
[Federal Register: September 8, 2008 (Volume 73, Number 174)]
[Rules and Regulations]               
[Page 51912-51919]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08se08-7]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food And Drug Administration

21 CFR Parts 16 and 1240

[Docket No. FDA-2003-N-0427] (formerly Docket No. 2003N-0400)

 
Control of Communicable Diseases; Restrictions on African 
Rodents, Prairie Dogs, and Certain Other Animals

AGENCY: Food and Drug Administration (HHS).

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is removing its 
regulation that established restrictions on the capture, transport, 
sale, barter, exchange, distribution, and release of African rodents, 
prairie dogs, and certain other animals. We are removing the 
restrictions because we believe they are no longer needed to prevent 
the further introduction, transmission, or spread of monkeypox, a 
communicable and potentially fatal disease, in the United States.

DATES: Effective September 8, 2008.

FOR FURTHER INFORMATION CONTACT: Philip L. Chao, Office of Policy, 
Planning, and Preparedness (HF-23), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-827-0587.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. What Is Monkeypox, and How Did It Spread in the United States?
II. How Did We Respond to the Monkeypox Outbreak?
III. What Other Actions Did the Department of Health and Human Services 
Take?
    A. Why Did the Interim Final Rule Continue After January 20, 2004?
    B. Were the New Data Available to the Public?
    C. Is There a Risk That Monkeypox

[[Page 51913]]

Still Exists in the United States?
IV. Given Recent Evidence, Is FDA Action Still Necessary?
    A. Are the Measures of the Interim Final Rule Needed Now to Prevent 
Disease Spread?
    B. How Many Comments Did We Receive?
V. Environmental Impact Analysis
VI. Analysis of Impacts
VII. References
VIII. Federalism

I. What Is Monkeypox, and How Did It Spread in the United States?

    Monkeypox is a sporadic, zoonotic, viral disease that occurs 
primarily in the rain forest countries in central and west Africa. (A 
zoonotic disease is a disease of animals that can be transmitted to 
humans under natural conditions.) The illness was first noted in a 
monkey in 1958 (which explains its name), but, in Africa, serologic 
evidence of monkeypox infection has been found in many other species, 
including some species of primates, rodents, and lagomorphs. Lagomorphs 
include animals such as rabbits. African rodents are considered to be 
the most likely natural host of the monkeypox virus (Ref. 1). In 
Africa, however, direct viral evidence of monkeypox has been found in 
only one native African rodent species (a rope squirrel), but this may 
be due to the limited scope of the ecologic studies that have been done 
in Africa (Ref. 1).
    In humans, monkeypox is marked by rashes that are similar to those 
seen in smallpox; other signs and symptoms include a temperature at or 
above 99.3 degrees, chills and/or sweats, headache, backache, 
lymphadenopathy (a disease of the lymph nodes), sore throat, cough, and 
shortness of breath (Ref. 2). The disease's incubation period in humans 
is approximately 12 days (Ref. 3). In Africa, monkeypox has a mortality 
(death) rate in humans ranging from 1 to 10 percent of the people who 
become infected, although higher mortality rates have been seen.
    In May and June of 2003, public health officials identified an 
outbreak of human monkeypox in the United States. Epidemiological and 
traceback investigations by State and Federal agencies revealed that 
the patients became infected primarily as a result of contact with 
prairie dogs that had contracted monkeypox from diseased African 
rodents. The investigations indicated that a Texas animal distributor 
imported a shipment of approximately 800 small mammals from Ghana on 
April 9, 2003. This shipment contained 762 African rodents, including 
rope squirrels (Funiscuirus sp.), tree squirrels (Heliosciurus sp.), 
Gambian giant pouched rats (Cricetomys sp.), brushtail porcupines 
(Atherurus sp.), dormice (Graphiurus sp.), and striped mice (Hybomys 
sp.). Some of these African animals were infected with monkeypox, and 
laboratory testing confirmed the presence of monkeypox in several 
rodent species, including two Gambian giant pouched rats, nine dormice, 
and three rope squirrels (Ref. 23). Of the 762 rodents from the 
original shipment, 584 were traced to distributors in 6 states. A total 
of 178 African rodents could not be traced beyond the point of entry in 
Texas because records were not available (Ref. 4).
    Some African rodents made their way to an animal distributor in 
Illinois who also sold prairie dogs (Ref. 5). The Illinois animal 
distributor had approximately 200 prairie dogs. Thirty-nine of these 
prairie dogs, along with one Gambian giant pouched rat, went to another 
animal distributor in Wisconsin in early May, 2003; it was at this time 
that several prairie dogs appeared to be ill, and several of the 
animals died (Ref. 5). By late May, the first human cases began to 
appear in Wisconsin (including the Wisconsin animal distributor), with 
other human cases appearing later in Kansas, Missouri, Illinois, 
Indiana, and Ohio (Refs. 5 and 6).
    Of the 200 prairie dogs that were at the Illinois animal 
distributor, only 93 were able to be traced during the traceback 
investigation (Ref. 4).
    The 2003 monkeypox outbreak in the United States eventually 
resulted in 72 human cases, with 37 of those cases being laboratory-
confirmed (Ref. 7). Most patients had direct or close contact with 
prairie dogs. For example, 28 children at an Indiana day care center 
were exposed to 2 prairie dogs that later became ill and died. Twelve 
of these exposed children reported handling or petting the prairie 
dogs, and seven of these children later became ill with symptoms that 
were consistent with monkeypox infection (Ref. 7). In Wisconsin, more 
than half of the human monkeypox cases occurred through occupational 
exposure to infected prairie dogs, with veterinary staff being at 
greater risk of acquiring monkeypox than pet store employees (Ref. 21). 
The human cases in the United States included children as young as 3 
years old, and 19 people were hospitalized, although some were 
hospitalized primarily for isolation purposes (Ref. 6). The initial 
signs or symptoms seen in some patients included skin lesions or fever 
with drenching sweats and severe chills (Ref. 5). Other signs and 
symptoms seen most often included:
     Headache;
     Persistent cough;
     Lymphadenopathy; and
     Sore throat (Ref. 5).
    Less frequent signs and symptoms included:
     Pharyngitis;
     Tonsillar hypertrophy;
     Tonsillar erosions;
     Malaise;
     Mild chest tightness;
     Diarrhea;
     Myalgias;
     Back pain;
     Nasal congestion;
     Blephartis; and
     Nausea (Ref. 5).
    In general, the human cases in the United States were milder than 
those seen in Africa (Ref. 6), and patients who had been vaccinated 
against smallpox appeared to have milder cases compared to those who 
had not been vaccinated against smallpox. However, two children 
suffered serious clinical illnesses. One child had severe encephalitis 
that improved during a 14-day hospital stay, and another child had pox 
lesions on many parts of her body, including lesions inside her mouth 
and throat which created difficulty in breathing and swallowing (Refs. 
6, 9, and 19). At least 5 patients (3 adults and 2 children) had 
temperatures greater than or equal to 38.3 [deg]C (100.94 [deg]F) and 
rashes comprised of 100 or more lesions (Ref. 9). One adult patient 
remained symptomatic for approximately 5 months; the patient became 
asymptomatic only after having a corneal transplant (Ref. 9).

II. How Did We Respond to the Monkeypox Outbreak?

    On June 11, 2003, the Director of the Centers for Disease Control 
and Prevention (CDC) and the Commissioner of Food and Drugs, under 42 
CFR 70.2 and 21 CFR 1240.30 respectively, issued a joint order (Refs. 
10 and 11) prohibiting, until further notice, the transportation or 
offering for transportation in interstate commerce, or the sale, 
offering for sale, or offering for any other type of commercial or 
public distribution, including release into the environment, of:
     Prairie dogs (Cynomys sp.);
     Tree squirrels (Heliosciurus sp.);
     Rope squirrels (Funisciurus sp.);
     Dormice (Graphiurus sp.);
     Gambian giant pouched rats (Cricetomys sp.);
     Brush-tailed porcupines (Atherurus sp.), and
     Striped mice (Hybomys sp.).
    The June 11, 2003, order did not apply to the transport of listed 
animals to veterinarians or animal control

[[Page 51914]]

officials or other entities pursuant to guidance or instructions issued 
by Federal, State, or local government authorities. In addition, under 
42 CFR 71.32(b), CDC implemented an immediate embargo on the 
importation of all rodents (order Rodentia) from Africa.
    FDA and CDC issued the June 11, 2003, order to address quickly what 
was then a new and rapidly developing monkeypox outbreak (Ref. 11). As 
the two agencies became more experienced with the order and more 
knowledgeable about the monkeypox outbreak, it became apparent that we 
and CDC needed a regulatory approach to prevent the monkeypox virus 
from becoming established and spreading in the United States and to 
modify the June 11, 2003, order, such as creating exemption procedures 
to accommodate special circumstances. Consequently, on November 4, 2003 
(68 FR 62353), FDA and CDC issued an interim final rule that superseded 
the June 11, 2003, order. The interim final rule created two 
complementary regulations. First, with respect to certain animals that 
are in the United States, the interim final rule added 21 CFR 1240.63 
entitled ``African rodents and other animals that may carry the 
monkeypox virus.'' Second, for African rodents that are being imported 
or offered for import to the United States, the interim final rule 
added 42 CFR 71.56 that is also entitled ``African rodents and other 
animals that may carry the monkeypox virus.'' We are responsible for 21 
CFR 1240.63, and CDC is responsible for 42 CFR 71.56; both sets of 
regulations are intended to prevent the further introduction, 
establishment, and spread of the monkeypox virus in the United States.
    We also indicated that we would revoke or amend, as warranted, all 
or parts of 21 CFR 1240.63 if we concluded that monkeypox is eradicated 
or adequately controlled so that the virus does not become established 
in the United States (see 68 FR at 62359).
    We issued the interim final rule under section 361 of the Public 
Health Service Act (PHS Act) (42 U.S.C. 264). Section 361 of the PHS 
Act gives the Secretary of Health and Human Services (the Secretary) 
the authority to make and enforce regulations to prevent the 
introduction, transmission, or spread of communicable diseases from 
foreign countries into the States or from one State to another State.

III. What Other Actions Did the Department of Health and Human Services 
Take?

A. Why Did the Interim Final Rule Continue After January 20, 2004?

    The preamble to the interim final rule stated that:
    Monkeypox is endemic in parts of Africa. Therefore, we do not 
anticipate revoking the prohibition on import of African rodents and 
any other animals that the Director of CDC has specified under 42 
CFR Sec.  71.56(a)(1)(i). However, FDA will revoke or amend, as 
warranted, all or parts of 21 CFR Sec.  1240.63 if FDA concludes 
that monkeypox is eradicated or adequately controlled so that the 
virus does not become established in the United States. FDA's 
decision would depend on scientific principles for controlling 
zoonotic diseases. For example, if the incubation period is known, 
then it would be prudent to continue the restrictions for a time 
period that is double the incubation period to ensure that there is 
little further risk of infection or restarting the monkeypox 
outbreak. CDC tests on some animals involved in the original April 
9, 2003, shipment from Ghana suggest that, insofar as dormice are 
concerned, the incubation period may be as long as 2.5 months. If 
FDA rounds this time frame up to 3 months, and then doubles the 
incubation period, there would appear to be little further risk of 
infection after 6 months had passed with no further evidence of 
monkeypox identified, and FDA would be able to take actions to 
revoke or amend 21 CFR Sec.  1240.63. The last infected animal from 
the April 9, 2003, shipment that died from monkeypox died on July 
20, 2003. There have been no identified monkeypox cases in animals 
or people in the United States since that date. If no further 
monkeypox cases are identified in the United States, and if there is 
no new information warranting an extension of the 6-month time 
period, FDA intends to revoke or amend 21 CFR Sec.  1240.63 as early 
as January 20, 2004, which will be six months after July 20, 2003. 
At that time, if FDA decided to revoke or amend 21 CFR Sec.  
1240.63, it would publish an appropriate document (such as a 
proposed rule or direct final rule) in the Federal Register. FDA 
invites comments on this approach.
    (Id. at page 62359.) However, the preamble to the interim final 
rule also cautioned that:
    We emphasize that any possible revocation or amendment of 21 CFR 
Sec.  1240.63 may also depend on new data or new developments. For 
example, various animal studies are being conducted to learn more 
about the incubation period and transmission dynamics of monkeypox. 
If those studies suggest that the period for incubation and 
transmission may be longer than 2.5 months, FDA could decide to 
recalculate the date on which it might revoke or amend 21 CFR Sec.  
1240.63. Studies are also underway to determine whether certain 
species that may be infected with the virus, but not display any 
symptoms, can infect other species. To illustrate how the virus 
could spread from an asymptomatic animal, assume that an animal can 
carry the monkeypox virus, but that the animal does not develop 
monkeypox. If that animal later comes into contact with prairie 
dogs, a species which is already known to be susceptible to 
monkeypox, then the prairie dogs could become infected, and another 
monkeypox outbreak in prairie dogs could erupt. Again, if the CDC 
studies suggest that species can be asymptomatic, but still 
infectious, those results could cause FDA to recalculate the date on 
which it could revoke or amend 21 CFR Sec.  1240.63.
(Id.)
    After the interim final rule's publication in the Federal Register 
on November 4, 2003, CDC notified us that it had test information that 
warranted our continued application and enforcement of 21 CFR 1240.63. 
This information confirmed monkeypox virus infection in several prairie 
dogs and in a few animals from other species, including a Gambian giant 
pouched rat, dormice, rope squirrels, a ground hog, a South American 
opossum, and a chinchilla. Some of these infections were subclinical 
(the animal was infected with the virus, but did not appear to be ill). 
Some of this preliminary information subsequently appeared in peer-
reviewed scientific journal articles, and, in a Federal Register notice 
dated February 21, 2007 (72 FR 7825), we announced the addition of 
those articles and other recent journal articles to the docket. 
However, follow-up investigations confirmed that the human monkeypox 
cases in the United States were not associated with exposure to any 
animals except prairie dogs.
    CDC also was monitoring the progress of a human case where a 
patient had developed monkeypox in late June 2003, but still had 
symptoms 5 months later. Conjunctival swabs from this patient were 
positive (following polymerase chain reaction (PCR) analysis) at 139 
days after onset and culture positive at 126 days after onset. This 
patient eventually required a corneal transplant (see Ref. 9 which 
discusses this case briefly).
    We also note that, when we wrote the interim final rule, efforts 
were continuing to track down animals from the original African 
shipment as well as prairie dogs from the Illinois distributor. 
Ultimately, over 170 African rodents from that shipment and 103 prairie 
dogs from the Illinois distributor were never recovered or located.

B. Were the New Data Available to the Public?

    In the Federal Register of April 14, 2004, the Department of Health 
and Human Services published a notice announcing that the Secretary's 
Council on Public Health Preparedness

[[Page 51915]]

(Secretary's Council) would hold a public meeting where one topic would 
be ``Transport of Possibly Infected Exotic Animals'' (see 69 FR 19854 
(April 14, 2004)). The Secretary's Council invited FDA and CDC to make 
presentations regarding the interim final rule. FDA made a presentation 
to the Secretary's Council seeking its advice on assessing the risk of 
monkeypox in the United States so that we could determine the 
appropriate way to manage that risk. CDC presented information 
concerning the new data, thus making the data publicly available. The 
Secretary's Council did not assess the risk of monkeypox; it 
recommended instead that the interim final rule's restrictions on 
prairie dogs and certain African rodents remain in place, although it 
also recommended that we make minor clarifications or changes to the 
rule so that prairie dog owners could take their animals to receive 
veterinary care and to transport their animals in certain situations. 
The Secretary's Council did not issue its recommendations in writing.

C. Is There a Risk That Monkeypox Still Exists in the United States?

    From mid-2004 through 2007, more information regarding the 2003 
monkeypox outbreak appeared in the scientific and medical literature. 
For example, two scientific articles demonstrated that the monkeypox 
virus easily infected prairie dogs and that infection in prairie dogs 
could occur through contact or through inhalation (Refs. 13 and 17). 
Another article described the laboratory evaluation of animals 
associated with the monkeypox outbreak; the authors examined tissue 
samples from 249 animals of 26 different species and found the 
monkeypox virus in 33 animals (Ref. 23). These animals included three 
rope squirrels, two Gambian giant pouched rats, and nine dormice from 
the shipment of African rodents (Ref. 23). Additionally, 14 of 20 
prairie dogs tested were PCR positive for the monkeypox virus 
deoxyribonucleic acid (DNA), and infectious virus was recovered from 9 
of 11 prairie dogs (Ref. 23). In general, prairie dogs also had higher 
levels of monkeypox virus or monkeypox virus DNA than other animal 
species (Ref. 23). The authors also found monkeypox virus DNA in 
tissues of other animal species housed at the Illinois establishment; 
this suggested that monkeypox could infect several animal species (Ref. 
23). The article also described the limited, live-trapping of wild 
animals that the United States Department of Agriculture's Wildlife 
Service and the United States Geologic Survey's National Wildlife 
Health Center completed after the United States monkeypox outbreak. 
Trapping of 201 animals occurred at sites located near where six human 
monkeypox cases (and associated captive prairie dogs) in Wisconsin 
occurred. No evidence of orthopox virus infection in any of these 
animals was detected. (The term ``orthopox virus'' refers to a genus (a 
term used in biology to denote a type or group that is above that of a 
species) of poxviruses. Examples of orthopox viruses include monkeypox 
virus, cowpox virus, and the variola virus; the variola virus causes 
smallpox.) The Illinois Wildlife Services program conducted further 
trapping studies in Illinois at three locations linked by trash 
disposal routes to the Illinois animal distributor. Forty-three animals 
were trapped, and all were negative for evidence of orthopox virus 
infection (Ref. 23).
    Other articles (Refs. 14, 15, and 9) shed more light as to why the 
2003 outbreak in the United States was not as deadly as those seen in 
Africa; for example, there are two different strains (or ``clades'') of 
the monkeypox virus, and the virus that appeared in the United States 
was representative of the less virulent (and less transmissible between 
humans) strain insofar as humans are concerned (Refs. 14 and 20). The 
risk of infection in humans correlated with the type of exposure to 
infected prairie dogs, and most human cases in the United States were 
associated with direct contact to (specifically the handling of) 
infected prairie dogs (Refs. 16 and 22). Children (persons under 18 
years old) who were infected were more likely to be hospitalized in 
intensive care compared to infected adults (Ref. 9). Additionally, 
while some adults had received smallpox vaccinations before 1972, it is 
unclear as to whether childhood smallpox vaccinations offer durable 
protection against monkeypox. Some articles indicated that there did 
not appear to be significant differences in serious clinical 
observations or complications between vaccinated and unvaccinated 
adults (Ref. 9 and 20), yet another suggested that an individual's 
history of smallpox vaccination might protect against monkeypox illness 
(Ref. 21). In brief, the recent publications validate and reinforce the 
facts that:
     Prairie dogs are easily infected with the monkeypox virus, 
and infected prairie dogs have higher levels of monkeypox virus than 
other infected animals;
     Human cases in the United States were linked to contact 
with infected prairie dogs; and
     Monkeypox is a serious disease, particularly in children, 
but the virus implicated in the United States was representative of the 
less virulent and less transmissible between humans strain.
    More significantly, one recent article assessed the risk for 
monkeypox associated with domestic trade in certain animal species in 
the United States (Ref. 18). The authors evaluated the data and 
uncertainties concerning monkeypox and its potential spread to animal 
and human populations in the United States and characterized in a 
qualitative analysis the probability of harm based on that data. They 
concluded that the risk for further domestically acquired human 
infections is low with the restrictions that FDA and CDC had 
established. The authors noted that there have been no new cases in 
humans or animals in the United States since the outbreak, despite the 
likelihood that some surviving infected animals may have been kept 
alive by pet owners or dealers. However, there have been no prospective 
surveillance activities that would fully address this question.

IV. Given Recent Evidence, Is FDA Action Still Necessary?

A. Are the Measures of the Interim Final Rule Needed Now to Prevent 
Disease Spread?

    As we explained in the preamble to the interim final rule, we 
issued the interim final rule under section 361 of the Public Health 
Service Act (PHS Act) (42 U.S.C. 264) (see 68 FR at 62360) to prevent 
the spread of communicable disease. Section 361 of the PHS Act 
authorizes the Secretary to make and enforce such regulations as judged 
necessary to prevent the introduction, transmission, or spread of 
communicable diseases from foreign countries into the States or from 
one State to another State. We may regulate intrastate transactions 
under this authority as appropriate (see State of Louisiana v. Mathews, 
427 F. Supp. 174 (E.D. La. 1977)).
    We have invoked section 361 of the PHS Act to regulate various 
activities and articles. For example, we have invoked this authority to 
prevent the transmission of communicable disease through certain 
shellfish, turtles, certain birds, and human tissue intended for 
transplantation (see 21 CFR 1240.60 (molluscan shellfish), 1240.62 
(turtles), 1240.65 (psittacine birds), and 1270.1 through 1270.43 
(human tissue)).
    Our regulations, at 21 CFR 1240.30, provide further insight as to 
when we will use our communicable disease

[[Page 51916]]

authority. The regulation, in relevant part, states that:
    Whenever the Commissioner of Food and Drugs determines that the 
measures taken by health authorities of any State or possession 
(including political subdivisions thereof) are insufficient to 
prevent the spread of any of the communicable diseases from such 
State or possession to any other State or possession, he may take 
such measures to prevent such spread of the diseases as he deems 
reasonably necessary * * *
    Thus, when we issued the June 11, 2003, order and later issued the 
interim final rule, we acted because we determined that measures taken 
by State health authorities, in 2003, were insufficient to prevent the 
spread of monkeypox. We took those actions because infected and 
potentially infected animals were crossing State lines, and human cases 
were appearing in several States; the multi-state impact, as well as 
the then-rapidly developing outbreak, indicated that measures taken by 
individual States would be insufficient to prevent the spread of 
monkeypox.
    The risk assessment published in 2006, however, suggests that the 
risk of further monkeypox transmission from the original events of 
2003, particularly to humans, in the United States is low. 
Consequently, based on that low risk, we believe that the import 
controls of CDC's interim final rule in 42 CFR 71.56 and routine State 
surveillance and disease prevention measures should be sufficient to 
prevent further human and animal monkeypox cases. Therefore, we have 
concluded that the domestic controls in 21 CFR 1240.63 are no longer 
necessary, and we are removing our regulation.
    Please note that this revocation pertains solely to FDA's 
provisions at 21 CFR 1240.63; the requirements imposed by the CDC at 42 
CFR 71.56 remain in effect.

B. How Many Comments Did We Receive?

    The interim final rule provided an opportunity for public comment; 
this comment period expired on January 20, 2004. We received over 570 
comments on the interim final rule. We received comments from State 
government agencies or departments, zoos, zoological associations, 
animal interest groups, animal breeders, animal vendors, and 
individuals, including foreign citizens. The comments reflected a wide 
array of differing and sometimes conflicting opinions. For example, 
most, but not all, State agencies supported the rule. Most State 
agencies appreciated Federal efforts in responding to the monkeypox 
outbreak, but one State agency criticized the rule as interfering with 
the State's wildlife management obligations, and another State agency 
commented that it, rather than FDA, should operate a permit system that 
would enable certain animals to move within a State. As another 
example, many individuals commenting on the rule either captured, sold, 
owned, or wanted to own prairie dogs and objected strongly to the 
rule's impact on the prairie dog trade and to continuing the rule. In 
contrast, a few individuals supported the rule and advocated more 
stringent measures regarding the pet trade, including animals that the 
interim final rule did not address.
    The comments also varied in their complexity and familiarity with 
the rule. For example, the American Zoo and Aquarium Association (AZA) 
recommended a specific change in the rule for AZA-accredited zoological 
parks because of the quarantine protocols used by AZA-accredited zoos; 
the AZA included its detailed accreditation standards as part of its 
comment. In contrast, many comments simply expressed their strong 
objections to the rule, particularly as it applied to prairie dogs, 
without explaining the reasons for their objections, discussing any 
specific regulatory provision, or suggesting any alternative 
approaches. Some comments advocated defiance or violations of the rule. 
Several comments denied that monkeypox is a serious disease, although 
they offered no evidence to contradict the scientific or medical 
reference we had cited. Other comments criticized the rule or FDA 
harshly, yet some criticisms pertained to issues that were not in the 
interim final rule or to actions, statements, or positions that were 
mistakenly attributed to us. For example, some comments accused us of 
killing or conspiring to kill prairie dogs. Virtually none of these 
comments mentioned any other animal covered by the interim final rule, 
and none offered any evidence to support their accusations.
    Additionally, we received over 120 more comments on a notice that 
appeared in the Federal Register on February 19, 2004 (69 FR 7752). The 
notice was a routine opportunity for public comment on the information 
collection provisions in a rule pursuant to the Paperwork Reduction Act 
of 1995. In this particular case, the notice pertained to the 
information we were requiring from persons who wanted our permission to 
capture, offer to capture, transport, offer to transport, sell, barter, 
or exchange, or offer to sell, barter, or exchange, distribute, offer 
to distribute, and/or release into the environment any animals covered 
by the rule. Specifically, the notice sought comment on the numerical 
estimates pertaining to the permit information, such as the estimated 
number of persons who would request a permit, the number of hours they 
would spend in preparing a permit request, the frequency at which 
permit requests would be submitted, etc. Most comments either 
interpreted or treated the notice as either a new opportunity to 
comment on the interim final rule or as finalizing the interim final 
rule. As a result, almost all comments submitted in response to the 
Paperwork Reduction Act notice focused on whether the interim final 
rule should remain in effect and did not address the collection of 
information under the Paperwork Reduction Act or any of our Paperwork 
Reduction Act estimates. Even though most comments submitted in 
response to the February 19, 2004, notice were not relevant to the 
Paperwork Reduction Act and were submitted months after the interim 
final rule's comment period had expired, we considered those comments 
in addition to the comments that were submitted in response to the 
interim final rule.
    Finally, we received seven comments in response to a Federal 
Register notice which we published on February 21, 2007 (72 FR 7825). 
The notice added new information, primarily in the form of peer-
reviewed scientific literature, to the administrative record, and we 
invited comment on the information being added. Of the seven comments, 
only one addressed a specific new reference. (The comment challenged 
the risk assessment article discussed earlier in section III.C of this 
document. The comment opined that the article ``may underestimate the 
potential disease transmission risk associated with wild-caught prairie 
dogs,'' but did not challenge the authors' methodology or the authors' 
conclusion that the risk of monkeypox associated with the 2003 
introduction of the virus into the United States was low. Rather, the 
comment noted a risk of transfer or importation of infectious pathogens 
risk remains due to illegal importation of animals, as well as the risk 
that domestic wild animals, particularly prairie dogs, may be a source 
for diseases other than monkeypox, such as plague and tularemia. The 
comment argued that there is no way to estimate the degree of illegal 
importation of African rodents or the legal importation of other 
potentially infected species. We note that the article does address 
each of these points.) Most comments discussed issues that were outside 
the scope of the Federal Register notice of February 21, 2007, such as 
urging FDA to retain its regulation, discussing the invasive

[[Page 51917]]

species potential of a Gambian Giant Pouched Rat population located in 
Florida, discussing plague and tularemia in prairie dogs, or discussing 
the pet trade, zoonotic diseases generally, or gaps in Federal 
authority.
    Given our decision to remove the regulation based on the current 
evidence and circumstances, we will not respond in detail to all of the 
comments that opposed the rule. However, we would like to clarify a few 
points as follows:
     Many individuals believed that the rule was unfair because 
the Federal Government did not act against other animals that are 
capable of transmitting disease to humans. These individuals often 
argued that the Federal Government did not ``ban'' cows despite bovine 
spongiform encephalopathy (BSE, or ``mad cow disease'') disease; dogs 
despite rabies; birds due to West Nile virus; or other animals 
associated with zoonotic diseases. Some claimed that we were 
discriminating against prairie dogs because they believed a rabbit had 
been infected with monkeypox, yet we did not include rabbits in the 
rule.
    As a preliminary matter, the existence of other zoonotic diseases 
does not, and cannot, mean that we must treat all diseases in the same 
manner and at the same time. We agree that BSE and several other 
diseases cited by the comments raise public health concerns, but that 
fact does not mean that we are compelled to promulgate regulations for 
other or all zoonotic diseases before we can issue regulations to deal 
with monkeypox. In addition, it is important to note that monkeypox, as 
we stated in the preamble to the interim final rule (see 68 FR at 
62353), is a zoonotic disease that, until mid-2003, occurred in central 
and west Africa. The monkeypox virus' appearance in the United States 
demanded our immediate attention because monkeypox is a potentially 
fatal disease in humans, so it was important to prevent the virus from 
becoming established in the United States. West Nile virus is an 
example of how a virus can become established in the United States and 
result in sickness and death. Before 1999, West Nile virus had not been 
recorded in the United States; in 2002 alone, more than 4,000 Americans 
had become ill, and 284 had died (see 68 FR at 62361). Many animal 
species also suffered as the West Nile virus became established in the 
United States (id.).
    To put it another way, unlike most of the pathogens or factors 
responsible for the diseases cited by the comments, the monkeypox virus 
was new to the United States in 2003, and (unlike West Nile virus) 
could be controlled through regulation of human activity; as a result, 
a regulatory approach was taken that we anticipated would prevent the 
virus from becoming established in the listed animal populations or in 
other domestic animal populations. To the best of our knowledge, the 
efforts undertaken in 2003 were fully successful.
    We also wish to point out that, contrary to the comments' 
assumptions, we have taken regulatory action regarding other animals 
and other diseases. Those regulatory actions varied depending on the 
risk presented. For example, we have issued regulations restricting the 
sale and commercial distribution of turtles (21 CFR 1240.62) and 
restricting the transportation of psittacine birds (21 CFR 1240.65) 
because of their potential to transmit certain diseases to humans. We 
prohibited the use of mammalian protein in ruminant feed (21 CFR 
589.2000) and have taken a number of additional actions to reduce the 
potential risk of BSE in cattle (see, e.g., 72 FR 1582 (January 12, 
2007) (proposed rule to prohibit the use of certain cattle material in 
or in the manufacture of drugs intended for use in ruminant animals); 
70 FR 58570 (October 6, 2005) (proposed rule to prohibit the use of 
certain cattle origin materials in the food or feed of all animals); 69 
FR 58448 (September 30, 2004) (notice of availability of a guidance 
titled ``Use of Material from Bovine Spongiform Encephalopathy-Positive 
Cattle in Animal Feed''); 69 FR 42288 (July 14, 2004) (advance notice 
of proposed rulemaking inviting comment on Federal measures to mitigate 
BSE risks)). We also have taken action to prohibit the use of certain 
cattle material (such as brain, skull, eyes, spinal cord, and other 
material) in human food to minimize human exposure to materials that 
are highly likely to contain the BSE agent (see 69 FR 42256 (July 14, 
2004); see also 69 FR 42275 (July 14, 2004) (proposed rule to require 
manufacturers and processors of human food and cosmetics that are 
manufactured from, processed with, or otherwise contain material from 
cattle to establish and maintain records sufficient to demonstrate that 
the food or cosmetic is not manufactured from, processed with, or does 
not otherwise contain prohibited cattle materials)). Thus, we have 
taken regulatory actions when necessary to protect the public health, 
and the nature of the risk presented shaped our regulatory response to 
that risk.
    Finally, insofar as rabbits and monkeypox are concerned, we 
acknowledge that a report issued as the 2003 outbreak was unfolding 
(Ref. 24) suggested that a rabbit might have transmitted the monkeypox 
virus to a human. However, subsequent tests on the rabbit in question 
and the human patient proved negative. Consequently, there are no 
documented cases of monkeypox transmission from rabbits to humans in 
the United States (Ref. 22).
     The 2003 monkeypox outbreak was significant because it 
involved a potentially fatal disease that had never been seen within 
the United States. It was important to stop monkeypox from becoming 
established in the United States because, once established, the disease 
could become a greater public health problem. If the virus became 
established in the United States, the potential impact on humans and 
other animal species could have been significant. In brief, final 
analysis of the 2003 monkeypox outbreak showed the following: (1) 
Besides rope squirrels, additional native species of African rodents 
(Gambian giant pouched rats and dormice) are susceptible to monkeypox; 
(2) prairie dogs are susceptible to monkeypox; (3) infected prairie 
dogs can transmit the disease to humans; and (4) children may be 
affected more severely than adults. Additionally, laboratory 
experiments demonstrated that additional North American animal species 
are susceptible to monkeypox (Ref. 23). We did not know, in 2003, and, 
in many cases, still do not know, whether the virus had spread or could 
spread to other domestic animal species (such as rodents) which, in 
turn, could expose more humans to monkeypox. In short, when dealing 
with a novel communicable disease, trying to prevent the disease from 
spreading has both present effects (i.e., fewer individuals become sick 
or die) and future effects (i.e., the potential for more animals and 
humans to become infected decreases if prevention efforts are 
successful).
     With respect to the comments that supported the interim 
final rule, we agree that the risks of communicable disease spread 
justified the measures taken in the interim final rule. Because we have 
decided to remove the regulation, we will not address the details of 
the comments that suggested variations on the permit system or other 
modifications to the rule. Nor will we address the issues related to 
other diseases of prairie dogs or to zoonotic diseases in general, 
which are outside the scope of this rule.
     The circumstances being addressed by most of the comments 
supporting the interim final rule have changed significantly, in large 
part because of the success of the interim final rule. As

[[Page 51918]]

discussed in section III.C above, the current evidence supports the 
conclusion that the risk of further infections from the monkeypox virus 
in the United States is low. Only one comment challenged the risk 
assessment that concluded that the current risk is low, but that 
comment did not challenge the authors' methodology. Instead, the 
comment expressed concern about future illegal importation of African 
rodents or legal importation of other animals that could be infected 
with monkeypox. Although we agree that the risk of future importations 
of animals infected with the monkeypox virus is not zero, we believe 
that the restrictions in 42 CFR 71.56 have been successful, and will 
continue to be successful, in keeping this risk low. Together, the 
measures taken by FDA and CDC under 21 CFR 1240.63 and 42 CFR 71.56 
have successfully brought the risk of further human or animal monkeypox 
infection in the United States associated with the 2003 outbreak to its 
current low level. Based on the evidence, we believe that the risk will 
remain low in the absence of the measures in FDA's interim final rule. 
Under these circumstances, including the fact that CDC's interim final 
rule at 42 CFR 71.56 remains in effect, we have decided to remove 21 
CFR 1240.63 in its entirety.

V. Environmental Impact Analysis

    We have determined under 21 CFR 25.32(g) 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.

VI. Analysis of Impacts

    We have examined the impacts of this regulatory action under 
Executive Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-
612), and the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). We believe that the 
removal of the regulation is not a significant regulatory action under 
the Executive order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because the removal of FDA's regulation would 
eliminate most of the small administrative costs imposed by the interim 
final rule, we certify that it will not 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 publishing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year.'' The current threshold after adjustment 
for inflation is $127 million, using the most current (2006) Implicit 
Price Deflator for the Gross Domestic Product. We do not expect the 
removal of FDA's regulation to result in any 1-year expenditure that 
would meet or exceed this amount.
    We issued a regulation on November 4, 2003, that modified existing 
restrictions on the import, capture, transport, sale, barter, exchange, 
distribution and release of African rodents, prairie dogs and certain 
other animals in order to prevent the spread of monkeypox. The decision 
to remove the regulation pertaining to domestic trade in prairie dogs 
and certain African rodents will eliminate most of the costs of the 
regulation to the extent that they have been realized.
    In the interim final rule, we stated that incomplete data precluded 
us from developing quantitative estimates of the economic costs and 
benefits of the rule. The analysis of the rule, however, did contain a 
discussion about the sale of prairie dogs prior to and immediately 
after the June 11, 2003, administrative order banning the sale of these 
animals in order to reduce the spread of monkeypox. In effect, the 
analysis described the loss of the market for these pets that resulted 
from the earlier administrative order restricting their further 
distribution. The removal of the regulation would reopen the domestic 
market for pet prairie dogs, which prior to 2003 was estimated at about 
30,000 animals per year with a retail value of about $4.5 million. The 
domestic markets for certain African rodents would also be reopened, 
but the CDC restrictions on the importation of African rodents would 
remain in effect. Although we do not have data to estimate the size of 
these markets in 2003, the analysis in the interim final rule concluded 
that they would be fairly small.
    The interim final rule also allowed for exemptions from the rule's 
restrictions on trade in these animals by requesting written permission 
from FDA. The analysis estimated that individuals requesting these 
exemptions would incur annual administrative costs ranging from about 
$3,500 to $6,500. FDA's administrative costs to process these requests 
each year were estimated at $13,300. These administrative costs will be 
eliminated with the removal of FDA's regulation.
    The analysis of the interim final rule also concluded that the 
regulation may have a significant impact on a substantial number of 
small entities, including trappers and distributors of prairie dogs, 
other small animal distributors, and retail pet stores. Most of these 
impacts will be negated with the removal of FDA's regulation.

VII. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday.
    1. Khodakevich, L., Jezek, Z. and Messinger, D., ``Monkeypox 
Virus: Ecology and Public Health Significance,'' Bulletin of the 
World Health Organization, 66: 747-752 (1988). This reference 
identifies several species of squirrels as playing a major role as a 
reservoir for the monkeypox virus.
    2. Centers for Disease Control and Prevention, ``Updated Interim 
Case Definition for Human Case of Monkeypox,'' dated July 2, 2003.
    3. Centers for Disease Control and Prevention, ``Questions and 
Answers About Monkeypox,'' dated July 7, 2003.
    4. Centers for Disease Control and Prevention, ``Update: 
Multistate Outbreak of Monkeypox--Illinois, Indiana, Kansas, 
Missouri, Ohio, and Wisconsin, 2003,'' Morbidity and Mortality 
Weekly Report, 52: 642-646 (July 11, 2003).
    5. Reed, K. D. et al., ``The Detection of Monkeypox in Humans in 
the Western Hemisphere,'' New England Journal of Medicine, 350: 342-
350 (January 22, 2004).
    6. DiGiulio, D. B., and Eckburg, P. B., ``Human Monkeypox: An 
Emerging Zoonosis,'' The Lancet--Infectious Diseases 4: 15-25 
(2004).
    7. Centers for Disease Control and Prevention, ``Update: 
Multistate Outbreak of Monkeypox - Illinois, Indiana, Kansas, 
Missouri, Ohio, and Wisconsin, 2003,'' Morbidity and Mortality 
Weekly Report, 52: 561-564 (June 20, 2003).
    8. Reynolds, G., ``Why Were Doctors Afraid to Treat Rebecca 
McLester?'' New York Times Magazine, section 6, page 32, column 1 
(April 18, 2004) (available at www.nytimes.com/2004/04/18/magazine/
18MONKEYPOX.html).
    9. Huhn, G.D., et al., ``Clinical Characteristics of Human 
Monkeypox, and Risk Factors for Severe Disease,'' Clinical 
Infectious Diseases 41: 1742-1751 (2005).

[[Page 51919]]

    10. Order dated June 11, 2003, signed by Julie Louise 
Gerberding, Director, Centers for Disease Control and Prevention, 
and Mark B. McClellan, Commissioner of Food and Drugs, titled 
``Joint Order of the Centers for Disease Control and Prevention and 
the Food and Drug Administration, Department of Health and Human 
Services.''
    11. 68 FR 36566 (June 18, 2003).
    12. Fleischauer, A. T., et al., ``Evaluation of Human-to-Human 
Transmission of Monkeypox from Infected Patients to Health Care 
Workers,'' Clinical Infectious Diseases, 40: 689-694 (2004).
    13. Xiao, S.Y., et al., ``Experimental Infection of Prairie Dogs 
with Monkeypox Virus,'' Emerging Infectious Diseases 11(4): 539-545 
(2005).
    14. Likos, A.M., et al., ``A Tale of Two Clades: Monkeypox 
Viruses,'' Journal of General Virology 86: 2661-2672 (2005).
    15. Nalca, A., Rimoin, A.W., Bavari, S. and Whitehouse, C.A., 
``Reemergence of Monkeypox: Prevalence, Diagnostics, and 
Countermeasures,'' Clinical Infectious Diseases 41: 1765-1771 
(2005).
    16. Kile, J.C., et al., ``Transmission of Monkeypox Among 
Persons Exposed to Infected Prairie Dogs in Indiana in 2003,'' 
Archives of Pediatric Adolescent Medicine 159: 1022-1025 (2005).
    17. Guarner, J. et al., ``Monkeypox Transmission and 
Pathogenesis in Prairie Dogs,'' Emerging Infectious Diseases, 10: 
426-431 (March 2004).
    18. Bernard, S., and Anderson, S., ``Qualitative Risk 
Assessment: Monkeypox in the United States Associated with Domestic 
Trade in Certain Animal Species,'' Emerging Infectious Diseases, 12: 
1827-1833 (2006).
    19. Anderson, M.G., et al., ``A Case of Severe Monkeypox Virus 
Disease in an American Child: Emerging Infections and Changing 
Professional Values,'' Pediatric Infectious Disease, 22: 1093-1096 
(2003).
    20. Croft, D.R., et al., ``Occupational Risks during a Monkeypox 
Outbreak, Wisconsin, 2003,'' Emerging Infectious Diseases, 13: 1150-
1157 (2007).
    21. Reynolds, M.G., et al., ``Spectrum of Infection and Risk 
Factors for Human Monkeypox, United States, 2003,'' Emerging 
Infectious Diseases, 13: 1332-1339 (2007).
    22. Reed, K. D., Davis, J. P., and Damon, I. K., ``Monkeypox in 
the Western Hemisphere,'' (Response to a Letter to the Editor), New 
England Journal of Medicine, 350: 1791 (April 22, 2004).
    23. Hutson, C.L., et al., ``Monkeypox Zoonotic Associations: 
Insights from Laboratory Evaluation of Animals Associated with the 
Multi-State US Outbreak,'' American Journal of Tropical Medicine and 
Hygiene, 76: 757-767 (2007).
    24. Centers for Disease Control and Prevention, ``Multistate 
Outbreak of Monkeypox - Illinois, Indiana, and Wisconsin, 2003,'' 
Morbidity and Mortality Weekly Report, 52: 537-540 (June 13, 2003).

VIII. Federalism

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

List of Subjects

21 CFR Part 16

    Administrative practice and procedure.

21 CFR Part 1240

    Communicable diseases, Public health, Travel restrictions, Water 
supply.

0
Therefore, under the Public Health Service Act and under authority 
delegated to the Commissioner of Food and Drugs, 21 CFR 16 and 1240 are 
amended as follows:

PART 16--REGULATORY HEARING BEFORE THE FOOD AND DRUG ADMINISTRATION

0
1. The authority citation for 21 CFR part 16 continues to read as 
follows:

    Authority: 15 U.S.C. 1451-1461; 21 U.S.C. 141-149, 321-394, 
467f, 679, 821, 1034; 28 U.S.C. 2112; 42 U.S.C. 201-262, 263b, 364.


Sec.  16.1 [Amended]  

0
2. Section 16.1 is amended in paragraph (b)(2) by removing the entry 
for ``Sec.  1240.63(c)(3) ''.

PART 1240--CONTROL OF COMMUNICABLE DISEASES

0
3. The authority citation for 21 CFR part 1240 continues to read as 
follows:

    Authority: 42 U.S.C. 216, 243, 264, 271.


Sec.  1240.63 [Removed]  

0
4. Remove Sec.  1240.63.

    Dated: August 27, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-20779 Filed 9-5-08; 8:45 am]

BILLING CODE 4160-01-S
