[House Report 104-823]
[From the U.S. Government Publishing Office]
104th Congress Report
HOUSE OF REPRESENTATIVES
2d Session 104-823
_______________________________________________________________________
ANIMAL DRUG AVAILABILITY ACT OF 1996
_______
September 24, 1996.--Committed to the Committee of the Whole House on
the State of the Union and ordered to be printed
_______
Mr. Bliley, from the Committee on Commerce, submitted the following
R E P O R T
[To accompany H.R. 2508]
[Including cost estimate of the Congressional Budget Office]
The Committee on Commerce, to whom was referred the bill
(H.R. 2508) 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, having considered
the same, report favorably thereon with an amendment and
recommend that the bill as amended do pass.
CONTENTS
Page
The Amendment.................................................... 1
Purpose and Summary.............................................. 8
Background and Need for Legislation.............................. 9
Hearings......................................................... 9
Committee Consideration.......................................... 9
Rollcall Votes................................................... 10
Committee Oversight Findings..................................... 10
Committee on Government Reform and Oversight..................... 10
New Budget Authority and Tax Expenditures........................ 10
Committee Cost Estimate.......................................... 10
Congressional Budget Office Estimate............................. 11
Inflationary Impact Statement.................................... 13
Advisory Committee Statement..................................... 13
Section-by-Section Analysis of the Legislation................... 13
Changes in Existing Law Made by the Bill, as Reported............ 18
Amendment
The amendment is as follows:
Strike out all after the enacting clause and insert in lieu
thereof the following:
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 Alimentarius 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.
Purpose and Summary
H.R. 2508, as reported, will facilitate the approval and
marketing of new animal drugs and medicated feeds. It builds
needed flexibility into the Food and Drug Administration (FDA)
animal drug review processes to enable more efficient approval
and more expeditious marketing of safe and effective animal
drugs. The legislation accomplishes this without decreasing
FDA's existing authority to ensure that animal drug products
are safe for the animals that use them and for the humans who
consume animal food products.
By redefining ``substantial evidence,'' H.R. 2508 provides
FDA with greater flexibility to determine what types of
studies, including field investigations, are necessary and
appropriate for demonstrating the effectiveness of any specific
animal drug product. The bill requires FDA to issue regulations
defining substantial evidence and the parameters of adequate
and well-controlled field investigations. Such regulations must
take into account the practical conditions that exist in the
field. The bill also requires FDA to hold a presubmission
conference at the request of a sponsor submitting a new animal
drug application or a request for an investigational exemption.
H.R. 2508 creates a streamlined process for the approval of
combination animal drug products when the individual active
ingredients or animal drugs used in combination have been
approved previously for the particular uses and conditions of
use for which they are intended for use in combination. It also
authorizes FDA to establish a scientifically-based safe
tolerance for new animal drugs.
The bill creates a new class of animal drugs, veterinary
feed directive drugs, intended for use in feed under the
professional supervision of a licensed veterinarian. The bill
eliminates the requirement for feed mills to submit individual
medicated feed applications to manufacture certain medicated
feeds and allows any medicated feed containing an approved new
animal drug to be manufactured at a licensed facility. Finally,
the bill authorizes FDA to establish import tolerances for new
animal drugs not approved in the United States.
The provisions of the bill are consistent with the
initiatives of the Committee on Commerce and the
Administration's Reinventing Government proposals to streamline
regulatory activities of the FDA.
Background and Need for Legislation
The animal health industry is vital to protecting both
humans and animals. Not only does it keep farm animals healthy
and protect the food supply, it also safeguards our pets,
including some 130 million dogs and cats in the United States.
The animal health products industry in the U.S. has sales of $3
billion a year; 90 percent of animal drugs have individual
sales of less than $1 million a year. The animal drug industry
is one-twentieth the size of the human pharmaceutical industry.
The number of new products approved by the FDA for use in
livestock, poultry and pets has dwindled in past years and
those who seek to keep animals healthy have an increasingly
limited arsenal available for this purpose. Since 1986 FDA has
approved only 13 new chemical entities for use in food-
producing animals. The swine and turkey industries have had
only one new approval in the past decade. This is despite the
fact that research and development expenditures by industry now
total more than $420 million a year. Manufacturers spend an
average of $22 million and 11 years to develop a new animal
drug for food animals.
While the law requires a decision on a new animal drug
application within 6 months, the process has averaged as high
as almost 5 years. Industry reports that these long review
times have encouraged a number of pharmaceutical companies to
divest themselves of animal drug development capability.
Congress, the Administration, the animal drug industry,
veterinarians, and animal producer groups all have recognized
the need to streamline the animal drug review process. Thus,
representatives of the Administration and affected industries
worked successfully with the Committee on Commerce to develop
the reforms contained in H.R. 2508, as reported by the
Committee. To underscore the success of this negotiation, the
Secretary of Health and Human Services wrote a letter to the
Committee Chairman on September 19, 1996, in support of H.R.
2508, as reported.
Hearings
On February 27, 1996, the Subcommittee on Health and
Environment held a hearing on The Need for FDA Reform.
Testimony relating to animal drugs was received from the
following witnesses: Dr. Kelly F. Lechtenberg, Midwest
Veterinary Service, Inc.; Mr. Alexander F. Mathews, President
and Chief Executive Officer, Animal Health Institute; and Mr.
Brendan P. Fox, President, Elanco Animal Health, on behalf of
the Coalition for Animal Health. On May 1 and May 2, 1996, the
Subcommittee held hearings on bills relating to FDA reform
including H.R. 3200, Title II of which contained legislative
language substantially similar to H.R. 2508. Testimony
regarding these provisions was presented by FDA Commissioner
David A. Kessler and by Mr. Larry Fanella, RoccoTurkeys, Inc.,
on behalf of the Coalition for Animal Health.
Committee Consideration
On September 19, 1996, the Committee on Commerce met in
open markup session and ordered H.R. 2508, the Animal Drug
Availability Act of 1996, reported to the House, as amended, by
a voice vote, a quorum being present.
Rollcall Votes
Clause 2(l)(2)(B) of Rule XI of the Rules of the House of
Representatives requires the Committee to list the recorded
votes to report legislation and on amendments thereto. There
were no recorded votes taken in connection with ordering H.R.
2508 reported or in adopting the amendment. The voice votes
taken in Committee are as follows:
committee on commerce--104th congress voice votes
Bill: H.R. 2508, Animal Drug Availability Act of 1996.
Unanimous Consent Request: Unanimous consent request by Mr.
Bliley to discharge the Subcommittee on Health and Environment
from further consideration of H.R. 2508 and to proceed to its
immediate consideration by the full committee.
Disposition: Agreed to, without objection.
Amendment: Amendment in the nature of a substitute offered
by Mr. Klug.
Disposition: Agreed to, by a voice vote.
Motion: Motion by Mr. Bliley to order H.R. 2508 reported to
the House, as amended.
Disposition: Agreed to, by a voice vote.
Committee Oversight Findings
Pursuant to clause 2(l)(3)(A) of Rule XI of the Rules of
the House of Representatives, the Subcommittee on Health and
Environment held legislative and oversight hearings and made
findings that are reflected in this report.
Committee on Government Reform and Oversight
Pursuant to clause 2(l)(3)(D) of Rule XI of the Rules of
the House of Representatives, no oversight findings have been
submitted to the Committee by the Committee on Government
Reform and Oversight.
New Budget Authority and Tax Expenditures
In compliance with clause 2(l)(3)(B) of Rule XI of the
Rules of the House of Representatives, the Committee states
that H.R 2508 would result in no new or increased budget
authority or tax expenditures or revenues.
Committee Cost Estimate
In compliance with clause 7(a) of Rule XIII of the Rules of
the House of Representatives, the Committee believes that
enactment of H.R. 2508 would result in no additional cost to
the Federal government. The Committee further adopts as its own
the cost estimate prepared by the Director of the Congressional
Budget Office (CBO) pursuant to section 403 of the
Congressional Budget Act of 1974.
Congressional Budget Office Estimate
Pursuant to clause 2(l)(3)(C) of Rule XI of the Rules of
the House of Representatives, the following is the cost
estimate provided by the Congressional Budget Office pursuant
to section 403 of the Congressional Budget Act of 1974:
U.S. Congress,
Congressional Budget Office,
Washington, DC, September 20, 1996.
Hon. Thomas J. Bliley, Jr.,
Chairman, Committee on Commerce,
House of Representatives, Washington, DC.
Dear Mr. Chairman: At your request, the Congressional
Budget Office (CBO) has reviewed H.R. 2508, the Animal Drug
Availability Act of 1996, as ordered reported by the House
Committee on Commerce on September 19, 1996. CBO estimates this
bill would result in savings to the federal government,
although these savings would not be substantial. The bill would
not affect direct spending or receipts and thus would not be
subject to pay-as-you-go procedures.
The bill would direct the Secretary of Health and Human
Services to establish tolerance levels for residues of
veterinary drugs in imported animal products intended for human
consumption. It would also change the licensing requirements
for manufacturers of animal feeds containing veterinary drugs.
Both of these provisions would impose new private-sector
mandates, as would a provision imposing new recordkeeping
requirements on veterinarians and distributors of animal feed
directive drugs. Only the new recordkeeping requirements would
be likely to impose any significant costs on the private
sector, and these costs would be well below the $100 million
threshold. The bill contains no intergovernmental mandates as
defined in the Unfunded Mandates Reform Act of 1995 (Public Law
104-4) and would impose no costs on state, local, or tribal
governments.
Tolerance Standards. Section 4 of the bill would require
that the residues from animal drugs in edible animals imported
into the United States meet tolerance standards to be set by
the Secretary. These animal products could not be deemed unsafe
unless their residue levels exceeded the specified tolerance
levels. Under current law, the United States Department of
Agriculture monitors residues in imported animal food products,
sometimes in consultation with the Food and Drug Administration
(FDA). However, this section would place a new formal
requirement on the importation of edible animals. Based on
information from FDA staff, CBO expects that the tolerance
standards set by the Secretary would not differ significantly
from current practice. Thus, this provision would not have
significant costs for the federal government or the private
sector.
Recordkeeping Requirements. Section 5(b) of the bill would
constitute a private-sector mandate by imposing new
recordkeeping requirements on the distributors of veterinary
feed directive drugs and on veterinarians that recommend their
use. A veterinary feed directive drug is ``a drug intended for
use in or on animal feed which is limited * * * to use under
professional supervision of a licensed veterinarian.'' The
veterinarian and the distributor of a veterinary feed directive
drug would be required to ``maintain a copy of the veterinary
feed directive applicable to each such feed.'' Distributors
would also be required to provide the Secretary with their
names and places of business. Both veterinarians and
distributors of veterinary feed directive drugs would be likely
to increase their current recordkeeping activities to comply
with this mandate, resulting in a small increase in their cost
of doing business.
Licensing Requirements. Additionally, the bill would change
the licensing requirements for the manufacture of animal feeds
containing veterinary drugs. Current law requires manufacturers
to file a separate application with the FDA for each type of
animal feed they produce that contains a veterinary drug. H.R.
2508 would require each manufacturer to obtain only one license
to produce a number of veterinary feed drugs. To apply for this
license, manufacturers would need to certify that their
products were manufactured and labeled in accordance with the
law and good manufacturing practice standards. This change
should reduce the overall costs of regulatory compliance for
the industry. The reduction in the number of license
applications to the FDA would also reduce costs for the federal
government.
Drug Approval Process. Two provisions of H.R. 2508 would
streamline the approval process for veterinary drugs, resulting
in a small savings to the federal government. One provision
would require manufacturers of new drugs to submit ``one or
more adequate and well-controlled investigations'' in support
of their drugs' efficacy, rather than the multiple
investigations required under current law. Another provision
would direct the FDA to approve animal drugs containing a
combination of drugs, provided each of the individual
ingredients had already been approved for use. The agency could
refuse to approve these combination drugs only under limited
circumstances. These provisions would cut the time needed for
the drug approval process by reducing the amount of data that
the FDA must review.
Additional provisions would increase the cost of approving
new veterinary drugs by escalating the FDA's administrative
activities. H.R. 2508 would allow a manufacturer to request one
or more conferences with the FDA to establish submission or
investigational requirements prior to submission of an
application for a new animal drug. The bill would also direct
the Secretary to issue new regulations regarding the kind of
investigations that must be submitted in support of a new
veterinary drug application. CBO estimates that the additional
costs associated with these activities would be less than the
savings from other provisions of this bill.
If you wish further details on this estimate, we will be
pleased to provide them. The staff contacts for this estimate
are Anne Hunt (federal cost estimate), John Patterson (state
and local estimate), and Anna Cook (private sector mandate
estimate).
Sincerely,
June E. O'Neill, Director.
Inflationary Impact Statement
Pursuant to clause 2(l)(4) of Rule XI of the Rules of the
House of Representatives, the Committee finds that the bill
would have no inflationary impact.
Advisory Committee Statement
No advisory committees within the meaning of section 5(b)
of the Federal Advisory Committee Act are created by this
legislation.
Section-by-Section Analysis of the Legislation
section 1. short title; reference
Section 1 provides that the short title of the bill is the
``Animal Drug Availability Act of 1996'' and specifies that the
provisions in the bill refer to the Federal Food, Drug, and
Cosmetic Act.
section 2. evidence of effectiveness
Section 2(a) amends the current definition of ``substantial
evidence'' of effectiveness found in section 512(d)(3). The
amended definition of substantial evidence permits the FDA more
flexibility in determining the types of studies required to
demonstrate that a particular new animal drug is effective for
its intended uses and conditions of use. The statutory
requirement for a field investigation has been eliminated, but
FDA continues to have the authority to require field
investigations when necessary. As part of its implementing
regulations for this Act, FDA must define by regulation an
adequate and well-controlled field investigation, taking into
account the practical conditions that exist in the field where
such investigations are conducted. Because a field
investigation on animal drugs is conducted under actual use
conditions, e.g., in feed lots, a determination regarding
whether such an investigation is scientifically sound must take
into account the differences between field conditions and
laboratory conditions.
As in current law, the evidence of effectiveness must
consist of one or more adequate and well-controlled studies
conducted by qualified experts on the basis of which qualified
experts can fairly and reasonably conclude that the drug is
effective. The individuals who conduct studies to demonstrate
the effectiveness of a new animal drug and the individuals who
evaluate those studies must be experts qualified by scientific
training and experience to do so.
Section 2(b) makes conforming changes to section
512(c)(2)(F) to reference the revised definition of substantial
evidence.
Section 2(c) adds section 512(d)(4) and establishes a
streamlined approval process for certain combination animal
drugs. Specifically, section 512(d)(4) sets forth the grounds
on which FDA may refuse to approve combination animal drugs
that contain active ingredients or drugs intended for use in
combination that previously have been approved separately for
the particular uses and conditions of use for which they are
intended for use in the combination.
To establish the human food safety of such a combination
animal drug, the application must demonstrate that none of the
active ingredients or drugs exceeds its previously established
tolerance at the longest withdrawal time of any of the active
ingredients or drugs and that 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.
FDA generally should not require full safety testing of
such a combination animal drug to establish target animal
safety. However, if there is a substantiated scientific basis
for believing that combining the individual ingredients or
drugs would endanger target animal safety, or if target animal
observations from studies in the application raise a scientific
issue regarding animal safety, FDA may require the sponsor of
the combination animal drug to conduct additional safety
testing. For example, if a drug or active ingredient to be used
in combination has a narrow margin of safety to the target
animal or is known either to stimulate or inhibit drug
metabolism or drug excretion, then FDA may require the sponsor
of the combination animal drug to conduct additional safety
testing of the combination. Similarly, if during testing of the
combination animal drug, clinical signs of morbidity or
mortality are observed, FDA may require additional safety
testing. FDA should explain to the sponsor the scientific
reason for a request for additional safety testing. Unless
FDA's substantiation for requiring additional testing is
contained in the proprietary files that belong to a different
drug applicant, FDA should provide copies of, or citations to,
the relevant scientific information.
To establish the effectiveness of a dosage form combination
animal drug composed of active ingredients or drugs that
previously have been approved separately for particular uses
and conditions of use for which they are intended in
combination, an application must demonstrate that: (1) there is
substantial evidence, as newly defined, that each 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 effectiveness; (2) each active
ingredient or animal drug intended for a use different from
that of all other active ingredients or animal drugs in the
combination provides appropriate concurrent therapy for the
intended target population; and (3) the active ingredients or
animal drugs are physically compatible and have compatible
dosing regimens if such compatibility could affect the
effectiveness of the combination. The intent of the third
provision (and a similar provision for drugs administered in
drinking water) is to authorize FDA to deny approval of a
combination animal drug if the physical compatibility or
compatibility of the dosing regimens may affect the
effectiveness of the combination animal drug and such
compatibility is not demonstrated.
In the case of dosage form combination animal drugs that
contain any nontopical ingredient or drug intended for use as
an antibacterial, the sponsor of such a drug must demonstrate
by substantial evidence, as newly defined, that such
combination animal drug is effective for its intended uses.
To establish the effectiveness of a combination animal drug
(composed of active ingredients or drugs that previously have
been approved separately for particular uses and conditions of
use for which they are intended in the combination) intended
for use in animal feed or drinking water, an application must
demonstrate that: (1) there is substantial evidence, as newly
defined, 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 effectiveness;
(2) each active ingredient or animal drug intended for at least
one use different from that of all other active ingredients or
animal drugs used in the combination provides appropriate
concurrent therapy for the intended target population; (3) when
a combination contains more than one antibacterial, each
antibacterial ingredient or drug makes a contribution to
effectiveness; and (4) if the combination animal drug is
intended for use in drinking water, the active ingredients or
animal drugs are physically compatible if FDA has a scientific
basis to believe they may be incompatible.
Section 2(d) adds section 512(b)(3) to entitle a person
intending to file a new animal drug application or a request
for investigational new animal drug exemption to request a
presubmission conference. The presubmission conference is a
forum for the applicant and FDA to discuss what studies the
applicant needs to conduct to support FDA's finding that the
new animal drug is safe and effective. When FDA and the sponsor
reach an agreement on a submission or investigational
requirement, such requirement is binding on FDA and the sponsor
unless such agreement is changed by mutual agreement or by an
FDA order with specific scientific justification. The binding
nature of the submission or investigational agreement gives the
sponsor assurance that development time and resources will be
used efficiently and predictably. As part of a presubmission
conference agreement, FDA may, but need not, require a sponsor
to conduct an adequate and well-controlled field investigation
to demonstrate effectiveness. If FDA concludes that more than
one field investigation is essential to demonstrate by
substantial evidence, as newly defined, the effectiveness of
the specific animal drug and intended uses under consideration,
FDA must provide within 25 days after such conference written
justification for requiring more than one field investigation.
Assessing the safety and effectiveness of new animal drugs
under conditions of use which closely approximate actual field
use conditions will remain an important element of many new
animal drug approvals. However, there are situations, e.g.,
approval of many therapeutic animal drugs, in which the
effectiveness of the animal drug can be demonstrated without a
field investigation. In some instances, laboratory animal
studies in the target species on farm settings controlled by
the sponsor can fulfill this need. There may be cases in which
field investigations would yield no more useful information
with regard to an animal drug's effectiveness than can be
obtained through laboratory studies. However, there will be
cases where at least one field investigation will generally be
required. In most instances in which a field investigation is
needed, one adequate and well-controlled field investigation
which adequately represents the intended target population of
animals and conditions of use will be sufficient.
Section 2(e) directs FDA to promulgate regulations to
implement the Animal Drug Availability Act of 1996. FDA is
directed, within 6 months after enactment, to propose
regulations to define ``adequate and well-controlled'' and to
issue final regulations not later than 18 months after
enactment. FDA is also required to propose regulations within
12 months and issue final regulations within 24 months to (1)
define ``substantial evidence'' in a manner that encourages the
submission of new animal drug applications and supplemental
applications; and (2) to encourage dose range labeling. This
section directs FDA, pending the adoption of implementing
regulations, to implement the Federal Food, Drug, and Cosmetic
Act, as amended by this Act, in a manner consistent with the
policies set forth in this bill for all pending and future
applications and supplemental applications from the date of
enactment.
Section 2(f) requires FDA to consider regulatory and
legislative options for facilitating the approval of animal
drugs intended for use in minor species and for minor uses, and
to announce proposals for regulatory or legislative change
within 18 months of enactment of this Act. Because the
population for which such drugs are intended is small, it is
often difficult or impossible to design and conduct studies to
establish safety and efficacy under the traditional approval
processes. Furthermore, there may not be economic incentives
for a sponsor to conduct such studies in light of the potential
market for the product. FDA is directed to consider regulatory
and legislative options for implementing an approval process
that takes into account these special circumstances and ensures
that more drugs are available for minor species and for minor
uses and that such drugs do not endanger the public health.
section 3. limitation on residues
Section 3 amends section 512(d)(1)(F) which, under existing
law, requires FDA not to approve a new animal drug application
if the tolerance limitation proposed exceeds that reasonably
required to accomplish the physical or other technical effect
for which the drug is intended. This provision of the current
statute derives from similar language relating to the
regulation of food additives, and directs the agency to (1)
determine, and to establish as a condition of use for new
animal drugs intended for use in food animals, the minimum dose
necessary to accomplish the intended effect; and (2) limit
tolerances based on such use conditions. The current
requirement to establish the minimum dose creates a burden on
the applicant and FDA to determine dose to a level of
specificity which is not scientifically necessary for the safe
use of all new animal drugs intended for use in food animals.
Furthermore, for a number of therapeutic drugs, use of the drug
at the minimum effective dose is not consistent with the best
medical practice. The change implemented by section 3 would
permit FDA to use the concept of dose-ranging in new animal
drug development and labeling to a greater extent and to
establish tolerances solely on the basis of scientifically
valid risk assessment procedures. The safeguards to animal and
human health built into the current statute will continue.
section 4. import tolerances
Section 4 amends section 512(a) to permit FDA to establish
a tolerance for residues of an animal drug in human foods, when
the drug is not approved for use in the United States but
imported food products of animal origin may contain residues of
that drug.
There are appropriate instances in which food producing
animals raised in other countries are treated with animal drugs
that are not approved in the United States. For example, the
disease or condition treated by the drug does not occur in the
United States. There have been concerns about residues of such
drugs in food products derived from these animals, imported
into the United States. This provision authorizes FDA to
establish a safe tolerance using criteria similar to those that
it would apply in reviewing the human food safety aspects of an
animal drug for which approval is sought in the United States.
FDA may rely on data generated by the drug manufacturer or on
data from a relevant international organization such as the
Codex Alimentarius Commission. This is a step in the direction
of international harmonization of regulatory requirements.
If an international standard on which FDA relied changes or
new information (from either experience or scientific data)
shows the tolerance is no longer safe, FDA may change or revoke
the tolerance. In addition, section 4 provides that the
tolerance may be revoked if information shows use of the animal
drug under actual use conditions results in food being imported
into the United States with residues exceeding the tolerance.
section 5. veterinary feed directives
Section 5 adds a new section 504, Veterinary Feed Directive
Drugs. Veterinary feed directive drugs are animal drugs
intended for use in or on animal feed which are limited, by an
approved application filed pursuant to section 512(b), to use
under the professional supervision of a licensed veterinarian
in the course of the veterinarian's professional practice.
A significant number of animal drugs are administered
through animal feed. All commercially available animal drugs
intended for use in feed are now available to animal owners and
producers without the involvement of the veterinarian. However,
FDA has determined that in the future certain animal drugs can
be approved for feed use only if they are used under a
veterinarian's supervision. Under the existing law, an animal
drug limited by an approved application to use under the
professional supervision of a licensed veterinarian is a
prescription animal drug. Because the distribution system for
medicated feeds is more complex than the distribution system
for dosage form animal drugs, regulation of animal feeds under
traditional prescription systems is not practical. This bill
provides that veterinary feed directive drugs and medicated
feeds containing them are not ``prescription'' articles under
any Federal or State law.
Under this bill, the labeling, distribution, holding, or
use of a veterinary feed directive drug or feed in a manner
inconsistent with its approval results in the drug or feed
being deemed adulterated. This bill requires each person
involved in the distribution or use of a veterinary feed
directive medicated feed and the veterinarian issuing the
veterinary feed directive to maintain a copy of the applicable
feed directive, except that a person distributing the feed to
another person for further distribution is required to maintain
a copy of a written acknowledgment from the consignee stating
that veterinary feed directive distribution limitations will be
followed. FDA is given correlative authority to inspect and
copy the veterinary feed directives and written
acknowledgments. Persons distributing veterinary feed directive
medicated feeds must provide a one-time notice to FDA.
While this section authorizes FDA to promulgate
implementing regulations for veterinary feed directive drugs
and feeds, FDA should not delay any drug approvals pending the
promulgation of such regulations. In the absence of such
regulations, FDA should set forth all necessary conditions
related to the labeling, advertising, distribution, holding, or
use of a veterinary feed directive drug or feed in the new
animal drug approval notice required by section 512(i).
section 6. feed mill licenses
Section 6 amends sections 512(a) and 512(m) to establish a
new regulatory system for licensing feed mills to manufacture
any or all medicated feeds that, under existing law, are the
subject of drug specific medicated feed applications (MFAs).
The underlying standards for the issuance of a license and for
revoking a license do not differ substantively from the
existing standards applicable to MFAs. As under existing law
dealing with MFAs, the principal criterion for the issuance of
a feed mill license is whether the establishment is operating
within current good manufacturing practices, as represented in
the application filed by the applicant and confirmed by FDA or
State inspections. But, by requiring a feed mill to submit for
approval an application for a single license for the facility,
this section eliminates a paperwork and administrative burden
on industry to file multiple product specific MFAs.
Persons holding an approved MFA under existing law are
deemed to hold a feed mill license for the site identified in
the MFA. Such license will expire within 18 months from
enactment of this bill unless the person submits a completed
license application for the manufacturing site along with a
copy of an approved MFA for such site.
Changes in Existing Law Made by the Bill, as Reported
In compliance with clause 3 of rule XIII of the Rules of the
House of Representatives, changes in existing law made by the
bill, as reported, are shown as follows (existing law proposed
to be omitted is enclosed in black brackets, new matter is
printed in italics, existing law in which no change is proposed
is shown in roman):
FEDERAL FOOD, DRUG, AND COSMETIC ACT
* * * * * * *
CHAPTER III--PROHIBITED ACTS AND PENALTIES
prohibited acts
Sec. 301. The following acts and the causing thereof are
hereby prohibited:
(a) * * *
* * * * * * *
(e) The refusal to permit access to or copying of any record
as required by section 412, 504, or 703; or the failure to
establish or maintain any record, or make any report, required
under section 412, 504, 505 (i) or (k), 507(d) or (g),
512(a)(4)(C), 512 (j), (l) or (m), 515(f), or 519 or the
refusal to permit access to or verification or copying of any
such required record.
* * * * * * *
CHAPTER V--DRUGS AND DEVICES
Subchapter A--Drugs and Devices
* * * * * * *
exemptions and consideration for certain drugs, devices, and biological
products
Sec. 503. (a) * * *
* * * * * * *
(f)(1)(A) A drug intended for use by animals other than man,
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, which--
(i) because of its toxicity or other potentiality or
harmful effect, or the method of its use, or the
collateral measures necessary for its use, is not safe
for animal use except under the professional
supervision of a licensed veterinarian, or
(ii) is limited by an approved application under
subsection (b) of section 512 to use under the
professional supervision of a licensed veterinarian,
shall be dispensed only by or upon the lawful written or oral
order of a licensed veterinarian in the course of the
veterinarian's professional practice.
* * * * * * *
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.
* * * * * * *
new animal drugs
Sec. 512. [(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) of this section 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) is the holder of an approved application under
subsection (m) of this section; or
[(ii) will, if the consignee is not a user of the
drug, ship such drug only to a holder of an approved
application under subsection (m) of this section.
[(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) of this section with
respect to such drug, as used in such animal feed,
[(B) there is in effect an approval of an application
pursuant to subsection (m)(1) of this section with
respect to such animal feed, and
[(C) such animal feed, its labeling, and such use
conform to the conditions and indications of use
published pursuant to subsection (i) of this section
and to the application with respect thereto approved
under subsection (m) of this section.]
(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 bears approved labeling and such
use conforms to the conditions and indications of use
published pursuant to subsection (i).
* * * * * * *
(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.
(b)(1) * * *
* * * * * * *
(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.
(c)(1) * * *
(2)(A) * * *
* * * * * * *
(F)(i) * * *
(ii) If an application submitted under subsection (b)(1) for
a drug, which includes an active ingredient (including any
ester or salt of the active ingredient) that has been approved
in another application approved under such subsection, is
approved after the date of enactment of this paragraph and if
such application contains [reports of new clinical or field
investigations (other than bioequivalence or residue studies)
and,] substantial evidence of the effectiveness of the drug
involved, any studies of animal safety, or, in the case of food
producing animals, human food safety studies (other than
bioequivalence or residue studies) [essential to] required for
the approval of the application and conducted or sponsored by
the applicant, the Secretary may not make the approval of an
application submitted under subsection (b)(2) for the
conditions of approval of such drug in the subsection (b)(1)
application effective before the expiration of 3 years from the
date of the approval of the application under subsection (b)(1)
for such drug.
(iii) If a supplement to an application approved under
subsection (b)(1) is approved after the date of enactment of
this paragraph and the supplement contains [reports of new
clinical or field investigations (other than bioequivalence or
residue studies) and,] substantial evidence of the
effectiveness of the drug involved, any studies of animal
safety, or, in the case of food producing animals, human food
safety studies (other than bioequivalence or residue studies)
[essential to] required for the approval of the supplement and
conducted or sponsored by the person submitting the supplement,
the Secretary may not make the approval of an application
submitted under subsection (b)(2) for a change approved in the
supplement effective before the expiration of 3 years from the
date of the approval of the supplement.
* * * * * * *
(v) If an application (including any supplement to a new
animal drug application) submitted under subsection (b)(1) for
a new animal drug for a food-producing animal use, which
includes an active ingredient (including any ester or salt of
the active ingredient) which has been the subject of a waiver
under [subparagraph (B)(iv)] clause (iv) is approved after the
date of enactment of this paragraph, and if the application
contains [reports of clinical or field investigations]
substantial evidence of the effectiveness of the drug involved,
any studies of animal safety, or human food safety studies
(other than bioequivalence or residue studies) [essential to]
required for the new approval of the application and conducted
or sponsored by the applicant, the Secretary may not make the
approval of an application (including any supplement to such
application) submitted under subsection (b)(2) for the new
conditions of approval of such drug in the subsection (b)(1)
application effective before the expiration of five years from
the date of approval of the application under subsection (b)(1)
for such drug. The provisions of this paragraph shall apply
only to the first approval for a food-producing animal use for
the same applicant after the waiver under [subparagraph
(B)(iv)] clause (iv).
* * * * * * *
(d)(1) If the Secretary finds, after due notice to the
applicant in accordance with subsection (c) and giving him an
opportunity for a hearing, in accordance with said subsection,
that--
(A) * * *
* * * * * * *
[(F) upon the basis of the information submitted to
him as part of the application or any other information
before him with respect to such drug, the tolerance
limitation proposed, if any, exceeds that reasonably
required to accomplish the physical or other technical
effect for which the drug is intended;]
(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;
* * * * * * *
[(3) As used in this subsection and subsection (e), the term
``substantial evidence'' means evidence consisting of adequate
and well-controlled investigations, including field
investigation, 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.]
(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.
(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.
* * * * * * *
(i) When a new animal drug application filed pursuant to
subsection (b) is approved, the Secretary shall by notice,
which upon publication shall be effective as a regulation,
publish in the Federal Register the name and address of the
applicant and the conditions and indications of use of the new
animal drug covered by such application, including any
tolerance and withdrawal period or other use restrictions and,
if such new animal drug is intended for use in animal feed,
appropriate purposes and conditions of use (including special
labeling requirements 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)
applicable to any animal feed for use in which such drug is
approved, and such other information, upon the basis of which
such application was approved, as the Secretary deems necessary
to assure the safe and effective use of such drug. Upon
withdrawal of approval of such new animal drug application or
upon its suspension, the Secretary shall forthwith revoke or
suspend, as the case may be, the regulation published pursuant
to this subsection (i) insofar as it is based on the approval
of such application.
* * * * * * *
[(m)(1) Any person may file with the Secretary an application
with respect to any intended use or uses of an animal feed
bearing or containing a new animal drug. Such person shall
submit to the Secretary as part of the application (A) a full
statement of the composition of such animal feed, (B) an
identification of the regulation or regulations (relating to
the new animal drug or drugs to be used in such feed),
published pursuant to subsection (i), on which he relies as a
basis for approval of his application with respect to the use
of such drug in such feed, (C) a full description of the
methods used in, and the facilities and controls used for, the
manufacture, processing, and packing of such animal feed, (D)
specimens of the labeling proposed to be used for such animal
feed, and (E) if so requested by the Secretary, samples of such
animal feed or components thereof.
[(2) Within ninety days after the filing of an application
pursuant to subsection (m)(1), or such additional period as may
be agreed upon by the Secretary and the applicant, the
Secretary shall either (A) issue an order approving the
application if he 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).
[(3) If the Secretary, after due notice to the applicant in
accordance with paragraph (2) and giving him an opportunity for
a hearing in accordance with such paragraph, finds, on the
basis of information submitted to him as part of the
application or on the basis of any other information before
him--
[(A) that there is not in effect a regulation under
subsection (i) (identified in such application) on the
basis of which such application may be approved;
[(B) that such animal feed (including the proposed
use of any new animal drug therein or thereon) does not
conform to an applicable regulation published pursuant
to subsection (i) referred to in the application, or
that the purposes and conditions or indications of use
prescribed, recommended, or suggested in the labeling
of such feed do not conform to the applicable purposes
and conditions or indications of use (including
warnings) published pursuant to subsection (i) or such
labeling omits or fails to conform to other applicable
information published pursuant to subsection (i);
[(C) 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
[(D) that, based on a fair evaluation of all material
facts, such labeling is false or misleading in any
particular;
he shall issue an order refusing to approve the application.
If, after such notice and opportunity for hearing, the
Secretary finds that subparagraphs (A) through (D) do not
apply, he shall issue an order approving the application. An
order under this subsection approving an application with
respect to an animal feed bearing or containing a new animal
drug shall be effective only while there is in effect a
regulation pursuant to subsection (i), on the basis of which
such application (or a supplement thereto) was approved,
relating to the use of such drug in or on such feed.
[(4)(A) The Secretary shall, after due notice and opportunity
for hearing to the applicant, issue an order withdrawing
approval of an application with respect to any animal feed
under this subsection if the Secretary finds--
[(i) that the application contains any untrue
statement of a material fact; or
[(ii) that the applicant has made any changes from
the standpoint of safety or effectiveness beyond the
variations provided for in the application unless he
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. The supplemental
application shall be treated in the same manner as the
original application.
If the Secretary (or in his absence the officer acting as
Secretary) finds that there is an imminent hazard to the health
of man or of the animals for which such animal feed is
intended, he may suspend the approval of such application
immediately, and give the applicant prompt notice of his 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, issue an order withdrawing the
approval of an application with respect to any 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 the applicant has refused to permit
access to, or copying or verification of, such records
as required by subparagraph (B) of such paragraph;
[(ii) that on the basis of new information before
him, evaluated together with the evidence before him
when such application was approved, the methods used
in, or the facilities and controls used for, the
manufacture, processing, and packing 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; or
[(iii) that on the basis of new information before
him, evaluated together with the evidence before him
when the application was approved, the labeling of such
animal feed, 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.
[(C) Any order under paragraph (4) of this subsection shall
state the findings upon which it is based.
[(5) In the case of any animal feed for which an approval of
an application filed pursuant to this subsection is in effect--
[(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) of this
subsection.
[(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.]
(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.
* * * * * * *