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

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

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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