[Federal Register Volume 79, Number 96 (Monday, May 19, 2014)]
[Notices]
[Pages 28736-28739]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-11446]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0176 (Formerly Docket No. 2008N-0011)]


Defining Small Numbers of Animals for Minor Use Designation; 
Periodic Reassessment

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing its 
periodic reassessment for defining the small numbers of animals for 
minor use in major species.

DATES: Submit either electronic or written comments at any time.

ADDRESSES: Submit electronic comments to http://www.regulations.gov/. 
Submit written comments to the Division of Dockets Management (HFA-
305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Margaret Oeller, Center for Veterinary 
Medicine (HVF-50), Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855, 240-402-0566, email: [email protected].

SUPPLEMENTARY INFORMATION:

I. Background

    The Minor Use and Minor Species Animal Health Act of 2004 (Pub. L. 
108-282) (the MUMS Act), defines the term minor use to mean the 
intended use of a new animal drug in a major species for an indication 
that occurs infrequently and in only a small number of animals 
annually, or in limited geographical areas and in only a small number 
of animals annually (21 U.S.C. 321(pp)). As provided by the MUMS Act, 
major species of animals are dogs, cats, horses, cattle, pigs, turkeys, 
and chickens (21 U.S.C. 321(nn). This statutory definition of minor use 
creates the need for FDA to establish a small number of animals for 
each of the major species of animals (small number). In accordance with 
the provisions of the MUMS Act, the small number is used to determine 
whether an intended use of a new animal drug in a major species of 
animal qualifies as a minor use.
    FDA established the small numbers by a final rule published in the 
Federal Register on August 26, 2009 (74 FR 43043). In the preamble for 
the final rule FDA responded to comments with the following:
    ``FDA agrees that there is a need to periodically reevaluate the 
definition of ``small number of animals.'' Because Congress did not 
establish by statute what a ``small number'' is, it affords FDA the 
opportunity to periodically reevaluate and update the definition of 
``small number'' as necessary. We further agree that such a 
reevaluation should take into account the potential for increases in 
the development cost of new animal drugs, but note that it also should 
take into account potential increases in the cost that animal owners 
are willing to pay to treat affected animals as well as other factors 
involved in establishing ``small numbers,'' such as changes in the 
total population of major animal species.''
    This is the first time FDA is reassessing the small numbers.

II. Processes Used to Determine Small Numbers of Animals for Minor Use 
in Major Species

    The process used to establish small numbers of animals in major 
species of food-producing animals is different from the process used to 
establish small numbers of companion animals (non-food-producing). The 
processes FDA uses to establish the small numbers were published in the 
preamble to the proposed rule (73 FR 14411).

[[Page 28737]]

    The process for determining small numbers of major food-producing 
animals is based on the amount of food going to market from sheep. 
Sheep are used because they were the most consumed minor food-producing 
species at the time the MUMS Act was passed in 2004. In determining 
that no limit needed to be set on the number of sheep going to 
slaughter after being treated with a designated new animal drug, 
Congress effectively established an upper limit for the quantity of 
food from the major food-producing species that would likewise not be a 
concern regarding drug residues and antimicrobial resistance. 
Therefore, FDA established the small numbers of food-producing animals 
by determining the number of animals of each major food-producing 
species that constituted an amount of food (biomass) from these species 
going to market that is equivalent to the amount of food (biomass) from 
sheep going to market in 2004.
    The process of establishing the small numbers of companion animals 
involves the following:
     Estimating the development cost for a new animal drug 
intended for each of the companion animal species.
     Estimating the amount of money that companion animal 
owners are willing to pay to treat each of their animals.
     Estimating the average percentage of companion animals 
that are likely to be treated.
     Estimating the uncertainty associated with the reported 
rate of occurrence of various uncommon conditions in companion animals.
    Assessing these various factors results in the following formula, 
as set forth in the preamble for the proposed rule (73 FR 14414):

[Average companion animal drug development cost in dollars] - \1/3\ = 
[minor use ``going market'' in dollars] / [average drug treatment value 
in dollars for each species] = [a preliminary small number of animals] 
x 2 (untreated factor) + 13% (uncertainty factor) + [increase to 
``round'' number) = [species-specific ``small number of animals'']

III. Data Sources

A. Food-Producing Animals

    The current assessment of small numbers for major food-producing 
animals is based on the number of sheep and lambs going to market in 
2013. These data are obtained from the National Agricultural Statistics 
Service (NASS) of the U. S. Department of Agriculture (USDA) (Ref. 1).

B. Companion Animals

    The data used for the estimates referred to in section II are 
obtained from several sources. These sources include two publicly 
available reports from an animal industry consulting firm and several 
publications from the American Veterinary Medicine Association (AVMA) 
(Refs. 2, 3, 4, 5, and 6).

C. Population Estimate Data Source

    As the determination of small numbers for companion animals is 
based on the size of the entire U.S. population of companion animals, 
FDA concluded that we should use a single source of population data for 
the periodic reassessments. Using a single source of population data 
for periodic reassessment of the small numbers ensures consistent 
application of the small numbers over time and among parties requesting 
minor use determinations.
    The AVMA U.S. Pet Ownership & Demographics Sourcebook (AVMA 
Sourcebook) is a comprehensive and statistically valid survey of 
approximately 50,000 companion animal owners. The AVMA Sourcebook has 
used the same survey techniques for many years; this makes the AVMA 
Sourcebook a consistent source for population information. The AVMA 
Sourcebook is published every 5 years and can be used as a source of 
up-to-date population information every time FDA reassesses the small 
numbers. For these reasons, FDA uses the AVMA Sourcebook as our single 
source of population data for reassessment of the small numbers. FDA 
used the 2007 AVMA Sourcebook to define the small numbers established 
in 2009. The latest AVMA Sourcebook was published in 2012 and provides 
the estimates of the dog, cat, and horse populations in the United 
States for the current reassessment of the small numbers.

D. Disease Rate Estimate Data Source

    Minor use determinations in major species of companion animals are 
based on an estimate of the rate of occurrence of a disease or 
condition in a limited population of a companion animal species. Such 
estimates are derived from published information, from various 
databases containing information collected from multiple veterinary 
practices, from current surveys of veterinary practices conducted by 
parties requesting a minor use determination, or various combinations 
of these sources of information. Once an estimate of the rate of 
occurrence of a disease or condition in a sample population is 
established, that rate must be extrapolated to the entire population of 
the major species of companion animals in the United States.

IV. Reassessment

A. Food-Producing Animals

    The small numbers for major food-producing animals were 
established, in large part, based on Congressional concern regarding 
food safety and a perceived need not to provide an incentive for 
``wider use'' of drugs in these animals. An acceptable scope of use for 
major food-producing animals was determined to be a level consistent 
with the population of the most common minor food-producing species 
going to market at the time of passage of the MUMS Act, which was 
sheep. Data from the USDA show that the amount of sheep and lamb going 
to market has steadily decreased since the MUMS Act was passed in 2004 
(Ref. 1). Since the scope of drug use in major food-producing animals 
was determined to be acceptable at a level equivalent to a higher level 
than the current level of marketing of sheep and lamb, we see no reason 
to revise the currently established small numbers for major food-
producing animals.

B. Companion Animals

    According to the 2012 AVMA Sourcebook, the population of the major 
species of companion animals in the United States has decreased since 
2007; from about 72.1 million to about 69.9 million dogs, from about 
81.7 million to about 74.0 million cats, and from about 7.3 million to 
about 4.9 million horses (Ref. 6).
    The potential effect of these population decreases is at least 
twofold. The first effect would appear to be a decrease in the 
potential market for animal drugs for uncommon diseases or conditions 
in companion animals because there are simply fewer animals to 
experience such diseases or conditions. However, the data indicate that 
while there may be fewer companion animals owned in 2012 than in 2007, 
at least with respect to dogs and cats, these animals are owned by 
persons more likely to pay for their health care.
    The second effect of the population decreases is to make any 
particular disease or condition more likely to be considered a minor 
use. For example, if the rate of occurrence of a disease or condition 
in a sample population of horses is estimated to be 0.7 percent (7 
horses per 1000) with +/- 10 percent uncertainty, when extrapolated to 
a U.S. population of 7.3 million horses, this

[[Page 28738]]

rate of occurrence would not represent a small number of horses and the 
intended use would not be considered a minor use. If, in our example, 
the population decreases to 4.9 million horses, then 0.7 percent of the 
horse population would represent a small number of horses and the 
intended use would be considered a minor use.
    The reassessment of the small numbers of companion animals is based 
on the estimates in section II. Current values for these estimates are 
based on data obtained from a 2013 survey (Ref. 3). The 2013 survey was 
conducted by the same source and using the same techniques as the 2005 
survey (Ref. 2). Significant changes in the values of these estimates 
and the relationship between these values could provide a basis for 
revising the small numbers of animals for major species of companion 
animals.
    Information from these surveys indicates that the development cost 
for new animal drugs intended for use in companion animals has risen 
from about $15 million in 2005 to about $20 million in 2013, an 
increase of about 33 percent (Refs. 2 and 3). Information from these 
surveys indicates that the cost for the treatment of companion animals 
has also risen. The rise in treatment cost differs by species, with the 
greatest increases associated with dogs and horses (about 40 percent 
and 37 percent, respectively), and the smallest increases associated 
with cats (about 24 percent). These increases reflect weighted averages 
(based on approximate sample size of the two surveys) of the amounts 
paid for routine companion animal health care based on information 
available in 2005 and 2013 (Refs. 2, 3, 4, 5, and 6). The cost 
estimates from these surveys reflect routine health care, not the care 
of uncommon, generally serious or life-threatening conditions of 
companion animals. However, the increase in the costs for routine 
health care does show the general willingness of companion animal 
owners to spend more money for the care of their animals now than in 
2009 when the small numbers were established.
    In addition, other information indicates that owners who consider 
their animals to be ``family members'' are generally willing to spend 
more money for the care of their animals than owners who do not. Based 
on data from AVMA Sourcebooks (Refs. 4, 5, and 6) CVM calculated that 
the percentage of dog owners and cat owners who consider their animals 
to be family members in 2012 rose 24 percent and 14 percent, 
respectively, since 2007, or 31 percent and 22 percent, respectively, 
since 2002.
    When comparing these data, it appears that the willingness of 
companion animal owners to pay for their animals' health care has 
increased by an amount similar to the increase in companion animal drug 
development cost since the establishment of the small numbers.
    While in the case of dogs and horses the increase in the 
willingness of owners to pay for treatment appears to be greater than 
the increase in the cost of drug development for those species, the 
uncertainty associated with these estimates does not permit a 
determination that the difference in the increases is meaningful. 
Similarly, while the increase in the willingness of cat owners to pay 
for treatment appears to be less than the increase in cost of drug 
development, the uncertainty associated with the estimates does not 
permit a determination that the difference in the increases is 
meaningful.
    Currently available information does not provide a basis to propose 
a change in the 50 percent estimate of companion animals likely to be 
treated or in the 13 percent estimate of the uncertainty routinely 
associated with estimates of the rates of occurrence of uncommon 
conditions in these species.
    Based on the information in this section, there is no reason to 
revise the currently established small numbers for companion animals.

V. Usefulness of the Small Numbers Used to Determine Minor Use in Major 
Species

    FDA believes that one way to estimate the usefulness of the small 
numbers used to determine minor use is to look at the accomplishments 
of FDA's MUMS program since the small numbers were proposed in March 
2008.
    Of 56 requests for a determination of minor use in a major species 
submitted to FDA since March 2008, 42 have been determined to be minor 
uses involving 29 different conditions in major species.
    Of the 58 MUMS designations that have been granted to new animal 
drugs since March, 2008, 23 have involved minor uses in major species.
    Most of the 23 new animal drugs designated for minor use in a major 
species are indicated for the treatment of neoplastic conditions in 
companion animals. These neoplastic conditions include sarcoids in 
horses, functional adrenal tumor, transitional cell carcinoma, mast 
cell tumor, brain tumors, squamous cell carcinoma, melanoma, mammary 
carcinoma, and lymphoma in dogs. Indications for treatment of non-
neoplastic conditions include the treatment of early onset emesis 
associated with chemotherapy in dogs, equine recurrent uveitis, repair 
of diaphyseal fractures in dogs, cattle fever tick eradication, equine 
protozoal myeloencephalitis, reduction of male aggressive behavior in 
boars, and prevention of diabetic cataracts in dogs.
    Based on this information and communications between FDA and 
sponsors during the new animal drug development process, FDA believes 
that the current small numbers are useful for implementing the 
provisions of the MUMS Act.
    Potential sponsors of new animal drugs for minor uses should note 
the importance of seeking a formal, extended minor use determination 
from FDA. This can be done by means of a written request for 
designation to the Office of Minor Use and Minor Species Animal Drug 
Development. Alternatively, it can be accomplished by a written request 
to the Director, Office of New Animal Drug Evaluation, for an extended 
minor use determination, either as a basis for establishing eligibility 
for conditional approval, or as a basis for full approval. Obtaining 
such a minor use determination is important because, if due diligence 
toward approval is maintained, the minor use determination will remain 
in effect in spite of future changes in small numbers or companion 
animal populations until the designation terminates or a product is 
approved in the absence of designation. Requests for certain user fee 
waivers based on minor use status are made and granted on an annual 
basis. Without a formal, extended minor use determination, granting of 
the fee waiver request is subject to the changes in small numbers

VI. Significance of Determinations

    While the small numbers will not be revised at this time, FDA 
concludes periodic reassessment is useful for implementing the 
provisions of the MUMS Act. FDA also concludes that 5 years between 
reassessments is an appropriate period of time; therefore, FDA expects 
the next reassessment to occur in 2018.
    Based on the current reassessment, the ``small numbers'' listed in 
21 CFR 516.3 will not be revised and will continue to be as follows: 
50,000 horses; 70,000 dogs; 120,000 cats; 310,000 cattle; 1,450,000 
pigs; 14,000,000 turkeys; and 72,000,000 chickens.

VII. Paperwork Reduction Act of 1995

    This reassessment of the small numbers of animals currently 
established by regulation relates to

[[Page 28739]]

previously approved collections of information. These collections of 
information are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-
3520). The relevant collections of information in 21 CFR part 516 have 
been approved under OMB control number 0910-0032.

VIII. Comments

    Interested persons may submit either electronic comments regarding 
this Notice to http://www.regulations.gov/ or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments with the docket number 
found in brackets in the heading of this document. Received comments 
may be seen in the Division of Dockets Management between 9 a.m. and 4 
p.m., Monday through Friday, and will be posted to the docket at http://www.regulations.gov/.

IX. References

1. Sheep and Goats--Sheep and Lamb Inventory by Class, National 
Agricultural Statistics Service (NASS), U. S. Department of 
Agriculture (USDA), February 1, 2013.
2. Brakke Consulting, Inc., ``Disease Incidence Rates, Drug 
Development and Treatment Costs,'' September 2005.
3. Brakke Consulting, Inc., ``Update of Population Estimates, 
Disease Incidence Rates, Drug Development Costs and Treatment Costs 
for Companion Animals,'' September 6, 2013.
4. Figures 8, 15, and 27 from U. S. Pet Ownership & Demographics 
Sourcebook 2002 Edition, reproduced by permission of the American 
Veterinary Medical Association.
5. Tables 1-5, 1-10, and 1-20 from U. S. Pet Ownership & 
Demographics Sourcebook 2007 Edition, reproduced by permission of 
the American Veterinary Medical Association.
6. Tables 1-5, 1-9, 1-10, 1-14, 1-20, 1-24, 2-8, 2-9, 2-22, 2-23, 2-
46, and 2-47 from U.S. Pet Ownership & Demographics Sourcebook 2012 
Edition, reproduced by permission of the American Veterinary Medical 
Association.

    Dated: May 12, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-11446 Filed 5-16-14; 8:45 am]
BILLING CODE 4160-01-P