OMB 0910 - 0012

[SUPPORTING STATEMENT]{.underline}

**[VETERINARY ADVERSE DRUG REACTION, LACK OF EFFECTIVENES]{.underline}**
**[PRODUCT DEFECT REPORT AND]{.underline} [TRANSMITTAL OF PERIODIC
]{.underline}** **[REPORTS]{.underline}**

**A. [JUSTIFICATION]{.underline}**

**1. [Circumstances Making the Information Collection
Necessary]{.underline}**

Implementation of Section 512(l) of the Federal Food, Drug and Cosmetic
Act, 21 CFR 510.300, 510. 301, and 510.302 requires applicants of
approved new animal drug applications ( NADA\`s), to submit within 15
working days of receipt, complete records of reports of certain adverse
drug reactions and unusual failure of new animal drugs. Other reporting
requirements of adverse reactions to these drugs and periodic drug
experience reports must be submitted annually or semi-annually in a
specific format.

This continuous monitoring of approved NADA\`s affords the primary means
by which FDA obtains information regarding potential problems in safety
and effectiveness of marketed animal drugs and potential manufacturing
problems. Current data on file with FDA is not adequate because animal
drug effects can change over time, and less apparent effects may take
years to manifest themselves.

Adverse reaction reports are required to be submitted by the drug
manufacturer on FDA Forms 1932 or 1932a (voluntary reporting form),
following complaints from animal owners or veterinarians. Also, product
defects and lack of effectiveness complaints are submitted to FDA by the
drug manufacturer following their own detection of a problem or
complaints from product users or their veterinarians using FDA forms
1932 and 1932a. Form FDA 2301 is used to submit the required transmittal
of periodic reports and promotional material for new animal drugs.

The specific citations under 21 CFR Part 300 with information collection
requirements for which we request OMB approval are:

**21 CFR 510.300(a) Recordkeeping.**

Specifies requirements for applicant(s) to establish and maintain
records and files containing full reports of information pertinent to
the safety and effectiveness of a new animal drug that have not been
previously submitted.

**21 CFR 510.300(b) Recordkeeping**

Specifies requirement(s) for maintenance of records for new animal drugs
and time frames for submitting reports to FDA concerning a mixup in the
new animal drug or its labeling with another article, information
regarding any unexpected side effects, injury, toxicity or sensitivity
reaction(s) and information concerning any unusual failure of the new
animal drug to exhibit its expected pharmacological activities.

**21 CFR 510.301(a) Recordkeeping**

Specifies requirements for maintenance of records and submission of
reports to FDA within the required time frame concerning experience with
animal feeds bearing or containing new animal drugs for which an
approved application is in effect, including information concerning any:
mixup in the new animal drug or its labeling with another article;
bacteriological, or significant chemical, physical or other change or
deterioration in the drug.

**21 CFR 510.301 (b) Recordkeeping**

Specifies requirements for maintenance of records and submission of 15
day reports to FDA

concerning experience with animal feeds bearing or containing new animal
drugs for which an approved application is in effect, including
information on any unexpected side effects, injury or toxicity or
sensitivity reactions; and unusual failure of the drug to exhibit its
expected pharmacological activity.

**21 CFR 510.302(a) Reporting**

Requires submission of periodic reports and promotional material for new
animal drugs on Form FDA 2301.

**21 CFR 510.302(b) Reporting.**

Cites reporting requirements that all adverse experiences with new
animal drugs or animal feeds bearing or containing new animal drugs and
information on product defects or lack of effectiveness of the new
animal drug must be reported on Form FDA 1932. or in the case of
voluntary reporting , Form FDA 1932a.

We are also requesting approval of the following OMB forms::

> **Form FDA - 1932,** Veterinary Adverse Drug Reaction, Lack of
> Effectivenes or Product Defect Report

**Form FDA 1932a**, Veterinary Adverse Reaction, Lack of Effectiveness

or Product Defect Report

**Form FDA-2301,** Transmittal of Periodic Reports and Promotional
Material for New Animal Drugs

**2. Purpose and Use of the Information**

The information on the FDA Form 1932 may originate from an owner of an
animal, or animals, who registers a complaint with the drug
manufacturer, who is then required to report the episode to the Food and
Drug Administration on the FDA Form 1932. Products which are the subject
of a complaint may be either an over-the-counter product available to
anyone, or a prescription product available only by order of a
veterinarian. In either case, the name of the owner of the animal(s) is
germane to the identification of the episode in order that a specific
reaction not be counted twice. The safety and effectiveness of
monitoring activities involving drug products also relies on voluntary
reports of suspected drug effects, or drug ineffectiveness complaints
from practicing veterinarians. These reports are usually submitted
directly to FDA, Center for Veterinary Medicine, on Form FDA 1932a, a
short, convenient, easily completed form. Each report is first reviewed
by an FDA Veterinary Medical officer to determine the probability that
the drug caused the adverse effect, or that the drug was ineffective.
After the individual report is reviewed, it is added to Division of
Epidemiology and Surveillances Adverse Drug Experience (ADE) computer
database file containing other previously reported ADE data for that
drug. The ADE database is reviewed as a whole to determine if any
changes in the specific product or labeling are needed. Careful
evaluation of the database sometimes leads to label or package insert
changes, dosage changes, additional warnings or contraindications,
product reformulation, or on rare occasions, withdrawal of the approved
new animal drug application.

Monitoring for product defects is also an essential part of the FDA\'s
regulatory mission. These product defect reports are used by CVM as a
primary means of obtaining information regarding potential manufacturing
problems with specific lots of marketed animal drug products. Reports
from veterinarians and others are essential because there is no other
effective way of obtaining this needed information. The reports are
reviewed by the chemists in the Division of Manufacturing Technologies
to identify any potential violation of the FD&C Act. If a violation of
the FD&C Act appears to exist, the report is followed up with an
assignment memorandum to the appropriate FDA field office requesting a
limited inspection of the firm to gather more facts and needed evidence
in support of a product recall or regulatory action such as seizure or
injunction. Alternatively, when the drug is the subject of a NADA the
sponsor may be asked to investigate the cause and effect of the product
defect and supplement their NADA to provide for appropriate changes in
the manufacturing control section of the NADA.

Form FDA-2301 is required to be submitted periodically by the drug
sponsor to inform the FDA of all reports of information from any source
pertinent to the safety and effectiveness of the new animal drug for the
purpose of determining whether there are ground for withdrawing or
suspending approval. All reports undergo a full and comprehensive review
by FDA scientists to evaluate the impact and significance of reported
clinical experiences, investigations and tests. Labeling is also
reviewed for accuracy of claims, directions for use and general
compliance with the Act and regulations.

If collection of information was not conducted, there would be no
continuous monitoring of the safety and effectiveness of marketed animal
drugs. Data already on file with CVM is not adequate because new animal
drugs are continually being approved, drug effects can change over time,
and less apparent effects sometimes take a number of years to detect.

**3. Use of Information Technology**

Many of the respondents have automated systems for reports of adverse
reactions to new animal drugs. This does have an impact on the amount of
time the respondents spend in making reports to FDA. Written
communications, in the form of computer printouts, may be forwarded to
be in compliance with the 15-day reporting time requirement. In
addition, CVM is working on the development of electronic submission
data standards for reporting of adverse drug reactions, lack of
effectiveness and product defects.

**4. Efforts to Identify Duplication and Use of Similar Information**

This information is not collected by any other agency in the government,
however, in order to avoid duplication and over-reporting, the name and
address of the owner of the animal(s) is essential to the identification
of an episode in order that a specific reaction will not be counted
twice. Other checks include the name/address of the veterinarian, and
the date(s) of the incident. There is no similar information available
because new animal drugs are continually being approved; drug effects
can change over time; and, less apparent effects sometimes take a number
of years to detect.

**5. Impact on Small Business or Other Small Entities**

Small businesses are not involved. FDA will provide help to small firms
through the Office of Small Manufacturers Assistance, if requested.

**6. Consequences of Collecting the Information Less Frequently**

It would definitely not be feasible to require less frequent collection
of information. New, unusual, and serious adverse reactions can suddenly
begin to appear due to many reasons and under many circumstances. Also,
when a new drug is approved, adverse reactions can appear at any time
due to the large distribution of the drug as compared to its use during
the preapproval clinical trials.

**7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5**

These reporting requirements are inconsistent with 5 CFR 1320.5 This
section requires justification for requesting respondents to report more
often than quarterly. In 21 CFR 510.300(b)(1), the sponsor of an
NADA/ANADA is required to notify FDA of any unexpected adverse reactions
within 15 working days of receipt of information on such a reaction by
the sponsor. This short time for reporting is necessary so that FDA is
informed as soon as possible of any serious problems with a drug
product, so that the agency can take appropriate action. The indefinite
maintenance period for keeping these records is also inconsistent with 5
CFR 1320.6. This extended period is due to the potential of litigation,
adverse drug experiences and needed for studies of delayed effects such
as carcinogenicity.

**8. Comments in Response to the Federal Register Notice and Efforts to
Consult Outside Agency**

Burden estimates are based on FDA data and experience, and on discussion
with affected industry in 1997. We believe estimates on industry burden
have not changed appreciably since that time . No comments were received
from industry in response to our 60 day notice.

**9. Explanation of Any Payment or Gifts to Respondents**

There are no payments or gifts to respondents.

**10. Assurance of Confidentiality Provided to Respondent**

Under the terms of the Freedom of Information Act, the veterinarian\'s
name, address, and phone number, and the owner\'s name, etc., cannot be
made available to a public request. During working hours, only FDA
employees have access to the computer files and database on a need to
know basis. When an FDA employee is not present during working hours,
the computer room containing the reports and database is locked. During
non-duty hours the rooms containing the confidential information are
locked, and building security is provided through a contract with a
private protection agency.

**11. Justification for questions of a sensitive nature.**

There are no questions of a sensitive nature for any of the forms used
as a data collection instrument for reporting requirements.

**12. Estimates of Hour Burden for Collection of Information**

A. Form FDA-1932 and Form FDA-1932a

An estimated 18,000 reports wi1l be filed annually by respondents. It is
estimated that it takes on the average one hour to complete each report.
Therefore, the 18,000 reports filed annually, requiring approximately
one hour per report results in a total burden estimate of 18,000 hours.

An estimated 100 reports from individual veterinarians are voluntarily
submitted directly to FDA on Form FDA-1932a each year. This voluntary
reporting is at no cost to the sponsor. Therefore, the 100 reports filed
annually, requiring approximately one hour per report, results in a
total burden of 100 hours.

B. Form FDA-2301

The burden on respondents varies with the complexities of each drug
product. Dependent on the type of product marketed, the burden varies
from 15 minutes to 20 hours, with an average estimate of 0.5 hours. With
2,500 reports during FY 2000, the reporting burden is therefore 1,250
hours, (0.5 X 2,500 = 1,250).

C. Recordkeeping

Under the provisions of 21 CFR 510.300(a) and 21 CFR 510.301(a), an
estimated 2,500 annual records will be prepared by the respondents. The
records are those concerned with experience with new animal drugs for
which an approved application is in effect and animal feeds bearing or
containing new animal drugs for which an approved application is in
effect. It is estimated that it takes an average of 10.35 hours per
record. Therefore 2,500 records prepared annually, requiring
approximately 10.35 hours per report, results in a total burden of
25,875 hours.

Under the recordkeeping provisions of 21 CFR 510.300(b) and 21 CFR
510.301(b), an estimated 18,000 annual records will be prepared by the
respondents. It is estimated that it takes approximately 0.50 hours per
record. Thus the 18,000 annual records prepared annually requiring an
average of approximatlely 0.50 hours per record results in a total
burden of 9,000 hours.

**13. [Estimate of annual cost burden other than hour burden to
respondents]{.underline}**

FDA believes that the collection of information would not result in a
cost burden beyond the hour burden to respondents.

**14. Annualized Cost to the Federal Government**

A. Form FDA-1932 and Form FDA 1932a

Approximately 18,100 adverse drug reaction reports will be received by
this program annually. These reports are reviewed by a veterinary
reviewer, GS-13, at an estimated \$32.00 per hour. Each report takes a
reviewer 1/2 hour, or 1/2 hour X 18,100 reports = 9,050 hours.

Cost to the Government:

Reviewers: 9,050 hours X \$32.00 per hour = \$289,600

B. Form FD-2301

Approximately 2,500 reports will be received by this program annually.
These reports are reviewed by a veterinary reviewer, GS-13, at an
estimated \$32.00 per hour. Each report takes a reviewer 2.5 hours to
complete or 2,500 reports X 2.5 hours = 6,250 hours.

Cost to the Government:

Reviewers: 6,250 hours X \$32.00 per hour = \$200,000

Total Cost to the Government:

Form FDA 1932 and 1932a \$289,600

Form FDA 2301 \$[200,000]{.underline}

Total Cost \$489,600

**15. Explanation of Program Changes or Adjustments**

A significant increase in the burden for submission of adverse drug
reactions on Form FDA-1932 and 1932a (2,900 to 18,000), results from a
greater awareness of the need for veterinarians and consumers to submit
this information to the drug manufacturer. While there is a marked
increase in the burden, the corresponding added information generated by
the additional submissions greatly enhances the FDAs ability to assess
safety and effectiveness of marketed drugs.

**16. Plans for Tabulation and Publication and Project Time Schedule**

There are no plans for tabulation and publication of information f for
statistical use.