[Federal Register Volume 62, Number 120 (Monday, June 23, 1997)]
[Proposed Rules]
[Pages 33781-33783]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-16340]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Chapter I

[Docket No. 97N-0217]


Request for Comments on Development of Options to Encourage 
Animal Drug Approvals for Minor Species and for Minor Uses

AGENCY: Food and Drug Administration, HHS.

ACTION: Request for comments.

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SUMMARY:  The Food and Drug Administration (FDA) is requesting comments 
and suggestions relating to legislative and regulatory options to 
facilitate the approval of new animal

[[Page 33782]]

drugs intended for use in minor species or intended for minor uses. The 
agency is seeking comments and suggestions to assist its Center for 
Veterinary Medicine (CVM) in fulfilling its responsibility under the 
Animal Drug Availability Act of 1996 (the ADAA) to issue a report 
setting forth legislative and regulatory options to facilitate 
approvals of new animal drugs that fall into these two categories. 
Facilitating approvals for minor uses and minor species will bring 
about an increase in approvals of new animal drugs intended for these 
uses, which would be desirable to address the scarcity of approved, 
legally marketed new animal drugs intended for minor species or minor 
uses.
DATES: Written comments by September 8, 1997.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23, 
Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:  George A. (Bert) Mitchell, Center for 
Veterinary Medicine (HFV-6), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1761.

SUPPLEMENTARY INFORMATION:

I. Background

    ``Minor use'' of new animal drugs is defined in the Code of Federal 
Regulations at Sec. 514.1(d)(1)(i) (21 CFR 514.1(d)(1)(i)) as ``the use 
of: (a) New animal drugs in minor animal species, or (b) new animal 
drugs in any animal species for the control of a disease that (1) 
occurs infrequently or (2) occurs in limited geographic areas.''
    ``Minor species'' are defined at Sec. 514.1(d)(1)(ii) as ``animals 
other than cattle, horses, swine, chickens, turkeys, dogs, and cats. 
Sheep are a minor species with respect to effectiveness and animal 
safety data collection requirements; sheep are a major species with 
respect to human safety data collection requirements arising from the 
possible presence of drug residues in food.''
    Because the markets are small for approved new animal drugs 
intended for minor species or for minor uses, there are often 
insufficient economic incentives to motivate sponsors to develop the 
data necessary to support approvals. Consequently, manufacturers have 
not, in many cases, been willing to fund research to obtain these data. 
Accordingly, only small numbers of new animal drugs intended for minor 
species or for minor uses have been approved and are legally marketed.
    Because of the limited availability of approved new animal drugs 
intended for use in minor species or for minor uses, veterinarians, 
animal owners, and livestock producers have limited options for 
treatment of sick animals. In many cases, the available choices are to 
leave a sick animal untreated or to treat the animal with an unapproved 
drug. Even though it might appear that the absence of drug treatment 
would be safe for both the public and the environment, in the absence 
of approved therapies, there are increased public health hazards 
associated with the failure to treat sick animals. For example, the 
transmission of zoonotic disease is a significant public health risk 
associated with leaving animals untreated, as is the reduced 
wholesomeness of food associated with higher morbidity and mortality 
resulting from failure to treat. The shedding of disease-producing 
organisms by untreated animals into the environment also increases 
health risks to other animals and to humans.
    Although FDA has attempted to encourage the submission of approvals 
for minor species and uses in various ways, the agency's efforts to 
promote such approvals have thus far met with only limited success.
    In addition, FDA recently issued final regulations implementing the 
Animal Medicinal Drug Use Clarification Act of 1994 (the AMDUCA) (Pub. 
L. 103-396). The AMDUCA and the implementing regulations allow 
veterinarians, if they follow the conditions set forth in the 
regulations, to prescribe approved drugs for extralabel therapeutic use 
in animals. While the AMDUCA does give veterinarians more legal 
treatment options, the AMDUCA will not, and was not intended to, 
facilitate the approval of new animal drugs for minor species or minor 
uses.

II. The ADAA

     On October 9, 1996, the President signed the ADAA (Pub. L. 104-
250) into law. The primary purpose of the ADAA is to facilitate the 
approval and marketing of new animal drugs and medicated feeds by 
building ``needed flexibility'' into the animal drug review processes 
``to enable more efficient approval and more expeditious marketing of 
safe and effective animal drugs'' (H. Rept. 104-823 at 8).
    Section 2(f) of the ADAA directs the Secretary of Health and Human 
Services (the Secretary) to consider legislative and regulatory options 
for facilitating approval under section 512 of the Federal Food, Drug, 
and Cosmetic Act (the act) (21 U.S.C. 360b) of new animal drugs 
intended for use in minor species or for minor uses. The ADAA further 
requires the Secretary to announce proposals for legislative or 
regulatory change to the approval process for new animal drugs intended 
for use in minor species or for minor uses within 18 months after the 
date of enactment (i.e., no later than April 9, 1998).
    CVM plans to publish a notice of availability in the Federal 
Register and solicit comments on a revised guidance entitled ``Minor 
Use Guidance Document: A Guide to the Approval of Animal Drugs for 
Minor Uses and for Minor Species.'' CVM intends this revised guidance 
will be published as a Level 1 guidance document to facilitate the 
submission of new animal drug applications for drugs intended for minor 
uses and for minor species by clarifying how the agency believes that 
new animal drug approvals for minor species and for minor uses can be 
achieved, even as FDA develops the proposals required under the ADAA.
    This notice requests comments from animal drug manufacturers, users 
of animal drugs, and interested groups and individuals so that the 
agency can fulfill this statutory mandate of the ADAA.

III. Agency Request for Comments

    FDA is in the process of developing legislative and regulatory 
options for encouraging approvals of new animal drugs for use in minor 
species and for minor uses. As part of this process, the agency 
believes that it would be helpful to obtain comments and additional 
information on particular issues, as well as additional suggestions of 
legislative or regulatory options. FDA would find especially helpful 
comments that address target animal safety, food safety, effectiveness, 
labeling, manufacturing, environmental impact, and other concerns 
related to the agency's statutory responsibilities.
    Accordingly, FDA is specifically requesting comments and 
information on the questions and subjects below. This list is not all-
inclusive, however, and is not intended to limit the range of options 
available for public comment. The agency asks that comments be as 
detailed as possible, with explanations and information to assist FDA 
in evaluating whether the approaches will effectuate the purposes of 
the ADAA: That products be safe and effective, accurately labeled, 
consistently produced, and, most critically, whether the result will be 
larger numbers of approved new animal drugs for use in minor species or 
for minor uses.
    FDA does not intend anyone to read this list as any indication of 
the agency's position on a particular approach or a determination that 
the agency has the resources to implement such an approach.

[[Page 33783]]

A. Scope

    The agency seeks comments on the criteria found at Sec. 514.1(d)(1) 
for the determination of a minor species or a minor use.

B. Creating Additional Statutory Authority

    Should there be different standards for target animal safety and 
effectiveness of new animal drugs intended for use in minor species or 
for minor uses? Should there be different standards for human food 
safety for new animal drugs intended for minor species and for minor 
uses? If so, what should those standards be? Should the standards be 
the same for all minor species or uses? Why? Should products be labeled 
to reflect the use of different standards? If not, why not? If the act 
were amended to permit FDA to approve new animal drugs for a minor 
species or minor use under different standards, how would appropriate 
doses be determined and how would residue depletion and withdrawal 
times for food animals be determined?
    On the human drug side, certain critical drugs for life-threatening 
and serious diseases are approved though an accelerated approval 
process in which followup studies are required to confirm approval (see 
21 CFR part 314, subpart H). Similarly, section 522 of the act (21 
U.S.C. 360l) requires and authorizes the agency to require postmarket 
surveillance of certain devices to protect the public health or provide 
safety and effectiveness data. Would sponsors and users accept 
conditional approvals and postmarket surveillance as a tradeoff for 
requiring less in the way of premarket target animal safety and 
effectiveness studies for new animal drugs for minor species or minor 
uses? Should a drug approved under such a mechanism bear labeling that 
reflects its conditional status?
    Should the act be amended to allow FDA to accept foreign reviews or 
approvals of new animal drugs for minor species or for minor uses? How 
should Congress or FDA determine whether the reviews or approvals of a 
particular country or countries are acceptable as a basis for approval 
of uses for minor species or for minor uses.
    Should the current statutory standard for new animal drug approval 
for drugs intended for minor species or minor uses or any alternative 
standard be implemented through a primary review process external to 
the agency? If so, how might this process be administered? Who should 
pay for the external reviews?
    Could determinations of animal safety and effectiveness by expert 
panels or compendia be used to support drug approvals for minor species 
and minor uses? If so, what information would serve as the basis for 
such determinations? Should the determinations of these panels or other 
information be used to issue monographs or similar standards? Who would 
draft monographs or similar standards and why?

C. Administrative and Regulatory Changes

    Should there be different standards for manufacturing of drugs for 
minor species or minor uses? If so, what should those standards be? 
Should products be labeled to reflect the use of different 
manufacturing standards?
    Would a strategy similar to that used by the agency to facilitate 
drug approvals for some aquatic species be successful if extended to 
other minor species? That strategy includes coordination of 
investigational new animal drug (INAD) information collected or 
generated by end users. It also includes a centrally-organized and CVM-
operated field education program directed at end users as potential 
INAD sponsors. In which species/uses would such an approach work or not 
work? Why?

D. Creating Incentives

    Would economic incentives, such as tax breaks, grants, and periods 
of market or label exclusivity, encourage the pursuit of approvals or 
supplemental approvals for labeling modifications for minor species or 
minor uses? If so, what kinds of incentives would be most effective? 
Would different kinds of incentives be appropriate for different 
classes of new animal drugs, such as drugs for hobbyist-owned tropical 
fish as contrasted with production drugs for fish intended for human 
consumption?
    What incentives would encourage sponsors to pursue approval of a 
drug for a minor species or for a minor use using data in public master 
files (PMF's)? Are there concerns about data in PMF's that make new 
animal drug sponsors reluctant to rely on such data? What are those 
concerns? How could they be addressed?
    If producer groups or other organizations were willing to conduct 
or otherwise fund studies to demonstrate safety and efficacy for new 
animal drug approvals for minor species or minor uses, would sponsors 
be willing to use the data from the studies to support approvals and 
new or revised labeling? If not, why not?
    Should a program similar to the U.S. Department of Agriculture's 
National Research Support Program #7 (NRSP-7), which currently funds 
studies for minor use therapeutic uses for food- and fiber-producing 
animals, be developed for wildlife and zoo animals and/or for 
production uses? Should the NRSP-7 program be expanded to cover such 
uses?
    Could and should philanthropic, public interest, or other not-for-
profit organizations be encouraged to fund research for the development 
of new animal drugs intended for use in minor species or for minor 
uses? If so, how, and by whom?
    Are there mechanisms other than the new animal drug approval 
process and extralabel uses of animal and human drugs under the AMDUCA 
that could enhance drug availability for minor species and for minor 
uses?

E. Extending Existing Legal Authority

    Would legislation be desirable to extend the AMDUCA to permit 
extralabel use of: (1) Medicated feeds or (2) reproductive hormones and 
implants? What are the pros and cons of approval versus extralabel use 
under the AMDUCA?

IV. Comments

    Interested persons may, on or before September 8, 1997, submit to 
the Dockets Management Branch (address above) written comments 
regarding this document. Two copies of any comments are to be 
submitted, except that individuals may submit one copy. Comments are to 
be identified with the docket number found in brackets in the heading 
of this document. Received comments may be seen in the office above 
between 9 a.m. and 4 p.m., Monday through Friday.

    Dated: June 12, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-16340 Filed 6-18-97; 1:40 pm]
BILLING CODE 4160-01-F