[104th Congress Public Law 250]
[From the U.S. Government Printing Office]
<DOC>
[DOCID: f:publ250.104]
[[Page 110 STAT. 3151]]
Public Law 104-250
104th Congress
An Act
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. <<NOTE: Oct. 9, 1996 - [H.R. 2508]>>
Be it enacted by the Senate and House of Representatives of the
United States of America in Congress assembled, <<NOTE: Animal Drug
Availability Act of 1996. 21 USC 301 note.>>
SECTION 1. SHORT TITLE; REFERENCE.
(a) Short Title.--This Act may be cited as the ``Animal Drug
Availability Act of 1996''.
(b) Reference.--Whenever in this Act an amendment or repeal is
expressed in terms of an amendment to, or repeal of, a section or other
provision, the reference shall be considered to be made to a section or
other provision of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
321 et seq.).
SEC. 2. EVIDENCE OF EFFECTIVENESS.
(a) Original Applications.--Paragraph (3) of section 512(d) (21
U.S.C. 360b(d)) is amended to read as follows:
``(3) As used in this section, the term `substantial evidence' means
evidence consisting of one or more adequate and well
controlled investigations, such as--
``(A) a study in a target species;
``(B) a study in laboratory animals;
``(C) any field investigation that may be required under
this section and that meets the requirements of subsection
(b)(3) if a presubmission conference is requested by the
applicant;
``(D) a bioequivalence study; or
``(E) an in vitro study;
by experts qualified by scientific training and experience to evaluate
the effectiveness of the drug involved, on the basis of which it could
fairly and reasonably be concluded by such experts that the drug will
have the effect it purports or is represented to have under the
conditions of use prescribed, recommended, or suggested in the labeling
or proposed labeling thereof.''.
(b) Conforming Amendments.--
(1) Clauses (ii) and (iii) of section 512(c)(2)(F) (21
U.S.C. 360b(c)(2)(F)) are each amended--
(A) by striking ``reports of new clinical or field
investigations (other than bioequivalence or residue
studies) and,'' and inserting ``substantial evidence of
the effectiveness of the drug involved, any studies of
animal safety, or,''; and
(B) by striking ``essential to'' and inserting
``required for''.
[[Page 110 STAT. 3152]]
(2) Section 512(c)(2)(F)(v) (21 U.S.C. 360b(c)(2)(F)(v)) is
amended--
(A) by striking ``subparagraph (B)(iv)'' each place
it appears and inserting ``clause (iv)'';
(B) by striking ``reports of clinical or field
investigations'' and inserting ``substantial evidence of
the
effectiveness of the drug involved, any studies of
animal safety,''; and
(C) by striking ``essential to'' and inserting
``required for''.
(c) Combination Drugs.--Section 512(d) (21 U.S.C. 360b(d)), as
amended by subsection (a) is amended by adding at the end the following:
``(4) In a case in which an animal drug contains more than one
active ingredient, or the labeling of the drug prescribes, recommends,
or suggests use of the drug in combination with one or more other animal
drugs, and the active ingredients or drugs intended for use in the
combination have previously been separately approved for particular uses
and conditions of use for which they are intended for use in the
combination--
``(A) the Secretary shall not issue an order under paragraph
(1)(A), (1)(B), or (1)(D) refusing to approve the application
for such combination on human food safety grounds unless the
Secretary finds that the application fails to establish that--
``(i) none of the active ingredients or drugs
intended for use in the combination, respectively, at
the longest withdrawal time of any of the active
ingredients or drugs in the combination, respectively,
exceeds its established tolerance; or
``(ii) none of the active ingredients or drugs in
the combination interferes with the methods of analysis
for another of the active ingredients or drugs in the
combination, respectively;
``(B) the Secretary shall not issue an order under paragraph
(1)(A), (1)(B), or (1)(D) refusing to approve the application
for such combination on target animal safety grounds unless the
Secretary finds that--
``(i)(I) there is a substantiated scientific issue,
specific to one or more of the active ingredients or
animal drugs in the combination, that cannot adequately
be evaluated based on information contained in the
application for the combination (including any
investigations, studies, or tests for which the
applicant has a right of reference or use from the
person by or for whom the investigations, studies, or
tests were conducted); or
``(II) there is a scientific issue raised by target
animal observations contained in studies submitted to
the
Secretary as part of the application; and
``(ii) based on the Secretary's evaluation of the
information contained in the application with respect to
the issues identified in clauses (i) (I) and (II),
paragraph (1) (A), (B), or (D) apply;
``(C) except in the case of a combination that contains a
nontopical antibacterial ingredient or animal drug, the
Secretary shall not issue an order under paragraph (1)(E)
refusing to approve an application for a combination animal drug
intended for use other than in animal feed or drinking water
[[Page 110 STAT. 3153]]
unless the Secretary finds that the application fails to
demonstrate that--
``(i) there is substantial evidence that any active
ingredient or animal drug intended only for the same use
as another active ingredient or animal drug in the
combination makes a contribution to labeled
effectiveness;
``(ii) each active ingredient or animal drug
intended for at least one use that is different from all
other active ingredients or animal drugs used in the
combination
provides appropriate concurrent use for the intended
target population; or
``(iii) where based on scientific information the
Secretary has reason to believe the active ingredients
or animal drugs may be physically incompatible or have
disparate dosing regimens, such active ingredients or
animal drugs are physically compatible or do not have
disparate dosing regimens; and
``(D) the Secretary shall not issue an order under paragraph
(1)(E) refusing to approve an application for a combination
animal drug intended for use in animal feed or drinking water
unless the Secretary finds that the application fails to
demonstrate that--
``(i) there is substantial evidence that any active
ingredient or animal drug intended only for the same use
as another active ingredient or animal drug in the
combination makes a contribution to the labeled
effectiveness;
``(ii) each of the active ingredients or animal
drugs intended for at least one use that is different
from all other active ingredients or animal drugs used
in the combination provides appropriate concurrent use
for the intended target population;
``(iii) where a combination contains more than one
nontopical antibacterial ingredient or animal drug,
there is substantial evidence that each of the
nontopical antibacterial ingredients or animal drugs
makes a contribution to the labeled effectiveness; or
``(iv) where based on scientific information the
Secretary has reason to believe the active ingredients
or animal drugs intended for use in drinking water may
be physically incompatible, such active ingredients or
animal drugs intended for use in drinking water are
physically compatible.''.
(d) Presubmission Conference.--Section 512(b) (21 U.S.C. 360b(b)) is
amended by adding at the end the following:
``(3) Any person intending to file an application under paragraph
(1) or a request for an investigational exemption under subsection (j)
shall be entitled to one or more conferences prior to such submission to
reach an agreement acceptable to the Secretary establishing a submission
or an investigational requirement, which may include a requirement for a
field investigation. A decision establishing a submission or an
investigational requirement shall bind the Secretary and the applicant
or requestor unless (A) the Secretary and the applicant or requestor
mutually agree to modify the requirement, or (B) the Secretary by
written order determines that a substantiated scientific requirement
essential to the determination of safety or effectiveness of the animal
drug involved has appeared after the conference. No later than 25
calendar days after each
[[Page 110 STAT. 3154]]
such conference, the Secretary shall provide a written order setting
forth a scientific justification specific to the animal drug and
intended uses under consideration if the agreement referred to in the
first sentence requires more than one field investigation as being
essential to provide substantial evidence of effectiveness for the
intended uses of the drug. Nothing in this paragraph shall be construed
as compelling the Secretary to require a field investigation.''.
(e) Implementation.--
(1) In general.-- <<NOTE: Regulations. Effective date. 21
USC 360b note.>> Not later than 6 months after the date of
enactment of this Act, the Secretary of Health and Human
Services shall issue proposed regulations implementing the
amendments made by this Act as described in paragraph (2)(A) of
this subsection, and not later than 18 months after the date of
enactment of this Act, the Secretary shall issue final
regulations implementing such amendments. Not later than 12
months after the date of enactment of this Act, the Secretary
shall issue proposed regulations implementing the other
amendments made by this Act as described in paragraphs (2)(B)
and (2)(C) of this subsection, and not later than 24 months
after the date of enactment of this Act, the Secretary shall
issue final regulations implementing such amendments.
(2) Contents.--In issuing regulations implementing the
amendments made by this Act, and in taking an action to review
an application for approval of a new animal drug under section
512 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
360b), or a request for an investigational exemption for a new
animal drug under subsection (j) of such section, that is
pending or has been submitted prior to the effective date of the
regulations, the Secretary shall--
(A) further define the term ``adequate and well
controlled'', as used in subsection (d)(3) of section
512 of such Act, to require that field investigations be
designed and conducted in a scientifically sound manner,
taking into account practical conditions in the field
and differences between field conditions and laboratory
conditions;
(B) further define the term ``substantial
evidence'', as defined in subsection (d)(3) of such
section, in a manner that encourages the submission of
applications and supplemental applications; and
(C) take into account the proposals contained in the
citizen petition (FDA Docket No. 91P-0434/CP) jointly
submitted by the American Veterinary Medical Association
and the Animal Health Institute, dated October 21, 1991.
Until the regulations required by subparagraph (A) are issued,
nothing in the regulations published at 21 C.F.R. 514.111(a)(5)
(April 1, 1996) shall be construed to compel the Secretary of
Health and Human Services to require a field investigation under
section 512(d)(1)(E) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 360b(d)(1)(E)) or to apply any of its
provisions in a manner inconsistent with the considerations for
scientifically sound field investigations set forth in
subparagraph (A).
(f) <<NOTE: 21 USC 360b note.>> Minor Species and Uses.--The
Secretary of Health and Human Services shall consider legislative and
regulatory options for facilitating the approval under section 512 of
the Federal Food, Drug, and Cosmetic Act of animal drugs intended for
minor species
[[Page 110 STAT. 3155]]
and for minor uses and, within 18 months after the date of enactment of
this Act, announce proposals for legislative or regulatory change to the
approval process under such section for animal drugs intended for use in
minor species or for minor uses.
SEC. 3. LIMITATION ON RESIDUES.
Section 512(d)(1)(F) (21 U.S.C. 360b(d)(1)(F)) is amended to read as
follows:
``(F) upon the basis of information submitted to the
Secretary as part of the application or any other information
before the Secretary with respect to such drug, any use
prescribed, recommended, or suggested in labeling proposed for
such drug will result in a residue of such drug in excess of a
tolerance found by the Secretary to be safe for such drug;''.
SEC. 4. IMPORT TOLERANCES.
Section 512(a) (21 U.S.C. 360b(a)) is amended by adding the
following new paragraph at the end:
``(6) For purposes of section 402(a)(2)(D), a use or intended use of
a new animal drug shall not be deemed unsafe under this section if the
Secretary establishes a tolerance for such drug and any edible portion
of any animal imported into the United States does not contain residues
exceeding such tolerance. In establishing such tolerance, the Secretary
shall rely on data sufficient to
demonstrate that a proposed tolerance is safe based on similar food
safety criteria used by the Secretary to establish tolerances for
applications for new animal drugs filed under subsection (b)(1). The
Secretary may consider and rely on data submitted by the drug
manufacturer, including data submitted to appropriate regulatory
authorities in any country where the new animal drug is lawfully used or
data available from a relevant international organization, to the extent
such data are not inconsistent with the criteria used by the Secretary
to establish a tolerance for applications for new animal drugs filed
under subsection (b)(1). For purposes of this paragraph, `relevant
international organization' means the Codex Alimenterius Commission or
other international organization deemed appropriate by the Secretary.
The Secretary may, under procedures specified by regulation, revoke a
tolerance established under this paragraph if information demonstrates
that the use of the new animal drug under actual use conditions results
in food being imported into the United States with residues exceeding
the tolerance or if scientific evidence shows the tolerance to be
unsafe.''.
SEC. 5. VETERINARY FEED DIRECTIVES.
(a) Section 503.--Section 503(f)(1)(A) (21 U.S.C. 353(f)(1)(A)) is
amended by inserting after ``other than man'' the following: ``, other
than a veterinary feed directive drug intended for use in animal feed or
an animal feed bearing or containing a veterinary feed directive
drug,''.
(b) Section 504.--The Federal Food, Drug, and Cosmetic Act is
amended by inserting after section 503 the following:
``veterinary feed directive drugs
``Sec. 504. <<NOTE: 21 USC 354.>> (a)(1) A drug intended for use in
or on animal feed which is limited by an approved application filed
pursuant to section 512(b) to use under the professional supervision of
a
[[Page 110 STAT. 3156]]
licensed veterinarian is a veterinary feed directive drug. Any animal
feed bearing or containing a veterinary feed directive drug shall be fed
to animals only by or upon a lawful veterinary feed directive issued by
a licensed veterinarian in the course of the veterinarian's professional
practice. When labeled, distributed, held, and used in accordance with
this section, a veterinary feed directive drug and any animal feed
bearing or containing a veterinary feed directive drug shall be exempt
from section 502(f).
``(2) A veterinary feed directive is lawful if it--
``(A) contains such information as the Secretary may by
general regulation or by order require; and
``(B) is in compliance with the conditions and indications
for use of the drug set forth in the notice published pursuant
to section 512(i).
``(3)(A) Any persons involved in the distribution or use of animal
feed bearing or containing a veterinary feed directive drug and the
licensed veterinarian issuing the veterinary feed directive shall
maintain a copy of the veterinary feed directive applicable to each such
feed, except in the case of a person distributing such feed to another
person for further distribution. Such person distributing the feed shall
maintain a written acknowledgment from the person to whom the feed is
shipped stating that that person shall not ship or move such feed to an
animal production facility without a veterinary feed directive or ship
such feed to another person for further distribution unless that person
has provided the same written acknowledgment to its immediate supplier.
``(B) Every person required under subparagraph (A) to maintain
records, and every person in charge or custody thereof, shall, upon
request of an officer or employee designated by the Secretary, permit
such officer or employee at all reasonable times to have access to and
copy and verify such records.
``(C) Any person who distributes animal feed bearing or containing a
veterinary feed directive drug shall upon first engaging in such
distribution notify the Secretary of that person's name and place of
business. The failure to provide such notification shall be deemed to be
an act which results in the drug being misbranded.
``(b) A veterinary feed directive drug and any feed bearing or
containing a veterinary feed directive drug shall be deemed to be
misbranded if their labeling fails to bear such cautionary statement and
such other information as the Secretary may by general regulation or by
order prescribe, or their advertising fails to conform to the conditions
and indications for use published pursuant to section 512(i) or fails to
contain the general cautionary statement prescribed by the Secretary.
``(c) Neither a drug subject to this section, nor animal feed
bearing or containing such a drug, shall be deemed to be a prescription
article under any Federal or State law.''.
(c) Conforming Amendment.--Section 512 (21 U.S.C. 360b) is amended
in subsection (i) by inserting after ``(including special labeling
requirements'' the following: ``and any requirement that an animal feed
bearing or containing the new animal drug be limited to use under the
professional supervision of a licensed veterinarian''.
(d) Section 301(e).--Section 301(e) (21 U.S.C. 331(e)) is
amended by inserting after ``by section 412'' the following: ``, 504,'';
and by inserting after ``under section 412,'' the following: ``504,''.
[[Page 110 STAT. 3157]]
SEC. 6. FEED MILL LICENSES.
(a) Section 512(a).--Paragraphs (1) and (2) of section 512(a) (21
U.S.C. 360b(a)) are amended to read as follows:
``(a)(1) A new animal drug shall, with respect to any particular use
or intended use of such drug, be deemed unsafe for the purposes of
section 501(a)(5) and section 402(a)(2)(D) unless --
``(A) there is in effect an approval of an application filed
pursuant to subsection (b) with respect to such use or intended
use of such drug, and
``(B) such drug, its labeling, and such use conform to such
approved application.
A new animal drug shall also be deemed unsafe for such purposes in the
event of removal from the establishment of a manufacturer, packer, or
distributor of such drug for use in the manufacture of animal feed in
any State unless at the time of such removal such manufacturer, packer,
or distributor has an unrevoked written statement from the consignee of
such drug, or notice from the Secretary, to the effect that, with
respect to the use of such drug in animal feed, such consignee (i) holds
a license issued under subsection (m) and has in its possession current
approved labeling for such drug in animal feed; or (ii) will, if the
consignee is not a user of the drug, ship such drug only to a holder of
a license issued under subsection (m).
``(2) An animal feed bearing or containing a new animal drug shall,
with respect to any particular use or intended use of such animal feed
be deemed unsafe for the purposes of section 501(a)(6) unless--
``(A) there is in effect an approval of an application filed
pursuant to subsection (b) with respect to such drug, as used in
such animal feed,
``(B) such animal feed is manufactured at a site for which
there is in effect a license issued pursuant to subsection
(m)(1) to manufacture such animal feed, and
``(C) such animal feed and its labeling, distribution,
holding, and use conform to the conditions and indications of
use
published pursuant to subsection (i) .''.
(b) Section 512(m).--Section 512(m) (21 U.S.C. 360b(m)) is amended
to read as follows:
``(m)(1) Any person may file with the Secretary an application for a
license to manufacture animal feeds bearing or containing new animal
drugs. Such person shall submit to the Secretary as part of the
application (A) a full statement of the business name and address of the
specific facility at which the manufacturing is to take place and the
facility's registration number, (B) the name and signature of the
responsible individual or individuals for that facility, (C) a
certification that the animal feeds bearing or containing new animal
drugs are manufactured and labeled in accordance with the applicable
regulations published pursuant to subsection (i), and (D) a
certification that the methods used in, and the facilities and controls
used for, manufacturing, processing, packaging, and holding such animal
feeds are in conformity with current good manufacturing practice as
described in section 501(a)(2)(B).
``(2) Within 90 days after the filing of an application pursuant to
paragraph (1), or such additional period as may be agreed upon by the
Secretary and the applicant, the Secretary shall (A) issue an order
approving the application if the Secretary then finds
[[Page 110 STAT. 3158]]
that none of the grounds for denying approval specified in paragraph (3)
applies, or (B) give the applicant notice of an opportunity for a
hearing before the Secretary under paragraph (3) on the question whether
such application is approvable. The procedure governing such a hearing
shall be the procedure set forth in the last two sentences of subsection
(c)(1).
``(3) If the Secretary, after due notice to the applicant in
accordance with paragraph (2) and giving the applicant an opportunity
for a hearing in accordance with such paragraph, finds, on the basis of
information submitted to the Secretary as part of the application, on
the basis of a preapproval inspection, or on the basis of any other
information before the Secretary--
``(A) that the application is incomplete, false, or
misleading in any particular;
``(B) that the methods used in, and the facilities and
controls used for, the manufacture, processing, and packing of
such animal feed are inadequate to preserve the identity,
strength, quality, and purity of the new animal drug therein; or
``(C) that the facility manufactures animal feeds bearing or
containing new animal drugs in a manner that does not accord
with the specifications for manufacture or labels animal feeds
bearing or containing new animal drugs in a manner that does not
accord with the conditions or indications of use that are
published pursuant to subsection (i),
the Secretary shall issue an order refusing to approve the application.
If, after such notice and opportunity for hearing, the Secretary finds
that subparagraphs (A) through (C) do not apply, the Secretary shall
issue an order approving the application. An order under this subsection
approving an application for a license to manufacture animal feeds
bearing or containing new animal drugs shall permit a facility to
manufacture only those animal feeds bearing or containing new animal
drugs for which there are in effect regulations pursuant to subsection
(i) relating to the use of such drugs in or on such animal feed.
``(4)(A) The Secretary shall, after due notice and opportunity for
hearing to the applicant, revoke a license to manufacture animal feeds
bearing or containing new animal drugs under this subsection if the
Secretary finds--
``(i) that the application for such license contains any
untrue statement of a material fact; or
``(ii) that the applicant has made changes that would cause
the application to contain any untrue statements of material
fact or that would affect the safety or effectiveness of the
animal feeds manufactured at the facility unless the applicant
has supplemented the application by filing with the Secretary
adequate information respecting all such changes and unless
there is in effect an approval of the supplemental application.
If the Secretary (or in the Secretary's absence the officer acting as
the Secretary) finds that there is an imminent hazard to the health of
humans or of the animals for which such animal feed is intended, the
Secretary may suspend the license immediately, and give the applicant
prompt notice of the action and afford the applicant the opportunity for
an expedited hearing under this subsection; but the authority conferred
by this sentence shall not be delegated.
[[Page 110 STAT. 3159]]
``(B) The Secretary may also, after due notice and opportunity for
hearing to the applicant, revoke a license to manufacture animal feed
under this subsection if the Secretary finds--
``(i) that the applicant has failed to establish a system
for maintaining required records, or has repeatedly or
deliberately failed to maintain such records or to make required
reports in accordance with a regulation or order under paragraph
(5)(A) of this subsection or section 504(a)(3)(A), or the
applicant has refused to permit access to, or copying or
verification of, such records as required by subparagraph (B) of
such paragraph or section 504(a)(3)(B);
``(ii) that on the basis of new information before the
Secretary, evaluated together with the evidence before the
Secretary when such license was issued, the methods used in, or
the facilities and controls used for, the manufacture,
processing, packing, and holding of such animal feed are
inadequate to assure and preserve the identity, strength,
quality, and purity of the new animal drug therein, and were not
made adequate within a reasonable time after receipt of written
notice from the Secretary, specifying the matter complained of;
``(iii) that on the basis of new information before the
Secretary, evaluated together with the evidence before the
Secretary when such license was issued, the labeling of any
animal feeds, based on a fair evaluation of all material facts,
is false or misleading in any particular and was not corrected
within a reasonable time after receipt of written notice from
the Secretary specifying the matter complained of; or
``(iv) that on the basis of new information before the
Secretary, evaluated together with the evidence before the
Secretary when such license was issued, the facility has
manufactured, processed, packed, or held animal feed bearing or
containing a new animal drug adulterated under section 501(a)(6)
and the facility did not discontinue the manufacture,
processing, packing, or holding of such animal feed within a
reasonable time after receipt of written notice from the
Secretary specifying the matter complained of.
``(C) The Secretary may also revoke a license to manufacture animal
feeds under this subsection if an applicant gives notice to the
Secretary of intention to discontinue the manufacture of all animal feed
covered under this subsection and waives an opportunity for a hearing on
the matter.
``(D) Any order under this paragraph shall state the findings upon
which it is based.
``(5) When a license to manufacture animal feeds bearing or
containing new animal drugs has been issued--
``(A) the applicant shall establish and maintain such
records, and make such reports to the Secretary, or (at the
option of the Secretary) to the appropriate person or persons
holding an approved application filed under subsection (b), as
the Secretary may by general regulation, or by order with
respect to such application, prescribe on the basis of a finding
that such records and reports are necessary in order to enable
the Secretary to determine, or facilitate a determination,
whether there is or may be ground for invoking subsection (e) or
paragraph (4); and
[[Page 110 STAT. 3160]]
``(B) every person required under this subsection to
maintain records, and every person in charge or custody thereof,
shall, upon request of an officer or employee designated by the
Secretary, permit such officer or employee at all reasonable
times to have access to and copy and verify such records.
``(6) To the extent consistent with the public health, the
Secretary may promulgate regulations for exempting from the operation of
this subsection facilities that manufacture, process, pack, or hold
animal feeds bearing or containing new animal drugs.''.
(c) <<NOTE: 21 USC 360b note.>> Transitional Provision.--A person
engaged in the manufacture of animal feeds bearing or containing new
animal drugs who holds at least one approved medicated feed application
for an animal feed bearing or containing new animal drugs, the
manufacture of which was not otherwise exempt from the requirement for
an approved medicated feed application on the date of the enactment of
this Act, shall be deemed to hold a license for the manufacturing site
identified in the approved medicated feed application. The revocation of
license provisions of section 512(m)(4) of the Federal Food, Drug, and
Cosmetic Act, as amended by this Act, shall apply to such licenses. Such
license shall expire within 18 months from the date of enactment of this
Act unless the person submits to the Secretary a completed license
application for the manufacturing site accompanied by a copy of an
approved medicated feed application for such site, which license
application shall be deemed to be approved upon receipt by the
Secretary.
Approved October 9, 1996.
LEGISLATIVE HISTORY--H.R. 2508 (S. 773):
---------------------------------------------------------------------------
HOUSE REPORTS: No. 104-823 (Comm. on Commerce).
CONGRESSIONAL RECORD, Vol. 142 (1996):
Sept. 24, considered and passed House. S. 773 considered and
passed Senate.
Sept. 25, H.R. 2508 considered and passed Senate.
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