[Federal Register Volume 72, Number 143 (Thursday, July 26, 2007)]
[Rules and Regulations]
[Pages 41010-41022]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-14444]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 20, 510, 514, and 516

[Docket No. 2005N-0329]
RIN 0910-AF60


Designation of New Animal Drugs for Minor Uses or Minor Species

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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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 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 final regulations to 
implement the act. These regulations describe the procedures for 
designating a new animal drug as a minor use or minor species drug. 
Such designation establishes eligibility for the incentives provided by 
the MUMS act.

DATES:  This rule is effective October 9, 2007.

FOR FURTHER INFORMATION CONTACT:  Bernadette Dunham, Center for 
Veterinary Medicine (HFV-50), Food and Drug Administration, 7519 
Standish Pl., Rockville, MD 20855, 240-276-9090, e-mail: 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    In enacting the MUMS act (Public Law 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 uses). 
Congress recognized that the markets for drugs intended to treat these 
species, diseases, or conditions are often so small that there are 
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 these animal drugs. As a result 
of these limitations, sponsors have generally not been willing or able 
to collect data to

[[Page 41011]]

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 (the act) to provide 
incentives to develop new animal drugs for minor species and minor 
uses, while still ensuring appropriate safeguards for animal and human 
health.
    In the Federal Register of September 27, 2005 (70 FR 56394), FDA 
issued proposed regulations to implement section 573 of the act (21 
U.S.C. 360ccc-2). These regulations proposed procedures for designating 
a new animal drug as a minor use or minor species drug. Such 
designation provides eligibility for certain incentives established by 
the MUMS act, including exclusive marketing rights associated with the 
conditional approval or approval of designated new animal drugs and for 
grants to support designated new animal drug development. The proposed 
rule initially provided for a 75-day public comment period during which 
the agency received several comments asserting that 75 days was not an 
adequate amount of time to prepare and submit meaningful comments. In 
response to this, in the Federal Register of December 28, 2005 (70 FR 
76732), FDA reopened the comment period allowing an additional 30 days 
of public comment.

II. Changes to the Proposed Rule

    In response to public comment, or in two places to provide added 
clarity, FDA has made the following changes to the proposed rule:
    Sec.  516.3 Definitions. The definition of ``Infrequently'' was 
changed by adding the words ``on an annualized basis'' to the end of 
the proposed definition. The definition now reads: ``Infrequently, as 
used in the minor use definition, means a disease or condition that is 
uncommon or that occurs only sporadically on an annualized basis.''
    Sec.  516.21 Documentation of minor use status. The language in 
Sec.  516.21(b) was revised for clarity.
    Sec.  516.28 Publication of MUMS-drug designations. In Sec.  
516.28(b), the term ``generic name'' was changed to ``established 
name'' to avoid confusion with abbreviated applications approved under 
section 512(b)(2) of the act.
    Sec.  516.31 Scope of MUMS-drug exclusive marketing rights. In 
Sec.  516.31(a)(2), the words ``or proposes to withdraw'' were removed.

III. Comments

    The agency received comments from 9 organizations or individuals on 
the September 27, 2005, proposal. Comments were received from a trade 
organization representing new animal drug manufacturers, a trade 
organization representing pet product manufacturers, an animal feed 
manufacturer, a professional association representing veterinarians, an 
association representing zoos and aquariums, a consumer advocacy 
organization, and 3 consumers.

A. Comments on the Proposed Rule

    (Comment 1) In Sec.  516.3(b) one comment stated that for added 
clarity and consistency we should add the words ``on an annualized 
basis'' to the end of the definition for infrequently.
    (Response) We agree. We explained in the preamble to the proposed 
rule why we thought that it was appropriate to annualize the data on 
the number of animals in which the indication occurs (see 70 FR at 
56395 to 56396). Therefore, we have revised the codified section 
accordingly.
    (Comment 2) Two comments stated that the requirement for a specific 
product development plan as part of a request for MUMS-drug designation 
in Sec.  516.20(b)(6) is unnecessarily arduous and premature in the 
designation process. Commentors also stated that frivolous requests for 
designation should not be burdensome to the agency; and, therefore, 
that the requirement for a specific product development plan is 
unnecessary.
    (Response) We do not agree that the requirement for submission of a 
description of the product development plan is arduous or premature. 
Also, the basis for this requirement is not primarily to reduce burden 
on the agency due to frivolous requests for designation. The primary 
reasons for requiring a specific product development plan as part of a 
request for MUMS-drug designation are as follows. As we explained in 
the preamble to the proposed rule (70 FR 56394 at 56399), for new 
animal drugs, unlike for human orphan drugs, each designation must be 
unique with respect to drug, dosage form, and intended use. In this 
way, the MUMS act, which was enacted to address the critical shortage 
of approved animal drugs for minor species/minor uses, facilitates the 
development of a broad range of animal drugs in part by discouraging 
multiple sponsors from pursuing identical uses. Because each MUMS 
designation is unique, it is important to the effective implementation 
of section 573 of the act that initial designation of a drug be based 
on evidence that requesting sponsors clearly understand their 
responsibilities in terms of drug research and development and are 
prepared to accept those responsibilities.
    Submission of a description of the product development plan helps 
to ensure that timely development of the drug, consistent with the 
requirement of section 573(a)(2)(B) to actively pursue approval with 
due diligence, is feasible. Designation of a drug that could not 
feasibly be approved under the sponsor's current drug development plan 
would inappropriately delay development and marketing of a needed drug 
by the same or a different sponsor and undermine the goals of the MUMS 
act. Submitting the description of the product development plan also 
facilitates meaningful communication between the sponsor and the agency 
to help ensure that safety and effectiveness testing, which for 
designated drugs may be supported by grants or contracts under section 
573(b) of the act, is efficiently designed and conducted. Efficient and 
effective use of sponsor and agency resources, which is enabled by this 
and other requirements of final Sec.  516.20, is critically important 
to alleviating the shortage of new animal drugs addressed by the MUMS 
act.
    (Comment 3) Two comments stated that the documentation requirements 
for minor use status in Sec.  516.21 are too burdensome. They believe 
there is a lack of balance between the documentation required for a 
minor use designation versus a minor species designation. More 
specifically, both commentors believe that Sec.  516.21(b) is asking 
sponsors to prove a negative concerning the lack of medical 
justification and one of these commentors stated that the financial 
information requested in Sec.  516.21(c) is, for the most part, 
confidential. As an alternative approach, these two commentors 
submitted similar two-part working definitions for minor use that could 
be used in place of the proposed provisions for Sec.  516.21 as 
follows:
    Either:
    1. The drug is not currently approved, it is unlikely the ``minor 
use'' designation for the drug will be applicable to a majority of the 
major species population, and the need for the drug for a specific 
disease or condition has been clearly identified by animal health 
professionals or an animal industry. One commentor also added a fourth 
provision that if the drug has the same active ingredient as other 
approved drugs, the environmental safety assessment of the combined 
active ingredient of all such drugs is shown to be adequate.
    Or;

[[Page 41012]]

    2. The annualized commercial return on investment for the product 
is not reasonably expected to exceed the development and maintenance 
costs of the product.
    (Response) We do not agree that the requirements for documentation 
of minor use status in Sec.  516.21 are too burdensome. FDA agrees that 
these implementing regulations should not be overly burdensome to drug 
sponsors in order to achieve the objectives set forth in the MUMS Act. 
However, it is unavoidable that a certain amount of additional 
information will be required in a request for minor use designation 
that will not be required in a request for minor species designation. 
Section 516.21 describes this additional information and comprises 
three paragraphs.
    Section 516.21(a) asks for an estimate of the total number of 
animals to which a drug could potentially be administered on an annual 
basis. Whether compared to a predetermined small number of animals or 
as part of a case-by-case determination, this number will be essential 
to any request for minor use designation. Simply put, this estimated 
number of animals serves as documentation that the intended use of a 
proposed MUMS drug is limited to a ``small number of animals'', as 
required by the MUMS Act.
    Section 516.21(b) describes how to define a minor use population if 
the proposed MUMS drug is under development for only a subset of the 
estimated total number of animals to which the drug could potentially 
be administered on an annual basis. In this situation, a sponsor may 
utilize the provisions of this paragraph to argue that administration 
of a proposed MUMS drug is only justified for a small subset of a 
larger major species population potentially affected by a particular 
disease or condition and that administration to the remaining larger 
affected population is medically inappropriate. If the number of 
animals in this medically justified subset is a small number of 
animals, then such a use is a minor use.
    The provisions in this paragraph were apparently misinterpreted by 
two of the commentors. Its purpose is not to require medical 
justification to the effect that a drug approved for disease A could 
not be used for disease B or C or D. Its purpose is to allow drug 
sponsors to restrict the intended use of a drug to a subset of the 
animals affected by disease A, thereby reducing their estimate of the 
total number of animals eligible to be treated as required in Sec.  
516.21(a), by providing medical justification that only a subset of 
animals afflicted with disease A are amenable to treatment. For 
improved clarity, we have revised the language of Sec.  516.21(b).
    Section 516.21(c) requires drug sponsors to provide economic 
information relevant to why their MUMS drug should be considered a 
minor use drug. In the preamble to the proposed MUMS designation rule 
(70 FR 56394) we cited the Senate report (S. Rept. 108-226) concerning 
the bill before the Senate (S. 741), which discusses the minor use 
definition and how minor use should be determined: ``This definition 
incorporates the existing definition in the Code of Federal Regulations 
(21 CFR 514.1(d)(1)) with a further limitation to ``small numbers'' to 
assure that such intended uses will not be extended to a wider use. The 
Secretary is expected to further clarify this definition in regulations 
implementing this section. FDA is given broad latitude in determining 
what constitutes a minor use in a major species. The Congress intends 
for FDA to make the determination of minor use by evaluating, in the 
context of the drug development process, whether the incidence of the 
disease or condition occurs so infrequently that the sponsor of a drug 
intended for such use has no reasonable expectation of its sales 
generating sufficient revenues to offset the costs of development. The 
Congress does not intend for FDA to establish a test of commercial 
value, but rather directs FDA to determine whether the expected low use 
of a drug would discourage its development.'' (S. Rept. 108-226 at 12-
13.)
    In evaluating whether the incidence of the disease or condition is 
so infrequent that the sales are not reasonably expected to offset 
development costs, we might take two different approaches. First, we 
could consider each request on a case-by-case basis utilizing the 
information provided in Sec.  516.21(c). Alternatively, we could 
establish, by regulation based on industry-wide economic data, a 
specific small number of animals for each of the seven major species to 
be used as a yardstick against which we would measure the estimated 
total number of animals to which a drug could potentially be 
administered on an annual basis, as documented under Sec.  516.21(a). 
If such ``small number'' for each major species is established by 
regulation at some point in the future, there would no longer be a need 
for requiring the information requested in Sec.  516.21(c).
    (Comment 4) With respect to Sec.  516.24, two comments stated that 
FDA should respond to requests for designation within 60 days from the 
time the request was submitted.
    (Response) FDA agrees that timely processing of requests for 
designation is important. However, because of limitations on agency 
resources, the agency does not believe that it is feasible to commit to 
responding to all requests for designation within 60 days. We intend to 
issue guidance in the future to describe target timelines for the 
designation process consistent with current resources.
    (Comment 5) Two comments stated that FDA should update the publicly 
available list of MUMS-designated drugs within 60 days of granting a 
new MUMS designation.
    (Response) We agree that timely updating of the list of MUMS-
designated drugs is appropriate. However, the agency does not believe 
it is feasible to commit to definite timelines in these regulations 
because of uncertain resource limitations. As discussed above, we 
intend to describe target timelines for our actions related to the 
designation process in future guidance.
    (Comment 6) Two comments stated that a 1-year advance notification 
for discontinuing the manufacture of a drug, as specified in Sec.  
516.29(b), is excessive and a 30-60 day timeframe would be more 
appropriate.
    (Response) A 1-year advance notification for discontinuing the 
manufacture of a MUMS-designated drug is required by section 
573(a)(2)(C) of the act and, therefore, is not subject to alteration by 
regulation.
    (Comment 7) One commentor requested clarification on the 
hypothetical situation in which FDA has withdrawn designation status 
after notification by a sponsor (sponsor A) of its intent to 
discontinue production, but the drug is still being sold, as permitted 
in accordance with the lengthy pre-notification required by the 
statute. The commentor asked if another sponsor (sponsor B) could 
potentially achieve designation and conditional approval, and thus 
block any further sale by sponsor A, even if sponsor A still has time 
left on their notification and still has drug to be sold.
    (Response) In this situation, FDA has only withdrawn sponsor A's 
designation and, therefore, its exclusivity. The approval or 
conditional approval remains intact. Therefore, while approval or 
conditional approval may be possible for sponsor B, designation cannot 
be granted for sponsor B because the MUMS Act only allows designation 
when a specific drug, dosage form, and intended use is not already 
approved or conditionally approved.

[[Page 41013]]

    (Comment 8) In Sec.  516.31(a)(2) one comment stated that the words 
Sec.  or proposes to withdraw'' should be removed because this appears 
to negate the right of the sponsor to due process.
    (Response) We agree that the exclusivity of an approved or 
conditionally approved MUMS-designated drug should not be abrogated by 
a proposal to withdraw the approval or conditional approval. We have 
revised the codified section accordingly.
    (Comment 9) One comment stated that oral dosage form new animal 
drugs and new animal drugs for use in animal feeds should not be 
considered two different dosage forms for the purpose of MUMS 
designation. It argues, for example, that if an oral dosage form new 
animal drug is designated and approved subsequent to the designation 
and approval of a medicated feed containing the same drug and for the 
same intended use, it will negatively impact the business case and 
success of the medicated feed.
    (Response) The agency believes that this same argument could apply 
to any drug that is available in more than one dosage form. For 
example, an approved injectable product could be negatively impacted by 
approval of an oral form of the drug.
    As stated in the preamble to the proposed rule (70 FR 56394 at 
56398), current federal regulations recognize the following dosage 
forms: Oral dosage forms (21 CFR part 520), implantation or injectable 
dosage forms (21 CFR part 522), ophthalmic and topical dosage forms (21 
CFR part 524), intramammary dosage forms (21 CFR part 526), 
miscellaneous dosage forms (21 CFR part 529), and drugs in animal feeds 
(21 CFR part 558). The preamble also notes that medicated feeds are 
subject to different limitations from those for other oral dosage forms 
(70 FR 56394 at 56398), which also supports treating medicated feeds as 
a different dosage form for the purpose of MUMS designation.
    In addition, the markets for medicated feeds and other oral dosage 
forms may be different. An oral dosage in the form of a drench or a 
water treatment may be appropriate in different settings than those 
requiring treatment through the use of medicated feeds. For example, 
pheasants in a hatchery setting can be treated with medicated water 
while those in large outdoor pens are more efficiently treated with 
medicated feeds. Because the populations served by medicated feeds and 
by other oral dosage forms can be different enough to represent 
separate markets and because, as already noted, the same potential 
overlap can occur between any two dosage forms, we believe it is 
appropriate to treat medicated feeds and other oral dosage forms as 
different for MUMS designation purposes.
    (Comment 10) In the definition section under Sec.  516.13, under 
Intended Use, one comment asked if treatment, control, and prevention 
are the same thing (i.e., one designation) or are they three different 
things (i.e., three possible designations).
    (Response) Given that requirements for approval may differ 
significantly for these three categories, they are considered to be 
different for purposes of designation.
    (Comment 11) One comment disagreed with the third principle of 
sameness discussed in the preamble to the proposed rule, under which an 
intended use for a disease or condition caused by one organism is 
considered different from an intended use for the same disease or 
condition caused by a different organism. The comment perceived this 
approach to determining sameness to be a disincentive to seeking MUMS 
designation.
    (Response) This comment raises the general issue of how different 
intended uses must be to be considered separate intended uses. If the 
uses are clearly separable and have different data requirements for 
approval, we believe it is appropriate to permit separate MUMS-drug 
designations. Intended uses for diseases or conditions caused by 
different organisms are clearly separable and would need to be 
supported by different data for approval; therefore, we believe that 
allowing separate MUMS-drug designations for drugs for such uses would 
be appropriate.
    (Comment 12) One comment was concerned that many zoo animals may be 
included in the broad major species categories. It stated that FDA 
should specifically identify the species and subspecies that are 
considered ``major species'' with the recognition that some species/
subspecies may be appropriate only for public display or exhibition, 
and that these non-domestic animals should be identified separately for 
appropriate drug approval under MUMS regulations.
    (Response) Zoo species will not be lumped with major species for 
the purposes of drug approval. The major species are the domesticated 
species only, not including hybrids or closely-related wild species. 
Whether an animal belongs to a major or minor species is not affected 
by its location or use; it is strictly a matter of the species.
    Currently, FDA considers the major species to be:
    Cattle--Bos taurus taurus / Bos taurus indicus
    Horses--Equus caballus
    Swine--Sus domesticus
    Dogs--Canis familiaris (also called Canis lupus familiaris)
    Cats--Felis domesticus (also called Felis catus or Felis silvestris 
catus)
    Chickens--Gallus gallus
    Turkeys--Meleagris gallopavo gallopavo
    All other species are considered to be minor. Therefore, there 
should be no cause for concern regarding the status of zoo animals in 
terms of new animal drug approval. The agency intends to clarify this 
issue in guidance to be published in the future.
    (Comment 13) One comment stated that a manufacturer of a drug that 
is already approved in countries with substantially the same approval 
requirements as the United States does not need incentives to develop 
data and should not be given a MUMS designation.
    (Response) The MUMS incentives exist to encourage pharmaceutical 
companies to pursue approval of new animal drugs for minor uses and 
minor species. Even in cases where foreign approvals exist, sponsors 
generally need to provide considerable new data to meet the 
requirements for FDA approval. Therefore, the MUMS incentives remain 
appropriate when a drug has been approved in a foreign country.
    (Comment 14) One comment stated that in order to monitor whether 
the MUMS rule is fulfilling its intended goal to increase the 
availability of drugs for minor uses, FDA should require annual reports 
on quantities sold of each designated and conditionally approved drug.
    (Response) The agency agrees that knowledge of the quantity of 
designated drugs distributed on an annual basis would be useful 
information in terms of assessing the success of the MUMS act. The MUMS 
act itself requires the annual submission of information regarding 
quantities of conditionally approved products distributed (see 21 
U.S.C. 360ccc(d)(2)(B)(ii)). All fully approved new animal drugs are 
required by regulation (21 CFR 514.80 (b)(4)(i)) to report the quantity 
of product distributed. The Office of Minor Use and Minor Species 
Animal Drug Development will have direct access to this information.

B. Comments on ``Small Number of Animals'' and Minor Use

    (Comment 15) Three comments stated that companion animal ``small 
numbers'' should be considered separately from food animal ``small

[[Page 41014]]

numbers.'' Two comments asked FDA to consider the numbers of animals 
eligible to be designated under a minor species provision (e.g., sheep) 
as a benchmark against which to compare numbers of animals to benefit 
from minor use provisions.
    (Response) The agency agrees that the ``small numbers'' for 
companion animals need to be considered separately from the ``small 
numbers'' for food animals. FDA also agrees that it is appropriate to 
consider the relationship between the number of animals of a minor 
species permitted to be designated under the MUMS act and the number of 
animals of a major species permitted to be designated in establishing 
``small numbers'' of animals under the definition of minor use in the 
statute. However, the agency views the primary basis for establishing 
``small numbers'' to be Congress' expression of intent in the report 
language accompanying the act that the agency further define minor use 
in a major species ``by evaluating, in the context of the drug 
development process, whether the incidence of the disease or condition 
occurs so infrequently that the sponsor of a drug intended for such use 
has no reasonable expectation of its sales generating sufficient 
revenues to offset the cost of development'' (S. Rept. 108-226 at 12-
13).
    Since Congress provided incentives in the MUMS act to stimulate 
drug development, the agency interprets the previous statement to mean 
that FDA should determine for each major species what the ``small 
number of animals'' eligible to be treated on an annual basis would 
need to be in order to represent a drug market value that (relative to 
drug development costs) would be considerably less likely to be pursued 
in the absence of the MUMS incentives, than in their presence.
    (Comment 16) Two comments stated that ``small numbers'' should be 
based on epidemiological data and not on a percentage of the total 
major species population. Commentors stated that since such 
epidemiological data are not yet available, FDA should make minor use 
designations on a case-by-case basis rather than setting hard numbers.
    (Response) In the preamble to the proposed rule for MUMS 
designation (70 FR 56394), the agency already rejected the idea of 
establishing ``small numbers'' based on a percentage of the major 
species population as overly simplistic. There the agency explained 
that using the human orphan drug prevalence limit of 200,000 cases 
(0.1% of the U.S. population in 1983) did not seem helpful for 
calculating ``small numbers'' in cattle, swine, chickens, and turkeys 
because the populations involved, the manner of drug use in those 
populations, and the drug development processes for those species are 
too dissimilar to the human drug scenario (70 FR 56394 at 56396). 
Further analysis made clear that these factors were not sufficiently 
comparable for this approach to be viable, even for dogs, cats, and 
horses (70 FR 56394 at 56396). On the other hand, as already noted, 
Congress directed the agency to define ``minor use'' and, by extension, 
``small numbers,'' on the basis of determining whether a population of 
animals of a major species needing drug treatment would provide 
sufficient drug market value to offset the cost of drug development 
given the incentives provided by the MUMS act.
    The use of epidemiological data comes into play at the point that 
the sponsor and the agency are trying to establish the population of 
animals eligible to be treated with a particular drug for a particular 
intended use. Such data need to be shared with the agency whether the 
determination of minor use is being made on a case-by-case basis or 
with respect to an established small number of animals.
    (Comment 17) One comment stated that FDA should consider the 
potential of a drug to be used extralabel when making a minor use 
designation.
    (Response) The agency understands the expressed concern regarding 
extra-label drug use, but extra-label drug use is an issue that clearly 
transcends the designation process. Extra-label use of approved new 
animal drugs is statutorily permissible under specified circumstances. 
(Extra-label use is not permitted for either conditionally approved or 
indexed drugs because such drugs have not met the full approval 
requirements of the statute.) There is no general prohibition regarding 
the extra-label use in minor species of products approved for use in 
major species or vice versa.
    Therefore, under designation, a product designated and approved for 
a minor species can be legally used in an extra-label manner in a major 
species (subject to established statutory and regulatory conditions). 
The same is true for a product designated for a minor use in a major 
species. It is difficult enough to determine whether the population of 
animals associated with the disease or condition for which a drug is 
labeled for use fails to provide sufficient market value to offset the 
cost of drug development (or falls above or below an established small 
number of animals). It would be impossible to determine the population 
of all animals subject to all potential extra-label uses of a drug. In 
fact, it must be assumed that this population (which may include all 
potential uses of a drug in all animal species) would very often exceed 
a small number of animals. Therefore, consideration of potential extra-
label use in the designation process would have the effect of 
essentially negating the designation provision of the statute and this 
would clearly be contrary to the intent of the legislation.
    (Comment 18) One comment stated that long term use of a drug, even 
in a small number of animals, would constitute a much larger market 
than for shorter term use and that FDA should not consider animal 
numbers as ``small'' if food animals are to receive drugs for a long 
duration, perhaps for a period longer than 21 days, consistent with 
FDA's Guidance for Industry (GFI) 152.
    (Response) As noted previously, the agency acknowledges the concern 
regarding the use of drugs in food animals and accepts that the concept 
of ``small numbers'' of animals included in the statutory definition of 
minor use is based, in part, on this concern. The agency will address 
the issue of establishing ``small numbers'' of animals for each major 
species in future rulemaking. However, a full assessment of the 
relative risks of individual drugs or drug uses is a matter that must 
be left to the comprehensive analysis associated with the review of 
individual new animal drug applications consistent with GFI 
152 and other applicable policies and regulatory requirements.

IV. Legal Authority

    FDA's authority for issuing this final 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 573 of the act, along with section 701(a) of the act (21 U.S.C. 
371(a)) provide authority for this final 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 final 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,

[[Page 41015]]

environmental, public health and safety, and other advantages; 
distributive impacts; and equity). The agency believes that this final 
rule is not a significant regulatory action under the Executive order.
    FDA finds that the final rule does not constitute an economically 
significant regulatory action as defined in section 3(f)(1) of 
Executive Order 12866. We believe that the annual impacts will not 
exceed $100 million since by its very nature the rule applies to animal 
drugs that have a very small market. 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 of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $122 million, using the most current (2005) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
final rule to result in any 1-year expenditure that would meet or 
exceed this amount.
    FDA received nine comments to the proposed rule. Only two of these 
comments contained any remarks that addressed the impacts analysis of 
the proposed rule. Both stated that the requirement for a specific 
development plan before a designation is granted would be too 
burdensome. Neither of the comments provided any estimates on the size 
of the burden that would be imposed. FDA responded previously in this 
preamble to the burden issue in these comments. Further, FDA believes 
that the development of the plan would not be overly burdensome 
because, in most cases, it would be the same plan that a sponsor would 
establish with FDA under the regular animal drug review process, and 
because its cost, estimated at less than one thousand dollars each, 
would represent less than 0.1% of revenues of even the smallest 
establishments. Additionally, the MUMS act requires that FDA measure 
the diligence with which sponsors work towards final approval of a 
MUMS-designated drug, and a drug development plan is necessary for FDA 
to measure a sponsor's progress towards this goal. FDA has therefore 
not changed this provision in the final rule.
    None of the changes made to the final rule would affect the 
expected impacts of the rule on the animal drug producers. Accordingly, 
lacking any other comments to its analysis of the proposed rule, FDA 
has reviewed its impacts analysis published in the proposed rule and 
retains it here for the final rule.
    The intention of this rule, and therefore its benefit, is the 
creation of a system that would stimulate the development and marketing 
of animal drugs for rare diseases in major species and diseases found 
in minor species in the United States, which would otherwise not be 
economically viable under current market conditions. The countervailing 
cost, or risk of this final rule, would be the possibility of limited 
competition for approved drugs for a minor use drug indication or in a 
minor species drug due to the granting of the 7-year exclusive 
marketing right. In addition to the benefit-risk tradeoff mentioned 
previously, there would be additional administrative costs for those 
companies seeking the MUMS designation for a new animal drug 
application (NADA). We estimate that the designation request would 
require about 16 hours of preparation by a regulatory affairs official. 
At a benefit adjusted wage rate of almost $48 per hour for these 
employees, each request would have administrative costs of about 
$760.\1\ We estimate that about 15 separate sponsors would each 
annually submit, on average, 5 MUMS designation requests. 
Administrative costs for these actions would total to about $57,300.
---------------------------------------------------------------------------

    \1\ 2000 National Industry-Specific Occupational Employment and 
Wage Estimates, U.S. Department of Labor, Bureau of Labor Statistics 
(www.bls.gov/oes/2000/oesi3_283.htm); Compliance officer wage rate 
adjusted to 2005 by 2000-20004 average annual wage inflator at BLS 
(http://data.bls.gov/cgi-bin/surveymost).
---------------------------------------------------------------------------

    The agency is also requiring in Sec.  516.22 that foreign sponsors 
requesting designation do so through a permanent resident U.S. agent. 
This is consistent with the current requirements of 21 CFR 514.1(a) 
since requests for MUMS designation will ultimately be submitted to an 
NADA file. The agency does not expect to receive many requests for 
designation from foreign sponsors, and estimates that number at less 
than one per year. As such, the agency has not quantified the cost of 
this provision but believes it would be negligible.
    Amendments made to existing designations are expected to occur 
infrequently. We estimate that three amendments will be filed annually, 
requiring about two hours of preparation. At the same wage rate, this 
would cost an additional $300. Sponsors may also transfer sponsorship 
of MUMS-designated drug or terminate the designation. We estimate that 
these activities would result in only 3 additional hours of 
administrative costs annually, totaling to $150. The preparation of the 
annual report that would be required for each MUMS-designated drug is 
estimated to take about 2 hours. In the first year, this would result 
in another 150 hours of administrative costs, or about $7,200 in total. 
FDA notifications to sponsors concerning insufficient quantities of 
approved MUMS-designated drugs are expected to be rare, about once each 
year. Sponsor responses are estimated to take 3 hours, at a cost of 
$150.
    Assuming a sponsor chooses to seek the MUMS designation for its 
NADA, total administrative costs for this rule across all sponsors are 
estimated at about $65,000 in the first year, and to increase each year 
thereafter due to the annual reporting requirements.

Regulatory Flexibility Analysis

1. Small Business Impacts
    The Regulatory Flexibility Act requires agencies to prepare a 
regulatory flexibility analysis if a rule is expected to have a 
significant economic impact on a substantial number of small entities. 
Although we believe it is unlikely that significant economic impacts 
would occur, the following along with other sections of this preamble 
constitute the regulatory flexibility analysis.
    One requirement of the Regulatory Flexibility Act is a succinct 
statement of any objectives of the rule. As stated previously in this 
analysis, with this rule the agency intends to create a system, 
provided for by statute, that would stimulate the development and 
marketing of animal drugs for rare diseases in major species and 
diseases found in minor species in the United States, which would 
otherwise not be economically viable under current market conditions.
    The Regulatory Flexibility Act also requires a description of the 
small entities that would be affected by the rule, and an estimate of 
the number of small entities to which the rule would apply. The Small 
Business Administration (SBA) defines the criteria for small businesses 
using the North American Industrial Classification System (NAICS). For 
pharmaceutical preparation manufacturers (NAICS number 325412), SBA 
defines small businesses as those with less than 750 employees. Census 
data shows that 723 companies with 901

[[Page 41016]]

establishments represent this category.\2\ While about two-thirds of 
the establishments would be considered small using the SBA criteria, 
the agency acknowledges that many requests for MUMS designation would 
likely be received from multi-establishment companies that exceed the 
750-employee limit on small businesses. Nonetheless, the cost of 
submitting a single request represents only about 0.1% of the revenues 
of the smallest set of establishments (those with 1-4 employees), and 
much smaller revenue percentages of all larger establishments. The 
agency believes that these costs would not represent a significant 
economic impact on these firms.
---------------------------------------------------------------------------

    \2\ 2002 Economic Census, US Census Bureau, Manufacturing 
Industry Series, Pharmaceutical Preparation Manufacturing, Table 4.
---------------------------------------------------------------------------

    All of the costs described previously would be incurred by any 
small business that applies for MUMS designation. These include costs 
for request preparation, amendments to designations, preparing annual 
reports and responding to FDA notifications of insufficient quantities. 
The firms submitting requests for MUMS designation are expected to 
already have the necessary administrative personnel with the skills 
required to prepare the requests and fulfill reporting requirements as 
identified previously.
2. Analysis of Alternatives
    The Regulatory Flexibility Act requires that the agency consider 
any alternatives to a rule that would accomplish the objective while 
minimizing significant impacts of the rule. As stated previously, the 
agency believes that the final rule, due to the relatively small costs, 
would not be likely to impose significant economic impacts on small 
businesses. As such, the agency believes the final rule achieves the 
objective with minimal costs to industry.
    The statute that creates this system, Public Law 108-282, does not 
provide the agency a great deal of flexibility in the implementing 
regulations, such as in determining the length of the exclusivity 
period or granting an exclusivity to more than one animal drug without 
regard to sameness of drug, dosage form and intended use. The agency 
did consider, however, applying an explicit threshold number of animals 
of each major species as the upper bound of disease incidence in the 
definition of ``minor use'' of animal drugs. The agency determined that 
the data needed to develop these estimates would not be available in 
time for the publication date of the final rule as mandated by statute. 
The agency intends in the future to propose a separate rule defining 
the threshold numbers of animals of each major species. The agency will 
continue to consider the acceptability of each request for designation 
as a minor use animal drug on a case-by-case basis as provided for in 
the Senate report concerning the legislation, until it issues any final 
rule based on such a proposal.

VI. Paperwork Reduction Act of 1995

    In the Federal Register of September 27, 2005, FDA published a 
proposed rule and invited comments on the proposed collection of 
information. Also in a Federal Register of December 28, 2005, FDA 
published a notice reopening the comment period for the proposed rule 
to allow interested persons additional time to comment. Concurrently, 
FDA submitted the information collection request to the Office of 
Management and Budget (OMB) for review and approval. OMB did not 
approve this collection of information, but as terms for clearance, 
filed comment. In filing comment on this collection of information, OMB 
requested that FDA examine public comment in response to the notice of 
proposed rulemaking and describe in the preamble of the final rule how 
the agency has maximized the practical utility of the collection and 
minimized the burden. Further, OMB requested for any future submissions 
of this information collection, FDA indicate the submission as ``new'' 
and reference OMB control number 0910-0590.
    In response to these Federal Register notices, FDA did not receive 
any comments regarding the information collection requirements 
contained in the final rule. In response to OMB's request that the 
agency describe how it has maximized the practical utility of this 
collection and minimized the burden, an explanation has been provided 
elsewhere in the preamble of this final rule.
    The information collection provisions of this final rule have been 
submitted to OMB for review. Prior to the effective date of this final 
rule, FDA will publish notice in the Federal Register, announcing OMB's 
decision to approve, modify, or disapprove the information collection 
provisions in this final rule. An agency may not conduct or sponsor, 
and a person is not required to respond to a collection of information, 
unless it displays a currently valid OMB control number.
    Title: Designated New Animal Drugs for Minor Use and Minor 
Species--21 CFR Part 516, OMB Control No. 0910-0590.
    Description: The MUMS act amended (the act) to authorize FDA to 
establish new regulatory procedures intended to make more medications 
legally available to veterinarians and animal owners for the treatment 
of minor animal species as well as uncommon diseases in major animal 
species. This legislation provides incentives designed to help 
pharmaceutical companies overcome the financial burdens they face in 
providing limited-demand animal drugs. These incentives are only 
available to sponsors whose drugs are ``MUMS-designated'' by FDA. Minor 
use drugs are drugs for use in major species (cattle, horses, swine, 
chickens, turkeys, dogs, and cats) that are needed for diseases that 
occur in only a small number of animals either because they occur 
infrequently or in limited geographic areas. Minor species are all 
animals other than the major species, for example, zoo animals, 
ornamental fish, parrots, ferrets, and guinea pigs. Some animals of 
agricultural importance are also minor species. These include animals 
such as sheep, goats, catfish, and honeybees. Participation in the MUMS 
program is completely optional for drug sponsors so the associated 
paperwork only applies to those sponsors who request and are 
subsequently granted ``MUMS designation.'' The proposed rule will 
specify the criteria and procedures for requesting MUMS designation as 
well as the annual reporting requirements for MUMS designees.
    Under the new part 516, Sec.  516.20 provides requirements on the 
content and format of a request for MUMS-drug designation, Sec.  516.26 
provides requirements for amending MUMS-drug designation, provisions 
for change in sponsorship of MUMS-drug designation can be found under 
Sec.  516.27, under Sec.  516.29 are provisions for termination of 
MUMS-drug designation, under Sec.  516.30 are requirements for annual 
reports from sponsor(s) of MUMS designated drugs, and under Sec.  
516.36 are provisions for insufficient quantities of MUMS-designated 
drugs.
    Description of Respondents: Pharmaceutical companies that sponsor 
new animal drugs.
    FDA estimates the burden for this collection of information as 
follows:

[[Page 41017]]



                                 Table 1.--Estimated Annual Reporting Burden\1\
----------------------------------------------------------------------------------------------------------------
                         No. of        Annual Frequency     Total Annual        Hours per
  21 CFR Section      Respondents        per Response        Responses           Response         Total Hours
----------------------------------------------------------------------------------------------------------------
516.20                            15                  5                 75                 16              1,200
----------------------------------------------------------------------------------------------------------------
516.26                             3                  1                  3                  2                  6
----------------------------------------------------------------------------------------------------------------
516.27                             1                  1                  1                  1                  1
----------------------------------------------------------------------------------------------------------------
516.29                             2                  1                  2                  1                  2
----------------------------------------------------------------------------------------------------------------
516.30                            15                  5                 75                  2                150
----------------------------------------------------------------------------------------------------------------
516.36                             1                  1                  1                  3                  3
----------------------------------------------------------------------------------------------------------------
Total                                                                                                      1,362
----------------------------------------------------------------------------------------------------------------
\1\ There is no capital or operating and maintenance cost associated with this collection of information.

VII. Environmental Impact

    We have carefully considered the potential environmental impacts of 
this final 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.

VIII. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. FDA has determined that the 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, the agency has concluded 
that the rule does not contain policies that have federalism 
implications as defined in the Executive order and, consequently, a 
federalism summary impact statement is not required.

List of Subjects

21 CFR Part 20

    Confidential business information, Courts, Freedom of information, 
Government employees.

21 CFR Part 510

    Administrative practice and procedure, Animal drugs, Labeling, 
Reporting and recordkeeping requirements.

21 CFR Parts 514 and 516

    Administrative practice and procedure, Animal drugs, Confidential 
business information, Reporting and recordkeeping requirements.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR 
chapter I is amended as follows:

PART 20--PUBLIC INFORMATION

0
1. The authority citation for 21 CFR part 20 continues to read as 
follows:

    Authority:  5 U.S.C. 552; 18 U.S.C. 1905; 19 U.S.C. 2531-2582; 
21 U.S.C. 321-393, 1401-1403; 42 U.S.C. 241, 242, 242a, 242l, 242n, 
243, 262, 263, 263b-263n, 264, 265, 300u-300u-5, 300aa-1.

0
2. Amend Sec.  20.100 by adding paragraph (c)(43) to read as follows:


Sec.  20.100   Applicability; cross-reference to other regulations.

* * * * *
    (c) * * *
    (43) Minor-use or minor-species (MUMS) drug designations, in Sec.  
516.52 of this chapter.

PART 510--NEW ANIMAL DRUGS

0
3. 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.

0
4. Amend Sec.  510.3 by revising paragraph (k) to read as follows:


Sec.  510.3   Definitions and interpretations.

* * * * *
    (k) Sponsor means the person requesting designation for a minor-use 
or minor-species drug as defined in part 516 of this chapter, who must 
be the real party in interest of the development and the intended or 
actual production and sales of such drug (in this context, the sponsor 
may be an individual, partnership, organization, or association). 
Sponsor also means the person responsible for an investigation of a new 
animal drug. In this context, the sponsor may be an individual, 
partnership, corporation, or Government agency or may be a 
manufacturer, scientific institution, or an investigator regularly and 
lawfully engaged in the investigation of new animal drugs. Sponsor also 
means the person submitting or receiving approval for a new animal drug 
application (in this context, the sponsor may be an individual, 
partnership, organization, or association). In all contexts, the 
sponsor is responsible for compliance with applicable provisions of the 
act and regulations.

PART 514--NEW ANIMAL DRUG APPLICATIONS

0
5. The authority citation for 21 CFR part 514 continues to read as 
follows:

    Authority:  21 U.S.C. 321, 331, 351, 352, 353, 360b, 371, 379e, 
381.


Sec.  514.1   [Amended]

0
6. Amend Sec.  514.1 by removing paragraph (d).

0
7. Add part 516 to read as follows:

PART 516--NEW ANIMAL DRUGS FOR MINOR USE AND MINOR SPECIES

Subpart A--General Provisions

Sec.
516.1 Scope.
516.2 Purpose.
516.3 Definitions.

Subpart B--Designation of a Minor Use or Minor Species New Animal Drug

516.11 Scope of this subpart.
516.12 Purpose.
516.13 Definitions.
516.14 Submission of requests for designation.
516.16 Eligibility to request designation.
516.20 Content and format of a request for MUMS-drug designation.
516.21 Documentation of minor use status.
516.22 Permanent-resident U.S. agent for foreign sponsor.
516.23 Timing of requests for MUMS-drug designation.

[[Page 41018]]

516.24 Granting MUMS-drug designation.
516.25 Refusal to grant MUMS-drug designation.
516.26 Amendment to MUMS-drug designation.
516.27 Change in sponsorship.
516.28 Publication of MUMS-drug designations.
516.29 Termination of MUMS-drug designation.
516.30 Annual reports for a MUMS-designated drug.
516.31 Scope of MUMS-drug exclusive marketing rights.
516.34 FDA recognition of exclusive marketing rights.
516.36 Insufficient quantities of MUMS-designated drugs.
516.52 Availability for public disclosure of data and information in 
requests.

Subpart C--[Reserved]

Subpart D--[Reserved]

    Authority:  21 U.S.C. 360ccc-2, 371.

Subpart A--General Provisions


Sec.  516.1   Scope.

    (a) This part implements section 573 of the Federal Food, Drug, and 
Cosmetic Act (the act) (21 U.S.C. 360ccc-2) and contains the following 
subparts:
    (1) Subpart A--General Provisions.
    (2) Subpart B--Designation of a Minor Use or Minor Species New 
Animal Drug.
    (3) Subpart C--[Reserved]
    (4) Subpart D--[Reserved]
    (b) References in this part to regulatory sections of the Code of 
Federal Regulations are to Chapter I of Title 21, unless otherwise 
noted.


Sec.  516.2   Purpose.

    This part establishes standards and procedures for implementing 
section 573 of the act, including designation of minor use or minor 
species new animal drugs and associated exclusive marketing rights.


Sec.  516.3   Definitions.

    (a) The definitions and interpretations contained in section 201 of 
the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321) 
apply to those terms when used in this part.
    (b) The following definitions of terms apply to all subparts of 
part 516:
    Active moiety means the molecule or ion, excluding those appended 
portions of the molecule that cause the drug to be an ester, salt 
(including a salt with hydrogen or coordination bonds), or other 
noncovalent derivative (such as a complex, chelate, or clathrate) of 
the molecule, responsible for the pharmacological action of the drug 
substance.
    Functionally superior means that a drug has been shown to provide a 
significant therapeutic or physiologic advantage over that provided by 
a conditionally-approved or approved MUMS drug, that is otherwise the 
same drug, in one or more of the following ways:
    (i) The drug has been shown to be more effective, as assessed by 
effect on a clinically meaningful endpoint in adequate and well-
controlled clinical trials, than a conditionally approved or approved 
MUMS drug, that is otherwise the same drug. Generally, this would 
represent the same kind of evidence needed to support a comparative 
effectiveness claim for two different drugs; in most cases, direct 
comparative clinical trials will be necessary; or
    (ii) The drug has been shown to be safer than a conditionally-
approved or approved MUMS drug, that is otherwise the same drug, in a 
substantial portion of the target population, for example, by the 
elimination of an ingredient or contaminant that is associated with 
relatively frequent adverse effects. In some cases, direct comparative 
clinical trials will be necessary.
    Infrequently, as used in the minor use definition, means a disease 
or condition that is uncommon or that occurs only sporadically on an 
annualized basis.
    Limited geographical areas, as used in the minor use definition, 
means regions of the United States distinguished by physical, chemical, 
or biological factors that limit the distribution of a disease or 
condition.
    Major species means cattle, horses, swine, chickens, turkeys, dogs, 
and cats.
    Minor species means animals, other than humans, that are not major 
species.
    Minor use means the intended use of a drug in a major species for 
an indication that occurs infrequently and in only a small number of 
animals or in limited geographical areas and in only a small number of 
animals annually.
    MUMS drug means a new animal drug, as defined in section 201 of the 
act, intended for a minor use or for use in a minor species.
    Same dosage form means the same as one of the dosage forms 
specified in the following parts of this chapter:
    (i) Part 520: Oral dosage form new animal drugs (excluding use in 
animal feeds as specified in part 558 of this chapter).
    (ii) Part 522: Implantation or injectable dosage form new animal 
drugs.
    (iii) Part 524: Ophthalmic and topical dosage form new animal 
drugs.
    (iv) Part 526: Intramammary dosage forms.
    (v) Part 529: Certain other dosage form new animal drugs.
    (vi) Part 558: New animal drugs for use in animal feeds.
    Same drug means a MUMS drug for which designation, indexing, or 
conditional approval is sought that meets the following criteria:
    (i) If it is a MUMS drug composed of small molecules and contains 
the same active moiety as a prior designated, conditionally-approved, 
or approved MUMS drug, even if the particular ester or salt (including 
a salt with hydrogen or coordination bonds) or other noncovalent 
derivative such as a complex, chelate or clathrate is not the same, it 
is considered the same drug; except that, if the prior MUMS drug is 
conditionally approved or approved and the second MUMS drug is shown to 
be functionally superior to the conditionally approved or approved MUMS 
drug for the same intended use, it is not considered the same drug.
    (ii) If it is a MUMS drug composed of large molecules 
(macromolecules) and contains the same principal molecular structural 
features (but not necessarily all of the same structural features) as a 
prior designated, conditionally approved, or approved MUMS drug, it is 
considered the same drug; except that, if the prior MUMS drug is 
conditionally approved or approved and the second MUMS drug is shown to 
be functionally superior to the conditionally approved or approved MUMS 
drug for the same intended use, it is not considered the same drug. 
This criterion will be applied as follows to different kinds of 
macromolecules:
    (A) Two protein drugs would be considered the same if the only 
differences in structure between them were due to post-translational 
events or infidelity of translation or transcription or were minor 
differences in amino acid sequence; other potentially important 
differences, such as different glycosylation patterns or different 
tertiary structures, would not cause the drugs to be considered 
different unless the subsequent drug is shown to be functionally 
superior.
    (B) Two polysaccharide drugs would be considered the same if they 
had identical saccharide repeating units, even if the number of units 
were to vary and even if there were postpolymerization modifications, 
unless the subsequent drug is shown to be functionally superior.
    (C) Two polynucleotide drugs consisting of two or more distinct 
nucleotides would be considered the same if they had an identical 
sequence of purine and pyrimidine bases (or their derivatives) bound to 
an identical sugar backbone (ribose, deoxyribose, or modifications of 
these sugars), unless

[[Page 41019]]

the subsequent drug is shown to be functionally superior.
    (D) Closely related, complex partly definable drugs with similar 
pharmacologic intent would be considered the same unless the subsequent 
drug is shown to be functionally superior.
    Same intended use means an intended use of a MUMS drug, for which 
designation, indexing, or conditional approval is sought, that is 
determined to be the same as (or not different from) a previously 
designated, conditionally approved, or approved intended use of a MUMS 
drug. Same intended use is established by comparing two intended uses 
and not by simply comparing the specific language by means of which the 
intent is established in labeling in accordance with the following 
criteria:
    (i) Two intended uses are considered the same if one of the 
intended uses falls completely within the scope of the other.
    (ii) For intended uses associated with diseases or conditions with 
multiple causative organisms, two intended uses are not considered the 
same when they involve different causative organisms or different 
subsets of causative organisms of that disease or condition when the 
causative organisms involved can reliably be shown to be clinically 
significant causes of the disease or condition.
    (iii) Two intended uses of a drug are not considered the same if 
they involve different intended species or different definable 
subpopulations (including ``production classes'') of a species.
    Sponsor means the person requesting designation for a MUMS drug who 
must be the real party in interest of the development and the intended 
or actual production and sales of such drug (in this context, the 
sponsor may be an individual, partnership, organization, or 
association). Sponsor also means the person responsible for an 
investigation of a new animal drug (in this context, the sponsor may be 
an individual, partnership, corporation, or Government agency or may be 
a manufacturer, scientific institution, or an investigator regularly 
and lawfully engaged in the investigation of new animal drugs). Sponsor 
also means the person submitting or receiving approval for a new animal 
drug application (in this context, the sponsor may be an individual, 
partnership, organization, or association). In all contexts, the 
sponsor is responsible for compliance with applicable provisions of the 
act and regulations.

Subpart B--Designation of a Minor Use or Minor Species New Animal 
Drug


Sec.  516.11   Scope of this subpart.

    This subpart implements section 573 of the act. Specifically, this 
subpart sets forth the procedures and requirements for submissions to 
FDA of requests for designation of a new animal drug for a minor use or 
a minor species.


Sec.  516.12   Purpose.

    This subpart establishes standards and procedures for determining 
eligibility for designation and the associated incentives and benefits 
described in section 573 of the act, including a 7-year period of 
exclusive marketing rights.


Sec.  516.13   Definitions.

    The following definitions of terms apply only in the context of 
subpart B of this part:
    Director means the Director of the Office of Minor Use and Minor 
Species Animal Drug Development of the FDA Center for Veterinary 
Medicine.
    Intended use means the intended treatment, control or prevention of 
a disease or condition, or the intention to affect the structure or 
function of the body of animals within an identified species, 
subpopulation of a species, or collection of species.
    MUMS-designated drug means a new animal drug, as defined in section 
201 of the act, intended for a minor use or for use in a minor species 
that has been designated under section 573 of the act.
    MUMS-drug exclusive marketing rights or exclusive marketing rights 
means that, effective on the date of FDA conditional approval or 
approval as stated in the approval letter of an application for a MUMS-
designated drug, no conditional approval or approval will be given to a 
subsequent application for the same drug, in the same dosage form, for 
the same intended use for 7 years, except as otherwise provided by law 
or in this subpart.


Sec.  516.14   Submission of requests for designation.

    All correspondence relating to a request for designation of a MUMS 
drug must be addressed to the Director of the Office of Minor Use and 
Minor Species Animal Drug Development. Submissions not including all 
elements specified in Sec.  516.20 will be returned to the sponsor 
without review.


Sec.  516.16   Eligibility to request designation.

    The person requesting designation must be the sponsor and the real 
party in interest of the development and the intended or actual 
production and sales of the drug or the permanent-resident U.S. agent 
for such a sponsor.


Sec.  516.20   Content and format of a request for MUMS-drug 
designation.

    (a) A sponsor that submits a request for designation of a new 
animal drug intended for a minor use or minor species must submit each 
request in the form and containing the information required in 
paragraph (b) of this section. While a request for designation may 
involve multiple intended uses, each request for designation must 
constitute a separate submission. A sponsor may request MUMS-drug 
designation of a previously unapproved drug, or a new intended use or 
dosage form for an already conditionally approved or approved drug. 
Only one sponsor may receive MUMS-drug designation of the same drug, in 
the same dosage form, for the same intended use.
    (b) A sponsor must submit two copies of a completed, dated, and 
signed request for designation that contains the following information:
    (1) A request for designation of a new animal drug for a minor use 
or use in a minor species, which must be specific.
    (2) The name and address of the sponsor; the name of the sponsor's 
primary contact person and/or permanent-resident U.S. agent including 
title, address, and telephone number; the generic and trade name, if 
any, of the drug; and the name and address of the source of the drug.
    (3) A description of the proposed intended use for which the drug 
is being or will be investigated.
    (4) A description of the drug and dosage form.
    (5) A discussion of the scientific rationale for the intended use 
of the drug; specific reference, including date(s) of submission, to 
all data from nonclinical laboratory studies, clinical investigations, 
copies of pertinent unpublished and published papers, and other 
relevant data that are available to the sponsor, whether positive, 
negative, or inconclusive.
    (6) A specific description of the product development plan for the 
drug, its dosage form, and its intended use.
    (7) If the drug is intended for a minor use in a major species, 
documentation in accordance with Sec.  516.21, with appended 
authoritative references, to demonstrate that such use is a minor use.
    (8) A statement that the sponsor submitting the request is the real 
party in interest of the development and the intended or actual 
production and sales of the product.
    (9) A statement that the sponsor acknowledges that, upon granting a

[[Page 41020]]

request for MUMS designation, FDA will make information regarding the 
designation publicly available as specified in Sec.  516.28.


Sec.  516.21   Documentation of minor use status.

    So that FDA can determine whether a drug qualifies for MUMS-drug 
designation as a minor use in a major species under section 573 of the 
act, the sponsor shall include in its request to FDA for MUMS-drug 
designation under Sec.  516.20 documentation demonstrating that the use 
is limited to a small number of animals (annualized). This 
documentation must include the following information:
    (a) The estimated total number of animals to which the drug could 
potentially be administered on an annual basis for the treatment, 
control, or prevention of the disease or condition for which the drug 
is being developed, including animals administered the drug as part of 
herd or flock treatment, together with a list of the sources (including 
dates of information provided and literature citations) for the 
estimate.
    (b) The estimated total number of animals referred to in paragraph 
(a) of this section may be further reduced to only a subset of the 
estimated total number of animals if administration of the drug is only 
medically justified for this subset. To establish this, requestors must 
demonstrate that administration of the drug to animals subject to the 
disease or condition for which the drug is being developed other than 
the subset is not medically justified. The sponsor must also include a 
list of the sources (including dates of information provided and 
literature citations) for the justification that administration of the 
drug to animals other than the targeted subset is medically 
inappropriate.
    (c) An estimate of the potential market associated with the total 
number of animals established in paragraph (a) of this section compared 
to an estimate of the development costs of the proposed drug, in the 
proposed dosage form, for the proposed intended use.


Sec.  516.22   Permanent-resident U.S. agent for foreign sponsor.

    Every foreign sponsor that seeks MUMS-drug designation shall name a 
permanent resident of the United States as the sponsor's agent upon 
whom service of all processes, notices, orders, decisions, 
requirements, and other communications may be made on behalf of the 
sponsor. Notifications of changes in such agents or changes of address 
of agents should preferably be provided in advance, but not later than 
60 days after the effective date of such changes. The permanent-
resident U.S. agent may be an individual, firm, or domestic corporation 
and may represent any number of sponsors. The name and address of the 
permanent-resident U.S. agent shall be provided to the Director of the 
Office of Minor Use and Minor Species Animal Drug Development.


Sec.  516.23   Timing of requests for MUMS-drug designation.

    A sponsor may request MUMS-drug designation at any time in the drug 
development process prior to the submission of an application for 
either conditional approval or approval of the MUMS drug for which 
designation is being requested.


Sec.  516.24   Granting MUMS-drug designation.

    (a) FDA may grant the request for MUMS-drug designation if none of 
the reasons described in Sec.  516.25 for refusal to grant such a 
request apply.
    (b) When a request for MUMS-drug designation is granted, FDA will 
notify the sponsor in writing and will give public notice of the MUMS-
drug designation in accordance with Sec.  516.28.


Sec.  516.25   Refusal to grant MUMS-drug designation.

    (a) FDA will refuse to grant a request for MUMS-drug designation if 
any of the following reasons apply:
    (1) The drug is not intended for use in a minor species or FDA 
determines that there is insufficient evidence to demonstrate that the 
drug is intended for a minor use in a major species.
    (2) The drug is the same drug in the same dosage form for the same 
intended use as one that already has a MUMS-drug designation but has 
not yet been conditionally approved or approved.
    (3) The drug is the same drug in the same dosage form for the same 
intended use as one that is already conditionally approved or approved. 
A drug that FDA has found to be functionally superior is not considered 
the same drug as an already conditionally approved or approved drug 
even if it is otherwise the same drug in the same dosage form for the 
same intended use.
    (4) The sponsor has failed to provide:
    (i) A credible scientific rationale in support of the intended use,
    (ii) Sufficient information about the product development plan for 
the drug, its dosage form, and its intended use to establish that 
adherence to the plan can lead to successful drug development in a 
timely manner, and
    (iii) Any other information required under Sec.  516.20.
    (b) FDA may refuse to grant a request for MUMS-drug designation if 
the request for designation contains an untrue statement of material 
fact or omits material information.


Sec.  516.26   Amendment to MUMS-drug designation.

    (a) At any time prior to conditional approval or approval of an 
application for a MUMS-designated drug, the sponsor may apply for an 
amendment to the designated intended use if the proposed change is due 
to new and unexpected findings in research on the drug, information 
arising from FDA recommendations, or other unforeseen developments.
    (b) FDA will grant the amendment if it finds:
    (1) That the initial designation request was made in good faith;
    (2) That the amendment is intended to make the MUMS-drug designated 
intended use conform to the results of new and unexpected findings in 
research on the drug, information arising from FDA recommendations, or 
other unforeseen developments; and
    (3) In the case of a minor use, that as of the date of the 
submission of the amendment request, the amendment would not result in 
the intended use of the drug no longer being considered a minor use.


Sec.  516.27   Change in sponsorship.

    (a) A sponsor may transfer sponsorship of a MUMS-designated drug to 
another person. A change of sponsorship will also transfer the 
designation status of the drug which will remain in effect for the new 
sponsor subject to the same conditions applicable to the former sponsor 
provided that at the time of a potential transfer, the new and former 
sponsors submit the following information in writing and obtain 
permission from FDA:
    (1) The former sponsor shall submit a letter to FDA that documents 
the transfer of sponsorship of the MUMS-designated drug. This letter 
shall specify the date of the transfer. The former sponsor shall also 
certify in writing to FDA that a complete copy of the request for MUMS-
drug designation, including any amendments to the request, and 
correspondence relevant to the MUMS-drug designation, has been provided 
to the new sponsor.
    (2) The new sponsor shall submit a letter or other document 
containing the following information:
    (i) A statement accepting the MUMS-drug designated file or 
application;
    (ii) The date that the change in sponsorship is intended to be 
effective;
    (iii) A statement that the new sponsor has a complete copy of the 
request for

[[Page 41021]]

MUMS-drug designation, including any amendments to the request and any 
correspondence relevant to the MUMS-drug designation;
    (iv) A statement that the new sponsor understands and accepts the 
responsibilities of a sponsor of a MUMS-designated drug established 
elsewhere in this subpart;
    (v) The name and address of a new primary contact person or 
permanent resident U.S. agent; and
    (vi) Evidence that the new sponsor is capable of actively pursuing 
approval with due diligence.
    (b) No sponsor may relieve itself of responsibilities under the act 
or under this subpart by assigning rights to another person without:
    (1) Assuring that the new sponsor will carry out such 
responsibilities; and
    (2) Obtaining prior permission from FDA.


Sec.  516.28   Publication of MUMS-drug designations.

    FDA will periodically update a publicly available list of MUMS-
designated drugs. This list will be placed on file at the FDA Division 
of Dockets Management, and will contain the following information for 
each MUMS-designated drug:
    (a) The name and address of the sponsor;
    (b) The established name and trade name, if any, of the drug;
    (c) The dosage form of the drug;
    (d) The species and the proposed intended use for which MUMS-drug 
designation was granted; and
    (e) The date designation was granted.


Sec.  516.29   Termination of MUMS-drug designation.

    (a) The sponsor of a MUMS-designated drug must notify FDA of any 
decision to discontinue active pursuit of conditional approval or 
approval of such MUMS drug. FDA must terminate the designation upon 
such notification.
    (b) A conditionally-approved or approved MUMS-designated drug 
sponsor must notify FDA at least 1 year before it intends to 
discontinue the manufacture of such MUMS drug. FDA must terminate 
designation upon such notification.
    (c) MUMS designation shall terminate upon the expiration of any 
applicable period of exclusive marketing rights under this subpart.
    (d) FDA may terminate designation if it independently determines 
that the sponsor is not actively pursuing conditional approval or 
approval with due diligence. At a minimum, due diligence must be 
demonstrated by:
    (1) Submission of annual progress reports in a timely manner in 
accordance with Sec.  516.30 that demonstrate that the sponsor is 
progressing in accordance with the drug development plan submitted to 
the agency under Sec.  516.20 and
    (2) Compliance with all applicable requirements of part 511 of this 
chapter.
    (e) Designation of a conditionally approved or approved MUMS-
designated drug and the associated exclusive marketing rights may be 
terminated if the sponsor is unable to provide sufficient quantities of 
the drug to meet the needs for which it is designated.
    (f) FDA may also terminate MUMS-drug designation for any drug if 
the agency finds that:
    (1) The request for designation contained an untrue statement of 
material fact; or
    (2) The request for designation omitted material information 
required by this subpart; or
    (3) FDA subsequently finds that the drug in fact had not been 
eligible for MUMS-drug designation at the time of submission of the 
request;
    (4) The same drug, in the same dosage form, for the same intended 
use becomes conditionally approved or approved for another sponsor; or
    (5) FDA withdraws the conditional approval or approval of the 
application for the new animal drug.
    (g) For a conditionally approved or approved drug, termination of 
MUMS-drug designation also terminates the sponsor's exclusive marketing 
rights for the drug but does not withdraw the conditional approval or 
approval of the drug's application.
    (h) Where a drug has been MUMS-designated for a minor use in a 
major species, its designation will not be terminated on the grounds 
that the number of animals to which the drug could potentially be 
administered on an annual basis for the treatment, control, or 
prevention of the disease or condition for which the drug is being 
developed, including animals administered the drug as part of herd or 
flock treatment, subsequently increases.
    (i) When a MUMS-drug designation is terminated, FDA will notify the 
sponsor in writing and will give public notice of the termination of 
the MUMS-drug designation.


Sec.  516.30   Annual reports for a MUMS-designated drug.

    Within 14 months after the date on which a MUMS drug is granted 
designation and annually thereafter until approval, the sponsor of a 
MUMS-designated drug shall submit a brief progress report on the drug 
to the investigational new animal drug file addressed to the Director 
of the Office of Minor Use and Minor Species Animal Drug Development 
that includes the following information:
    (a) A short account of the progress of drug development including a 
description of studies initiated, ongoing, and completed, and a short 
summary of the status or results of such studies;
    (b) A description of the investigational plan for the coming year, 
as well as any anticipated difficulties in development, testing, and 
marketing; and
    (c) A brief discussion of any changes that may affect the MUMS-
designated drug status of the product. For example, situations in which 
testing data demonstrate that the proposed intended use is 
inappropriate due to unexpected issues of safety or effectiveness.


Sec.  516.31   Scope of MUMS-drug exclusive marketing rights.

    (a) After conditional approval or approval of an application for a 
MUMS-designated drug in the dosage form and for the intended use for 
which MUMS-drug designation has been granted, FDA will not 
conditionally approve or approve another application or abbreviated 
application for the same drug in the same dosage form for the same 
intended use before the expiration of 7 years after the date of 
conditional approval or approval as stated in the approval letter from 
FDA, except that such an application can be conditionally approved or 
approved sooner if, and at such time as, any of the following occurs:
    (1) FDA terminates the MUMS-drug designation and associated 
exclusive marketing rights under Sec.  516.29; or
    (2) FDA withdraws the conditional approval or approval of the 
application for the drug for any reason; or
    (3) The sponsor with exclusive marketing rights provides written 
consent to FDA to conditionally approve or approve another application 
before the expiration of 7 years; or
    (4) The sponsor fails to assure a sufficient quantity of the drug 
in accordance with section 573 of the act and Sec.  516.36.
    (b) If an application for a MUMS drug cannot be approved until the 
expiration of the period of exclusive marketing of a MUMS-designated 
drug, FDA will so notify the sponsor in writing.


Sec.  516.34   FDA recognition of exclusive marketing rights.

    (a) FDA will send the sponsor (or the permanent-resident U.S. 
agent, if applicable) timely written notice recognizing exclusive 
marketing rights when an application for a MUMS-

[[Page 41022]]

designated drug has been conditionally approved or approved. The 
written notice will inform the sponsor of the requirements for 
maintaining MUMS-designated drug exclusive marketing rights for the 
full 7-year term. This notice will generally be contained in the letter 
conditionally approving or approving the application.
    (b) When an application is conditionally approved or approved for a 
MUMS-designated drug that qualifies for exclusive marketing rights, FDA 
will publish this information in the Federal Register at the time of 
the conditional approval or approval. This notice will generally be 
contained in the notice of conditional approval or approval of the 
application.


Sec.  516.36   Insufficient quantities of MUMS-designated drugs.

    (a) Under section 573 of the act, whenever FDA has reason to 
believe that sufficient quantities of a conditionally-approved or 
approved, MUMS-designated drug to meet the needs for which the drug was 
designated cannot be assured by the sponsor, FDA will so notify the 
sponsor of this possible insufficiency and will offer the sponsor the 
following options, one of which must be exercised by a time that FDA 
specifies:
    (1) Provide FDA information and data regarding how the sponsor can 
assure the availability of sufficient quantities of the MUMS-designated 
drug within a reasonable time to meet the needs for which the drug was 
designated; or
    (2) Provide FDA in writing the sponsor's consent for the 
conditional approval or approval of other applications for the same 
drug before the expiration of the 7-year period of exclusive marketing 
rights.
    (b) If, within the time that FDA specifies, the sponsor fails to 
consent to the conditional approval or approval of other applications 
and if FDA finds that the sponsor has not shown that it can assure the 
availability of sufficient quantities of the MUMS-designated drug to 
meet the needs for which the drug was designated, FDA will issue a 
written order terminating designation of the MUMS drug and the 
associated exclusive marketing rights. This order will state FDA's 
findings and conclusions and will constitute final agency action. An 
order terminating designation and associated exclusive marketing rights 
may issue whether or not there are other sponsors that can assure the 
availability of alternative sources of supply. Such an order will not 
withdraw the conditional approval or approval of an application. Once 
terminated under this section, neither designation, nor exclusive 
marketing rights may be reinstated.


Sec.  516.52   Availability for public disclosure of data and 
information in requests.

    (a) FDA will not publicly disclose the existence of a request for 
MUMS-drug designation under section 573 of the act prior to final FDA 
action on the request unless the existence of the request has been 
previously publicly disclosed or acknowledged.
    (b) Whether or not the existence of a pending request for 
designation has been publicly disclosed or acknowledged, no data or 
information in the request are available for public disclosure prior to 
final FDA action on the request.
    (c) Except as provided in paragraph (d) of this section, upon final 
FDA action on a request for designation, the public availability of 
data and information in the request will be determined in accordance 
with part 20 of this chapter and other applicable statutes and 
regulations.
    (d) In accordance with Sec.  516.28, FDA will make a cumulative 
list of all MUMS-drug designations available to the public and update 
such list periodically. In accordance with Sec.  516.29, FDA will give 
public notice of the termination of all MUMS-drug designations.

Subpart C--[Reserved]

Subpart D--[Reserved]

    Dated: March 12, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.

    Editorial Note: This document was received at the Office of the 
Federal Register on July 23, 2007.
[FR Doc. E7-14444 Filed 7-25-07; 8:45 am]
BILLING CODE 4160-01-S