[Federal Register Volume 73, Number 174 (Monday, September 8, 2008)]
[Rules and Regulations]
[Pages 51912-51919]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E8-20779]
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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