[Federal Register Volume 67, Number 10 (Tuesday, January 15, 2002)]
[Proposed Rules]
[Pages 1910-1913]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-938]


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 Proposed Rules
                                                 Federal Register
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 This section of the FEDERAL REGISTER contains notices to the public of 
 the proposed issuance of rules and regulations. The purpose of these 
 notices is to give interested persons an opportunity to participate in 
 the rule making prior to the adoption of the final rules.
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  Federal Register / Vol. 67, No. 10 / Tuesday, January 15, 2002 / 
Proposed Rules  

[[Page 1910]]



DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Parts 101 and 116

[Docket No. 00-071-1]


Viruses, Serums, Toxins, and Analogous Products; Records and 
Reports

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Proposed rule.

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SUMMARY: We are proposing to amend the Virus-Serum-Toxin Act 
regulations concerning records and reports. First, we are proposing to 
require veterinary biologics licensees and permittees to record and 
submit reports to the Animal and Plant Health Inspection Service 
concerning adverse events associated with the use of biological 
products that they produce or distribute. Second, we are proposing to 
require veterinary biologics licensees and permittees to report to the 
Animal and Plant Health Inspection Service the number of doses of each 
licensed product that they distribute. Third, we are proposing to 
provide definitions for adverse event and adverse event report. These 
actions would assist the Animal and Plant Health Inspection Service in 
providing complete and accurate information to consumers regarding 
adverse reactions or other problems associated with the use of licensed 
biological products.

DATES: We will consider all comments we receive that are postmarked, 
delivered, or e-mailed by March 18, 2002.

ADDRESSES: You may submit comments by postal mail/commercial delivery 
or by e-mail. If you use postal mail/commercial delivery, please send 
four copies of your comment (an original and three copies) to: Docket 
No. 00-071-1, Regulatory Analysis and Development, PPD, APHIS, Station 
3C71, 4700 River Road Unit 118, Riverdale, MD 20737-1238. Please state 
that your comment refers to Docket No. 00-071-1. If you use e-mail, 
address your comment to [email protected]. Your comment must 
be contained in the body of your message; do not send attached files. 
Please include your name and address in your message and ``Docket No. 
00-071-1'' on the subject line.
    You may read any comments that we receive on this docket in our 
reading room. The reading room is located in room 1141 of the USDA 
South Building, 14th Street and Independence Avenue SW., Washington, 
DC, between 8 a.m. to 4:30 p.m., Monday through Friday, except 
holidays. To be sure someone is there to help you, please call (202) 
690-2817 before coming.
    APHIS documents published in the Federal Register, and related 
information, including the names of organizations and individuals who 
have commented on APHIS dockets are available on the Internet at http://www.aphis.usda.gov/ppd/rad/webrepor.html.

FOR FURTHER INFORMATION CONTACT: Dr. Albert P. Morgan, Chief of 
Operational Support, Center for Veterinary Biologics, Licensing and 
Policy Development, VS, APHIS, 4700 River Road Unit 148, Riverdale, MD, 
20737-1231; (301) 734-8245.

SUPPLEMENTARY INFORMATION:

Background

    The regulations in 9 CFR part 116 contain requirements for 
maintaining detailed records of information necessary to give a 
complete accounting of all the activities within a veterinary biologics 
establishment.
    In this document, we are proposing amendments to that part. First, 
we are proposing to require veterinary biologics licensees and 
permittees to record and submit reports to the Animal and Plant Health 
Inspection Service (APHIS) concerning adverse events associated with 
the use of biological products that they produce or distribute. Second, 
we are proposing to require veterinary biologics licensees and 
permittees to report to APHIS the number of doses of each licensed 
product that they distribute. Third, we are proposing definitions for 
adverse event and adverse event report.

Definitions

    The regulations at 9 CFR part 101 contain definitions of terms used 
in the regulations concerning veterinary biologics. The proposed 
changes to part 116 of the regulations would make it necessary for us 
to add definitions in Sec. 101.2 for two terms used in the proposed 
regulations: Adverse event and adverse event report. We would define 
adverse event as ``any undesirable and unintended occurrence after the 
use of a biological product, whether or not the cause of the event is 
known. For products administered to animals, adverse events are those 
involving the health of the treated animal, including the apparent 
failure to protect against disease. For products intended to diagnose 
disease, adverse events refer to anything that hinders discovery of the 
correct diagnosis.'' We would define adverse event report as ``a 
communication concerning the occurrence of one or more adverse events 
which identifies the product(s), animal(s), and person making the 
report.'' The receipt of an adverse event report does not necessarily 
imply that the product caused the adverse event.

Adverse Event Records and Reports

    Currently, Sec. 116.1(a) requires each licensee, permittee, and 
foreign manufacturer of biological products imported into the United 
States to maintain, at the licensed or foreign establishment in which 
the products are prepared, detailed records of information necessary to 
give a complete accounting of all the activities within each 
establishment. Section 116.1, paragraph (a), further states that such 
records must include, but are not limited to, the items listed in part 
116, which are inventory and disposition records (Sec. 116.2), label 
records (Sec. 116.3), sterilization and pasteurization records 
(Sec. 116.4), product development and preparation and market 
suspensions and recalls (Sec. 116.5), animal records (Sec. 116.6), and 
test records (Sec. 116.7).
    In addition, Secs. 116.1(b) and 116.5(b) state that 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, the licensee, permittee, or foreign manufacturer must 
immediately notify APHIS concerning the circumstances and the action 
taken, if any.

[[Page 1911]]

    However, the regulations in Sec. 116.1(a) and (b) and Sec. 116.5(b) 
do not explicitly require licensees and permittees to maintain records 
of reports of adverse events associated with the use of veterinary 
biologics, nor do the regulations provide specific guidance in 
determining when an adverse event report may raise questions regarding 
the purity, safety, potency, efficacy, preparation, testing, or 
distribution (PSPEPTD) of such product. Consequently, each veterinary 
biologics manufacturer makes independent determination concerning (1) 
whether an adverse event report raises PSPEPTD questions and (2) when 
and in what manner such report of the adverse event will be provided to 
APHIS.
    To limit the harm to animals posed by unsatisfactory veterinary 
biologics, APHIS currently must rely primarily on adverse event reports 
provided by the manufacturer. Unexpected or unexplained adverse events 
associated with the use of veterinary biologics in animals are reported 
to the veterinary biologics manufacturer either by the consumer or in 
the form of a report from a technical service veterinarian employed by 
the manufacturer to monitor the performance of their products in the 
field.
    Currently, licensees and permittees are using nonstandardized 
methods to record and submit reports regarding adverse events to APHIS. 
In addition, adverse event reports that may signal problems concerning 
the use of veterinary biologics products are not all being submitted to 
APHIS in a timely manner. Unless we have complete and timely reports, 
we may not be able to take expeditious action to limit the harm in 
animals caused by veterinary biological products that may be harmful or 
dangerous to animals. Therefore, we are proposing to add to the 
regulations a new Sec. 116.9 for adverse event records. New Sec. 116.9 
would require licensees and permittees to record reports of all adverse 
events that they receive concerning the use of biological products that 
they produce or distribute and submit a summary of such reports to 
APHIS on an annual basis. Licensees and permittees would be required to 
record information concerning adverse events that includes: (1) The 
date of the report; (2) identification of the person initiating the 
report; (3) the true name of the product involved and product trade 
name; (4) the product serial number, if available; (5) a description of 
the adverse event; (6) the animal(s) involved; and (7) any other 
pertinent identifying information regarding the product.
    In addition, in new Sec. 116.9, we would propose that licensees and 
permittees prepare summaries of the adverse event report records for 
submission to APHIS. Beginning with the date the product is licensed, 
such summaries would have to include intervals of 6 months during the 
first year and intervals of 1 year thereafter. We would also require 
summaries to be received by APHIS within 30 days after the end of the 
interval.
    We would require records for each 6-month interval after the 
product is licensed because little is known about newly licensed 
products, except for observations made during the immunogenicity 
studies, safety tests, and field trials for these products. We believe 
that more frequent reporting requirements for newly licensed products 
would ensure that we have adequate data to support a decision to take 
regulatory action against products that are associated with an unusual 
number of adverse event reports.
    We are also proposing to revise Secs. 116.1(a)(3) and 116.8 of the 
regulations to allow adverse event records to be excluded from the list 
of records to be completed before serials may be marketed because 
adverse event records cannot be completed before a product has been 
distributed and used in animals.
    The proposed amendments would standardize the adverse event 
reporting system and the information that should be included when 
making records of adverse event reports.

Number of Doses Distributed

    In order to provide an objective measure of when it may be 
necessary to take action against a veterinary biologic to limit the 
harm in animals, and as a component of the adverse event reporting 
system, we would use the number of doses of product distributed instead 
of the number of doses of product administered to animals to calculate 
the incidence of adverse events associated with a particular product. 
Typically, the number of doses of product administered to animals would 
be used to calculate incidence. Because we must take timely action and 
may not know precisely how many animals have been treated with a 
product, we believe that the number of marketed doses of a product 
should be representative of the number of doses that were administered 
to animals.
    Currently, the regulations in part 116 do not require veterinary 
biologics manufacturers to report to APHIS the number of doses of each 
licensed product that are distributed. Therefore, we are proposing to 
add this requirement in new Sec. 116.5(c). In addition, we are 
proposing that the records include the number of doses for each 6-month 
interval after the product is licensed during the first year and each 
yearly interval thereafter. We would also require the reports to be 
received within 30 days after the end of the interval.
    We would require records for each 6-month interval after the 
product is licensed based on the reasons provided previously in this 
document under ``Adverse Event Reports.''

Miscellaneous

    We are also proposing to make minor, nonsubstantive, editorial 
changes to the regulations, as set out in the rule portion of this 
document, for clarity.

Executive Order 12866 and Regulatory Flexibility Act

    This proposed rule has been reviewed under Executive Order 12866. 
The 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.
    We are proposing to amend the Virus-Serum-Toxin Act regulations for 
records and reports. First, we are proposing to require veterinary 
biologics licensees and permittees to record and submit reports to 
APHIS concerning adverse events associated with the use of biological 
products that they produce or distribute. Second, we are proposing to 
require veterinary biologics licensees and permittees to report to 
APHIS the number of doses of each licensed product that they 
distribute. Third, we are proposing to provide definitions for adverse 
event and adverse event report. These actions would assist us in 
providing complete and accurate information to consumers regarding 
adverse reactions or other problems associated with the use of licensed 
biological products.
    This proposed rule would affect most, if not all, licensed 
manufacturers of veterinary biologics. Currently, there are 
approximately 150 veterinary biologics manufacturers, including 
permittees. According to the standards of the Small Business 
Administration, most veterinary biologics establishments would be 
classified as small entities.
    We believe that this proposed rule would not have a significant 
effect on small entities because most veterinary biologics 
manufacturers currently maintain recordkeeping systems for adverse 
event reports, and this proposed rule does not restrict manufacturers 
from using their discretion to choose the most appropriate 
recordkeeping system

[[Page 1912]]

for maintaining records of these reports. However, one of the purposes 
of this proposed rule is to provide veterinary biologics manufacturers 
with criteria that should be included in the reports so that the 
reports are standardized from manufacturer to manufacturer and 
submitted to APHIS in a timely manner.
    In addition, the proposed requirement that veterinary biologics 
manufacturers report the number of doses of each licensed or permitted 
product that has been distributed would not have a significant effect 
on small entities. Veterinary biologics manufacturers currently 
maintain records of the number of doses of a product produced and 
distributed. This proposed rule would only require veterinary biologics 
manufacturers to report the number of doses to APHIS as required by the 
proposed regulations.
    Under these circumstances, the Administrator of the Animal and 
Plant Health Inspection Service has determined that this action would 
not have a significant economic impact on a substantial number of 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 7 CFR part 3015, subpart V.)

Executive Order 12988

    This proposed rule has been reviewed under Executive Order 12988, 
Civil Justice Reform. It is not intended to have retroactive effect. 
This rule would not preempt any State or local laws, regulations, or 
policies, unless they present an irreconcilable conflict with this 
rule. The Act does not provide administrative procedures which must be 
exhausted prior to a judicial challenge to the provisions of this rule.

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 proposed rule have been 
submitted for approval to the Office of Management and Budget (OMB). 
Please send written comments to the Office of Information and 
Regulatory Affairs, OMB, Attention: Desk Officer for APHIS, Washington, 
DC 20503. Please state that your comments refer to Docket No. 00-071-1. 
Please send a copy of your comments to: (1) Docket No. 00-071-1, 
Regulatory Analysis and Development, PPD, APHIS, Suite 3C03, 4700 River 
Road Unit 118, Riverdale, MD 20737-1238, and (2) Clearance Officer, 
OCIO, USDA, room 404-W, 14th Street and Independence Avenue SW., 
Washington, DC 20250. A comment to OMB is best assured of having its 
full effect if OMB receives it within 30 days of publication of this 
proposed rule.
    This proposed rule would require manufacturers of veterinary 
biological products to maintain records of adverse event reports that 
they receive concerning the use of veterinary biological products that 
they produce or distribute for 2 years or longer and submit a summary 
of such reports to APHIS. The reports would have to be submitted at 6-
month intervals during the first year the product is licensed and at 1-
year intervals thereafter. In addition, licensees and permittees would 
have to report to APHIS the number of doses of each licensed product 
distributed every 6 months during the first year the product is 
licensed or permitted and at 1-year intervals thereafter. These 
information collection and recordkeeping requirements would allow us to 
monitor and provide the appropriate level of regulatory oversight.
    We are soliciting comments from the public (as well as affected 
agencies) concerning this proposed amendment to the records and reports 
requirements in the regulations. We need this outside input to help us:
    (1) Evaluate whether the proposed information collection in the 
form of records and reports is necessary for the proper performance of 
our agency's functions, including whether the information will have 
practical utility;
    (2) Evaluate the accuracy of our estimate of the burden of the 
proposed information collection, including the validity of the 
methodology and assumptions used;
    (3) Enhance the quality, utility, and clarity of the information to 
be collected; and
    (4) Minimize the burden of the information collection on those who 
are to respond (such as through the use of appropriate automated, 
electronic, mechanical or other technological collection techniques or 
other forms of information technology, e.g., permitting electronic 
submission of responses).
    Estimate of burden: Public reporting burden for this collection of 
information is estimated to average 1 hour per response.
    Respondents: Veterinary biologics licensees and permittees.
    Estimated annual number of respondents: 125.
    Estimated annual number of responses per respondent: 8.
    Estimated annual number of responses: 1,000.
    Estimated total annual burden on respondents: 1,000 hours.
    Copies of this information collection can be obtained from: Mrs. 
Celeste Sickles, APHIS' Information Collection Coordinator, at (301) 
734-7477.

List of Subjects

9 CFR Part 101

    Animal biologics.

9 CFR Part 116

    Animal biologics, Reporting and recordkeeping requirements.

    Accordingly, we propose to amend 9 CFR parts 101 and 116 as 
follows:

PART 101--DEFINITIONS

    1. The authority citation for part 101 would be revised to read as 
follows:

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

    2. In Sec. 101.2, definitions of adverse event and adverse event 
report would be added in alphabetical order to read as follows:


Sec. 101.2  Administrative terminology.

* * * * *
    Adverse event. Any undesirable and unintended occurrence after the 
use of a biological product, whether or not the cause of the event is 
known. For products administered to animals, adverse events are those 
involving the health of the treated animal, including the apparent 
failure to protect against disease. For products intended to diagnose 
disease, adverse events refer to anything that hinders discovery of the 
correct diagnosis.
    Adverse event report. A communication concerning the occurrence of 
one or more adverse events which identifies the product(s), animal(s), 
and person making the report.
* * * * *

PART 116--RECORDS AND REPORTS

    3. The authority citation for part 116 would be revised to read as 
follows:

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

    4. In Sec. 116.1, paragraph (a)(3) would be 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

[[Page 1913]]

may be marketed in the United States or exported.
* * * * *
    5. Section 116.5 would be amended by adding a new paragraph (c) to 
read as follows:


Sec. 116.5  Reports.

* * * * *
    (c) The licensee and/or permittee must report to APHIS the number 
of doses of each licensed or permitted product that has been 
distributed. Reports must include the number of doses for each 6 month 
interval during the first year the product is licensed and at yearly 
intervals thereafter. Reports must be received by APHIS within 30 days 
after the end of the interval.
* * * * *
    6. Section 116.8 would be 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 place of business for the licensee, 
permittee, or foreign manufacturer 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)

    7. A new Sec. 116.9 would be added to read as follows:


Sec. 116.9  Adverse event records.

    (a) A detailed record must be maintained for every adverse event 
report the licensee or permittee receives for any biological product it 
produces or distributes. Each record must include:
    (1) The date of the report;
    (2) The identification of the person initiating the report;
    (3) The true name of the product involved and product trade name;
    (4) The serial number(s) of the product(s), if available;
    (5) A description of the adverse event;
    (6) The animal(s) involved; and
    (7) Any other pertinent identifying information regarding the 
product.
    (b) For each product, summaries of adverse event report records 
must be compiled and submitted to APHIS. Beginning with the date the 
product is licensed, such summary compilations must cover intervals of 
6 months during the first year the product is licensed and yearly 
intervals thereafter. Summaries must be received within 30 days after 
the end of the interval.

    Done in Washington, DC, this 10th day of January, 2002.
W. Ron DeHaven,
Acting Administrator, Animal and Plant Health Inspection Service.
[FR Doc. 02-938 Filed 1-14-02; 8:45 am]
BILLING CODE 3410-34-U