[Federal Register Volume 68, Number 102 (Wednesday, May 28, 2003)]
[Proposed Rules]
[Pages 31645-31652]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-12974]
[[Page 31645]]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Parts 510 and 558
[Docket No. 93P-0174]
Requirements for Liquid Medicated Animal Feed and Free-Choice
Medicated Animal Feed
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to change
the regulations for liquid medicated feed and free-choice medicated
feed. By changing the regulations for liquid medicated feed, FDA wants
to clarify: What data are required to demonstrate chemical and physical
stability of a drug in liquid feed; how such data may be submitted for
use in the new animal drug approval process; and which liquid medicated
feeds may be manufactured in a feed manufacturing facility that has not
obtained a medicated feed mill license from FDA. By changing the
regulations for free-choice medicated feed, FDA wants to ensure that
they are consistent with the requirements for liquid medicated feed,
and that provisions for free-choice medicated feed and liquid medicated
feed comply with the terms of the Animal Drug Availability Act (ADAA)
of 1996.
DATES: We invite you to comment on this proposed rule. We will consider
all comments that we receive by August 26, 2003. Send comments on the
information collection provisions by July 28, 2003.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.
The Office of Management and Budget (OMB) is still experiencing
significant delays in the regular mail, including first class and
express mail, and messenger deliveries are not being accepted. To
ensure that comments on the information collection are received, OMB
recommends that written comments be electronically mailed to
[email protected] or faxed to the Office of Information and
Regulatory Affairs, OMB, Attn: Stuart Shapiro, Desk Officer for FDA,
FAX: 202-395-6974. Comments must be identified with the docket number
found in brackets in the heading of this document.
FOR FURTHER INFORMATION CONTACT: Dragan Momcilovic, Center for
Veterinary Medicine (HFV-226), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-827-0169, e-mail:
[email protected].
SUPPLEMENTARY INFORMATION: Section I of the preamble addresses the
proposed changes in the regulation for liquid medicated feeds. Section
II addresses the proposed changes for free-choice medicated feeds.
I. Liquid Medicated Feed
A. Current Regulations
According to the new animal drugs for use in animal feeds
regulations under part 558 (21 CFR part 558), provided specifically in
Sec. 558.3(b) are three types of medicated products for use in feed; a
Type A medicated article and two types of medicated feed, Type B and
Type C. A Type A medicated article is a new animal drug that is used
for the manufacture of another Type A medicated article or a Type B or
Type C medicated feed. Under the current rule, the use of a drug in the
manufacture of a liquid Type B medicated feed requires that the feed
mill obtain an approved new animal drug application (NADA) (Sec.
558.5(a)) and an approved medicated feed mill license (Sec. 558.5(b)).
A Type B medicated feed is used solely for the manufacture of other
medicated feeds, Type B or Type C (Sec. 558.3(b)(3)). A Type C
medicated feed can be either fed as the complete feed, ``top dressed''
(added on top of usual ration), offered ``free-choice'' in conjunction
with other animal feed, or further diluted to produce another Type C
medicated feed (Sec. 558.3(b)(4)).
B. Chronology of the American Feed Industry Association (AFIA) Citizen
Petitions on Liquid Feed Regulations, FDA Responses, and ADAA
On April 30, 1993, the AFIA filed a citizen petition (docket number
93P-0174/CP1), requesting that FDA:
1. Amend Sec. 558.5 to clarify the information and data needed to
demonstrate chemical and positional (physical) stability in liquid
medicated feeds, and
2. Describe the circumstances under which a medicated feed
application (MFA) (Form FDA 1900) will or will not be required.
In our November 10, 1993, tentative response to AFIA, we stated
that we agreed ``in principle'' to modify Sec. 558.5 to include
appropriate directions on submission of chemical and positional
(physical) stability data. We stated, however, that we disagreed with
the request to eliminate the requirement for an approved MFA for the
manufacture of Type B or Type C liquid medicated feeds from a Type A
medicated article, Category I drug. Finally, we stated that we were
preparing to propose a change to Sec. 558.5 and would provide a final
response to the citizen petition once the notice of proposed rulemaking
was published in the Federal Register.
AFIA modified the requested actions in letters of March 3, 1994,
and January 6, 1995, to ask that no MFA be required where a specific
formula or the specifications for the finished liquid Type B product is
published in a regulation for a Category I drug.
On April 19, 1995, we sent a second tentative response to AFIA that
modified some of what was explained in our letter of November 10, 1993.
We stated, in the April 19, 1995, letter that we agreed ``in principle
that an MFA (Form FDA-1900) should not be required if a specific
formula or the specifications for the finished liquid Type B product is
published in the regulations and the drug is a Category I product.'' We
explained that our position is based on the text of 21 CFR 558.5(a),
``which addresses the concern for drug stability in liquid feeds,
except where specific approval has been granted for such use'' and that
``We interpret this exception to be the basis for not requiring MFA
approval for these Category I Type B liquid feeds 21 CFR 558.5(b).'' We
continued to believe, however, that the manufacture of a liquid Type B
medicated feed from an approved Category I drug will require an
approved MFA if a formula or the specifications for the liquid Type B
product were not published in the regulation. Also stated in the
letter, we considered that since ``the formula or specifications are
not published and are privileged information, the MFA is needed to
ensure that only the manufacturer is authorized to utilize the intended
formula or specifications.'' We also noted that an approved MFA was
required to manufacture all Category II Type B liquid feeds.
In a letter of May 19, 1995, AFIA requested that we convert the
process for development of an amendment to Sec. 558.5 into a
negotiated rulemaking. However, in a letter of June 15, 1995, AFIA
asked that its request for negotiated rulemaking be held ``in
abeyance.'' The letter stated that AFIA anticipated that its concerns
would be addressed in the proposed rule and that ``If further
rulemaking is necessary, then we believe negotiated rulemaking would be
in order.''
On October 9, 1996, the ADAA became a law. The ADAA provided for
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a system of medicated feed mill licensing that replaces the provisions
for the MFA. Therefore, the requirements specified in the current
regulation for liquid medicated feeds, including those in part 558 that
provide for the use of specific animal drugs in liquid medicated feeds,
must be amended to be consistent with the ADAA provisions for feed mill
licensing.
On December 6, 1996, in response to the passage of the ADAA, AFIA
filed another amendment to its citizen petition from April 30, 1993.
The amended petition revised AFIA's suggested regulation for liquid
medicated feeds so that the terms of the regulation are consistent with
the provisions for feed mill licensing. Both petitions, the amended and
the original, suggested revised language for Sec. 558.5 that would
clarify the procedures and requirements for demonstrating chemical and
positional (physical) stability for liquid Type B medicated feeds. The
suggested language on chemical and positional (physical) stability
specifies that the submitted data should describe the relevant ranges
of conditions under which the drug would be chemically stable and the
conditions under which the drug would be positionally (physically)
stable if labeling requiring agitation is not proposed.
The suggested language also stated that the stability data might be
submitted by either the sponsor of the new animal drug in an NADA or
abbreviated NADA (ANADA) or by a feed manufacturer in a master file
(MF), which could be referenced in the NADA or the ANADA. The suggested
language also provided that FDA would notify the feed manufacturer by
letter that the liquid feed addressed in the MF could be manufactured.
As we have preliminarily stated in correspondence with AFIA, we
agree with its request for modification of Sec. 558.5 and inclusion of
appropriate directions on chemical and positional (physical) stability.
We agree that the clarification of these requirements will enhance the
approval process for liquid feeds. We also agree to permit submission
of stability data through an MF that can be referenced by a subsequent
applicant. This is consistent with the current free-choice medicated
feed rule in Sec. 510.455 (21 CFR 510.455).
Where feed manufacturers would like to use Type A medicated
articles in the manufacture of liquid medicated feeds with formulas or
specifications differing from those in approvals codified in the CFR,
there must be a separate NADA approved under part 514 (21 CFR part 514)
for such use containing the safety and effectiveness data required by
Sec. 514.1, and the stability data required by Sec. Sec. 514.1 and
558.5. In such circumstances, under this proposed rule, the drug
sponsor could submit an NADA containing the safety and effectiveness
data required by Sec. 514.1, the feed manufacturer (or any other third
party) could submit the stability data for the liquid feed in an MF,
and the sponsor could reference the MF in its NADA rather than
including its own stability data. On request of the owner of the
formula (i.e. ingredient list, product composition) and/or
specifications (i.e. other product specific parameters, such as pH
data, viscosity, etc.), the formula and/or specifications for the
liquid medicated feed will be included in the published approval. We
otherwise will not publish the formula and/or specifications because
they generally are trade secret information entitled to protection
under section 301(j) of the Federal Food, Drug, and Cosmetic Act (the
act) (21 U.S.C 331(j)). Where we do not publish the formula and/or
specifications, we will include a statement that the liquid medicated
feed has been approved under procedures outlined in proposed Sec.
558.5(f)(2). Because the formula and/or specifications are generally
protected information, we expect that such liquid medicated feeds will
be manufactured only by the NADA holder, the MF holder, or someone
authorized by them. We intend to provide the NADA holder and the MF
holder with a certified letter citing the approved formula and/or
specifications of the liquid feed where that information is not
published. The letter will demonstrate to FDA inspectors that the
liquid medicated feed is manufactured using an approved formula and/or
specifications.
Since the term ``positional stability,'' as suggested in the
citizen petition, is not appropriate in relation to the state of
matter, which is either chemical or physical, we are using the term
``physical stability'' instead of ``positional stability.'' Also, our
chemists will determine during the NADA approval process what
specifications are required for approval a particular liquid medicated
feed.
Finally, we agree with AFIA's request to eliminate the requirement
for an approved medicated feed mill license for the manufacture of some
liquid medicated feeds that contain a Category I drug. Under this
proposed rule an approved feed mill license is required for the
manufacture of a liquid medicated feed that contains either any
Category II drug or a Category I drug that is manufactured with a
formula and/or specifications that are not published (i.e.,
proprietary).
Where the formula and/or specifications are published, FDA has an
assurance that all medicated feed mills have access to the information
necessary to manufacture the approved liquid medicated feed. Where the
formula and/or specifications are proprietary, medicated feed mills
might attempt to manufacture the liquid medicated feed knowing only
that the drug is approved for use in liquid feed, but not knowing the
formula and/or specifications. Manufacture of a liquid medicated feed
without such crucial information could endanger animal health and
public health due to unsafe drug residues. Section 510(h) of the act
(21 U.S.C. 360(h)) requires that FDA inspect licensed medicated feed
mills at least once every 2 years. During such inspections, we can
ensure that medicated feed mills manufacturing liquid medicated feeds
with proprietary formulas and/or specifications have the approved
formula and/or specifications. For this reason, we tentatively conclude
that it is necessary for FDA to maintain greater regulatory oversight
over facilities manufacturing liquid medicated feeds with proprietary
formulas and/or specifications, and we are proposing that they must
have an approved medicated feed mill license. The proposed rule also
requires that facilities manufacturing liquid medicated feeds
containing Category II drugs have an approved feed mill license because
of the potential for unsafe residues associated with Category II drugs
(Sec. 558.3(b)(1)(ii)).
We are proposing to exempt from the feed mill license requirement
facilities manufacturing liquid feeds containing a Category I drug with
a published formula and/or specifications. Given the reduced risk of
unsafe residues from a Category I drug and the assurance that medicated
feed mills have the information necessary to manufacture the liquid
medicated feed where the formula and/or specifications are published,
we believe this exemption is consistent with public health, as required
by section 512(m)(6) of the act (21 U.S.C. 360b(m)(6)).
C. Description of the Proposed Sec. 558.5
The proposed rule: (1) Replaces the references to ``medicated feed
application'' in the current rule with the term ``medicated feed mill
license''; (2) defines the types of liquid medicated feed covered by
this regulation; (3) clarifies the types of approvals required for
liquid medicated feed; (4) explains that an approval is required for a
drug intended for use in a liquid feed and
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clarifies the procedures and requirements for demonstrating chemical
and physical stability of a drug in liquid feed; (5) permits submission
of the stability data through a MF for reference by a subsequent
applicant; (6) explains what information will be included in the
published approval of a drug for use in liquid feed; (7) identifies the
conditions under which an approved medicated feed mill license will be
required for the manufacture of a liquid medicated feed; and (8)
describes the labeling provisions for several drugs approved for use in
water but not in liquid feed.
D. Discussion of Proposed Sec. 558.5
Proposed Sec. 558.5(a) and (b) describe the types of liquid
medicated feed covered by the proposed rule.
Proposed Sec. 558.5(c) states that an approved NADA, a
supplemental NADA, or an abbreviated NADA is required for new animal
drugs intended for use in liquid feed.
An approved, supplemental, or abbreviated NADA for new animal drugs
intended for use in liquid feed is required for the same reasons we
described when Sec. 558.5 was proposed in 1973. First, some reports
had demonstrated the instability of certain drugs (bacitracin,
oxytetracyclin, and chlortetracycline) in liquid feed (37 FR 27634,
December 19, 1972). Second, liquid animal feed differs substantially
from dry feeds or dry feed supplements in that small variations in some
of the components of liquid feed have a marked effect on the stability
of added drugs that may compromise the safety and efficacy of such
drugs (38 FR 21178, August 6, 1973). We concluded that the manufacture
of liquid feed is inherently more difficult to control than the
manufacture of dry feed; and therefore, it should be more closely
regulated (38 FR 21178).
Proposed Sec. 558.5(d) clarifies approval requirements for new
animal drugs intended for use in liquid feed including the specific
stability data necessary for liquid medicated feed to meet the
requirements of Sec. 514.1(b)(5)(x). Chemical stability data must be
submitted for all drugs intended for use in liquid medicated feed.
Because of the potential for the uneven distribution of an animal drug
in a liquid feed, the physical stability for liquid medicated feeds
must also be demonstrated for an appropriate period of time under field
conditions. If not demonstrated, labeling must include instructions for
agitation or recirculation before use of the liquid medicated feed.
Proposed Sec. 558.5(e) specifies that the stability data may be
submitted either directly as part of the NADA by the sponsor or to an
MF that a sponsor may then reference in its NADA with written consent
of the MF holder.
Proposed Sec. 558.5(f) explains that the formulas and/or
specifications for the liquid medicated feed will be codified in the
CFR if requested by the sponsor or MF holder. Otherwise, the approval
codified in the CFR will not include the formula and/or specifications,
but instead will state that the approval has been granted for a
proprietary formula and/or specifications.
Proposed Sec. 558.5(g) states that an approved medicated feed mill
license is required for the manufacture of a liquid feed that contains
any Category II drug, or a Category I drug that is manufactured with a
proprietary formula and/or specifications.
Proposed Sec. 558.5(h) spells out labeling requirements for
certain drugs that are intended for use in animal feed and/or drinking
water. As previously noted, we are concerned about these drugs because
of their demonstrated instability in liquid feed. The purpose of this
paragraph is to prevent use of such drugs in liquid medicated feeds.
Proposed Sec. 558.5(i) explains conditions and procedures for
obtaining a waiver from labeling provisions outlined in Sec. 558.5(h).
We are considering removing this waiver option because since its
inception in 1973 it has never been utilized. We are seeking comments
on this issue.
Proposed Sec. 558.5(j) includes additional information on the
labeling provisions of Sec. 558.5(h).
II. Free-Choice Medicated Feed
A. Current Regulation in Sec. 510.455
The current regulation explains that free-choice medicated feed
products such as medicated blocks (agglomerated feed compressed or
rendered into a solid mass cohesive enough to hold its form), mineral
mixes, and liquid feed tank supplements containing one or more animal
drugs, are placed in feeding or grazing areas for consumption and are
not intended to be consumed fully at a single feeding or to constitute
the entire diet of the animal. This regulation reflects our concerns
about the safety and effectiveness of animal drugs when administered
free-choice by stating that an approved NADA is required for a drug
intended for use in free-choice medicated feed, and that a medicated
feed mill license is required for feed mills that manufacture free-
choice medicated feeds.
Finally, as with all drugs intended for use in animal feeds, all
applicants have to demonstrate that such drugs are stable and safe and
effective when offered free-choice (Sec. 514.1(b)(5)(x) and (b)(8)).
B. The Advance Notice of Proposed Rulemaking (ANPR) and AFIA Response
On November 21, 1996 (61 FR 59209), we issued an ANPR seeking
comments concerning various issues for the development of regulations
implementing the provisions of the ADAA. In a comment in response to
the ANPR, dated December 6, 1996, the AFIA suggested a revised version
of Sec. 510.455 that would adopt the terms of feed mill licensing in
accordance with the ADAA and allow a feed manufacturer to submit an
NADA for the approval of a Type A medicated article for use in the
subsequent manufacture of a free-choice medicated feed. In this
response, as well as in its other response from April 30, 1993, the
AFIA suggested language for Sec. 558.5 that would clarify that liquid
medicated feeds intended for use free-choice are also subject to the
requirements of Sec. 510.455.
We agree that the terms of feed mill licensing in accordance with
the ADAA must be adopted in the provisions for free-choice feed. As we
already stated for liquid feeds, where feed manufacturers would like to
use Type A medicated articles in the manufacture of free-choice
medicated feeds with formulas and/or specifications differing from
those in approvals already codified in the CFR, there must be a
separate NADA approved for such use containing the safety and
consumption/effectiveness data required by Sec. 514.1, and the
stability data required by Sec. Sec. 514.1 and 558.5. In such
circumstances, under this proposed rule the drug sponsor could submit
an NADA containing the safety and consumption/effectiveness data
required by Sec. 514.1, the feed manufacturer (or any other third
party) could submit the stability data for the free-choice feed in an
MF, and the sponsor could reference the MF in its NADA rather than
including its own stability data. Under the proposed rule, on request
of the owner of the formula and/or specifications for the free-choice
feed, this information will be included in the published approval.
Otherwise, we will not publish the formula and/or specifications
because it is generally trade secret information entitled to protection
under section 301(j) of the act. Where we do not publish the formula
and/or specifications, we will include a statement that the free-choice
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medicated feed has been approved under procedures outlined in Sec.
510.455(e)(2). Because the formula and/or specifications are generally
protected information we expect that these free-choice medicated feeds
will be manufactured only by the NADA holder, the MF holder, or someone
authorized by them.
We intend to provide the NADA holder and the MF holder with a
certified letter citing the approved formula and/or specifications of
the free-choice feed where that information is not published. The
letter will demonstrate to FDA inspectors that the free-choice feed is
manufactured using an approved formula and/or specifications.
C. Description of Proposed Sec. 510.455
This proposal for free-choice medicated feed, in most respects,
mirrors the liquid medicated feed proposal. Thus, the required chemical
and physical stability data and consumption/effectiveness data may be
submitted by the sponsor in the NADA, or to an MF that a sponsor may
subsequently reference in its NADA with written consent of the MF
holder. Likewise, the method of submission of stability data for the
drug approval process, and the determination of whether product
formulas are included in the approval codified in the CFR are similar
to those discussed for liquid medicated feeds. It also incorporates the
provisions of feed mill licensing in accordance with the ADAA.
The proposed rule: (1) Modifies the current rule by providing a
definition of free-choice medicated feed; (2) explains that one of
three types of NADAs is required for a drug intended for use in a free-
choice feed; (3) specifies the data required for such applications and
the procedures for their submission; (4) explains how such data must be
submitted; (5) states what information will be included in the
published approval of a new animal drug intended for use in free-choice
feed; and (6) explains the situations that will require a medicated
feed mill license for the manufacture of a free-choice medicated feed.
D. Discussion of Proposed Sec. 510.455
Section 510.455(a) remains largely unchanged because the
definitions appear adequate; however, the first statement is modified
to define free-choice medicated feed. Proposed Sec. 510.455(b)
explains that new animal drugs intended for use in free-choice feed
must be approved as an NADA, a supplemental NADA, or an abbreviated
NADA.
Proposed Sec. 510.455(c) explains that any new animal drug
intended for use in free-choice feed must be approved under section 512
of the act (21 U.S.C. 360b) and that data showing that the target
animal consumes the new animal drug in an amount that is safe and
effective (consumption/effectiveness data) and chemical and physical
stability data are required for approval of such drugs.
Proposed Sec. 510.455(d) clarifies that the consumption/
effectiveness and physical stability data must be submitted directly in
the NADA and/or to an MF that a sponsor may then reference in an NADA
with written consent of the MF holder. Therefore, the information in an
MF can serve as a substitute for, or as an addition to, data submitted
by the applicant.
Proposed Sec. 558.455(e) explains that the formula and/or
specifications for the free-choice medicated feed would be codified in
the CFR on request of the NADA or MF holder. Otherwise, the approval
codified in the CFR will not include the formula and/or specifications,
but instead state that the approval has been granted for a proprietary
formula and/or specifications.
Proposed Sec. 558.455(f) clarifies that an approved feed mill
license is required for the manufacture of free-choice medicated feeds
that contain a Category II drug and those that contain a Category I
drug with a proprietary formula and/or specifications.
As with liquid feeds, where the formula and/or specifications are
published, FDA has an assurance that all medicated feed mills have
access to the information necessary to manufacture an approved free-
choice medicated feed. Where the formula and/or specifications are
proprietary, medicated feed mills might attempt to manufacture the
free-choice medicated feed knowing only that the drug is approved for
use in free-choice feed, but not knowing the formula and/or
specifications. Manufacture of a free-choice medicated feed without
such crucial information could endanger animal health and public health
due to unsafe drug residues. Section 510(h) of the act requires that
FDA inspect licensed medicated feed mills at least once every 2 years.
During such inspections, we can insure that medicated feed mills
manufacturing free-choice medicated feeds with proprietary formulas
and/or specifications have the approved formula. For this reason, we
tentatively conclude that it is necessary for FDA to maintain greater
regulatory oversight of facilities manufacturing free-choice medicated
feeds with proprietary formulas and/or specifications, and we are
proposing that they must have an approved medicated feed mill license.
The proposed rule also requires that facilities manufacturing free-
choice medicated feeds containing Category II drugs have an approved
feed mill license because of the potential for unsafe residues
associated with Category II drugs (Sec. 558.3(b)(1)(ii)).
We are proposing to exempt from the feed mill license requirement
facilities manufacturing free-choice feeds containing a Category I drug
with a published formula and/or specifications. Given the reduced risk
of unsafe residues from a Category I drug and the assurance that
medicated feed mills have the information necessary to manufacture the
free-choice medicated feed where the formula and/or specifications are
published, we believe this exemption is consistent with public health,
as required under section 512(m)(6) of the act.
III. Environmental Impact
We have carefully considered the potential environmental impacts of
this rule and determined under 21 CFR 25.30(h) that this action is of a
type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
The proposed action merely clarifies existing regulations
concerning liquid medicated feeds and free-choice medicated feeds.
IV. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages, distributive impacts and equity). We believe that this
proposed rule is consistent with the regulatory philosophy and
principles identified in Executive Order 12866. We have also determined
that the proposed rule is not a significant regulatory action as
defined by the Executive order and so is not subject to review under
the Executive order. Under the Regulatory Flexibility Act, if a
regulation has a significant impact on a substantial
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number of small entities, the agency must analyze regulatory options
that would minimize the impact on small entities. FDA certifies in
accordance with the Regulatory Flexibility Act (5 U.S.C. 601-612) that
this proposed rule would not have a significant economic impact on a
substantial number of small entities, and therefore, a regulatory
flexibility analysis is not required.
Section 202(a) of the Unfunded Mandates Reform Act requires that
agencies prepare a written statement of anticipated costs and benefits
before proposing any regulation that may result in an expenditure by
State, local and tribal governments in the aggregate, or by the private
sector, of $100 million or more (adjusted annually for inflation) in
any 1 year. The Unfunded Mandates Reform Act does not require FDA to
prepare a statement of costs and benefits for the proposed rule because
the proposed rule is not expected to result in any 1-year expenditure
that would exceed $100 million adjusted for inflation. The current
inflation-adjusted statutory threshold is approximately $110 million.
The proposed rule is intended to clarify, simplify, and elaborate
on the current regulations concerning liquid medicated feeds and free-
choice medicated feeds. This rule, which offers more precise and
detailed language than do the current regulations, responds to requests
submitted in citizen petitions and comments by an industry association.
It would also make changes to the current regulatory language for free-
choice medicated feeds in order to be consistent with the ADAA
provision that replaced the medicated feed application system with the
medicated feed mill licensing system.
A. Liquid Medicated Feeds
The proposal for liquid medicated feeds would clarify the types of
liquid medicated feeds for which a separate new animal drug approval is
necessary and for which a feed mill license is necessary. In
particular, it elaborates more fully on the procedures and requirements
for demonstrating the chemical and physical stability of a drug in
liquid feeds, as well as how the data from such a demonstration can be
submitted to the agency.
The proposed rule references requirements under Sec. 514.1 that
are currently required for the approval of all new animal drugs. As
these requirements do not represent a new burden, there is no cost
associated with this aspect of the proposed rule. Likewise, the
proposed rule adds to the current labeling provisions for certain drugs
that are approved for use in animal feed or drinking water but not
approved for use in certain liquid feeds. The proposed rule describes
the waiver process for the exclusion of certain products from these
labeling requirements. Because this waiver process already exists under
the current rule, it would not impose any additional cost to industry.
B. Free-Choice Medicated Feed
The proposed revisions to Sec. 510.455 concern free-choice
medicated feed and very closely follow the liquid medicated feed
proposal. Proposed Sec. 510.455 would clarify and elaborate on the
NADA requirements for drugs intended for use in free-choice medicated
feeds. In addition, it would replace the language that provided for the
medicated feed application with language for the medicated feed mill
system that was created by the ADAA. Since the estimated costs and
benefits of the feed mill system were prepared for the proposed and
final regulations implementing that system, these costs and benefits
would not be considered to be effects of this proposed rule. In total,
the proposed rule would not be expected to impose any new compliance
burdens on the industry and are not associated with any costs.
It is possible that the proposed rule would, in fact, result in
some cost savings due to the proposed provision that would eliminate
the requirement for a medicated feed mill license for the manufacture
of some liquid and free-choice medicated feeds that contain a Category
I drug. In recent years, we have received an average of 128 medicated
feed mill license applications annually. Since the applications do not
explicitly specify the types of medicated feed that would be
manufactured, we are not able to estimate the size of the decrease in
applications that would be expected as a result of the proposed rule.
However, we would expect there to be some decrease in applications as
some feed mills would be exempted from this requirement in the future.
We believe this could lead to a modest cost savings for these feed
mills. Further, the increased clarity and simplification of Sec. Sec.
510.455 and 558.5 would be expected to result in additional cost
savings to industry in the preparation of new animal drug applications
to the agency. We cannot precisely quantify such savings, but believe
the impact to be modest.
V. Federalism
We have analyzed this proposed rule in accordance with the
principles in Executive Order 13132. We have determined that the
proposed rule does not contain policies that have substantial direct
effects on the States, on the relationship between the National
Government and the States, or on the distribution of power and
responsibilities among the various levels of government. Accordingly,
we have tentatively concluded that the proposed rule does not contain
policies that have federalism implications as defined in the order and,
consequently, a federalism summary impact statement has not been
prepared.
VI. Paperwork Reduction Act of 1995
This proposed rule contains information collection provisions that
are subject to review by the Office of Management and Budget (OMB)
under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501-
3520). A description of these provisions is given below with an
estimate of the annual reporting burden. Included in the estimate is
the time for reviewing instructions, searching existing data sources,
gathering and maintaining the data needed, and completing and reviewing
each collection of information.
FDA invites comments on: (1) Whether the proposed collection of
information is necessary for the proper performance of FDA's functions,
including whether the information will have practical utility; (2) the
accuracy of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on respondents, including through the use of
automated collection techniques, when appropriate, and other forms of
information technology.
Title: Waivers from Labeling Requirements for New Animal Drugs
Intended for Use in Liquid Medicated Animal Feed
Description: Proposed Sec. 558.5 specifies procedures for
obtaining a waiver from labeling requirements for certain drugs
intended for use in animal feed or drinking water but not approved for
use in liquid medicated feed. The request for waiver must include: (1)
A copy of the product label; (2) a description of the formulation; and
(3) information to establish that the physical, chemical, or other
properties of the product are such that diversion to use in liquid
medicated feeds is unlikely. This information would be collected if the
manufacturer or sponsor chose not to include the required warning ``FOR
USE IN -------- ONLY, NOT
[[Page 31650]]
FOR USE IN LIQUID MEDICATED FEEDS'' on its product label. The sponsor
or manufacturers would then need to satisfy the requirements of the
waiver section of the regulation. All other data collections are
covered under OMB control number 0910-0032.
Description of Respondents: Medicated feed manufacturing facilities
and sponsors of new animal drugs used in the manufacture of medicated
feed.
Table 1.--Estimated Annual Reporting Burden\1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
Annual Frequency of
21 CFR Section No. of Respondents Responses Total Annual Responses Hours per Response Total Hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
558.5(i) 1 1 1 5 5
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
The burden estimate for this reporting requirement was derived from
data by FDA's Division of Animal Feeds in the Center for Veterinary
Medicine. Only one respondent was used in these figures because
although this particular waiver has been part of the regulations since
1973, it has never been utilized. We estimated it would take 5 hours to
compile the required information because of the time necessary to
explain why the drug would not be diverted to use in liquid feed.
In compliance with the PRA (44 U.S.C. 3507(d)), the agency has
submitted the information collection provisions of this proposed rule
to OMB for review. Interested persons are requested to send comments
regarding information collection to the Office of Information and
Regulatory Affairs, OMB.
OMB is still experiencing significant delays in the regular mail,
including first class and express mail, and messenger deliveries are
not being accepted. To ensure that comments on the information
collection are received, OMB recommends that written comments be
electronically mailed to [email protected] or faxed to the Office of
Information and Regulatory Affairs, OMB, Attn: Stuart Shapiro, Desk
Officer for FDA, FAX: 202-395-6974.
VII. Conforming Changes
FDA is proposing conforming changes in its regulations in
Sec. Sec. 558.95, 558.305, 558.311, 558.342, 558.355, and 558.625 to
remove reference to the term ``medicated feed application.'' These
conforming changes will ensure the accuracy and consistency of the
regulations.
List of Subjects
21 CFR Part 510
Administrative practice and procedure, Animal drugs, Labeling,
Reporting and recordkeeping requirements.
21 CFR Part 558
Animal drugs, Animal feeds.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs and
redelegated to the Center for Veterinary Medicine, it is proposed that
21 CFR parts 510 and 558 be amended as follows:
PART 510--NEW ANIMAL DRUGS
1. The authority citation for 21 CFR part 510 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e.
2. Section 510.455 is revised to read as follows:
Sec. 510.455 Requirements for free-choice medicated feeds.
(a) What is free-choice medicated feed? For the purpose of this
part, free-choice medicated feed is medicated feed that is placed in
feeding or grazing areas and is not intended to be consumed fully at a
single feeding or to constitute the entire diet of the animal. Free-
choice feeds include, but are not limited to, medicated blocks
(agglomerated feed compressed or rendered into a solid mass and
cohesive enough to hold its form), mineral mixes, and liquid feed tank
supplements (``lick tank'' supplements) containing one or more animal
drugs. The manufacture of medicated free-choice feeds is subject to the
current good manufacturing practice regulations in part 225 of this
chapter for medicated feeds.
(b) What types of approvals are required for new animal drugs
intended for use in free-choice feed? New animal drugs intended for use
in free-choice feed must be approved for such use under section 512 of
the Federal Food, Drug, and Cosmetic Act (the act), as:
(1) An original new animal drug application (NADA);
(2) A supplemental NADA; or
(3) An abbreviated NADA.
(c) What are approval requirements for new animal drugs intended
for use in free-choice feed? (1) An approval under section 512 of the
act is required for any new animal drug intended for use in a free-
choice feed.
(2) An approved NADA for a Type A medicated article intended for
use in free-choice feed must contain the following information:
(i) Data, or reference to data in a master file (MF), showing that
the target animal consumes the new animal drug in the Type C free-
choice feed in an amount that is safe and effective (consumption/
effectiveness data); and
(ii) Data, or reference to data in an MF, showing the relevant
ranges of conditions under which the drug will be chemically and
physically stable in the Type C free-choice feed under field
conditions.
(d) How are consumption/effectiveness and/or stability data to be
submitted? The data must be submitted:
(1) Directly in the NADA, by a sponsor; and/or
(2) To an MF that a sponsor may then reference in its NADA with
written consent of the MF holder.
(e) What will be stated in the published approval for a new animal
drug intended for use in free-choice feed? The approval of a new animal
drug intended for use in free-choice feed, as published in this
subchapter, will include:
(1) The formula and/or specifications of the free-choice medicated
feed, where the owner of this information requests such publication; or
(2) A statement that the approval has been granted for a
proprietary formula and/or specifications.
(f) When is a medicated feed mill license required for the
manufacture of a free-choice medicated feed? An approved medicated feed
mill license is required for the manufacture of:
(1) All free-choice medicated feeds that contain a Category II
drug; and
(2) Free-choice medicated feeds that contain a Category I drug and
use a proprietary formula and/or specifications.
PART 558-NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS
3. The authority citation for 21 CFR part 558 continues to read as
follows:
Authority: 21 U.S.C. 360b, 371.
[[Page 31651]]
4. Section 558.5 is revised to read as follows:
Sec. 558.5 Requirements for liquid medicated feed.
(a) What types of liquid medicated feeds are covered by this
section? This section covers the following types of liquid medicated
feed:
(1) Type B feed that is intended for further manufacture of other
medicated feeds (Sec. 558.3(b)(3) of this chapter); or
(2) Type C feed that is intended for:
(i) Further manufacture of another Type C feed; or
(ii) Top-dressing (adding on top of the usual ration) (Sec.
558.3(b)(4) of this chapter).
(b) How is liquid free-choice medicated feed regulated? Liquid
free-choice medicated feed is covered by this section and by Sec.
510.455 of this chapter.
(c) What types of approvals are required for new animal drugs
intended for use in liquid feed? New animal drugs intended for use in
liquid feed must be approved for such use under section 512 of the act,
as:
(1) An original NADA;
(2) A supplemental NADA; or
(3) An abbreviated NADA.
(d) What are the approval requirements for new animal drugs
intended for use in liquid feed? (1) An approval under section 512 of
the act is required for any new animal drug intended for use in a
liquid feed; and
(2) An approved NADA for a drug intended for use in liquid feed
must contain the following information:
(i) Data, or a reference to data in an MF, that shows the relevant
ranges of conditions under which the drug will be chemically stable in
liquid feed under actual field use conditions; and
(ii) Data, or a reference to data in an MF, that shows that the
drug is physically stable in liquid feed under field conditions; or
(iii) Feed labeling with recirculation or agitation directions as
follows:
(A) For liquid feeds stored in recirculating tank systems:
Recirculate immediately prior to use for not less than 10 minutes,
moving not less than 1 percent of the tank contents per minute from the
bottom of the tank to the top. Recirculate daily as described even when
not used.
(B) For liquid feeds stored in mechanical, air, or other agitation-
type tank systems: Agitate immediately prior to use for not less than
10 minutes, creating a turbulence at the bottom of the tank that is
visible at the top. Agitate daily as described even when not used.
(e) How are chemical and physical stability data to be submitted?
The data must be submitted:
(1) Directly in the NADA;
(2) By a sponsor; or
(3) To a master file (MF) that a sponsor may then reference in its
NADA with written consent of the MF holder.
(f) What will be stated in the published approval for a new animal
drug intended for use in liquid feed? The approval of a new animal drug
intended for use in liquid feed as published in this subchapter will
include:
(1) The formula and/or specifications of the liquid medicated feed,
where the owner of this information requests such publication; and/or
(2) A statement that the approval has been granted for a
proprietary formula and/or specifications.
(g) When is a medicated feed mill license required for the
manufacture of a liquid medicated feed? An approved medicated feed mill
license is required for the manufacture of:
(1) All liquid medicated feeds that contain a Category II drug; and
(2) Liquid medicated feeds that contain a Category I drug and use a
proprietary formula and/or specifications.
(h) What measures are in place to prevent certain drugs, approved
for use in animal feed or drinking water but not in liquid medicated
feed, from being diverted to use in liquid feeds? Any product
containing any form of bacitracin, oxytetracycline, or
chlortetracycline, intended for oral administration via animal feed
and/or drinking water, and not approved for use in a liquid medicated
feed must include in its labeling the following statement: ``FOR USE IN
-------- ONLY. NOT FOR USE IN LIQUID MEDICATED FEEDS.'' The blank may
be filled in with the words: ``DRY FEEDS'', ``DRINKING WATER'', or
``DRY FEEDS AND DRINKING WATER''.
(i) Can the labeling provisions of paragraph (h) of this section be
waived, and how can I apply for waiver? (1) The labeling provisions of
paragraph (h) may be waived if there is evidence to indicate that it is
unlikely a new animal drug would be used in the manufacture of a liquid
medicated feed.
(2) To obtain a waiver, you must submit a letter requesting a
waiver to the Food and Drug Administration, Center for Veterinary
Medicine, 7500 Standish Place, Office of New Animal Drug Evaluation
(HFV-100), Rockville, MD 20855.
(3) The letter must include a copy of the product label; a
description of the formulation; and information to establish that the
physical, chemical, or other properties of the new animal drug are such
that diversion to use in liquid medicated feed is unlikely.
(j) What else do I need to know about the labeling provisions of
paragraph (h)? The labeling provisions of paragraph (h) may be
implemented without prior approval as provided for in Sec. 514.8(d)
and (e) of this chapter.
Sec. 558.95 [Amended]
5. Section 558.95 Bambermycins is amended in paragraph
(d)(4)(iii)(d) by removing the last sentence.
Sec. 558.305 [Amended]
6. Section 558.305 Laidlomycin is amended in paragraphs (c)(1)(i)
and (c)(1)(ii) by removing ``Type B'' whenever it appears.
Sec. 558.311 [Amended]
7. Section 558.311 Lasalocid is amended:
a. In paragraphs (d)(1)(i), (d)(1)(ii), (d)(2), (d)(3),
(d)(3)(iii), and (d)(4) by removing ``Type B'' wherever it appears;
b. In paragraph (d)(2) by removing the last sentence;
c. In paragraphs (d)(2), (d)(3), and (d)(3)(iii) by removing
``positionally'' and by adding in its place ``physically'';
d. In paragraph (d)(3)(ii) by removing ``positional'' and by adding
in its place ``physical'';
e. In paragraph (d)(3)(iii) by removing the second complete
sentence ``Approval of the supplement will not be published in the
Federal Register because such approval will not affect or alter
conditions or use of the product in the new animal drug application or
the regulation.''; and in the third complete sentence by removing
``will, however, provide'' and by adding in its place ``will provide'';
f. In paragraph (d)(3)(iii) by removing the phrase ``submit, and
for the agency to approve, a medicated feed application under section
512(m) of the act for liquid Type B feed'' and by adding in its place
the phrase ``manufacture under a medicated feed mill license the liquid
medicated feed described in the master file'';
g. In paragraph (e)(2)(iv) by removing the phrase ``; each use of
this Type C free-choice feed must be the subject of an approved FD-1900
as provided in Sec. 510.455 of this chapter.''; and
h. In paragraph (e)(3)(iv) by removing the last sentence.
Sec. 558.342 [Amended]
8. Section 558.342 Melengestrol is amended in paragraphs (d)(1)(i)
and (d)(1)(ii) by removing the phrase ``Type B or C''; and in paragraph
(d)(2) by removing ``positionally'' and by adding in its place
``physically''.
[[Page 31652]]
9. Section 558.355 is amended:
a. In paragraph (f)(3)(i)(b)(1) by adding the phrase ``as defined
in paragraph (d)(12) of this section'' at the end of the fourth
sentence; and by removing the rest of the paragraph after the fourth
sentence;
b. In paragraph (f)(6)(i)(b)(1) by adding the phrase ``as defined
in paragraph (d)(12) of this section'' at the end of the fifth
sentence; and by removing the rest of the paragraph after the fifth
sentence;
c. In paragraphs (f)(3)(i)(b)(2), (f)(3)(i)(b)(2)(iii),
(f)(6)(i)(b)(2), and (f)(6)(i)(b)(2)(iii) by removing ``Type B''
wherever it appears;
d. In paragraphs (f)(3)(i)(b)(2), (f)(3)(i)(b)(2)(ii),
(f)(6)(i)(b)(2), and (f)(6)(i)(b)(2)(ii) by removing ``positionally''
and ``positional'' wherever they appear and by adding in their
respective places ``physically'' and ``physical'';
e. In paragraphs (f)(3)(i)(b)(2) and (f)(6)(i)(b)(2) in the first
sentence after the word ``directions'' by adding the phrase ``defined
in paragraph (d)(12) of this section'';
f. In paragraphs (f)(3)(i)(b)(2)(iii) and (f)(6)(i)(b)(2)(iii) by
removing the second complete sentence ``Approval of the supplement will
not be published in the Federal Register because such approval will not
affect or alter conditions or use of the product in the new animal drug
application or the regulation.''; and in the third complete sentence by
removing the phrase ``will, however, provide'' and by adding in its
place ``will provide'';
g. In paragraphs (f)(3)(i)(b)(2)(iii) and (f)(6)(i)(b)(2)(iii) by
removing the phrase ``submit, and for the agency to approve, a
medicated feed application under section 512(m) of the act for the
liquid Type B feed'' and by adding in its place the phrase
``manufacture the liquid medicated feed under a medicated feed mill
license described in the master file'';
h. In paragraph (f)(3)(i)(b)(2)(iii) in the last sentence by
removing ``(f)(3)(i)(b)(1)'' and by adding in its place ``(d)(12)'';
i. In paragraph (f)(3)(ix)(b) in the seventh sentence by removing
the phrase ``: Recirculate or agitate immediately prior to use for not
less than 10 minutes, moving at least 1 percent of the tanks contents
per minute from the bottom of the tank to the top'' and by adding in
its place ``as defined in paragraph (d)(12) of this section''; and by
removing the eighth and tenth sentences;
j. In paragraph (f)(6)(i)(b)(2) and in (f)(6)(i)(b)(2)(iii) in the
last sentence by removing ``(f)(6)(i)(b)(1)'' and by adding in its
place ``(d)(12)''; and
k. By adding paragraph (d)(12) to read as follows:
Sec. 558.355 Monensin.
* * * * *
(d) * * *
(12) Mixing directions for liquid feeds requiring recirculation or
agitation:
(i) For liquid feeds stored in recirculating tank systems:
Recirculate immediately prior to use for not less than 10 minutes,
moving not less than 1 percent of the tank contents per minute from the
bottom of the tank to the top. Recirculate daily as described even when
not used.
(ii) For liquid feeds stored in mechanical, air, or other
agitation-type tank systems: Agitate immediately prior to use for not
less than 10 minutes, creating a turbulence at the bottom of the tank
that is visible at the top. Agitate daily as described even when not
used.
* * * * *
Sec. 558.625 [Amended]
10. Section 558.625 Tylosin is amended in paragraphs (c)(1)(i) and
(c)(1)(ii) by removing ``Type B'' and by removing the phrase ``no fewer
than 10 minutes'' and adding in its place the phrase ``not less than 10
minutes''.
Dated: May 12, 2003.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 03-12974 Filed 5-27-03; 8:45 am]
BILLING CODE 4160-01-S