New Animal Drugs Intended for Use in Minor Species

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.

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 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. [p33782]

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. [p33783]

* 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]