Index of Legally Marketed Unapproved New Animal Drugs for Minor Species, 48840-48864 [06-7070]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 71, Number 162 (Tuesday, August 22, 2006)]
[Proposed Rules]
[Pages 48840-48864]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 06-7070]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 20, 25, 201, 202, 207, 225, 226, 500, 510, 511, 515, 
516, 558, and 589

[Docket No. 2006N-0067]
RIN 0910-AF67


Index of Legally Marketed Unapproved New Animal Drugs for Minor 
Species

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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[[Page 48841]]

SUMMARY: The Minor Use and Minor Species Animal Health Act of 2004 
(MUMS act) amended the Federal Food, Drug, and Cosmetic Act (the act) 
to authorize the U.S. Food and Drug Administration (FDA, the agency) to 
establish new regulatory procedures that provide incentives intended to 
make more drugs legally available to veterinarians and animal owners 
for the treatment of minor animal species and uncommon diseases in 
major animal species. At this time, FDA is issuing proposed regulations 
to implement section 572 of the act entitled ``Index of Legally 
Marketed Unapproved New Animal Drugs for Minor Species.'' These 
regulations propose administrative procedures and criteria for index 
listing a new animal drug for use in a minor species. Such indexing 
provides a basis for legally marketing an unapproved new animal drug 
intended for use in a minor species.

DATES: Submit written or electronic comments on this document by 
November 20, 2006. Interested persons are requested to submit comments 
on the information collection provisions by September 21, 2006.

ADDRESSES: You may submit comments, identified by [Docket No. 2006N-
0067 and/RIN number 0910-AF67], by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
     Agency Web site: https://www.fda.gov/dockets/ecomments. 
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal or the agency Web site, as described in the 
Electronic Submissions portion of this paragraph.
    Instructions: All submissions received must include the agency name 
and Docket No(s). and Regulatory Information Number (RIN) for this 
rulemaking. All comments received may be posted without change to 
https://www.fda.gov/ohrms/dockets/default.htm, including any personal 
information provided. For detailed instructions on submitting comments 
and additional information on the rulemaking process, see the 
``Comments'' heading of the SUPPLEMENTARY INFORMATION section of this 
document.
    Docket: For access to the docket to read background documents or 
comments received, go to https://www.fda.gov/ohrms/dockets/default.htm 
and insert the docket number(s), found in brackets in the heading of 
this document, into the ``Search'' box and follow the prompts and/or go 
to the Division of Dockets Management, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.
    To ensure that comments on the information collection are received, 
OMB recommends that written comments be faxed to the Office of 
Information and Regulatory Affairs, OMB, Attn: FDA Desk Officer, FAX: 
202-395-6974.

FOR FURTHER INFORMATION CONTACT:  Andrew Beaulieu, Center for 
Veterinary Medicine (HFV-50), Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855, 240-276-9090, e-mail: 
Andrew.Beaulieu@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Background

    In enacting the MUMS act (Pub. L. 108-282), Congress sought to 
encourage the development of animal drugs that are currently 
unavailable to minor species (species other than cattle, horses, swine, 
chickens, turkeys, dogs, and cats) in the United States or to major 
species afflicted with uncommon diseases or conditions (minor use). 
Congress recognized that the markets for drugs intended to treat these 
species, diseases, or conditions, are so small that there are often 
insufficient economic incentives to motivate sponsors to develop data 
to support approvals. Further, Congress recognized that some minor 
species populations are too small or their management systems too 
diverse to make it practical to conduct traditional studies to 
demonstrate safety and effectiveness of animal drugs for such uses. As 
a result of these limitations, sponsors have generally not been willing 
or able to collect data to support legal marketing of drugs for these 
species, diseases, or conditions. Consequently, Congress enacted the 
MUMS act, which amended the Federal Food, Drug, and Cosmetic Act to 
provide incentives to develop new animal drugs for minor species and 
minor use, while still ensuring appropriate safeguards for animal and 
human health.
    The major incentives of the MUMS act include the following:
    (1) Designation, established by section 573 of the act (21 U.S.C. 
360ccc-2), which provides for eligibility for grants and contracts to 
defray the costs of qualified safety and effectiveness testing expenses 
and manufacturing expenses incurred in the development of designated 
new animal drugs. Designation also provides for eligibility for a 7-
year period of exclusive marketing rights to enable sponsors to recover 
costs of drug development without competition. FDA proposed regulations 
to implement the designation provision of the act on September 27, 2005 
(70 FR 56394) (the designation proposed rule).
    (2) Conditional approval, established by section 571 of the act (21 
U.S.C. 360ccc), which provides for animal drug marketing after all 
safety and manufacturing components of a new animal drug approval have 
met the standards of section 512 of the act (21 U.S.C. 360b). For the 
effectiveness component, a reasonable expectation of effectiveness must 
be established, after which sponsors have up to 5 years to complete the 
demonstration of effectiveness by the standards of section 512 of the 
act and achieve a full approval. Regulations to implement the 
conditional approval provision will be proposed in the future.
    (3) Indexing, established under section 572 of the act (21 U.S.C. 
360ccc-1), which provides for the legal marketing of unapproved new 
animal drugs intended for use in a minor species through an integrated 
process of agency and expert panel review.
    At this time, FDA is issuing proposed regulations to implement the 
indexing provisions of the MUMS act. These regulations propose 
procedures and criteria for index listing a new animal drug for use in 
a minor species. They describe a process whereby the agency makes a 
determination regarding the following: (1) The eligibility of a new 
animal drug, (2) the selection of a qualified expert panel, and (3) the 
findings of the qualified expert panel.

II. Proposed Regulations

A. Definitions (proposed Sec.  516.115).

    Most of the proposed definitions are straightforward. The proposed 
definition of ``qualified expert panel'' is drawn from the statutory 
definition, given in section 572(d)(3) of the act. The proposed 
definition of ``transgenic animal'' comes from the statutory

[[Page 48842]]

definition, given in section 571(j) of the act (21 U.S.C. 360ccc). The 
proposed definition of ``intended use'' is identical to one proposed 
with respect to the designation proposed rule of September 27, 2005 (70 
FR 56394). The designation proposed rule also included definitions for 
the phrases ``same intended use,'' ``same drug,'' and ``same dosage 
form'' that would be applicable to all subparts of part 516, including 
the indexing regulations.

B. Permanent-resident U.S. agent for a foreign requestor (proposed 
Sec.  516.119).

    The proposed rule would require a foreign requestor or holder to 
name a permanent-resident U.S. agent so that the agency may ensure that 
notifications of decisions regarding indexing and all other 
communications with the requestor or holder are legally and effectively 
made.

C. Meetings (proposed Sec.  516.121)

    The act provides that any person intending to file a request for 
eligibility or a request for addition to the index may have an 
opportunity to meet with the agency to discuss the requirements for 
indexing a new animal drug.

D. Informal conferences regarding agency administrative actions 
(proposed Sec.  516.123)

    The act also provides that a requestor or holder be offered an 
informal conference in association with an agency decision to deny a 
request for a determination of eligibility to index, to deny a request 
for index listing or to remove an index listing. Proposed Sec.  516.123 
establishes the nature of and the procedures for requesting and 
conducting such conferences. FDA would give notice of the grounds for 
the initial decision and provide an opportunity to respond to that 
decision. As proposed, the conference's presiding officer would not 
have significantly participated in the initial decision, would prepare 
a written summary of the informal conference to share with the 
participants, and would issue a written report describing the basis for 
his or her findings. The proposed regulation also provides for an 
informal conference associated with a decision to terminate an 
investigational exemption for a new animal drug proposed for indexing 
or a decision not to affirm an expert panel because it does not meet 
the selection criteria of Sec.  516.141. In the case of conferences 
associated with adverse agency decisions, the proposed regulation 
establishes that decisions to deny, remove, terminate, or not affirm 
will be made by the Director, Office of Minor Use and Minor Species 
Animal Drug Development (OMUMS) and a subsequent conference, if 
requested, will be conducted by the Director, Center for Veterinary 
Medicine or his designee, other than the Director, OMUMS. These 
procedures were adapted from the process for holding regulatory 
hearings before the agency under 21 CFR part 16.

E. Investigational use of new animal drugs to support indexing 
(proposed Sec.  516.125).

    As required by section 512(a)(1) of the act, a new animal drug may 
not be legally marketed unless it is the subject of an approved New 
Animal Drug Application (NADA), the subject of a conditionally approved 
NADA, or on FDA's list of legally marketed unapproved new animal drugs. 
The act contains two exemptions for drugs intended solely for 
investigational use by experts qualified by scientific training and 
experience to investigate the safety and effectiveness of drugs. The 
first, in section 512(j) of the act, applies to new animal drugs 
generally, including animal feeds bearing or containing new animal 
drugs. FDA's regulations implementing this investigational use 
exemption are at part 511 (21 CFR part 511). The second, in section 
572(g) of the act, is parallel to the first exemption but is for the 
purposes of indexing and applies only to minor species new animal 
drugs, including animal feeds bearing or containing such new animal 
drugs. Note that the coverage of these exemptions overlaps and, 
therefore, in some circumstances an investigational use might qualify 
for an exemption under either section 512(j) of the act or section 
572(g) of the act.
    Proposed Sec.  516.125 would implement section 572(g) of the act. 
It states that certain investigational uses, although they involve a 
minor species new animal drug, are nonetheless subject to part 511. 
Such uses include investigations to demonstrate safety with respect to 
individuals exposed to the new animal drug through its manufacture and 
use under section 572(c)(1)(F) of the act, to conduct an environmental 
assessment under section 572(c)(1)(E) of the act, or to obtain approval 
of a new animal drug application or abbreviated new animal drug 
application under section 512(b) of the act. These investigational uses 
would be required to be conducted under part 511 because, whether these 
types of studies are conducted to support indexing or approval, the 
agency would evaluate the study results using the same standards. Thus, 
the agency believes it should apply the same substantive and procedural 
requirements for these investigational uses for minor species new 
animal drugs as it does for new animal drugs generally.
    For other types of investigational uses, proposed Sec.  516.125 
establishes separate exemption regulations, although they are very 
similar to part 511. The agency believes the regulations should be 
similar because of the similarity of the purpose and the language of 
the two investigational use exemptions in the act. Proposed Sec.  
516.125 states that, with certain modifications, part 511 applies to 
minor species new animal drugs or animal feeds bearing or containing 
such new animal drugs intended for investigational use for all other 
purposes in support of a drug index listing (such as to demonstrate 
target animal safety and effectiveness). Among the proposed 
modifications is the need to specifically identify that the 
investigational use is in support of index listing, which would be done 
when labeling the drugs involved and when notifying the agency of the 
claimed investigational exemption. Another modification is that FDA 
would provide notice and an opportunity for an informal conference 
before terminating an investigational use exemption. While part 511 
provides for notice and an opportunity for a hearing under 21 CFR part 
16 concerning whether the exemption should be terminated, the 
administrative process in the proposed regulations reflects the fact 
that section 572 of the act provides for an informal conference with 
respect to other agency decisions regarding indexing, such as removal 
of a new animal drug from the index. FDA does not believe it should 
have an administrative process for terminating an investigational use 
exemption relating to indexing that is different from the informal 
conference process for other decisions relating to indexing.

F. Content and format of a request for determination of eligibility for 
indexing (proposed Sec.  516.129).

    To be added to the index, a new animal drug must meet certain 
criteria. The act establishes what can be described as a two-part 
regulatory decision-making process for determining whether these 
criteria have been met. The first part in this regulatory process is 
FDA's determination of whether the new animal drug is eligible for 
indexing. This involves an evaluation of most of the indexing criteria, 
with the major exceptions being target animal safety and effectiveness. 
The second part

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includes the agency's determination of the suitability of the qualified 
expert panel and a review of whether the new animal drug meets the 
statutory criteria regarding target animal safety and effectiveness.
    The determination of eligibility for indexing is initiated by a 
request to the agency that must be accompanied by sufficient 
information to permit the agency to make an informed decision regarding 
the request. The information proposed by the agency to determine 
eligibility for indexing, described in proposed Sec.  516.129(c), is 
based on the requirements of 572(c)(1) of the act. The categories of 
information are described below:
1. Food safety
    The act allows the indexing of new animal drugs that are intended 
for use in food-producing animals only in limited circumstances. The 
new animal drug must be for use in an early, non-food life stage of a 
minor species; it must be intended for use only in a hatchery, tank, 
pond, or other similar contained man-made structure; and there must be 
sufficient information to demonstrate food safety in accordance with 
the standards of section 512(d) of the act (including, for an 
antimicrobial new animal drug, with respect to antimicrobial 
resistance).
    When a new animal drug proposed for indexing is not intended for 
use in an early life stage of a food-producing minor species animal, 
the requestor must demonstrate that there is a reasonable certainty 
that the minor species or edible products from the minor species will 
not be consumed by humans or food-producing animals. For many minor 
species, this should be as straightforward as an affirmation that the 
species has never been traditionally consumed by humans and is not 
subject to being used in the feed of food-producing animals. A new 
animal drug intended for use in a wildlife species might be eligible 
for indexing if it could be demonstrated that there is a reasonable 
certainty that treated animals would not be subsequently harvested and 
consumed by humans or food-producing animals.
    Under the proposed rule, FDA would rely on its existing regulations 
regarding the food safety standards of section 512(d) of the act, which 
are in part 514 (21 CFR part 514) at Sec.  514.111, and be guided by 
relevant policies and guidance such as FDA's Guidance for Industry 
(GFI) 152.
2. Environmental assessments
    Under the proposal, a request for eligibility would be required to 
contain either an environmental assessment or sufficient information to 
support a categorical exclusion from the requirement to prepare an 
environmental assessment. The proposal would rely on the process and 
the standards for environmental assessments that are already defined in 
part 25 (21 CFR part 25). It would also amend part 25 to have 
categorical exclusions relating to indexing that parallel those 
relating to new animal drug approvals.
3. Occupational and user safety
    As with new animal drug approvals, indexing includes a provision 
for a demonstration of safety to individuals exposed to the new animal 
drug during the drug's manufacture and use. FDA intends to rely on the 
same user safety standards for both drug approval and drug indexing.
4. Chemistry, manufacturing, and control information
    The required chemistry, manufacturing, and control information, and 
the agency's review of that information, are much different for 
indexing than they are for approval.
    A request for a determination of eligibility for a new animal drug 
for indexing must include ``information regarding'' the components and 
composition of the involved drug (section 572(c)(1)(C) of the act) and 
must also include ``a description'' of the methods used in, and the 
facilities and controls used for, the manufacture, processing, and 
packing of the new animal drug (section 572(c)(1)(D) of the act) for 
the purpose of determining whether the requestor has an understanding 
of current Good Manufacturing Practices (cGMPs) and has established 
appropriate specifications for the manufacture and control of the new 
animal drug (section 572(c)(2)(C) of the act). In addition, before a 
new animal drug can be added to the index, the requestor must make a 
commitment that the indexed drug will be manufactured in compliance 
with cGMPs (section 572(d)(1)(F) of the act).
    In contrast, an NADA must include a ``full list'' of the articles 
used as components of the drug and ``a full statement'' of the 
composition of the drug (section 512(b)(1)(B), (C) of the act) as well 
as ``a full description'' of the methods used in, and the facilities 
and controls used for, the manufacture, processing, and packing of the 
new animal drug (section 512(b)(1)(D) of the act). These statutory 
requirements, as implemented by regulation (21 CFR 514.1(b)(4), (5)), 
result in a highly detailed NADA submission which must contain 
sufficient information to permit FDA to determine the adequacy of the 
``full description'' with respect to preserving the identity, strength, 
quality, and purity of the subject new animal drug (see section 
512(d)(1)(C) of the act).
    As previously stated, FDA believes that the submission of 
chemistry, manufacturing, and control information for a new animal drug 
proposed for indexing that would meet the relevant statutory standard 
would consist of a comprehensive summary of the manufacturing process 
that is sufficient to permit a determination that the requestor 
understands cGMPs and has established appropriate specifications in 
accordance with that understanding. FDA believes that the ``full 
description'' and underlying confirmatory information that are required 
in an NADA would not be necessary in a request for determination of 
eligibility for indexing.
5. Other Information
    Proposed 21 CFR 516.129 also requires that a request for 
determination of eligibility contain the following: (1) Identification 
of the minor species or groups of minor species for which indexing is 
sought; (2) a statement of the intended use(s) in those species; (3) a 
statement of the conditions of use, such as dosage, route of 
administration, warnings, contraindications or other significant 
limitations associated with the intended use(s); (4) a brief discussion 
of the need for the drug for the intended use(s); and (5) an estimate 
of the anticipated annual distribution after indexing.
    Additionally, the regulation provides that a single request for 
eligibility may involve only one drug (or combination of drugs) in one 
dosage form, may involve multiple intended uses or multiple minor 
species, may not involve a new animal drug that is contained in or a 
product of a transgenic animal, and may not involve the same drug in 
the same dosage form for the same intended use as a new animal drug 
that is already approved or conditionally approved.

G. Granting and denying requests for a determination of eligibility and 
notification thereof (proposed Sec.  516.133, Sec.  516.135, and Sec.  
516.137).

    FDA will deny a request for determination of eligibility if a 
requestor fails to submit information required by section 572(c)(1) of 
the act, or the submitted information, evaluated together with other 
information available to the agency, is insufficient to support a 
decision to grant a request in

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accordance with section 572(c)(2) of the act.
    The new animal drug that is the subject of the request must be 
sufficiently characterized to enable the agency to determine whether 
the same drug in the same dosage form for the same intended use is 
already approved or conditionally approved. The proposed designation 
rule contains a definition of sameness regarding these three elements 
that would also apply to indexing (see proposed Sec.  516.3 published 
in the Federal Register of September 27, 2005 (70 FR 56394)).
    FDA believes that the estimate of the quantity of the indexed drug 
likely to be distributed on an annual basis following indexing is 
primarily required because of concern over extralabel use of indexed 
drugs, which is statutorily prohibited. The anticipated quantity to be 
distributed for the intended purpose(s) can serve as a baseline against 
which actual distribution can be measured. Significant differences 
between expected and actual distribution may indicate that an indexed 
drug is being used for other than its intended purposes. An estimation 
of the quantity of drug likely to be distributed may also inform 
decisions associated with the extent of environmental or user exposure 
following indexing.
    As previously noted, a new animal drug which is contained in or is 
the product of a transgenic animal may not be indexed. A transgenic 
animal is defined, in section 571(j) of the act, as an animal whose 
genome contains a nucleotide sequence that has been intentionally 
modified in vitro, and the progeny of such an animal; provided that the 
term ``transgenic animal'' does not include an animal of which the 
nucleotide sequence of the genome has been modified solely by selective 
breeding.
    Under the proposal, FDA cannot determine a drug to be eligible for 
indexing if the information submitted in support of the request 
evaluated together with other information available to the agency is 
insufficient to do the following: (1) Demonstrate food safety in an 
early, non-food life stage of a food-producing minor species animal or 
demonstrate that there is a reasonable certainty that treated animals 
will not be consumed by humans or food-producing animals, (2) determine 
that the requestor has established appropriate specifications for the 
manufacture and control of the new animal drug, (3) demonstrate that 
the requestor has an understanding of current good manufacturing 
practices, or (4) determine that the new animal drug is safe with 
respect to individuals exposed to the new animal drug during 
manufacture or use; or the request fails to include an adequate 
environmental assessment or sufficient information to support a 
categorical exclusion from the requirement to prepare an environmental 
assessment.
    In addition, under the proposal a request for a determination of 
eligibility for indexing may be denied if it contains any untrue 
statement of a material fact or omits material information.
    Within 90 days after the submission of a request for a 
determination of eligibility for a non food-producing animal, or 180 
days for a request for an early, non-food life stage of a food-
producing animal, FDA must grant or deny the request and notify the 
requestor of its decision in writing. If FDA denies the request, the 
agency will provide due notice and an opportunity for an informal 
conference regarding its decision. A decision of FDA to deny a request 
for determination of eligibility for indexing following an informal 
conference would constitute the final agency action subject to judicial 
review.

H. Qualified expert panels (proposed Sec.  516.141).

    Once a requestor has received a letter granting eligibility for 
indexing, as the first step in the process of requesting an index 
listing, it can propose a qualified expert panel. The panel, which 
operates external to FDA, plays a central role in the indexing 
process--evaluating target animal safety and effectiveness information 
and making a recommendation to FDA based on its evaluation. Section 
572(d) of the act requires the agency to ``define the criteria for 
selection of a qualified expert panel and the procedures for the 
operation of the panel.'' The same section states that the panel is not 
subject to the Federal Advisory Committee Act, also known as FACA. 
Section 516.141 of the proposed implementing regulations describes the 
process for selecting the qualified expert panel and describes how the 
panel operates. It does this by stating the responsibilities of each of 
the parties involved--the requestor, FDA, the panel members, and the 
panel leader.
    Because of the diverse nature of the products that are subject to 
indexing and anticipated differences in the availability and 
accessibility of experts qualified to review different product classes, 
the proposed rule does not specify the day-to-day operations of a 
qualified expert panel other than to require that the activities of the 
panel be conducted in accordance with generally accepted professional 
and ethical business practices and that one member of the panel be 
identified to serve as the ``leader'' of the review process. The leader 
would serve as the principal spokesperson for the panel and be 
responsible for submitting the panel's final written report to the 
requestor and maintaining records of the final report. In addition, the 
agency plans to issue guidance documents regarding other aspects of the 
operation of expert panels and the preparation of written reports.
    In developing the selection criteria for the qualified expert 
panel, FDA adapted some aspects of the agency's implementation of 
section 523 of the act (21 U.S.C. 360m). That provision deals with FDA 
accreditation of persons in the private sector to conduct the initial 
pre-market review for certain medical devices. FDA also considered its 
use of advisory committees that review information and make 
recommendations to FDA on various technical and scientific issues 
relating to product approval. In addition, FDA tried to minimize the 
burden on the potential members to help ensure that qualified 
individuals will be willing to participate while still establishing 
adequate controls to help ensure that FDA obtains objective, high 
quality evaluations and recommendations.
    To maintain the integrity of the review process, one proposed 
selection criterion is that a qualified expert panel member must not 
have a conflict of interest or the appearance of a conflict of 
interest, unless FDA makes a determination to allow participation 
notwithstanding an otherwise disqualifying financial interest. The 
proposed rule describes the factors that are, and are not, relevant to 
determining whether there is a conflict of interest or the appearance 
of a conflict of interest and identifies the information needed from 
potential panel members to support this determination by the agency. 
Proposed Sec.  516.141(e)(7) requires qualified expert panel members to 
immediately notify the requestor and FDA of any change in conflict of 
interest status. For purposes of this regulation, the agency believes 
that this generally requires a panelist to report changes in his 
conflict of interest status within 30 days.
    In selecting members for the qualified expert panel, the person 
requesting the index listing would be required to ensure that the 
members have the requisite scientific training and experience to 
evaluate the target animal safety and effectiveness of the new animal 
drug at issue for the proposed intended use. The group of identified 
experts would also be required to

[[Page 48845]]

represent an adequate range of expertise to fully evaluate the product.
    After identifying potential panel members, the requestor would be 
required to provide their names and addresses to FDA, along with 
sufficient information about each proposed member for FDA to determine 
whether the panel meets the selection criteria other than with respect 
to potential conflicts of interest. Each proposed panel member would 
provide information regarding potential conflicts of interest directly 
to the agency. If the agency determines that the qualified expert panel 
does not meet the selection criteria, it will provide information to 
the requestor so that a suitable panel can be proposed. For example, 
FDA may decline some candidates and request replacements or request 
that the panel include additional members to provide needed expertise. 
If the requestor disagrees with FDA's determination regarding the 
panel, under the proposal it may request review through an informal 
conference.
    The work of the expert panel centers around its primary task, which 
is to prepare a written report that describes the panel's evaluation of 
all available target animal safety and effectiveness information 
relevant to the proposed use of the new animal drug and the panel's 
conclusions based on its evaluation. In preparing the written report, 
panel members would be required to review all relevant information 
provided by the requestor and should also consider any other relevant 
information otherwise known by panel members, including anecdotal 
information. Panel members would be required to participate in the 
preparation of the written report. Members could be paid a reasonable 
fee to serve on expert panels by the requestor.

I. Written report (proposed Sec.  516.143).

    The qualified expert panel's written report must meet the 
requirements of section 572(d)(2) of the act. Under proposed Sec.  
516.143, which would implement this provision, the report must describe 
the panel's evaluation of all available target animal safety and 
effectiveness information relevant to the proposed use of the new 
animal drug; provide citations of all literature reviewed and summaries 
of unpublished information considered; and state the panel's opinion 
regarding whether the benefits of using the new animal drug for the 
proposed use in a minor species outweigh its risks to the target 
animal, taking into account the harm being caused by the absence of an 
approved or conditionally approved new animal drug for the minor 
species in question. The purpose of these requirements is to provide 
sufficient information to permit the agency to assess the quality and 
quantity of the information relating to target animal safety and 
effectiveness of the new animal drug assessed by the panel. Therefore, 
the panel's evaluation should be such that FDA can understand the basis 
for the panel's conclusion regarding the drug's benefits and risks. If 
the expert panel concludes that the benefits of using the drug outweigh 
its risks, it would also be required to provide as part of the report 
either draft labeling, which includes all conditions of use deemed 
necessary by the expert panel to assure that the benefits of the drug 
will outweigh its risks, or narrative information on the basis of which 
such labeling can be drafted by the requestor. All panel members would 
be required to sign the report or otherwise approve it in writing.

J. Content and format of a request for addition to the index (proposed 
Sec.  516.145).

    As noted previously, the second part of the indexing regulatory 
process involves FDA's review of whether the new animal drug meets the 
statutory criteria regarding target animal safety and effectiveness 
information. FDA's review is based on the qualified expert panel's 
written report and recommendation. The agency's review begins with the 
requestor's submission asking for addition of the new animal drug to 
the index. This submission must contain the information required by 
section 572(d)(1) of the act. FDA's decision to grant or deny the 
request for indexing is governed by section 572(d)(4) of the act. 
Therefore, the request for addition to the index needs to contain 
sufficient information to permit FDA to grant the request. The sections 
of the proposed rule that implement these statutory provisions are 
sections 516.145 and 516.149, respectively.

K. Refusal to file and review a request for addition to the index 
(proposed Sec.  516.147).

    The agency proposes that if a request for indexing fails to contain 
information required by Sec.  516.145, FDA will not file or review it 
and will so notify the requestor within 30 days of receiving the 
request.

L. Granting or denying a request for addition to the index and 
notification thereof (proposed Sec.  516.149, Sec.  516.151, and Sec.  
516.153).

    FDA must deny a request for indexing if the same drug in the same 
dosage form for the same intended use is approved or conditionally 
approved. While this is also a basis for denying eligibility for 
indexing, it is possible that a new animal drug may be approved or 
conditionally approved between the time that a determination for 
eligibility is made and the request for indexing is submitted, thus 
preventing the indexing of a new animal drug previously determined to 
be eligible.
    It is also possible that new scientific information may arise 
between the time of a determination of eligibility and submission of a 
request for indexing. Section 572(d)(4) of the act (by reference to 
section 572(a) of the act) and proposed Sec.  516.151 require the 
agency in reviewing a request for index listing to evaluate any new 
information together with the information available at the time of a 
determination of eligibility to determine whether the new animal drug 
is still eligible for indexing.
    If a request for indexing fails to contain, or appropriately 
reference, information required by the statute, as implemented by 
proposed Sec.  516.145, the agency would be required to deny the 
request.
    In general, FDA intends to rely heavily on the recommendations of 
the qualified expert panel regarding target animal safety and 
effectiveness, including the necessary conditions of use. However, the 
written report of a qualified expert panel may not be sufficiently 
clear or complete with respect to the basis for a panel recommendation 
to index a new animal drug to permit FDA to make an informed decision 
regarding whether it agrees with the recommendation. In this case, FDA 
would either deny the request for indexing or, under proposed Sec.  
516.145(c), require that the requestor submit the information provided 
to the panel. It is also possible that, in some cases, the written 
report of an expert panel may be sufficiently clear and complete for 
the agency to make a decision regarding the panel recommendations, but 
the agency may disagree in whole or in part with the recommendations. 
Such disagreement may be based on the written report itself or the 
report along with additional information available to the agency. In 
such a case, FDA would deny the request. If FDA denies a request for 
addition to the index, the requestor

[[Page 48846]]

could submit another request, which contains information to overcome 
the agency's grounds for denial.
    One of the grounds for denying a request for addition to the index 
is that the qualified expert panel failed to meet one or more of the 
selection criteria. Proposed Sec.  516.141 would require panel members 
to submit any new information regarding conflicts of interest to the 
agency so that FDA can determine whether a disqualifying conflict has 
arisen since the agency's initial review.
    Under the proposal, and consistent with FDA's regulations governing 
new animal drug applications, FDA may also deny a request for addition 
to the index if it contains any untrue statement of a material fact or 
omits material information.
    Within 180 days after the filing of a request for addition of a new 
animal drug to the index, FDA will grant or deny the request, and 
notify the person requesting indexing of FDA's decision in writing. If 
FDA denies the request for indexing of a new animal drug, the agency 
will provide due notice and an opportunity for an informal conference. 
A decision by FDA to deny a request to index a new animal drug 
following an informal conference will constitute final agency action 
subject to judicial review.

M. Publication of the index and content of an index listing (proposed 
Sec.  516.157).

    FDA proposes to meet the requirement of section 572(e)(2) of the 
act by maintaining and updating, at least annually, a publicly 
available list of indexed drugs. Each index listing would contain the 
following: (1) The name and address of the person who holds the index 
listing, (2) the name of the new animal drug and the intended use and 
conditions of use for which it is indexed, (3) product labeling, and 
(4) conditions and any limitations that the agency deems necessary 
regarding the use of the new animal drug.

N. Modifications to indexed drugs (proposed Sec.  516.161).

    As with approved new animal drugs, and as provided for by section 
572(e)(3) of the act, there will almost certainly be a need to change 
the conditions under which a new animal drug is indexed or other 
aspects of an indexed drug at some point after indexing. The proposed 
regulations for making such changes are based on those governing new 
animal drug applications, although the proposed regulations are 
generally less burdensome than the regulatory requirements of the 
corresponding section of 21 CFR part 514.
    Proposed Sec.  516.161 provides for three classes of changes to 
indexed drugs.
    The first class of changes involves the following: (1) The addition 
to labeling or prescription drug advertising of additional warning, 
contraindication, side effect, or cautionary information, (2) the 
deletion from labeling or prescription drug advertising of false, 
misleading, or unsupported indications for use or claims of 
effectiveness, or (3) changes in manufacturing methods or controls 
required to correct product or manufacturing defects that may result in 
serious adverse drug events. Changes of this nature should be made as 
soon as possible and a request for modification of an index listing 
containing information describing the need for the change should be 
concurrently submitted to the agency.
    The second class of changes involves the following: (1) Addition of 
an intended use, (2) addition of a species, (3) addition or alteration 
of an active ingredient, (4) alteration of the concentration of an 
active ingredient, (5) alteration of the dose or dosage regimen, or (6) 
alteration of prescription or over-the-counter status. Changes of this 
nature can be made only after a request to make such a change has been 
granted by FDA. Each such change must go through the same review 
process as the original index listing. Therefore, the initial 
submission to FDA relating to such a change should be a request for a 
determination of eligibility for indexing that relates specifically to 
the proposed change. However, while the process for modifications to 
index listings of this kind follows the same process as a new index 
listing, much of the work to support the initial listing might also 
support the change to the listing and so would not have to be 
duplicated. Likewise, the panel that reviewed the original request for 
listing would likely be acceptable to review the proposed change as 
well. The agency notes, however, that the nature of the change or new 
information about, for example, the product's safety or effectiveness, 
may mean that previous work would no longer be adequate to support the 
change.
    The third class of changes involves any change to the conditions 
established in labeling or otherwise described in the request for 
determination of eligibility or request for indexing at the time a new 
animal drug was indexed other than those noted above. Information 
describing such changes would be required to be submitted as part of 
the annual indexed drug experience report. These changes include 
changes to the formulation of the product or to the manufacturing 
methods or controls other than those to correct defects that may cause 
serious adverse drug events. Changes to the formulation or 
manufacturing process would be required to be reported at the same 
level of detail as the level of detail at which the formulation or 
manufacturing process were initially described in the request for 
determination of eligibility for indexing.
    The proposed provisions under Sec.  516.161 would apply only to 
modifications to the indexed drug. Regardless of which class of changes 
is requested, these provisions would not apply to changes that would 
cause an indexed drug to be a different drug (or different combination 
of drugs) or a different dosage form. In the case of such a submission, 
the agency would deny the request for modification and notify the 
holder that a new index listing is required for the new drug or dosage 
form. The designation proposed rule (September 27, 2005, 70 FR 56394) 
contains proposed definitions for ``same drug'' and ``same dosage 
form.'' The holder could then initiate the new listing by submitting a 
request for eligibility for the new drug or dosage form.

O. Change in ownership of an index file (proposed Sec.  516.163).

    The agency proposes that, in order to meet the requirement of 
section 572(e)(1)(A) of the act, the owner of an index file supporting 
an index listing may transfer ownership of the file provided that the 
agency is appropriately notified of this. The agency would then update 
the index listing accordingly.

P. Records and reports (proposed Sec.  516.165).

    Section 572(i) of the act requires the maintenance of records and 
the submission of reports sufficient to permit a determination of 
whether an indexed drug should be removed from the index. The 
information FDA believes is necessary to make this determination is 
described in proposed Sec.  516.165. This information would be similar 
in nature but less extensive than the information required with respect 
to approved new animal drugs. Most of the information required would be 
submitted annually, on, or within 60 days of, the anniversary date of 
the letter granting the request for indexing.
    Under the proposed regulation, product or manufacturing defects 
that may result in serious adverse drug experiences must be reported to 
the appropriate FDA District Office or resident post within three 
working days of their discovery. Serious and unexpected adverse drug 
experiences must be reported to the Director,

[[Page 48847]]

OMUMS within 15 working days of the index holder first receiving the 
information.
    Distribution of an indexed drug by a distributor would be 
permissible provided that the holder of the index listing submits a 
special report at the time of initial distribution by the distributor 
containing the information required under proposed Sec.  516.165. This 
includes a signed statement from the distributor that the indexed drug 
will be distributed and promoted only in accordance with the index 
listing.
    The agency proposes that all other required information be 
submitted annually. This includes the following: The quantity of the 
drug distributed (domestically and for export), holder and distributor 
current package labeling with a summary of any changes in labeling 
since the previous annual report, a summary of changes in the 
manufacturing process (at the level of detail that the manufacturing 
process was described in the request for determination of eligibility) 
not already reported under proposed Sec.  516.161, any pertinent safety 
or effectiveness information not previously reported, and any adverse 
drug experience information not previously reported.

Q. Removal from the index (proposed Sec.  516.167).

    Proposed Sec.  516.167 provides for removal of a new animal drug 
from the index, after due notice to the holder of the index listing and 
an opportunity for an informal conference.
    The proposed grounds for removal, which track those in the act, 
include that the same drug in the same dosage form for the same 
intended use has been approved or conditionally approved.
    In accordance with section 572(f)(1) of the act, if FDA determines, 
subsequent to the indexing of a new animal drug, that the qualified 
expert panel failed to meet its applicable requirements, FDA would 
remove the drug from the index.
    In light of the purpose of the MUMS act to increase the 
availability of legally marketed new animal drugs to treat minor 
species, the agency proposes to only partially remove an index listing 
if it believes that doing so would satisfactorily resolve a safety or 
effectiveness issue otherwise warranting complete removal of the drug 
from the index. For example, if an index listing provides for the use 
of a new animal drug in several minor species and new information 
indicates that the benefits of using the drug in one of those minor 
species does not outweigh its risks to that species, the agency may 
remove only the use of the new animal drug in that minor species from 
the index listing.
    In accordance with section 572(f)(2) of the act, the regulation 
proposes that FDA may immediately suspend a new animal drug from the 
index if it determines that there is a reasonable probability that the 
use of the drug would present a risk to the health of humans or other 
animals. The agency would subsequently offer the holder of the index 
listing an opportunity for an informal conference.
    A decision by FDA to remove a new animal drug from the index 
following an informal conference would constitute final agency action 
subject to judicial review.

R. Confidentiality of data and information in an index file (proposed 
Sec.  516.171).

    This proposed regulation is based on Sec.  514.11, which applies to 
new animal drug application files. It would apply to index files, which 
would encompass all data and information submitted to or incorporated 
by reference into the index file including requests for determination 
of eligibility for indexing, information supporting selection of expert 
panel members, requests for addition to the index, claimed 
investigational exemptions under proposed Sec.  516.125, requests for 
modification to indexed drugs, reports submitted under proposed Sec.  
516.165, and master files.

III. Conforming Changes

    FDA is proposing conforming changes to certain applicable sections 
of the Code of Federal Regulations (CFR) that would add a reference to 
new animal drugs that are index listed under section 572 of the act. 
The affected sections in title 21 of the CFR are:
    Sec.  20.100 Applicability; cross-reference to other regulations.
    Sec.  25.33 Animal drugs.
    Sec.  201.105 Veterinary drugs.
    Sec.  201.115 New drugs or new animal drugs.
    Sec.  201.122 Drugs for processing, repacking, or manufacturing.
    Sec.  202.1 Prescription-drug advertisements.
    Sec.  207.21 Times for registration and drug listing.
    Sec.  207.35 Notification of registrant; drug establishment 
registration number and drug listing number.
    Sec.  225.1 Current good manufacturing practice.
    Sec.  225.35 Use of work areas, equipment, and storage areas for 
other manufacturing and storage purpose.
    Sec.  225.135 Work and storage areas.
    Sec.  226.1 Current good manufacturing practice.
    Sec.  500.25 Anthelmintic drugs for use in animals.
    Sec.  500.26 Timed-release dosage form drugs.
    Sec.  510.301 Records and reports concerning experience with animal 
feeds bearing or containing new animal drugs for which an approved 
medicated feed mill license application is in effect.
    Sec.  510.305 Maintenance of copies of approved medicated feed mill 
licenses to manufacture animal feed bearing or containing new animal 
drugs.
    Sec.  510.455 Requirements for free-choice medicated feeds.
    Sec.  511.1 New animal drugs for investigational use exempt from 
section 512(a) of the act.
    Sec.  515.10 Medicated feed mill license applications.
    Sec.  515.21 Refusal to approve a medicated feed mill license 
application.
    Sec.  558.3 Definitions and general considerations applicable to 
this part.
    Sec.  558.5 Requirements for liquid medicated feed.
    Sec.  558.6 Veterinary feed directive drugs.
    Sec.  589.1000 Gentian violet.
    In Sec.  201.105, FDA is also proposing to remove a reference to 
certification requirements applicable to preparations of antibiotic 
drugs. FDA no longer certifies or recognizes certification of 
antibiotic drugs.
    In addition, FDA is proposing to remove the last sentence in Sec.  
500.25(c) because it cites Sec.  514.9 which no longer exists. Labeling 
revisions for animal feeds bearing or containing anthelmintic drugs are 
now subject to the same requirements under 21 CFR 500.25 as dosage form 
drugs. Medicated animal feeds covered by approved applications are 
subject to the provisions of Sec.  514.8 (d) and (e). Medicated animal 
feeds covered by an index listing are subject to the provisions of 21 
CFR 516.161(b)(1).

IV. Legal Authority

    FDA's authority for issuing this proposed rule is provided by the 
MUMS act (21 U.S.C. 360ccc et seq.). When Congress passed the MUMS act, 
it directed FDA to publish implementing regulations (see 21 U.S.C. 
360ccc note). In the context of the MUMS act, the statutory 
requirements of section 572 of the act, along with section 701(a) of 
the act (21 U.S.C. 371(a)) provide authority for this proposed rule. 
Section 701(a) authorizes the agency to issue regulations for the 
efficient enforcement of the act.

V. Analysis of Economic Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order

[[Page 48848]]

12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the 
Unfunded Mandates Reform Act (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; and distributive impacts and equity). The Regulatory 
Flexibility Act (5 U.S.C. 601-612) requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities.
    FDA tentatively finds that the proposed rule does not constitute an 
economically significant regulatory action as defined in 3(f)(1) of 
Executive Order 12866. We base this on the following analysis that 
estimates annual costs ranging from about $342,000 in the first year to 
about $735,000 in the 10th year. Similarly, the administrative costs 
are unlikely to have a significant economic impact on a substantial 
number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act requires that 
agencies prepare a written statement, which includes an assessment of 
anticipated costs and benefits, before proposing ``any rule that may 
result in an annual expenditure by State, local and tribal governments, 
in the aggregate, or by the private sector, of $100 million (adjusted 
annually for inflation) in any one year.'' The current threshold after 
adjustment for inflation is $115 million, using the most current (2003) 
implicit price deflator for the Gross Domestic Product. FDA does not 
expect this proposed rule to result in any 1-year expenditure that 
would meet or exceed this amount. As such, no further analysis of 
anticipated costs and benefits is required by the Unfunded Mandates 
Reform Act.
Summary
    The proposed rule is expected to result in about 30 requestors, 
each averaging about 2 requests for a determination of eligibility for 
indexing of individual animal drugs annually, submitting a total of 60 
requests annually. We estimate that requestors for 20 of these products 
will create and convene expert panels to review the safety and efficacy 
data. Further, the recommendations of these panels are expected to lead 
to the addition of 20 animal drug index listings each year.
Benefit
    This rule intends to create administrative practices and procedures 
for index listing a new animal drug for use in a minor species, thereby 
providing the benefit of a legal basis for marketing an unapproved new 
animal drug intended for use in a minor species. The need for the rule 
arises from the existence of some minor species populations that are 
too small to support traditional drug approval studies. The 
countervailing risk of this rule is that sponsors of animal drugs that 
are marginally economically viable could use this system to avoid the 
traditional animal drug approval process. Under this proposed rule, 
however, the voluntary indexing of a new animal drug for use in a minor 
species would only be allowed when the same drug in the same dosage 
form for the same intended use is not already approved or conditionally 
approved, thereby reducing this risk.
Administrative Costs
    This section will describe and estimate the annual administrative 
costs by proposed provision for both producers of currently unapproved 
drugs that would request an index listing and FDA. First, we address 
the efforts required by requestors concerned with index listing. The 
estimates of the number of requestors, frequencies of responses, and 
hours per procedure for each of the provisions of the proposed rule 
were determined by Center for Veterinary Medicine personnel.
    We estimate that, on average, two foreign requestors of drug 
indexing would need to hire a permanent resident agent to represent 
them. We expect this to require about 1 hour of administrative time for 
a requestor's management employee in regulatory affairs. We estimate 
the loaded wage estimate at $42.29 per hour (including a 30 percent 
increase for benefits) for regulatory affairs personnel.\1\ This 
provision would cost the two requestors a total of about $85. We expect 
that a resident agent would expend only about 6 hours of administrative 
effort per year per indexed drug. We estimate the wage rate of the 
resident agent at $100 to $150 per hour, and use the midpoint, $125, 
for our calculations. Total annual costs for resident agents are 
estimated at $1,500 (two agents times 6 hours times $125 per hour) in 
the first year. In the 10th year this is expected to rise to about 
$15,000 as two more resident agents each provide 6 more hours of 
administrative effort each additional year. Due to the uncertainty in 
the costs for resident agents, we request public comment and data on 
this issue.
---------------------------------------------------------------------------

    \1\2004 National Industry-Specific Occupational Employment and 
Wage Estimates, U.S. Department of Labor, Bureau of Labor Statistics 
(https://www.bls.gov/oes/current/naics4_325400.htm); compliance 
officer wage rate for pharmaceutical and medicine manufacturing 
(NAICS 325400).
---------------------------------------------------------------------------

    Proposed Sec.  516.121 provides for one or more meetings between 
requestors and FDA to discuss the requirements for indexing a new 
animal drug. We estimate that 30 requestors will each request, on 
average, 2 meetings annually, for a total of 60 meetings. Preparation 
and participation in these meetings is estimated at 4 hours each, for 
an annual total of 240 hours. Proposed Sec.  516.123 concerns informal 
conferences regarding agency administrative actions. These would 
include conferences to discuss a request for determination of 
eligibility that has been denied, the removal of an expert panel 
member, a request for indexing that was denied or an indexed drug that 
was removed from the list. We estimate that about three requestors 
would request one conference with FDA annually for any of these 
reasons. We expect that each requestor would expend about 8 hours (24 
hours total) to prepare for and attend each of these conferences. The 
combined efforts for preparation and participation in all conferences 
are estimated at 264 hours (240 plus 24). At the same loaded wage 
estimate of $42.29 per hour, this provision is expected to cost about 
$11,200 annually.
    For proposed Sec.  516.125, we estimate that two requestors would 
each annually submit three notices of claimed investigational 
exemptions for new animal drugs for index listing. We estimate that 
each submission would require about 20 hours for regulatory affairs 
personnel to prepare. At the loaded wage estimate of $42.29 per hour, 
the total of 120 hours would cost about $5,100.
    We estimate that about 30 requestors would each average about 2 
requests for determination of eligibility for indexing of individual 
animal drugs annually, totaling to 60 requests annually for proposed 
Sec.  516.129. At the loaded wage estimate of $42.29 per hour, and our 
estimate of 12 hours of preparation for each request, this provision 
would require about 720 hours equal to about $30,400. Included in this 
estimate of 60 requests are any resubmitted requests that were 
previously denied.
    Proposed Sec.  516.141 would require the creation of a qualified 
expert panel to review all information, provided by any source, 
relevant to a determination of the target animal safety and 
effectiveness of the new animal drug. FDA would be required to approve 
the panel members before the panel formally convened. We estimate that 
requestors of 20 animal drugs, or about one-third of the 60 animal 
drugs that

[[Page 48849]]

annually are determined to be eligible for indexing, would create 
qualified expert panels to further study the safety and efficacy data. 
The creation of each panel by a requestor is estimated to take about 8 
hours of effort by regulatory affairs personnel. At the same loaded 
wage estimate, these 160 hours would cost about $6,800 annually.
    Proposed Sec.  516.143 describes how the expert panel would prepare 
a written report for FDA with its findings concerning the new animal 
drug under consideration for index listing. The review of the relevant 
information and preparation of the report by each panel would take an 
estimated 80 hours. This equates to 1,600 hours for 20 panels. The 
proposed rule allows for fees to be paid to panel members for their 
time. We estimated the average wage rate for panel members at $100 to 
$150/hr, and use the midpoint ($125) in our calculations. At this wage, 
we estimate these activities to cost up to $200,000 annually for the 
total industry, or $10,000 per requestor for each animal drug under 
consideration. An additional 0.5 hours is estimated for recordkeeping 
of the final written report described in proposed Sec.  516.143 by the 
panel leader. This would result in an additional $400 in costs 
annually. We request comment and data on the range of hourly wage rates 
for qualified panel members.
    We estimate that the formal request for addition to the index, 
provided for in proposed Sec.  516.145, would require about 12 hours to 
prepare. This would result in another 240 hours of effort (20 requests 
times 12 hours) for regulatory affairs personnel. We project the 
compliance cost of this effort at $10,200 annually.
    We only expect to receive one request each for a modification to an 
indexed listed drug and a change in ownership of an index file annually 
(provided for in proposed Sec. Sec.  516.161 and 516.163), and estimate 
the preparation of each to require 4 and 2 hours, respectively. In 
total, these compliance efforts would cost about $250 in the first 
year. Total modification requests and ownership change notifications 
are expected to increase by 1 each year so that 10 of each would be 
expected to be submitted in year 10. The cost of these provisions in 
year 10 is estimated at about $2,500.
    This proposed rule would require, in Sec.  516.165, that records 
and reports be created, submitted and retained by the holder of the 
indexed drug. These records include a 3-day indexed drug field alert 
report, a 15-day indexed drug field alert report and an annual indexed 
drug experience report. We expect that the vast majority of compliance 
efforts will be associated with the annual indexed drug experience 
report. Because the number of expected requests that are granted for 
addition to the index is 20 per year (on average, 20 requestors with 1 
request granted each), the number of reports to be created, submitted 
and stored is also estimated at 20 per year. We estimate the reports 
for each index listing would require 8 hours annually, totally about 
160 hours for all 20 listings. At the loaded wage estimate of $42.29 
per hour, we estimate the first-year reporting costs at about $6,800. 
These annual costs will increase by an additional $6,800 each year as 
an additional 20 indexed drugs are added to the list. In year 10 we 
estimate the cost of this provision at about $67,700. Further, we 
expect that the maintenance of these records (recordkeeping) would 
require an additional hour of administrative time for each indexed drug 
listing. These additional 20 hours would cost about $850 at the same 
loaded wage estimate in the first year, and would also increase in 
succeeding years by an additional $850 as additional indexed drugs are 
added to the list. We estimate the cost of this provision in year 10 at 
about $8,500.
    For those choosing to seek a MUMS index listing of an unapproved 
animal drug, total requestor compliance costs are expected to sum to 
about $273,000 in the first year. These costs would be borne by 30 
requestors at an average cost per requestor of about $9,100 per indexed 
drug. Costs in succeeding years would be expected to increase slightly 
due to the annual reporting requirements for all indexed drugs 
resulting in year-10 costs of about $358,000.
Costs to Government
    The Government would also incur costs for this proposed rule. We 
expect that about 60 percent of a full-time equivalent employee at a 
GS-14 salary would be needed to handle the administrative work of the 
indexing of MUMS drugs in the first year. This would include all 
administrative efforts from responding to requests for presubmission 
meetings to making