[Federal Register: June 23, 1997 (Volume 62, Number 120)]
[Proposed Rules]
[Page 33781-33783]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr23jn97-19]
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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