      pharmacovigilance data.
                                           pharmacovigilance and consider them                     inspected.                                               One commenter recommended that
                                           when developing future guidance                            Proposed § 116.9(a) provides that                  APHIS remove the adverse event
                                           documents, and will provide an                          records must be maintained for 3 years                reporting restrictions on the licenses for
                                           opportunity for the industry to review                  after the date that the adverse event                 conditionally licensed products. The
                                           and comment on any such documents.                      report is received.                                   commenter also recommended that
                                              One commenter stated that this rule                     One commenter asked for clarification              APHIS engage with State veterinarians
                                           should not be implemented until APHIS                   on the aspects of the adverse event data              and inform them that adverse events
                                           has the capability to receive                           that will be subject to the Freedom of                will be made public and that the
                                           submissions electronically. The                         Information Act (FOIA) and/or routinely               industry should not be required by the
                                           commenter further stated that in                        made available on the APHIS website.                  State to provide additional reports.
                                           establishing this capability APHIS                      The commenter stated that they                           APHIS intends to engage with State
                                           should utilize the VICH Guidelines for                  expected that FOIA requests for this                  veterinarians and other public groups to
                                           the Electronic Standards for Transfer of                data will be received and that this data              advise them of the availability of
                                           Data, and Data Elements for Submission                  has tremendous potential for misuse.                  adverse event reports on the APHIS
                                           of Adverse Event Reports (VICH GL42,                    The commenter strongly suggested that                 website. However, we will not remove
                                           30, and 35).                                            if the data is made available on the                  adverse reporting restrictions on
                                              APHIS agrees on the importance of                    APHIS website, information should also                licenses because there may be specific
                                           electronic submission and we will                       be provided about the limitations on                  issues associated with a product that
                                           prioritize the development of an                        interpreting the data.                                require clarification on the license.
                                           electronic submission portal. However                      In general, if APHIS receives a FOIA                  One commenter noted that the
                                           we do not agree that this rule should not               request for publicly available                        definition of an adverse event for
                                           be implemented until we have the                        information, we do not need to supply                 diagnostic products includes ‘‘failure in
                                           capacity to receive electronic                          the information to the requester.                     product performance.’’ The commenter
                                           submissions. As noted above by another                  Instead, we provide guidance on where                 stated that most customer reports of
                                           commenter, the current system for                       the information is available and how                  problems can either be traced to
                                           detecting safety signals with products                  often it is updated. If the FOIA request              technical errors, or cannot be replicated
                                           has historically worked well. APHIS                     is for specific data that is not available            with the product itself. The commenter
                                           has, and will continue to have, the                     publicly, then we are mandated to                     further stated that unverified reports
                                           capability to receive adverse event                     supply the information in its entirety                should not be the basis of adverse event
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                                           information by phone, fax, email, etc. It               without redaction. If it is information               reports to APHIS. The commenter stated
                                           is important to implement this rule in                  owned by a biologics manufacturer,                    that it is fairly straightforward to verify
                                           order to clarify specific reporting                     then APHIS will send the FOIA request                 a problem with kit performance, and it
                                           requirements and to harmonize with                      and responsive records to the                         seems appropriate that this be part of
                                           international standards. Since we                       manufacturer for review and redaction,                the determination that an adverse event
                                           already receive adverse event reports,                  if the responsive records contain                     has occurred.


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                                           22834               Federal Register / Vol. 83, No. 96 / Thursday, May 17, 2018 / Rules and Regulations

                                             The commenter is correct that for                     discovery of the correct diagnosis.                   made available for review and comment
                                           diagnostic kits a ‘‘failure in product                  APHIS believes that the two definitions               by the industry and public before they
                                           performance’’ refers to a verified failure              are generally consistent and that the                 are finalized. APHIS will work with the
                                           of the product itself, and would not                    APHIS definition is appropriate for the               industry to develop guidance on these
                                           include reports associated with                         regulation of veterinary biological                   topics as the need arises.
                                           equipment failure or technical errors.                  products as compared to the regulation                   One commenter asked for clarification
                                           We will clarify this in guidance                        of all other veterinary medicinal                     that APHIS is seeking spontaneous
                                           documents.                                              products.                                             reports of adverse events, and not the
                                             In the proposed rule, we estimated                       One commenter stated that the                      results that could occur in clinical trials
                                           that each report would require 0.33                     definition of adverse event report in                 or other studies that would already be
                                           hours to generate and submit. One                       VICH GL24 requires a ‘‘direct                         reported to APHIS in a study report, or
                                           commenter stated that this estimate is                  communication’’ while the proposed                    adverse events that may be reported in
                                           too low. The commenter stated that any                  APHIS definition referred to ‘‘any                    the literature.
                                           formal communication with a regulatory                  communication.’’ The commenter stated                    The commenter is correct. Adverse
                                           agency requires fact-checking and                       APHIS should use the words ‘‘direct                   event reports should address events that
                                           review, which add to the time required                  communication’’ because this language                 occur in field use of the product, not the
                                           to generate the report. The commenter                   would trigger reporting based upon                    results of clinical trials.
                                           stated that they believe that a minimum                 reliable information; and specifically                   One commenter stated that, in
                                           of two full-time equivalent hours would                 would not trigger reporting simply                    § 116.9(b)(1), ‘‘immediate’’ should be
                                           be required for a simple report, with 4                 because the licensee became aware of,                 interpreted to mean ‘‘within 3 business
                                           to 6 hours being a likely average for all               for example, an unsubstantiated blog                  days’’ to be consistent with Veterinary
                                           reports.                                                post or anti-product activity on the                  Services Memorandum 800.57 ‘‘Market
                                             APHIS recognizes the variability in                   internet.                                             Suspensions.’’ The commenter stated
                                           the time that it will take to gather,                      APHIS agrees with the commenter.                   that this would allow time for
                                           review, assess, and report adverse event                We have amended the definition of                     preliminary investigation. The
                                           cases to the agency. For example, the                   adverse event report to read ‘‘direct                 commenter also stated that APHIS
                                           type of product (vaccine, diagnostic test               communication’’ instead of ‘‘any                      should replace the term ‘‘immediate’’
                                           kits, etc.) can have a significant                      communication’’.                                      with ‘‘3 business days’’ in this section,
                                           influence in the respective time                           One commenter noted that an adverse                as well as in § 116.5(b).
                                           required to process a case. The reporting               event report is defined as a                             APHIS agrees that it is practical to
                                           time would also vary depending on                       communication received by a firm                      interpret ‘‘immediately’’ as ‘‘within 3
                                           whether a licensee/permittee submits                    regarding an adverse event and which                  business days’’ and will clarify this in
                                           cases individually or batches multiple                  includes several pieces of information,               guidance documents, which will be
                                           ones in a single submission. Therefore,                 including an ‘‘identifiable animal.’’ The             needed to establish a consistent
                                           considering the variability of processing               commenter stated that test kits for                   application to the interpretation of a
                                           adverse event reports for licensees/                    diseases of livestock and poultry are                 serious event. The requirement in
                                           permittees, we would agree that a more                  most often used in laboratories, not at               § 116.9(b)(1) is consistent with the
                                           accurate estimate of burden would be a                  the location of the animals. The                      established requirement in § 116.5(b), so
                                           range of 1 to 3 hours.                                  commenter further stated that                         we are making no changes to either
                                                                                                   laboratories would only rarely have                   paragraph.
                                           Definitions                                                                                                      One commenter recommended that
                                                                                                   access to individual animal
                                              One commenter stated that the                        identification devices in the normal                  APHIS eliminate the 15 business day
                                           proposed definition of adverse event                    course of their work. The commenter                   reporting requirement and any use of
                                           should align with the definition in VICH                stated that if the intent of the rule is that         the concepts of ‘‘product-related’’,
                                           GL24.                                                   all information listed must be available              ‘‘serious’’, and ‘‘expected’’ for case
                                              VICH GL24, which refers to all                       before a report to APHIS is required,                 management timelines. The commenter
                                           veterinary medicinal products (VMP),                    that could greatly limit the number of                stated that even if these are eliminated,
                                           defines an adverse event as ‘‘any                       reports. The commenter asked for                      APHIS would still receive those adverse
                                           observation in animals, whether or not                  clarification of the intent of the rule in            event reports that impact the purity,
                                           considered to be product-related, that is               this regard.                                          potency, safety, or efficacy of the
                                           unfavorable and unintended and that                        APHIS agrees that this could be                    product on a 3 business day basis, and
                                           occurs after any use of VMP (off-label                  clearer. In cases where specific                      its ability to react very quickly to the
                                           and on-label uses). Included are events                 information regarding an animal                       most urgent situations would not be
                                           related to a suspected lack of expected                 identity is not readily available, we                 compromised. The commenter
                                           efficacy according to approved labeling                 consider the species for which the                    suggested that all other reports be
                                           or noxious reactions in humans after                    product was used to be the minimum                    submitted on the 90 calendar day
                                           being exposed to VMP(s).’’                              information for an ‘‘identifiable                     requirement, which would provide
                                              We proposed to define an adverse                     animal.’’                                             sufficient time for a thorough
                                           event as any observation in animals,                                                                          investigation. A second commenter
                                           whether or not the cause of the event is                Frequency of Reporting                                stated that a 90 day reporting period is
                                           known, that is unfavorable and                            One commenter noted that the terms                  too brief a period of time to submit
                                           unintended, and that occurs after any                   serious adverse event and unexpected                  reports; many of which will have
                                           use (as indicated on the label or any off-              adverse event, which appear in VICH                   nothing to report. The commenter
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                                           label use) of a biological product,                     GL24, were not defined in the proposed                suggested changes in the length of the
                                           including events related to a suspected                 rule. The commenter stated that those                 reporting period over time
                                           lack of expected efficacy. For products                 terms should not be considered factors                   APHIS agrees with the first
                                           intended to diagnose disease, adverse                   that determine frequency of reporting.                commenter that serious and unexpected
                                           events refer to a failure in product                      APHIS intends to define these terms                 adverse events will be reported
                                           performance that hinders an expected                    in guidance documents that will be                    immediately within 3 business days and


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                                                               Federal Register / Vol. 83, No. 96 / Thursday, May 17, 2018 / Rules and Regulations                                            22835

                                           as such the requirement of 15 business                  safety, potency, efficacy, preparation,               which were filed under 0579–0209,
                                           days is not necessary. We have amended                  testing, or distribution. Current                     have been submitted for approval to the
                                           § 116.9(b)(2) to remove the 15 day                      regulations may hinder APHIS from                     Office of Management and Budget
                                           reporting requirement. Adverse event                    taking expeditious action in cases where              (OMB). When OMB notifies us of its
                                           reports will continue to be received                    veterinary biologics are unsatisfactory.              decision, if approval is denied, we will
                                           immediately or within 90 calendar days.                   For animal owners, the monetary                     publish a document in the Federal
                                           We have also amended § 116.9(b) to                      benefits of the proposal are difficult to             Register providing notice of what action
                                           require that adverse event reports                      estimate because they would depend on                 we plan to take.
                                           determined to be product-related,                       unknowable factors—the significance or
                                           serious, and unexpected will be                         gravity of the harm that would be                     E-Government Act Compliance
                                           reported immediately and that other                     avoided with the rule in effect, and the                 The Animal and Plant Health
                                           reports will be received within 90 days.                number and value of animals thereby                   Inspection Service is committed to
                                           We will also clarify that ‘‘immediately’’               protected. Manufacturer costs to comply               compliance with the E-Government Act
                                           means ‘‘within 3 business days’’ in                     with the proposed rule are expected be                to promote the use of the internet and
                                           guidance documents. We do not agree                     minimal; most establishments that                     other information technologies, to
                                           with the second commenter regarding                     would be affected already maintain                    provide increased opportunities for
                                           the need for the 90 day reporting period,               recordkeeping systems for adverse event               citizen access to Government
                                           with changes in the length of the                       reports that capture most if not all of the           information and services, and for other
                                           reporting period changing over time.                    information that would be required.                   purposes. For information pertinent to
                                           Since we have removed the 15 day                        Most of the establishments that would                 E-Government Act compliance related
                                           reporting period, the 90 day period will                be affected by the proposed rule are                  to this rule, please contact Ms. Kimberly
                                           need to remain as a standard time.                      small entities.                                       Hardy, APHIS’ Information Collection
                                           However, as pharmacovigilance data is                                                                         Coordinator, at (301) 851–2483.
                                           accumulated APHIS will consider                         Executive Order 12372
                                           exemptions and will clarify in future                     This program/activity is listed in the              Lists of Subjects
                                           guidance documents.                                     Catalog of Federal Domestic Assistance                9 CFR Part 101
                                             Therefore, for the reasons given in the               under No. 10.025 and is subject to
                                           proposed rule and in this document, we                                                                            Animal biologics.
                                                                                                   Executive Order 12372, which requires
                                           are adopting the proposed rule as a final               intergovernmental consultation with                   9 CFR Part 116
                                           rule, with the changes discussed in this                State and local officials. (See 2 CFR                   Animal biologics, Reporting and
                                           document.                                               chapter IV.)                                          recordkeeping requirements.
                                           Executive Orders 12866 and 13771 and                    Executive Order 12988                                   Accordingly, we are amending 9 CFR
                                           Regulatory Flexibility Act                                This final rule has been reviewed                   parts 101 and 116 as follows:
                                              This final rule has been determined to               under Executive Order 12988, Civil
                                           be not significant for the purposes of                                                                        PART 101—DEFINITIONS
                                                                                                   Justice Reform. It is not intended to
                                           Executive Order 12866 and, therefore,                   have retroactive effect. This rule will               ■ 1. The authority citation for part 101
                                           has not been reviewed by the Office of                  not preempt any State or local laws,                  continues to read as follows:
                                           Management and Budget. This rule is                     regulations, or policies where they are
                                           not an Executive Order 13771 regulatory                                                                         Authority: 21 U.S.C. 151–159; 7 CFR 2.22,
                                                                                                   necessary to address local disease                    2.80, and 371.4.
                                           action because this rule is not                         conditions or eradication programs.
                                           significant under Executive Order                       However, where safety, efficacy, purity,              ■ 2. Section 101.2 is amended by adding
                                           12866.                                                  and potency of biological products are                definitions for Adverse event and
                                              In accordance with 5 U.S.C. 604, we                  concerned, it is the Agency’s intent to               Adverse event report in alphabetical
                                           have performed a final regulatory                       occupy the field. This includes, but is               order to read as follows:
                                           flexibility analysis, which is                          not limited to, the regulation of labeling.
                                           summarized below, regarding the                         Under the Act, Congress clearly                       § 101.2    Administrative terminology.
                                           economic effects of this rule on small                  intended that there be national                       *     *     *      *    *
                                           entities. Copies of the full analysis are               uniformity in the regulation of these                   Adverse event. Any observation in
                                           available on the Regulations.gov website                products. There are no administrative                 animals, whether or not the cause of the
                                           (see footnote 1 in this document for a                  proceedings which must be exhausted                   event is known, that is unfavorable and
                                           link to Regulations.gov) or by contacting               prior to a judicial challenge to the                  unintended, and that occurs after any
                                           the person listed under FOR FURTHER                     regulations under this rule.                          use (as indicated on the label or any off-
                                           INFORMATION CONTACT.                                                                                          label use) of a biological product,
                                              We are amending the Virus-Serum-                     Executive Order 13175                                 including events related to a suspected
                                           Toxin Act regulations concerning                          This rule does not significantly or                 lack of expected efficacy. For products
                                           records and reports. This change would                  uniquely affect the communities of                    intended to diagnose disease, adverse
                                           require veterinary biologics licensees                  Indian Tribal governments. The rule                   events refer to a failure in product
                                           and permittees to record and submit                     does not impose any mandate on Tribal                 performance that hinders an expected
                                           reports concerning adverse events                       governments or impose any duties on                   discovery of the correct diagnosis.
                                           associated with the use of biological                   these entities. Thus, no further action is              Adverse event report. Direct
                                           products they produce or distribute. The                required under Executive Order 13175.                 communication concerning the
                                           type of information that must be                                                                              occurrence of an adverse event from an
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                                           included in the adverse event reports                   Paperwork Reduction Act                               identifiable first-hand reporter which
                                           submitted to APHIS would be provided                      In accordance with section 3507(d) of               includes the following information:
                                           in separate guidance documents.                         the Paperwork Reduction Act of 1995                     (1) An identifiable reporter;
                                              We are taking this action in order to                (44 U.S.C. 3501 et seq.), the information               (2) An identifiable animal;
                                           limit the harm to animals due to adverse                collection or recordkeeping                             (3) An identifiable biologic product;
                                           events related to a product’s purity,                   requirements included in this final rule,             and


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                                           22836               Federal Register / Vol. 83, No. 96 / Thursday, May 17, 2018 / Rules and Regulations

                                               (4) One or more adverse events.                        (b) A report of all adverse events                 penetrating the fuselage, causing a loss
                                           *       *    *    *    *                                reports received by a licensee or                     of pressurization, and prompting an
                                                                                                   permittee must be compiled and                        emergency descent. We are issuing this
                                           PART 116—RECORDS AND REPORTS                            submitted to the Animal and Plant                     AD to address the unsafe condition on
                                                                                                   Health Inspection Service. The                        these products.
                                           ■ 3. The authority citation for part 116                frequency of report submission is as                  DATES: This AD is effective June 1, 2018.
                                           continues to read as follows:                           follows:                                                The Director of the Federal Register
                                             Authority: 21 U.S.C. 151–159; 7 CFR 2.22,                (1) Immediate notification is required             approved the incorporation by reference
                                           2.80, and 371.4.                                        if at any time there are indications that             of a certain publication listed in this AD
                                           ■ 4. In § 116.1, paragraph (a)(3) is                    raise questions regarding the purity,                 as of June 1, 2018.
                                           revised to read as follows:                             safety, potency, or efficacy of a product,              The Director of the Federal Register
                                                                                                   or if it appears that there may be a                  approved the incorporation by reference
                                           § 116.1 Applicability and general                       problem regarding the preparation,                    of a certain other publication listed in
                                           considerations.                                         testing, or distribution of a product.                this AD as of May 14, 2018 (83 FR
                                             (a) * * *                                                (2) Adverse event reports determined               19176, May 2, 2018).
                                             (3) Records (other than disposition                   by the licensee or permittee to be                      We must receive any comments on
                                           records and adverse event records)                      product-related, serious, and                         this AD by July 2, 2018.
                                           required by this part must be completed                 unexpected must also be reported
                                                                                                                                                         ADDRESSES: You may send comments,
                                           by the licensee, permittee, or foreign                  immediately.
                                                                                                      (3) All other adverse event reports                using the procedures found in 14 CFR
                                           manufacturer, as the case may be, before                                                                      11.43 and 11.45, by any of the following
                                           any portion of a serial of any product                  must be reported within 90 calendar
                                                                                                   days of the date the report was first                 methods:
                                           may be marketed in the United States or                                                                         • Federal eRulemaking Portal: Go to
                                           exported.                                               received.
                                                                                                                                                         http://www.regulations.gov. Follow the
                                           *     *    *     *      *                               (Approved by the Office of Management and             instructions for submitting comments.
                                           ■ 5. Section 116.8 is revised to read as
                                                                                                   Budget under control number 0579–0209)                  • Fax: 202–493–2251.
                                           follows:                                                  Done in Washington, DC, this 11th day of              • Mail: U.S. Department of
                                                                                                   May 2018.                                             Transportation, Docket Operations, M–
                                           § 116.8 Completion and retention of                     Kevin Shea,                                           30, West Building Ground Floor, Room
                                           records.
                                                                                                   Administrator, Animal and Plant Health                W12–140, 1200 New Jersey Avenue SE,
                                              All records (other than disposition                  Inspection Service.                                   Washington, DC 20590.
                                           records and adverse event records)                      [FR Doc. 2018–10540 Filed 5–16–18; 8:45 am]             • Hand Delivery: U.S. Department of
                                           required by this part must be completed                 BILLING CODE 3410–34–P                                Transportation, Docket Operations, M–
                                           by the licensee, permittee, or foreign                                                                        30, West Building Ground Floor, Room
                                           manufacturer before any portion of a                                                                          W12–140, 1200 New Jersey Avenue SE,
                                           serial of any product may be marketed                                                                         Washington, DC 20590, between 9 a.m.
                                                                                                   DEPARTMENT OF TRANSPORTATION
                                           in the United States or exported. All                                                                         and 5 p.m., Monday through Friday,
                                           records must be retained at the licensed                Federal Aviation Administration                       except Federal holidays.
                                           or foreign establishment or permittee’s                                                                         For service information identified in
                                           place of business for a period of 2 years               14 CFR Part 39                                        this final rule, contact CFM
                                           after the expiration date of a product or                                                                     International Inc., Aviation Operations
                                           longer as may be required by the                        [Docket No. FAA–2018–0443; Product
                                                                                                   Identifier 2018–NE–14–AD; Amendment 39–
                                                                                                                                                         Center, 1 Neumann Way, M/D Room
                                           Administrator.                                                                                                285, Cincinnati, OH 45125; phone: 877–
                                                                                                   19286; AD 2018–10–11]
                                           (Approved by the Office of Management and                                                                     432–3272; fax: 877–432–3329; email:
                                           Budget under control number 0579–0013)                  RIN 2120–AA64                                         aviation.fleetsupport@ge.com. You may
                                           ■ 6. Section 116.9 is added to read as                                                                        view this service information at the
                                                                                                   Airworthiness Directives; CFM                         FAA, Engine and Propeller Standards
                                           follows:                                                International S.A. Turbofan Engines                   Branch, 1200 District Avenue,
                                           § 116.9 Recording and reporting adverse                 AGENCY:  Federal Aviation                             Burlington, MA. For information on the
                                           events.                                                 Administration (FAA), DOT.                            availability of this material at the FAA,
                                             (a) Licensees and permittees must                     ACTION: Final rule; request for                       call 781–238–7759. It is also available
                                           maintain a detailed record for every                    comments.                                             on the internet at http://
                                           adverse event report the licensee or                                                                          www.regulations.gov by searching for
                                           permittee receives for any biological                   SUMMARY:    We are superseding                        and locating Docket No. FAA–2018–
                                           product it produces or distributes.                     Airworthiness Directive (AD) 2018–09–                 0443.
                                           These records shall be maintained for a                 10 for all CFM International S.A. (CFM)
                                           period of 3 years after the date the                    Model CFM56–7B engines. AD 2018–                      Examining the AD Docket
                                           adverse event report is received. The                   09–10 required initial and repetitive                   You may examine the AD docket on
                                           adverse event report form and guidance                  inspections of the concave and convex                 the internet at http://
                                           on how to complete it, including                        sides of the fan blade dovetail to detect             www.regulations.gov by searching for
                                           guidance specific to the various                        cracking and replacement of any blades                and locating Docket No. FAA–2018–
                                           information blocks on the form, is                      found cracked. This AD requires the                   0443; or in person at Docket Operations
                                           available on the APHIS website at                       same initial and repetitive inspections               between 9 a.m. and 5 p.m., Monday
amozie on DSK3GDR082PROD with RULES




                                           https://www.aphis.usda.gov/aphis/                       but revises the compliance time for the               through Friday, except Federal holidays.
                                           ourfocus/animalhealth/veterinary-                       initial inspections of certain higher-risk            The AD docket contains this final rule,
                                           biologics or by writing to APHIS Center                 fan blades. This AD was prompted by a                 the regulatory evaluation, any
                                           for Veterinary Biologics, 1920 Dayton                   recent engine failure due to a fractured              comments received, and other
                                           Avenue, P.O. Box 844, Ames, Iowa                        fan blade that resulted in the engine                 information. The street address for
                                           50010.                                                  inlet cowl disintegrating and debris                  Docket Operations (phone: 800–647–


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Document Created: 2018-05-17 00:51:24
Document Modified: 2018-05-17 00:51:24
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 June 18, 2018.
ContactDr. Donna L. Malloy, Section Leader, Operational Support, Center for Veterinary Biologics Policy, Evaluation, and Licensing, VS, APHIS, 4700 River Road Unit 148, Riverdale, MD 20737-1231; (301) 851-3426.
FR Citation83 FR 22832 
RIN Number0579-AE11
CFR Citation9 CFR 101
9 CFR 116
CFR AssociatedAnimal Biologics and Reporting and Recordkeeping Requirements

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