FILE h2508.enr
--H.R.2508--
H.R.2508
One Hundred Fourth Congress
of the
United States of America
AT THE SECOND SESSION
Begun and held at the City of Washington on Wednesday,
the third day of January, one thousand nine hundred and ninety-six
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.
[Italic] Be it enacted by the Senate and House of
Representatives of the United States of America in Congress
assembled, [Italic]
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'.
(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 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 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- 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) 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
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. (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
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,'.
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 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.
`(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
`(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) 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.
Speaker of the House of Representatives.
Vice President of the United States and
President of the Senate.