II

104TH CONGRESS

1ST SESSION S. 773

To amend the Federal Food, Drug, and Cosmetic Act to provide for improvements in the process of approving and using animal drugs, and for

other purposes.

IN THE SENATE OF THE UNITED STATES

MAY 9 (legislative day, MAY 1), 1995

Mrs. KASSEBAUM (for herself, Mr. GREGG, Mr. GORTON, Mr. COATS, Mr.

JEFFORDS, Mr. FRIST, Mr. HARKIN, Mr. CRAIG, Mr. LUGAR, Mr.

INHOFE, Mr. GRASSLEY, Mr. MCCONNELL, Mr. KYL, Mr. SANTORUM,

Mr. HEFLIN, Mr. BOND, Mr. PRYOR, Mr. KERREY, Mr. BENNETT, and

Mr. HELMS) introduced the following bill; which was read twice and referred to the Committee on Labor and Human Resources

A BILL

To amend the Federal Food, Drug, and Cosmetic Act to

provide for improvements in the process of approving

and using animal drugs, and for other purposes.

1 Be it enacted by the Senate and House of Representa2 tives of the United States of America in Congress assembled,

3 SECTION 1. SHORT TITLE; REFERENCE.

4 (a) SHORT TITLE.—This Act may be cited as the

5 ‘‘Animal Drug Availability Act of 1995’’.

6 (b) REFERENCE.—Whenever in this Act an amend7 ment or repeal is expressed in terms of an amendment
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1 to, or repeal of, a section or other provision, the reference

2 shall be considered to be made to a section or other provi3 sion of the Federal Food, Drug, and Cosmetic Act (21

4 U.S.C. 321 et seq.).

5 SEC. 2. FINDINGS.

6 Congress finds that—

7 (1) the new animal drug approval process has

8 been proceeding too slowly, with the result that nec9 essary and useful drug therapies are being kept from

10 the marketplace;

11 (2) the lack of drug approvals for new animal

12 drugs places the health and well-being of animals at

13 risk;

14 (3) the expense and delays caused by effective15 ness testing for new animal drugs have begun to

16 outweigh the benefits of such testing;

17 (4) the overreliance on field investigations to es18 tablish the effectiveness of new animal drugs is a

19 primary reason the new animal drug approval proc20 ess has become so burdensome;

21 (5) there are not sufficient approved animal

22 drugs available to treat every specific disease or con23 dition found in each species of animal;
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1 (6) it would benefit the public health and safety

2 to have many additional animal drugs reviewed and

3 approved by the Food and Drug Administration;

4 (7) economic and regulatory incentives are nec5 essary to encourage manufacturers of animal drugs

6 to convert unlabeled uses of the drugs to approved,

7 labeled uses; and

8 (8) it is important that the Center for Veteri9 nary Medicine of the Food and Drug Administration

10 promptly implement the recently developed mission,

11 vision, and guiding principles of the Center so that

12 the Food and Drug Administration is a global leader

13 as a public health organization that enables the mar14 keting of safe and effective products.

15 SEC. 3. EVIDENCE OF EFFECTIVENESS.

16 (a) ORIGINAL APPLICATIONS.—Section 512(d) (21

17 U.S.C. 360b(d)) is amended by striking paragraph (3) and

18 adding at the end the following new paragraph:

19 ‘‘(4)(A) As used in this subsection and subsections

20 (c)(2)(F)(iii) and (e)(1)(C), the term ‘substantial evi21 dence’ means evidence from 1 or more scientifically sound

22 studies, including as appropriate in vitro studies, studies

23 in laboratory animals (including a target species),

24 bioequivalence studies, tissue residue studies, and any

25 studies voluntarily undertaken by or for the applicant,
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1 that taken together provide reasonable assurance that the

2 drug will have the claimed or intended effect of the drug.

3 ‘‘(B) For purposes of subparagraph (A), a study shall

4 be considered to be scientifically sound if the study is de5 signed and conducted in a manner that is consistent with

6 generally recognized scientific procedures and principles.’’.

7 (b) SUPPLEMENTAL APPLICATIONS.—Section

8 512(c)(2)(F)(iii) (21 U.S.C. 360b(c)(2)(F)(iii)) is amend9 ed—

10 (1) by striking ‘‘reports of new clinical or field

11 investigations (other than bioequivalence or residue

12 studies) and’’ and inserting ‘‘substantial evidence (as

13 defined in subsection (d)(4)) of the effectiveness of

14 the drug involved, any studies of animal safety, or’’;

15 and

16 (2) by striking ‘‘essential to’’ and inserting ‘‘,

17 required for’’.

18 (c) MINOR SPECIES AND USES.—Section 512(d)(1)

19 (21 U.S.C. 360b(d)(1)) is amended by adding at the end

20 the following new sentence: ‘‘Subparagraph (E) shall not

21 apply to a claim for use of the drug described in subpara22 graph (E) in a minor species, or for a minor use of the

23 drug, as the terms ‘minor species’ and ‘minor use’ are de24 fined in regulations issued by the Secretary, if there is

25 an application filed under subsection (b) for the drug, and
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1 the application is approved, prior to the submission of the

2 claim.’’.

3 (d) COMBINATION DRUGS.—Section 512(d) (21

4 U.S.C. 360b(d)) is amended by inserting before paragraph

5 (4) (as added by subsection (a)) the following new para6 graph:

7 ‘‘(3) In a case in which a new animal drug contains

8 more than 1 active ingredient, or the labeling of the drug

9 prescribes, recommends, or suggests use of the drug in

10 combination with another animal drug, in evaluating the

11 safety and effectiveness of the ingredients or the combina12 tion, respectively, the Secretary shall consider—

13 ‘‘(A) whether any of the active ingredients or

14 any of the drugs in the combination, respectively, al15 ters the safe concentration of another of the active

16 ingredients or drugs in the combination, respectively,

17 or interferes with the methods of analysis for an18 other of the active ingredients or drugs in the com19 bination, respectively;

20 ‘‘(B) whether each of the active ingredients or

21 drugs in the combination, respectively, that is

22 claimed to have the same intended effect has been

23 shown to contribute to the effect; and

24 ‘‘(C) to the extent that subparagraph (B) does

25 not apply, whether each of the active ingredients or
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1 drugs in the combination has an identified target

2 population for which dosing with the active ingredi3 ents or combination represents appropriate concur4 rent therapy.’’.

5 (e) WITHDRAWAL OF APPROVAL.—Section

6 512(e)(1)(C) (21 U.S.C. 360b(e)(1)(C)) is amended by in7 serting after ‘‘substantial evidence’’ the following: ‘‘(as de8 fined in subsection (d)(4))’’.

9 (f) IMPLEMENTATION.—

10 (1) IN GENERAL.—Not later than 6 months

11 after the date of enactment of this Act, the Sec12 retary shall issue proposed regulations implementing

13 the amendments made by this section. Not later

14 than 18 months after the date of enactment of this

15 Act, the Secretary shall issue final regulations imple16 menting the amendments.

17 (2) CONTENTS.—In issuing regulations imple18 menting the amendments made by this section, and

19 in taking an action to review an application for ap20 proval of a new animal drug under section 512 of

21 the Federal Food, Drug, and Cosmetic Act (21

22 U.S.C. 360b), or a request for an investigational ex23 emption for a new animal drug under subsection (j)

24 of such section, that is pending or has been submit-
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1 ted prior to the effective date of the regulations, the

2 Secretary shall—

3 (A) further define the term ‘‘substantial

4 evidence’’, as defined in subsection (d)(4) of

5 such section, in a manner that encourages the

6 submission of applications for production drugs

7 that conserve food resources, of applications for

8 veterinary prescription drugs whose use is de9 signed to rely on the experience and training of

10 practitioners in establishing effective doses for

11 such drugs, and of supplemental applications,

12 including applications seeking approval for uses

13 of animal drugs in minor species, for minor

14 uses of such drugs, and for permitted unlabeled

15 uses of such drugs;

16 (B) take into account the proposals con17 tained in the citizen petition (FDA Docket No.

18 91P–0434/CP) jointly submitted by the Amer19 ican Veterinary Medical Association and the

20 Animal Health Institute, dated October 21,

21 1991;

22 (C)(i) provide for a conference prior to the

23 submission of an application for approval of a

24 new animal drug under such section, and prior

25 to the submission of a request for an investiga-
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1 tional exemption under subsection (j) of such

2 section, to make a decision establishing a sub3 mission or an investigational requirement

4 (which decision shall bind the Secretary and the

5 applicant or requester unless the Secretary by

6 order determines that a documented scientific

7 requirement essential to the determination of

8 safety or effectiveness of the animal drug in9 volved has appeared after the conference); and

10 (ii) not later than 10 days after each such

11 conference, by written order, provide a scientific

12 justification specific to the animal drug and in13 tended uses under consideration for requiring

14 studies of types other than the types of studies

15 specified in subsection (d)(4) of such section, as

16 being essential to provide substantial evidence

17 of effectiveness for the intended uses of the

18 drug;

19 (D) define the kinds of evidence that an

20 applicant may use to establish the contribution

21 of each active ingredient in a new animal drug,

22 or new animal drug used in combination with

23 another animal drug, for the same intended ef24 fect, as described in subsection (d)(3)(B) of

25 such section; and
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1 (E) define the kinds of evidence that an

2 applicant may use to establish the appropriate3 ness of concurrent therapy represented by each

4 active ingredient in a new animal drug, or new

5 animal drug used in combination with another

6 animal drug, for the same intended effect, as

7 described in subsection (d)(3)(C) of such sec8 tion.

9 (g) REPORT TO CONGRESS.—The Secretary shall

10 study any efficiencies in the new animal drug approval

11 process that are caused by the amendments made by this

12 Act. Not later than 24 months after the date of enactment

13 of this Act, the Secretary shall submit to the appropriate

14 committees of Congress a report containing the results of

15 the study.

16 SEC. 4. TIMEFRAME FOR APPROVAL.

17 The first sentence of section 512(c)(1) (21 U.S.C.

18 360b(c)(1)) is amended by striking ‘‘one hundred and

19 eighty’’ and inserting ‘‘90’’.

20 SEC. 5. DISPUTE RESOLUTION.

21 Section 512(c)(1) (21 U.S.C. 360b(c)(1)) is

22 amended—

23 (1) in the first sentence—

24 (A) by redesignating subparagraphs (A)

25 and (B) as clauses (i) and (ii), respectively; and
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1 (B) by inserting ‘‘(A)’’ after ‘‘(1)’’;

2 (2) in the second sentence, by striking ‘‘If’’ and

3 inserting the following:

4 ‘‘(C) If’’; and

5 (3) by inserting after subparagraph (A) (as des6 ignated by paragraph (1)(B)) the following new sub7 paragraph:

8 ‘‘(B)(i) At any time prior to the issuance of the notice

9 under subparagraph (A)(ii), the applicant may, in writing,

10 notify the Secretary that an impasse exists in the review

11 of the application with respect to a specifically identified

12 issue that is preventing the issuance of an order under

13 subparagraph (A)(i).

14 ‘‘(ii) On receipt of the notification from the applicant,

15 the Secretary shall refer the disputed issue—

16 ‘‘(I) to an existing (as of the date of the notifi17 cation) advisory committee having expertise related

18 to the issue;

19 ‘‘(II) to an advisory committee convened in ac20 cordance with the procedure in section 721(b)(5)(D);

21 or

22 ‘‘(III) to a special Government employee, as de23 fined in section 202(a) of title 18, United States

24 Code, who is acceptable to the Secretary and the ap25 plicant.
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1 ‘‘(iii) The applicant and representatives of the Sec2 retary may consult with the committee or employee on the

3 matter referred. The committee or employee shall submit

4 to the Secretary and the applicant a report containing rec5 ommendations (including a statement of reasons for the

6 recommendations) regarding the matter not later than 60

7 days after the date of the referral, or not later than 90

8 days after the date of the referral if the committee or em9 ployee considers the additional 30 days to be necessary.

10 Not later than 30 days after the date of receiving the re11 port, the Secretary shall, in writing, confirm or modify the

12 recommendations received, providing reasons and ref13 erence to data before the committee or employee for any

14 modification.’’.

15 SEC. 6. LIMITATION ON RESIDUES.

16 Section 512(d)(1)(F) (21 U.S.C. 360b(d)(1)(F)) is

17 amended to read as follows:

18 ‘‘(F) on the basis of information submitted to

19 the Secretary as part of the application or any other

20 information before the Secretary with respect to

21 such drug, any use prescribed, recommended, or

22 suggested in labeling proposed for such drug will re23 sult in a residue of such drug in excess of a toler24 ance found by the Secretary to be safe for such

25 drug;’’.
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1 SEC. 7. EXPORT OF NEW ANIMAL DRUGS.

2 (a) EXPORT IN ACCORDANCE WITH FOREIGN

3 LAW.—Section 801(e)(1) (21 U.S.C. 381(e)(1)) is amend4 ed by striking the last sentence.

5 (b) EXPORTS OF CERTAIN UNAPPROVED PROD6 UCTS.—Section 802 (21 U.S.C. 382) is amended—

7 (1) in subsection (a)(1)(A), by striking ‘‘or sec8 tion 512’’;

9 (2) in subsection (b)(1)—

10 (A) in subparagraph (A)—

11 (i) by striking the comma at the end

12 of clause (ii) and inserting ‘‘, or’’;

13 (ii) by striking ‘‘or’’ at the end of

14 clause (iii); and

15 (iii) by striking clause (iv); and

16 (B) in subparagraph (C)—

17 (i) by striking ‘‘or 512,’’ and inserting

18 a comma; and

19 (ii) by striking ‘‘or 512(d) or’’ and in20 serting ‘‘of this Act or section’’;

21 (3) in subsection (c)(1)(C), by striking ‘‘505 or

22 512,’’ and inserting ‘‘505,’’; and

23 (4) in subsection (d)—

24 (A) in paragraph (3), by striking ‘‘505 or

25 512,’’ and inserting ‘‘505,’’; and

26 (B) in paragraph (4)—
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1 (i) by striking ‘‘or 512(j)’’; and

2 (ii) by striking ‘‘505 or 512,’’ and in3 serting ‘‘505,’’.

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