56394 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

* * * * * 

Issued in Washington, DC, on September 

19, 2005. 

Edith V. Parish, 

Acting Manager, Airspace and Rules. 

[FR Doc. 05–19205 Filed 9–26–05; 8:45 am] 

BILLING CODE 4910–13–P 

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: Proposed rule. 

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 

proposed regulations to implement the 

act. These regulations propose 

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: Submit written or electronic 

comments on this document by 

December 12, 2005. Submit comments 

on the information collection provisions 

by October 27, 2005. 

ADDRESSES: You may submit comments, 

identified by Docket No. 2005N–0329 

and/or RIN number 0910–AF60, by any 

of the following methods: 

Electronic Submissions 

Submit electronic comments in the 

following ways: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• Agency Web site: http:// 

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 (HFA305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. 

To ensure timely processing of 

electronic 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 and agency Web 

site, as described in the Electronic 

Submissions portion of this paragraph. 

Instructions: All submissions received 

must include the agency name and 

docket number or regulatory 

information number for this rulemaking. 

All comments received may be posted 

without change to http://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 http:// 

www.fda.gov/ohrms/dockets/ 

default.htm and insert the docket 

number 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. 

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, email: Andrew.Beaulieu@fda.gov. 

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 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 these animal drugs. 

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 (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. 

At this time, FDA is issuing proposed 

regulations to implement section 573 of 

the act (21 U.S.C. 360ccc-2). These 

regulations propose 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. In accordance with 

section 573 of the act, these proposed 

regulations provide for designation of a 

new animal drug to be granted only 

when the drug is intended for a minor 

use or use in a minor species and only 

when the same new animal drug, in the 

same dosage form, for the same 

intended use is not already approved 

under section 512 of the act (21 U.S.C. 

360b), conditionally approved under 

section 571 of the act (21 U.S.C. 360ccc), 

or designated under section 573 of the 

act at the time that a sponsor requests 

designation. 

The incentives in the MUMS act and 

these proposed regulations are modeled 

on those provided by the human orphan 

drug program. These incentives include 

the following: (1) 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 and (2) a 

7-year period of exclusive marketing 

rights to enable sponsors to recover 

costs of drug development without 

competition. Marketing exclusivity for 

nondesignated drugs is limited to 3 or 

5 years of protection from generic 

copying (section 512(c)(2)(F) of the act). 

The exclusive marketing rights for 

designated drugs provide protection 

from generic copying and from approval 

of another pioneer application for the 

same drug, in the same dosage form, for 

the same intended use. 

Other major incentives of the MUMS 

act include the following: (1) 

Conditional approval, which is 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56395 

established by section 571 of the act and 

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 (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) and (2) 

indexing, which is established by 

section 572 of the act (21 U.S.C. 360ccc1) and provides for legal marketing of 

unapproved new animal drugs through 

an integrated process of agency and 

expert panel review of drugs intended 

only for use in minor species. 

Regulations to implement these 

provisions of the MUMS act will be 

proposed in the future. 

II. Proposed Regulations 

A. Definitions (Proposed §§ 516.3 and 

516.13) 

Under the MUMS act, there are two 

key factors in determining the eligibility 

of a new animal drug for designation: (1) 

The new animal drug must be intended 

for minor use or use in a minor species 

and (2) the new animal drug must not 

be the same drug, in the same dosage 

form, and for the same intended use as 

an animal drug already designated, 

conditionally approved, or approved. 

The agency is proposing definitions for 

terms or phrases relevant to the 

proposed regulations. Discussion 

regarding key definitions follows. 

1. Minor Species 

The MUMS act defines minor species 

as animals other than humans that are 

not major species. The MUMS act 

defines major species as cattle, horses, 

swine, chickens, turkeys, dogs, and cats, 

along with any species the Secretary of 

Health and Human Services adds to this 

definition by regulation (see section 

201(nn) and (oo) of the act (21 U.S.C. 

321 (nn) and (oo)).) The proposed rule 

includes these definitions for ‘‘major 

species’’ and ‘‘minor species’’ in 

proposed § 516.3(b)(5) and (b)(6). 

2. Minor Use 

The MUMS act defines ‘‘minor use’’

to mean ‘‘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’’ (section 

201(pp) of the act). 

With respect to the definition of 

minor use, the Senate report (S. Rept. 

108–226) concerning the bill before the 

Senate (S. 741), which included 

proposed definitions and a section on 

the designation of new animal drugs 

that were identical to those contained in 

the MUMS legislation enacted by 

Congress, stated the following: 

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.) 

As is clear from the quoted discussion 

in the Senate report, Congress 

incorporated part of FDA’s existing 

definition of ‘‘minor use’’ in § 514.1 (21 

CFR 514.1) into the MUMS act 

definition of ‘‘minor use.’’ In 1983 FDA 

issued a definition of ‘‘minor use’’ as 

part of regulations to provide for the 

agency’s interpretation as to what data 

for minor use drugs would be sufficient 

to meet the current statutory standards 

(see 48 FR 1922, January 14, 1983). 

FDA’s definition of ‘‘minor use’’

included use of drugs ‘‘in any animal 

species for the control of a disease that 

(1) occurs infrequently or (2) occurs in 

limited geographic areas’’

(§ 514.1(d)(1)(i)). Thus, minor use was 

previously only defined qualitatively by 

one of two factors that limited the size 

of the population needing treatment. 

The first limiting factor was that a 

disease occurred infrequently (i.e., 

rarely) in the total population of 

animals. FDA believes that the term 

‘‘infrequently’’ includes both diseases or 

conditions that are uncommon in that 

they have a low but regular rate of 

occurrence over time in a given 

population and diseases or conditions 

that occur only sporadically as irregular 

outbreaks in a given population with a 

significantly higher rate of occurrence 

than normal when they occur and may 

not occur at all between outbreaks. The 

second limiting factor was that a disease 

or condition occurred in only a limited 

geographic area. 

With the MUMS act, in respect to 

minor uses in major species, Congress 

added a ‘‘small number’’ limitation to 

both prongs of FDA’s earlier definition: 

‘‘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’’ (21 U.S.C. 321(pp)). The 

Senate report indicates that the ‘‘small 

number’’ limitation added to both 

prongs was to ensure that the intended 

uses would not be ‘‘extended to a wider 

use.’’ (S. Rept. 108–226 at 12). By doing 

this, Congress not only required that the 

population of animals be limited by one 

of the two qualitative factors, but also 

required that, in either case, the 

population of animals affected must also 

meet the ‘‘small number’’ quantitative 

criteria. As a result, while some 

indications may be infrequent (because 

they are uncommon or occur only 

sporadically), they must also meet the 

requirement that they occur in only a 

small number of animals. Similarly, an 

indication may occur in a limited 

geographical area, but it must also occur 

in only a small number of animals 

annually. Congress defined ‘‘minor use’’

populations as limited to a ‘‘small 

number,’’ but did not specify the small 

number(s), leaving it to the agency to 

further clarify the definition in this 

regard by regulation. 

With respect to the term 

‘‘infrequently,’’ the Senate report states 

that FDA should determine whether the 

‘‘incidence’’ of the disease ‘‘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’’ (S. Rept. 108–226 at 12–

13). With respect to both prongs of the 

‘‘minor use’’ definition, Congress did 

not intend FDA to establish a test of 

commercial value, but rather to 

determine ‘‘whether the expected low 

use of a drug would discourage its 

development’’ (S. Rept. 108–226 at 13). 

Consequently, FDA in these regulations 

has not established a dollar value or 

profit margin criterion in relation to 

‘‘minor use.’’

The term ‘‘annually’’ only appears in 

the second prong of the statutory 

definition of ‘‘minor use’’ in connection 

with the small number of animals with 

the disease ‘‘in limited geographical 

areas.’’ Thus, a minor use indication 

that occurs in a limited geographical 

area must also occur in a small number 

of animals annually. While ‘‘annually’’

does not apply to the first prong of the 

definition of minor use, ‘‘infrequently 

and in only a small number of animals’’, 

FDA believes that for ‘‘a small numbers 

of animals’’ to have meaning, data on 

the number of animals in which the 

indication occurs must be considered 

56396 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

over a period of time. FDA believes that 

to give effect to the statutory language, 

it is appropriate to annualize the data. 

For example, if a particular disease 

appears only once every 5 years, the 

number of animals may be relatively 

large, but when annualized, the disease 

may occur in only a ‘‘small number of 

animals.’’ Looking at annualized 

numbers of affected animals is a 

reasonable approach under the ‘‘minor 

use’’ definition to considering whether 

there are sufficient drug development 

incentives in the absence of the MUMS 

incentives. 

The term ‘‘limited geographical areas’’

is defined in proposed section 

516.3(b)(4) as follows: ‘‘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.’’ If, for example, an area’s 

mineral profile or moisture availability 

(chemical factors) can cause a medical 

condition directly (nutrient deficiency) 

or indirectly (suitable environment for 

specific parasites or bacteria), the case 

may be argued that the condition will 

only affect animals in that particular 

region. Chemical factors might also 

include possible environmental 

exposure to pesticides or other toxins 

used in a limited area. Physical factors 

such as altitude, proximity to salt or 

fresh water, or temperature can also 

influence the presence of parasites, 

vectors for parasites, as well as other 

microbes. These factors can also 

influence an animal’s susceptibility to 

disease directly (high altitude disease) 

or indirectly if conditions cause stresses 

that weaken the immune system. 

Biological factors include the presence 

of vectors for disease, presence of toxic 

plants, and inherent limitations of a 

species to live in a particular 

environment (e.g., saltwater versus 

freshwater fish). 

As is clear from the minor use 

definition, geographic limitations alone 

will not be sufficient to make a 

particular intended use a minor use in 

a major species. The number of animals 

that live in a particular limited 

geographic area can still be very large. 

It was clearly the intent of Congress to 

limit the definition of minor use to a 

small number of animals and that is the 

intent of the definitions included in this 

proposed rule. 

Small Number of Animals 

The agency intends at some time in 

the future to propose that ‘‘small 

number of animals’’ be defined in 

regulations as a specific number for 

each of the seven major species. 

However, the number of animals that 

will provide the upper limit for the 

definition of ‘‘small number of animals’’

for each major species is, at this time, 

difficult to identify. Many factors need 

to be considered in establishing these 

numbers. 

With respect to defining minor use, 

and by implication ‘‘small number of 

animals,’’ Congress further noted in the 

Senate report (S. Rept. 108–226) 

accompanying the MUMS act that: 

FDA may initially make such 

determinations on a case-by-case basis. These 

initial determinations may form the basis for 

establishing or revising regulations which 

clarify the grounds or the process for 

determining whether a new animal drug is 

intended for a ‘‘minor use’’. 

(S. Rept. 108–226 at 13). 

Therefore, at this time, the agency is 

proposing only to clarify various other 

aspects of the current statutory 

definition of minor use, to gather further 

information to support the 

establishment of a ‘‘small number of 

animals’’ for each major species, and to 

use the information currently available 

to make minor use determinations on a 

case-by-case basis. The agency 

particularly requests comment on the 

criteria it should use to determine the 

number that constitutes a ‘‘small 

number of animals’’ for each major 

species. Comments should clearly 

explain the rationale for any criteria 

suggested including economic, 

scientific, or other relevant factors. In an 

effort to stimulate comment and to 

increase the specificity of comments, 

the agency has summarized in the 

following paragraphs certain 

information it has considered to date 

regarding defining ‘‘small number of 

animals.’’

a. Human orphan drugs as a model. 

For human orphan drugs, the act 

provides that a disease or condition that 

affects less than 200,000 cases in the 

United States qualifies as a ‘‘rare disease 

or condition’’ (21 U.S.C. 360bb(a)(2)). As 

one approach to defining ‘‘small number 

of animals’’ for the purpose of 

implementing the MUMS act, the 

agency determined what percentage of 

the U.S. population of humans the 

number 200,000 represented when 

Congress enacted this meaning of ‘‘rare 

disease or condition.’’ This calculation 

provided a figure of roughly 0.1 percent 

of the population. This percentage was 

then applied to populations of major 

species in the United States. Initial 

analysis indicated that using the 0.1 

percent figure might be helpful with 

respect to dogs, cats, and horses. 

However, using this figure did not seem 

helpful for 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. Further analysis made clear 

that these factors were not sufficiently 

comparable for this approach to be 

viable, even for dogs, cats, and horses, 

and the approach was rejected. 

While FDA recognizes classes of 

animals within species in the animal 

drug development process (examples 

include beef versus dairy cattle and 

broiler versus laying chickens), the 

diversity of these classes and the 

difficulty in determining whether a 

disease or condition might be unique to 

a class would make using these 

subpopulations of a species problematic 

in determining a maximum number of 

animals for a minor disease or 

condition. Therefore, using one 

maximum number would appear to be 

appropriate for animal species as well as 

humans, because for each major animal 

species the small number is intended to 

be a reflection of the market potential 

for a drug. It is immaterial whether that 

market potential exists because the 

disease or condition is relatively evenly 

distributed throughout the population 

or is largely confined to a particular age, 

gender, breed, or production class 

within that population. If the same 

number of animals is involved in each 

case, the market potential is essentially 

the same in each case. Therefore, one 

number appears to be appropriate as a 

means of determining the ‘‘small 

number’’ for a ‘‘minor use’’ for each of 

the seven species, regardless of 

subpopulations. 

b. Characterizing the population of 

animals affected by a disease or 

condition. The human orphan drug 

maximum number for ‘‘rare disease or 

condition’’ is based on the prevalence of 

a disease or condition. That is the total 

number of people affected by the 

disease or condition at a given time. 

This differs from the incidence of a 

disease or condition, which is the 

number of new cases diagnosed over a 

period of time, e.g., the number of cases 

diagnosed per year. For several reasons, 

using prevalence of disease or condition 

is problematic for determining the 

number of animals for MUMS 

designation purposes. 

In the case of cattle, swine, chickens, 

and turkeys, the number of animals 

affected with a given disease or 

condition at a given time does not take 

into account the fact that for animals 

like broiler chickens, the lifespan is so 

short that several flocks will go through 

the same facility in a year. Therefore, 

the number of birds potentially ill and/ 

or treated over a year is much greater 

than the population that is ill on any 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56397 

given day. This suggests that the use of 

an incidence rate would be more 

appropriate in such cases. 

However, incidence rates alone are 

also an imperfect descriptor even in the 

case of cattle, swine, chickens, and 

turkeys. The number of animals 

diagnosed with a disease or condition 

does not accurately reflect the number 

that will be administered a drug. For 

example, in the case of chickens, 

treatment of individual birds is 

impractical. When there is an outbreak 

of disease the entire flock is treated, 

including individuals with no signs of 

illness. In an attempt to limit minor use 

to a small number of animals, the way 

that drugs are actually administered 

should be taken into account. The 

number should refer to all birds 

administered a drug, not just to those 

clinically ill. This is significant for the 

determination of small number of 

animals because the actual size of the 

market is larger than the number of sick 

birds. A similar situation exists with 

respect to drugs intended for diagnosis 

or prevention of a disease or condition 

in major species. Such drugs will be 

subject to the same small number as 

those intended for treatment of a disease 

or condition. 

Prevalence rates can be more 

appropriately used for horses, dogs, and 

cats because these animals’ life spans 

typically exceed 1 year. Such animals 

are likely to be treated for chronic 

diseases over several years. These are 

added to newly diagnosed cases to 

provide the prevalence of the disease. 

The number of humans diagnosed 

with a disease or condition (i.e., the 

prevalence of a disease in humans) is a 

close approximation of the number that 

will be treated for that disease or 

condition, if a treatment exists. For 

animals, there may be a very significant 

difference in the numbers of animals 

afflicted with a disease or condition and 

the number that will actually be 

diagnosed and treated. Many animals do 

not get regular veterinary care and, 

therefore, the probability of diagnosis is 

lower for animals than for humans. 

Furthermore, depending on the 

diagnosis, prognosis, and cost, a much 

higher percentage of animals will not be 

treated even after diagnosis. 

Economic issues figure prominently 

in the calculation of the number of 

animals that will be treated for a disease 

or condition. In contrast to human 

medicine, there is essentially no thirdparty payment for animal drugs. Thus, 

cost for the treatment of animals is a 

major consideration. Because euthanasia 

is an option for animals, expensive or 

difficult treatment may be rejected by 

animal owners. On the other hand, 

because dogs, cats, and horses may be 

highly valued as ‘‘family members,’’ the 

amount of money expended on 

individual animals of these species may 

far exceed that generally spent on 

individuals of the other major species of 

animals. 

In the case of animals of agricultural 

importance, the decision to treat is 

based almost entirely on economic 

factors. In the case of chickens, where 

the profit margin is pennies per bird, it 

is often not worthwhile to treat. 

It appears that for dogs, cats, and 

horses, the market potential for a drug 

at the time of its designation is 

reasonably represented by the total 

number of cases of the disease or 

condition estimated to exist over the 

course of a year at the time of a request 

for designation, taking into 

consideration that only a portion of the 

total affected population will actually be 

treated. 

In the case of cattle, swine, chickens, 

and turkeys, the market potential for a 

drug at the time of its designation is 

reasonably represented by an estimation 

of the number of cases of a disease or 

condition that will occur in the total 

population of animals that will be alive 

over the course of a year at the time of 

a request for designation, taking into 

consideration that herd/flock treatment 

increases the number of animals 

administered a drug, and also taking 

into consideration that only a portion of 

the total affected population (and 

associated herd/flock mates) will 

actually be treated. 

c. Other information to be considered. 

The agency is seeking information to 

help clarify three general issues with 

respect to each major animal species: 

• The cost of drug development for a 

new chemical entity, adding an 

intended use for a new major species to 

a drug already approved for an intended 

use in another major species, and 

adding a new intended use to an 

existing approved drug for the same 

major species; 

• The annual return on investment 

over a 7-year period necessary to 

stimulate the development of each of 

the previously mentioned costs; and 

• The number of animals eligible to 

be administered the drug on an annual 

basis necessary to produce these returns 

on investment. 

The information made available to 

FDA from all sources will be analyzed 

and used to establish the ‘‘small 

numbers of animals’’ for each major 

species needed to complete the 

clarification of the definition of minor 

use in major species. The agency 

reiterates its request for comment and 

solicits as much additional information 

as those commenting are willing to 

share regarding this issue. The FDA 

emphasizes that it is not now proposing 

a specific small number of animals for 

each major species, but is only 

proposing to establish such numbers in 

the future after it has collected 

additional information. In the 

meantime, it is proposing to make such 

decisions on a case-by-case basis using 

the best information available at the 

time a decision is required. 

3. Same Drug/Same Dosage Form/Same 

Intended Use 

For a new animal drug to be eligible 

for designation under section 573 of the 

act, it must be intended for minor use 

or use in a minor species and must not 

be the same drug, in the same dosage 

form, for the same intended use as an 

animal drug already designated, 

conditionally approved, or approved. 

Therefore, the agency is also proposing 

to define ‘‘same drug,’’ ‘‘same dosage 

form,’’ and ‘‘same intended use’’ in 

proposed section 516.3. 

a. Same drug. The first test of 

sameness to determine eligibility of an 

animal drug for designation is ‘‘same 

drug.’’ The legislative history of the 

MUMS act in Senate Committee Report 

108–226 states: 

The Secretary has discretion to define the 

term ‘‘same drug’’ as used in this section. In 

defining ‘‘same drug’’ the Secretary should 

take into account the purpose of this 

legislation to promote the development of 

minor use and minor species new animal 

drugs. A sponsor should be able to reap the 

benefits of designation only for products that 

are materially different from products that 

have already been approved, conditionally 

approved, or designated. So, for example, 

where two products differ only with respect 

to one or more inactive ingredients, they are 

the ‘‘same drug’’ for purposes of this section. 

(S. Rept. 108–226 at 19). 

The definition of ‘‘same drug’’

contained in this proposed rule is 

intended to give protection to the first 

conditionally-approved or approved 

MUMS-designated drug against a 

second sponsor’s attempts to defeat 

exclusive marketing rights by 

introducing minor molecular changes. 

Because one goal of the MUMS act is to 

increase the availability of new animal 

drugs for minor species and minor uses, 

a subsequent drug with minor chemical 

differences will be considered different 

only if the subsequent drug can be 

shown to be functionally superior to the 

first. The burden of proof is on the 

sponsor of the subsequent drug to 

demonstrate that its drug is safer or 

more effective in some way. 

FDA is proposing this approach 

because it provides the best available 

mechanism to protect the integrity of 

56398 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

marketing exclusivity, the chief 

incentive for MUMS drug development 

established by Congress, while allowing 

functionally superior drugs with similar 

chemical structure to be approved in a 

timely manner. This proposal is 

consistent with the human orphan drug 

regulations as codified in 21 CFR part 

316 (see 21 CFR 316.3(b)(13)). 

Functional superiority of a 

subsequent drug cannot be determined 

until the first drug is conditionally 

approved or approved because an 

unapproved drug has no labeled dosage 

and corresponding safety and 

effectiveness profile to which the 

challenger can be compared. Therefore, 

a sponsor of a subsequent drug with 

minor chemical differences from a 

MUMS-designated drug may not seek 

designation of the subsequent drug 

based on functional superiority until 

after the designated drug is 

conditionally approved or approved. If 

a drug is found to be functionally 

superior to a designated new animal 

drug after the designated drug is 

approved or conditionally approved, it 

will be considered a different drug and 

may be granted MUMS designation. 

After conditional approval or approval, 

it will enjoy its own 7-year period of 

exclusive marketing rights and the first 

drug’s designation, conditional approval 

or approval, and period of exclusive 

marketing will remain in effect. 

b. Same dosage form. The second test 

of sameness which the statute 

establishes to determine eligibility of an 

animal drug for designation is ‘‘same 

dosage form.’’ The agency proposes to 

use the long-established dosage form 

categories listed in Title 21 of the Code 

of Federal Regulations to implement 

this statutory requirement. 

The categories follow: Oral dosage 

forms (21 CFR 520), implantation or 

injectable dosage forms (21 CFR 522), 

ophthalmic and topical dosage forms 

(21 CFR 524), intramammary dosage 

forms (21 CFR 526), miscellaneous 

dosage forms (21 CFR 529), and drugs in 

animal feeds (21 CFR 558). 

Dosage forms that do not clearly fit 

within a specific category would fall 

within the miscellaneous category and 

the sameness of dosage form would be 

determined on a case-by-case basis. 

Drugs currently in the miscellaneous 

category include, for example, products 

administered by inhalation to terrestrial 

animals and products formulated for use 

by immersion of aquatic species. 

Although medicated animal feeds (i.e., 

drugs in animal feeds) have much in 

common with certain oral dosage forms, 

they are treated as a separate category 

because they are regulated quite 

differently. For example, drugs for use 

in animal feeds are subject to different 

manufacturing practices than other 

drugs and may not be used in an 

extralabel manner (21 CFR 530.11(b)). 

Thus, they are treated as separate dosage 

forms for purposes of implementing the 

MUMS act. 

c. Same intended use. The third test 

of sameness which the statute 

establishes to determine the eligibility 

of an animal drug for designation is 

‘‘same intended use.’’ ‘‘Intended use’’ is 

defined in proposed 516.3(b)(11) for the 

purposes of subpart B of part 516 as 

‘‘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.’’

Although this definition is generally 

consistent with the manner in which the 

phrase has been used in the context of 

new animal drug approval, the 

definition proposed here is to be 

applied solely to the phrase ‘‘intended 

use’’ as it is used in these proposed 

regulations to determine whether two 

intended uses are the ‘‘same intended 

use’’ for purposes of qualifying for 

designation. It is not meant to define 

‘‘intended use’’ in any other context. 

This interpretation of ‘‘intended use’’

for the purpose of designation is meant 

to protect the value of the exclusivity 

incentive provided by the statute. 

Because there can only be one 

designation for the ‘‘same drug,’’ ‘‘same 

dosage form,’’ and ‘‘same intended use,’’

it is important that a minor difference in 

the intended use not permit a second 

sponsor to be granted designation for 

virtually the same product. For the 

purpose of new animal drug approval, it 

is important that every intended use to 

be included on the label be supported 

by data. Thus, the definition of 

‘‘intended use’’ for purposes of 

designation reflects the need to protect 

product exclusivity. 

Accordingly, the agency identified 

four basic principles for evaluating 

whether two intended uses represent 

the ‘‘same intended use.’’ The first 

principle of ‘‘same intended use’’

establishes that whether two intended 

uses are considered the same, will not 

depend on whether exactly the same 

words are used to describe that intent 

on the labels of the products. Despite 

attempts over the years by FDA to 

increase the consistency of labeled 

intended uses (often also referred to as 

indications or claims), there remain 

many different ways to state the same 

intended use on a label. Differences in 

language alone do not necessarily result 

in different intended uses in the context 

of drug designation. For example, a 

disease or a causative organism may be 

known by several different names. The 

fact that two intended uses involve 

different names for the same disease or 

causative organism does not cause the 

intended uses to be different. 

The second principle of same 

intended use establishes that if one of 

the intended uses falls completely 

within the scope of the other, they are 

considered the same intended use for 

the purposes of designation. For 

example, an intended use for a 

particular disease or condition in all 

aquarium fish would include use for 

that disease or condition in black 

mollies (a type of aquarium fish) and, 

therefore, would be considered the same 

intended use for the same disease or 

condition in black mollies. Similarly, 

designation for black mollies would 

preclude a designation for all aquarium 

fish (but not a designation for all 

aquarium fish except black mollies). 

This interpretation is driven by the 

marketing exclusivity provisions of the 

designation provision of the statute 

because marketing exclusivity for all 

aquarium fish includes exclusivity with 

respect to that intended use in all 

species within that designation. 

The third principle of same intended 

use establishes that an intended use for 

a disease or condition caused by one (or 

a subset) of causative organisms is 

considered different from an intended 

use for the same disease or condition 

caused by a different causative organism 

(or subset of organisms) when the 

causative organisms involved can 

reliably be shown to be clinically 

significant causes of the disease or 

condition. For example, intended use 

for the treatment of pneumonia in cattle 

caused by Pasteurella multocida is not 

the same as intended use for the 

treatment of pneumonia in cattle caused 

by Histophilus somni (Haemophilus 

somnus). 

The fourth principle of same intended 

use establishes that two intended uses 

that involve the same disease or 

condition but in different species, or in 

different generally recognized subsets of 

the same species (such as production 

classes of food species), are not the same 

intended use. For example, an intended 

use for a particular disease or condition 

in growing turkeys is not the same as an 

intended use for the same disease or 

condition in laying turkeys. 

B. Submission of Requests for 

Designation (Proposed § 516.14) 

The agency proposes that all 

correspondence relating to a request for 

designation of a MUMS drug must be 

addressed to the Director, Office of 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56399 

Minor Use and Minor Species Animal 

Drug Development. 

C. Eligibility to Request Designation 

(Proposed §§ 516.16 and 516.22) 

The agency proposes that the person 

requesting designation must be the real 

party in interest of the development and 

the intended or actual production and 

sales of the drug because only this party 

can assure active pursuit of approval 

under section 512 or 571 of this act with 

due diligence required by section 

573(a)(3)(B) of the act. In proposed 

§ 516.22, the agency is proposing that 

foreign sponsors must have a 

permanent-resident U.S. agent to submit 

the request for designation so that the 

agency may assure that certain 

notifications (such as under section 

573(c)(2)(A) of the act) and other 

communications with the sponsor are 

legally and effectively made. 

D. Content and Format of a Request for 

MUMS-Drug Designation (Proposed 

§ 516.20) 

Proposed § 516.20 describes the 

content and format for a request for 

MUMS designation. Under proposed 

§ 516.20, the request must be specific 

and must include certain information 

about the sponsor; a description of the 

proposed intended use for the drug; a 

description of the drug and dosage form; 

a discussion of the scientific rationale 

for the intended use of the drug with 

reference to data; a specific description 

of the product development plan for the 

drug, its dosage form, and the intended 

use; if MUMS designation is based on a 

minor use, documentation that the 

proposed intended use is a minor use; 

a statement that the requestor is the real 

party in interest of the development and 

the intended or actual production and 

sales of the product; and a statement 

that the sponsor acknowledges that FDA 

will make certain information regarding 

the designation public. The information 

required to be included in a request for 

designation parallels that required for 

human orphan drug designation, but 

with some differences due to differences 

in the governing statutes and to 

differences between the health care 

practices for animals and humans in the 

United States. 

For new animal drugs, each 

designation must be unique. That is, 

each designation is unique with respect 

to the drug and dosage form for use in 

the species or group of species for the 

treatment, control, or prevention of the 

disease or condition; or to affect the 

structure or function. This differs from 

the provisions of the human orphan 

drug legislation, which permits 

designation of multiple identical drugs 

prior to approval of any one of the 

drugs. The MUMS act 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 in this way, it is important for 

the effective implementation of section 

573(a)(2)(B) of the act that the 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. The most 

effective means of ensuring this is for 

the sponsor to work closely with the 

personnel in the agency who will be 

responsible for reviewing the 

information submitted in support of the 

drug’s conditional approval or approval. 

The parties should mutually agree that 

the scientific rationale for the drug is 

credible and that timely development of 

the drug in accordance with a drug 

development plan is possible. While not 

required, this is most effectively 

accomplished to the benefit of both the 

sponsor and the agency through the 

presubmission conference provisions of 

the investigational new animal drug 

(INAD) review process of the Center for 

Veterinary Medicine (CVM). Such 

presubmission conferences are held 

with members of CVM’s Office of New 

Animal Drug Evaluation under the 

provisions of § 514.5 and may be held 

in person or via teleconference. The 

memorandum of conference that is 

created under the provisions of 

§ 514.5(f) would suffice to document 

that the requirements of proposed 

§ 516.20(b)(5) and (b)(6) have been met. 

Because a clear understanding by 

sponsors of agency approval 

requirements and the mutual 

development of a drug development 

plan to meet those requirements is so 

obviously beneficial to the effective 

utilization of resources by both parties, 

most new animal drug sponsors 

routinely follow this process and, 

therefore, for these sponsors, many of 

the requirements for submission of 

information under proposed § 516.20 to 

support designation would be met by 

reference to information routinely 

present in an INAD file. 

Given the relatively limited return on 

investment associated with new animal 

drugs intended for minor uses or minor 

species, it is particularly critical, in 

keeping with the intent of the MUMS 

legislation, to enhance the availability of 

such drugs, that both sponsor and 

agency resources associated with 

MUMS drug development be used 

effectively and efficiently. The 

information proposed under 

§ 516.20(b)(5) and (b)(6) as a condition 

of granting a designation is essential for 

evaluation of a request for designation. 

Furthermore, as noted previously, the 

person requesting the designation must 

be the real party in interest of the 

development, production, and sale of 

the subject drug as proposed under 

§ 516.20(b)(8). The information 

described in § 516.20(b)(1) through 

(b)(4) of the proposed rule is required to 

make the statutorily required 

determination under section 

573(a)(2)(B) of the act that the drug 

requested for designation is not the 

same drug, in the same dosage form, for 

the same intended use as a drug already 

approved or conditionally approved. 

Proposed § 516.20(b)(7) and (b)(9) is 

similarly a reflection of specific 

requirements of the MUMS legislation. 

E. Documentation of Minor Use Status 

(Proposed § 516.21) 

Under proposed § 516.21, if the 

sponsor seeks MUMS-drug designation 

for a drug intended to be used as a 

minor use in a major species, the 

sponsor must include documentation 

that the use is limited to a small number 

of animals. Proposed § 516.21 details 

the documentation that is required. 

The agency is proposing to define 

‘‘intended use’’ of a drug and, more 

specifically, ‘‘same intended use’’ of a 

drug in these regulations. The primary 

discussion of these definitions can be 

found in section II.A.2.c of this 

document. It is important to reiterate 

here that this definition of intended use 

is to determine whether two intended 

uses are the ‘‘same intended use’’ for 

purposes of qualifying for designation; 

the definition is not directly applicable 

to the determination of whether a 

particular use in a major species is a 

minor use. As previously discussed, it is 

clear that Congress intended the 

agency’s determination of whether a use 

is minor to depend upon the existence 

of a disease or condition in a major 

species that occurs in such a small 

number of animals that it would not 

warrant drug development in the 

absence of special incentives. Thus, 

whether a use is a minor use in a major 

species is determined on the basis of the 

existence or occurrence of a disease or 

condition in the total population of a 

major species, and not by any 

population of animals that the sponsor 

may choose to define by the intended 

use or conditions of use that it places on 

its label. 

Once the use of a drug for a given 

disease or condition is determined to be 

a minor use in a major species, a 

sponsor may establish an intended use 

for the product that represents only a 

56400 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

subset of that minor use. That is, while 

a sponsor might be encouraged by the 

agency to develop the product for use in 

the entire population of animals 

comprising the minor use so that the 

drug would provide maximum benefit 

when used in accordance with its label, 

a sponsor generally may limit the 

intended use to only a portion of the 

eligible population. Marketing 

exclusivity will, however, be 

determined by the scope of the intended 

use on the label of the product. 

Until the number for ‘‘small number 

of animals’’ for each major species has 

been formally established by regulation, 

a request for designation of a drug as a 

minor use in a major species needs to 

be supported by evidence that such 

intended use involves only a small 

number of animals of a major species as 

represented by the market associated 

with the potential population of animals 

to be administered the drug relative to 

the cost of drug development as 

discussed previously. Thus, such a 

request for designation must include 

information regarding the presence of 

the relevant disease or condition in the 

relevant major species on an annual 

basis, as well as information regarding 

the potential market represented by that 

number of animals relative to the 

development cost for the particular 

intended use being proposed. 

The agency recognizes that such 

information is not readily available for 

uncommon animal diseases or 

conditions. Because there are no 

insurance records and national 

databases are lacking for diseases of 

animal species, except perhaps 

databases for diseases reportable 

because of their public health 

significance, it is difficult to determine 

verifiable numbers of cases for animal 

diseases or conditions on a National 

basis. Nevertheless, the agency 

understands that sponsors routinely do 

their own marketing research to 

determine the economic feasibility of 

pursuing any new animal drug 

approval. 

As discussed previously, the number 

of concern with respect to minor use is 

the total number of animals that could 

potentially be administered a drug in 

association with the treatment, control, 

or prevention of a given disease or 

condition (annualized) taking into 

account that, for a variety of reasons, not 

all of those animals will actually be 

administered the drug. 

Therefore, a sponsor needs to 

demonstrate through verifiable sources 

(surveys, literature, etc.) that the 

number of animals that could 

potentially be administered a drug in 

association with the treatment, control, 

or prevention of a given disease or 

condition (annualized) represents a 

market potential sufficient to support 

drug development with the added 

incentives of the MUMS act, but not 

without them. 

A sponsor may request that the 

agency determine that the total 

population of animals that is affected by 

a particular disease or condition for 

which a MUMS drug is being 

considered for development should be 

decreased by the size of any subset of 

the total population to which 

administration of the drug can be 

demonstrated to be not medically 

justified. If such a demonstration can be 

made to the satisfaction of the agency, 

the remaining population of animals 

affected by that disease or condition 

would be used to estimate the market 

potential for the drug. 

A sponsor may demonstrate that 

administration is not medically justified 

in a subset of animals by, for example, 

referencing a consensus standard of 

practice established by an authoritative 

source that recommends against the 

administration of either the MUMS drug 

itself or drugs of the class of which the 

MUMS drug is a member to a subset of 

the population. In the absence of a 

consensus standard, the sponsor would 

need to provide reliable evidence that 

there is some attribute of the MUMS 

drug that renders its administration to 

the identified subset of animals not 

medically justified. A specific analysis 

of the relative risks and benefits of 

administering the MUMS drug to the 

subset of animals at issue, supported by 

all reliable information available to the 

sponsor, would be needed. 

F. Timing of Requests for MUMS-Drug 

Designation (Proposed § 516.23) 

In accordance with the requirement of 

section 573(a)(1) of the act, the agency 

is proposing that requests for 

designation of a new animal drug be 

accepted only prior to submission of a 

new animal drug application (NADA) 

for the drug under section 512 or 571 of 

the act. 

G. Granting and Refusal to Grant 

MUMS-Drug Designation (Proposed 

§§ 516.24 and 516.25) 

As required by sections 573(a)(2)(A) 

and (a)(2)(B) of the act, FDA proposes to 

refuse to grant a request for designation 

when the involved new animal drug is 

not intended for use in a minor species 

or for a minor use in a major species or 

the same drug in the same dosage form 

for the same intended use is already 

designated, conditionally approved, or 

approved. The agency is also proposing 

to refuse to grant a request for MUMSdrug designation if the request is found 

to contain any untrue statement of a 

material fact, or to omit material 

information. As noted previously, the 

agency also proposes to refuse to grant 

designation if the request fails to 

contain a credible scientific rationale 

supporting the intended use, or fails to 

contain documentation sufficient to 

support an agency determination that 

successful drug development in a timely 

manner is possible. 

H. Amendment to MUMS-Drug 

Designation (Proposed § 516.26) 

The agency is proposing to allow 

sponsors to apply for amendments to 

MUMS-drug designation up to the time 

of approval of their marketing 

applications. The purpose of this 

proposal is to allow for situations in 

which testing data demonstrate that the 

proposed intended use is inappropriate 

due to unexpected issues of safety or 

effectiveness. This can occur when data 

demonstrate that the effectiveness of a 

drug in different populations or for 

different diseases or conditions differs 

from that for which the drug was 

initially designated. It can also occur 

when a group of species was originally 

designated, such as ‘‘all finfish’’ and it 

is subsequently discovered that the drug 

is not safe for use in a subset of fish 

species. The proposed intended use may 

have to be expanded or narrowed based 

on such unexpected findings. FDA 

would grant such an amendment 

request only if it found that the initial 

designation request was made in good 

faith and that the amendment is sought 

only to render the MUMS-drug 

designation consistent with 

unanticipated test results. If an 

amendment request for a minor use 

designation was to involve a new or 

expanded disease or condition and the 

number of animals affected would then 

exceed what would be considered a 

small number of animals annually, the 

amendment could not be granted. 

I. Change in Sponsorship (Proposed 

§ 516.27) 

The agency proposes that the sponsor 

of a MUMS-designated drug may 

transfer sponsorship to another person. 

Such a transfer of sponsorship of the 

MUMS-designated drug will include 

transfer of the designation provided that 

this transfer of sponsorship is 

appropriately documented by both 

parties to the transfer and that the 

sponsor accepting the transfer certifies 

understanding of the responsibilities 

associated with developing or 

maintaining a MUMS-designated drug 

and demonstrates the capability of 

meeting those responsibilities as a 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56401 

condition of agency approval of the 

transfer. 

Because MUMS-drug designations are 

unique and because the initial sponsor 

obtained designation after request and 

demonstration of capability to meet the 

requirements of section 573 of the act 

with respect to development and 

production of the designated drug, 

transfer of sponsorship of a MUMSdesignated drug must depend upon a 

similar demonstration and agency 

approval. 

J. Publication of MUMS-Drug 

Designations (Proposed § 516.28) 

As required by section 573(a)(4) of the 

act, the agency will make public the 

designation and termination of 

designation of MUMS drugs. The agency 

proposes to meet this requirement by 

periodically updating a publicly 

available list of MUMS-designated drugs 

which would include basic identifying 

information regarding each MUMS drug 

on the list. 

K. Termination of MUMS-Drug 

Designation (Proposed § 516.29) 

The agency proposes to terminate 

designation of a MUMS drug on any of 

the grounds specified in section 573 of 

the act, or because the request is found 

to contain an untrue statement of 

material fact or to omit material 

information, or because the agency 

withdraws approval of the application 

for the drug. 

For the purposes of this proposed 

rule, the phrase ‘‘actively pursuing 

approval or conditional approval with 

due diligence’’ is intended to 

encompass a MUMS drug developer’s 

good faith effort to pursue drug 

development and approval, or drug 

development, conditional approval, and 

subsequent approval, in a timely 

manner. Under proposed § 516.29(d), at 

a minimum, due diligence must be 

demonstrated by submission of annual 

progress reports in accordance with 

proposed § 516.30 that demonstrate the 

sponsor is progressing in accordance 

with the drug development plan 

submitted to the agency under proposed 

§ 516.20 and by compliance with all 

applicable INAD requirements. 

However, FDA will consider the 

circumstances and may determine that 

other factors demonstrate an absence of 

due diligence. 

L. Annual Reports for a MUMSDesignated Drug (Proposed § 516.30) 

The agency proposes to require brief 

annual progress reports to the INAD file 

as one effective means of ensuring 

sponsor compliance with the 

requirement of section 573(a)(3)(B) of 

the act that new animal drug approval 

for a MUMS-designated drug be pursued 

with due diligence. 

M. Exclusive Marketing Rights 

(Proposed §§ 516.31 and 516.34) 

Under proposed § 516.34, the agency 

will send the sponsor of a conditionallyapproved or approved MUMSdesignated drug timely written notice 

recognizing exclusive marketing rights 

and make the same information publicly 

available by Federal Register 

publication. Under section 573(c)(1) of 

the act, FDA may not conditionally 

approve or approve another application 

for the same new animal drug, in the 

same dosage form, for the same 

intended use within 7 years after FDA 

has approved or conditionally approved 

a designated MUMS drug. For this 

reason, no further action by FDA to 

bring about exclusive marketing rights is 

necessary. Proposed § 516.31 reflects the 

grounds for termination of designation 

and associated exclusive marketing 

rights established by section 573 of the 

act and discussed in association with 

proposed § 516.29 in section II.K of this 

document. 

N. Insufficient Quantities of MUMSDesignated Drugs (Proposed § 516.36) 

Proposed § 516.36 addresses 

situations where insufficient quantities 

of MUMS-designated drugs are being 

produced to meet demand. Under 

section 573(c)(2)(A) of the act, whenever 

the agency finds that a conditionallyapproved or approved MUMSdesignated drug sponsor cannot assure 

the availability of sufficient quantities of 

the drug to meet the needs of animals 

for which it was designated, the act 

provides that the agency may approve 

another application for the same drug in 

the same dosage form for the same 

intended use. Proposed § 516.36 

provides a procedure whereby the 

agency would notify the approved 

MUMS-designated drug sponsor of the 

possible insufficiency of supply and 

would request, within a specified time, 

that the sponsor provide in writing 

information and data regarding how the 

sponsor can assure the availability of 

sufficient quantities of the drug, or 

consent to the approval of other 

marketing applications. 

Following evaluation of the submitted 

information, the agency would issue an 

order with findings and conclusions, 

either reaffirming or terminating the 

MUMS-drug designation and the 

associated exclusive marketing rights. 

Any such order which the agency issues 

would constitute final agency action. In 

the event the agency’s decision is to 

terminate the MUMS-drug designation 

and the associated exclusive marketing 

rights, FDA may approve any number of 

applications for the same drug, in the 

same dosage form, for the same 

intended use, even if the additional 

sponsors cannot themselves assure the 

availability of sufficient quantities of the 

MUMS drug in question. 

Once designation and exclusive 

marketing rights are terminated for 

failure to ensure the availability of 

adequate supplies, they cannot be 

restored even if the sponsor losing these 

privileges is later able to assure the 

availability of adequate supplies. It 

would be unreasonable to expect a 

second sponsor to invest in drug 

development to fill a gap if it could be 

shut out of the market at any time that 

the original sponsor could assure 

adequate supplies. 

O. Availability for Public Disclosure of 

Data and Information in Requests and 

Applications (Proposed § 516.52) 

Proposed § 516.52 provides rules for 

public disclosure of information. The 

agency recognizes that designation 

requests will contain confidential 

commercial information and, indeed, 

that the very existence of a MUMS-drug 

designation request may itself be 

confidential commercial information. In 

addition, a request for MUMS-drug 

designation is, in most instances, 

supported by information that will be 

incorporated into a sponsor’s 

application for conditional approval or 

approval. 

For all these reasons, proposed 

§ 516.52(a) provides that unless 

previously publicly disclosed or 

acknowledged, FDA will not make 

public the existence of any pending 

MUMS-drug designation request prior to 

such time as FDA takes final action on 

the request. Proposed § 516.52(b) 

provides that, irrespective of whether 

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. 

Upon final FDA action on a request 

for designation, proposed § 516.52(c) 

provides that FDA will determine the 

public availability of data and 

information in the designation request 

in accordance with part 20 (21 CFR part 

20) and other applicable statutes and 

regulations. Under proposed 

§ 516.52(d), via reference to proposed 

§ 516.28, FDA will make a cumulative 

list of all MUMS-drug designations 

available to the public and update it 

periodically. Under proposed § 516.28, 

the list will contain the following 

information regarding each MUMSdesignated drug: The name and address 

56402 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

1 2000 National Industry-Specific Occupational 

Employment and Wage Estimates, U.S. Department 

of Labor, Bureau of Labor Statistics (http:// 

www.bls.gov/oes/2000/oesi3_283.htm). 

of the sponsor; the generic name and 

trade name, if any, of the drug; the date 

of granting MUMS-drug designation; the 

dosage form; and the species and 

intended use of the drug. In accordance 

with proposed § 516.29, FDA will give 

public notice of the termination of all 

MUMS-drug designations. 

III. Conforming Changes 

FDA is proposing to revise the 

definition of ‘‘sponsor’’ currently 

appearing in § 510.3 (21 CFR 510.3) to 

be consistent with the definition of 

‘‘sponsor’’ proposed in the MUMS 

regulations in proposed § 516.3. The 

agency has recognized for some time 

that the scope of the definition in 

§ 510.3 is overly narrow. It is 

inconsistent with one of the major 

subparts of part 510, Subpart G–

Sponsors of Approved Applications, in 

failing to recognize that persons 

submitting and receiving approval for 

NADAs are also considered sponsors. 

The agency is taking this opportunity to 

resolve this long-standing 

inconsistency. 

FDA is also proposing conforming 

changes in its regulations by removing 

§ 514.1(d). The definitions under 

§ 514.1(d)(1) were redefined by Congress 

in the MUMS act and are further 

clarified under proposed § 516.3. The 

provisions of § 514.1(d)(2) regarding the 

availability of guidance relating to 

MUMS drugs are now covered under 

FDA’s good guidance practices in 21 

CFR 10.115. 

FDA also proposes to add a crossreference to the MUMS designation 

records to 21 CFR 20.100, which lists 

regulations on the availability of 

specific categories of FDA records. 

IV. Legal Authority 

FDA’s authority for issuing this 

proposed rule is provided by the Minor 

Use and Minor Species Animal Health 

Act of 2004 (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 

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 

12866, the Regulatory Flexibility Act (5 

U.S.C. 601–612), and the Unfunded 

Mandates Reform Act of 1995 (Public 

Law 104–4). Executive Order 12866 

directs agencies to assess all costs and 

benefits of available regulatory 

alternatives and, when regulation is 

necessary, to select regulatory 

approaches that maximize net benefits 

(including potential economic, 

environmental, public health and safety, 

and other advantages; and distributive 

impacts; and equity). The Regulatory 

Flexibility Act 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 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 

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 of 1995. 

The intention of this proposed 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 

proposed 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 an 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 MUMSdesignation requests. Administrative 

costs for these actions would total about 

$57,300. 

The agency is also proposing in 

§ 516.22 that foreign sponsors 

requesting designation, do so through a 

permanent-resident U.S. agent. This is 

consistent with the current 

requirements of § 514.1(a) because 

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 2 hours of preparation. 

At the same wage rate, this would cost 

an additional $300. Sponsors may also 

transfer sponsorship of a MUMSdesignated drug or terminate the 

designation. We estimate that these 

activities would result in only 3 

additional hours of administrative costs 

annually, totaling $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. FDA notifications 

to sponsors concerning insufficient 

quantities of approved MUMSdesignated drugs are expected to be rare, 

about once each year. Sponsor 

responses are estimated to take 3 hours, 

for a cost of $150. 

Assuming a sponsor chooses to seek 

the MUMS designation for its NADA, 

total administrative costs for this 

proposed rule 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 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56403 

2 2002 Economic Census, U.S. Census Bureau, 

Manufacturing Industry Series, Pharmaceutical 

Preparation Manufacturing, Table 4. 

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 initial 

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 

proposed 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 

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 

percent of the revenues of the smallest 

set of establishments (those with one to 

four 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. 

All of the costs described previously 

in this document 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 in 

this document. 

2. Analysis of Alternatives 

The Regulatory Flexibility Act 

requires that the agency consider any 

alternatives to the proposed rule that 

would accomplish the objective while 

minimizing significant impacts of the 

proposed rule. As stated previously, the 

agency believes that the proposed rule, 

due to the relatively small size of the 

costs, would not be likely to impose 

significant economic impacts on small 

businesses. As such, the agency believes 

the proposed 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 this proposed rule as 

mandated by statute. The agency has 

therefore decided to address this issue 

in a later rulemaking, and instead 

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. 

VI. Paperwork Reduction Act of 1995 

This proposed rule contains 

information collection provisions that 

are subject to review by the Office of 

Management and Budget (OMB), under 

the Paperwork reduction Act of 1995 

(the PRA) (44 U.S.C. 3501–3520). A 

description of these provisions follows 

with an estimate of the annual reporting 

burden. Included in the estimate is the 

time for reviewing instructions, 

searching existing data sources, 

gathering and maintaining the data 

needed, and completing and reviewing 

each collection of information. 

FDA invites comments on these 

topics: (1) Whether the proposed 

collection of information is necessary 

for the proper performance of FDA’s 

functions, including whether the 

information will have practical utility; 

(2) the accuracy of FDA’s estimate of the 

burden of the proposed collection of 

information including the validity of the 

methodology and assumptions used; (3) 

ways to enhance the quality, utility, and 

clarity of the information to be 

collected; and (4) ways to minimize the 

burden of the collection of information 

on respondents, including through the 

use of automated collection techniques 

and other forms of information 

technology. 

Title: Designated New Animal Drugs 

for Minor Use and Minor Species 21 

CFR Part 516 

Description: The Minor Use and 

Minor Species (MUMS) Animal Health 

Act of 2004 amended the Federal Food, 

Drug, and Cosmetic Act (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 proposed new part, 

§ 516.20 provides requirements on the 

content and format of a request for 

MUMS-drug designation, § 516.26 

provides requirements for amending 

MUMS-drug designation, provisions for 

change in sponsorship of MUMS-drug 

designation can be found under 

§ 516.27, under § 516.29 are provisions 

for termination of MUMS-drug 

designation, under § 516.30 are 

requirements for annual reports from 

sponsor(s) of MUMS-designated drugs, 

and under § 516.36 are provisions for 

56404 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

insufficient quantities of MUMSdesignated drugs. Description of Respondents: 

Pharmaceutical companies that sponsor 

new animal drugs. 

FDA estimates the burden for this 

collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

21 CFR Section No. of 

Respondents 

Annual Frequency 

per Response 

Total Annual 

Responses 

Hours per 

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 

1There are no capital or operating and maintenance costs associated with this collection of information. 

The burden estimate for this reporting 

requirement was derived in our Office 

of Minor Use and Minor Species Animal 

Drug Development by extrapolating the 

current INAD/NADA reporting 

requirements for similar actions by this 

same segment of the regulated industry 

and from previous interactions with the 

minor use/minor species community. 

As required by section 3504(h) of the 

PRA, FDA has submitted a copy of this 

proposed rule to OMB for its review of 

these information collection provisions. 

Other organizations and individuals 

desiring to submit comments on the 

information collection requirements 

should send their comments to OMB. 

Submit written comments on the 

information collection provisions to the 

Office of Information and Regulatory 

Affairs, Office of Management and 

Budget (OMB). 

OMB is still experiencing significant 

delays in the regular mail, including 

first class and express mail, and 

messenger deliveries are not being 

accepted. To ensure that comments on 

the information collection are received, 

OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: Fumie Yokota, Desk Officer 

for FDA, FAX: 202–395–6974. 

VII. Environmental Impact 

We have carefully considered the 

potential environmental impacts of this 

proposed 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 

We have analyzed this proposed rule 

in accordance with the principles set 

forth in Executive Order 13132. We 

have determined that the proposed rule 

does not contain policies that have 

substantial direct effects on the States, 

on the relationship between the 

National Government and the States, or 

on the distribution of power and 

responsibilities among the various 

levels of government. Accordingly, we 

have tentatively concluded that the 

proposed rule does not contain policies 

that have federalism implications as 

defined in the Executive order and, 

consequently, a federalism summary 

impact statement has not been prepared. 

IX. Comments 

You may submit to the Division of 

Dockets Management (see ADDRESSES) 

written or electronic comments 

regarding this document. Please submit 

a single copy of electronic comments or 

two paper copies of any mailed 

comments, except that individuals may 

submit one paper copy. Identify your 

comments with the docket number 

found in brackets in the heading of this 

document. You may view received 

comments in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

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. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act and under 

authority delegated to the Commissioner 

of Food and Drugs, it is proposed that 

21 Chapter I be amended as follows: 

PART 20—PUBLIC INFORMATION 

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. 

2. Amend § 20.100 by adding 

paragraph (c)(43) to read as follows: 

§ 20.100 Applicability; cross-reference to 

other regulations. 

* * * * * 

(c) * * * 

(43) Minor-use or minor-species 

(MUMS) drug designations, in § 516.52 

of this chapter. 

PART 510—NEW ANIMAL DRUGS 

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. 

4. Amend § 510.3 by revising 

paragraph (k) to read as follows: 

§ 510.3 Definitions and interpretations. 

* * * * * 

(k) Sponsor means the person 

requesting designation for a minor-use 

or minor-species drug as defined in part 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56405 

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 

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. 

§ 514.1 [Amended] 

6. Amend § 514.1 by removing 

paragraph (d). 

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 

Sec. 

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. 

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 MUMSdesignated drug. 

516.31 Scope of MUMS-drug exclusive 

marketing rights. 

516.34 FDA recognition of exclusive 

marketing rights. 

516.36 Insufficient quantities of MUMSdesignated drugs. 

516.52 Availability for public disclosure of 

data and information in requests and 

applications. 

Subpart C—[Reserved] 

Subpart D—[Reserved] 

Authority: 21 U.S.C. 360ccc–2, 371. 

Subpart A—General Provisions 

§ 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. 

§ 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. 

§ 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. 

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, 

56406 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

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, conditionallyapproved, 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 

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 

§ 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. 

§ 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. 

§ 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. 

§ 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 § 516.20 will be returned to 

the sponsor without review. 

§ 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. 

§ 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 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56407 

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 § 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 

request for MUMS designation, FDA 

will make information regarding the 

designation publicly available as 

specified in § 516.28. 

§ 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 

§ 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) If the 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 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, 

a demonstration that administration of 

the drug to animals 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. 

§ 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. 

§ 516.23 Timing of requests for MUMSdrug 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. 

§ 516.24 Granting MUMS-drug designation. 

(a) FDA may grant the request for 

MUMS-drug designation if none of the 

reasons described in § 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 

§ 516.28. 

§ 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 MUMSdrug 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 § 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. 

56408 Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 

§ 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. 

§ 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 MUMSdesignated 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 MUMSdrug 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 MUMSdrug 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 

MUMS-drug designation, including any 

amendments to the request and any 

correspondence relevant to the MUMSdrug 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 permanentresident 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. 

§ 516.28 Publication of MUMS-drug 

designations. 

FDA will periodically update a 

publicly available list of MUMSdesignated 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 generic 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. 

§ 516.29 Termination of MUMS-drug 

designation. 

(a) The sponsor of a MUMSdesignated 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 the 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 § 516.30 that 

demonstrate that the sponsor is 

progressing in accordance with the drug 

development plan submitted to the 

agency under § 516.20 and 

(2) Compliance with all applicable 

requirements of part 511 of this chapter. 

(e) Designation of a conditionallyapproved or approved MUMSdesignated 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 MUMSdrug 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 MUMSdrug 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 MUMSdesignated 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. 

§ 516.30 Annual reports for a MUMSdesignated drug. 

Within 14 months after the date on 

which a MUMS drug is granted 

designation and annually thereafter 

until approval, the sponsor of a MUMSdesignated 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: 

Federal Register / Vol. 70, No. 186 / Tuesday, September 27, 2005 / Proposed Rules 56409 

(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. 

§ 516.31 Scope of MUMS-drug exclusive 

marketing rights. 

(a) After conditional approval or 

approval of an application for a MUMSdesignated drug in the dosage form and 

for the intended use for which MUMSdrug 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 § 516.29; or 

(2) FDA withdraws or proposes to 

withdraw 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 § 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. 

§ 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 MUMSdesignated drug has been conditionally 

approved or approved. The written 

notice will inform the sponsor of the 

requirements for maintaining MUMSdesignated 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. 

§ 516.36 Insufficient quantities of MUMSdesignated drugs. 

(a) Under section 573 of the act, 

whenever the 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, the 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. 

§ 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 § 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 

§ 516.29, FDA will give public notice of 

the termination of all MUMS-drug 

designations. 

Subpart C—[Reserved] 

Subpart D—[Reserved] 

Dated: August 31, 2005. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 05–19196 Filed 9–26–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Part 135 

[Docket Nos. 2003P–0132 and 2000P–1491 

(formerly 03P–0132 and 00P–1491)] 

Frozen Desserts; Petition to Revoke 

Standards for Goat’s Milk Ice Cream 

and Mellorine and to Amend Standards 

for Ice Cream and Frozen Custard, 

Sherbet, and Water Ices; Petition to 

Amend Standards for Parmesan and 

Reggiano Cheese 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Advance notice of proposed 

rulemaking. 

SUMMARY: The Food and Drug 

Administration (FDA) is announcing 

that the following two petitions have