[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

[[Page 31649]]

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