Natural Resources Defense Council, Inc. et al v. United States Food and Drug Administration et al

Filing 1

COMPLAINT against Center for Veterinary Medicine, Bernadette Dunham, Margaret Hamburg, Kathleen Sebelius, United States Department of Health and Human Services, United States Food and Drug Administration. (Filing Fee $ 350.00, Receipt Number 7624)Document filed by Center For Science In The Public Interest, Public Citizen, Inc., Union Of Concerned Scientists, Inc., Natural Resources Defense Council, Inc., Food Animal Concerns Trust.(ama)

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'THE UNITED
DIS
T COURT
FOR THE SOUTHERN DISTRICT OF NEW YORK
NATURAL RESOURCES DEFENSE
COUNCIL, INC.; CENTER FOR SCIENCE
IN THE PUBLIC INTEREST; FOOD
ANIMAL CONCERNS TRUST; PUBLIC
CITIZEN, INC.; and UNION OF
CONCERNED SCIENTISTS, INC.,

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Plaintiffs,

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v.

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UNITED STATES FOOD AND DRUG
ADMINISTRATION; MARGARET
HAMBURG, in her official capacity as
Commissioner, United States Food and Drug
Administration; CENTER FOR
VETERINARY MEDICINE; BERNADETTE
DUNHAM, in her official capacity as
Director, Center for Veterinary Medicine;
UNITED STATES DEPARTMENT OF
HEALTH AND HUMAN SERVICES; and
KATHLEEN SEBELIUS, in her official
capacity as Secretary, United States
Department of Health and Human Services,
Defendants.

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COMPLAINT FOR DECLARATORY AND INJUNCTIVE RELIEF
INTRODUCTION
1.

The misuse and overuse of antibiotics has given rise to a growing and dangerous

trend of antibiotic resistance. Increasingly, bacteria are resistant to not one but multiple
antibiotics, resulting in infections that are difficult to treat, require longer and more expensive
hospital stays, and are more likely to be fatal. The Institute of Medicine of the National Academy
of Sciences has warned that "[t]he specter of untreatable infections-a regression to the preantibiotic era-is looming just around the comer."

2.

Approximately 80 percent of all antibiotics used in the United States today are

used in livestock. Most of these drugs are not used to treat disease. Instead, they are given to
healthy animals in their feed or water, both to promote faster growth and to prevent infections
that tend to occur when animals are kept in cramped, unsanitary conditions. Research has shown
that the use of antibiotics in livestock leads to the development of antibiotic-resistant bacteria
that can be-and have been-transferred from animals to people through direct contact,
environmental exposure, and the consumption and handling of contaminated meat and poultry
products.
3.

The U.S. Food and Drug Administration (FDA) is charged with regulating the use

of antibiotics in livestock. FDA has approved the use of antibiotics in animal feed for
nontherapeutic purposes-such as growth promotion and routine disease prevention-since the
1950s. These antibiotics are generally given to animals at "subtherapeutic" levels (i.e., doses too
low to treat disease). Many of the antibiotics currently approved for such uses, including
penicillin and tetracyclines, are also important in human medicine.
4.

The Federal Food, Drug, and Cosmetic Act ("Food and Drug AcC), 21 U.S.C.

§ 360b(e)(l), requires FDA to withdraw approval for an animal drug if FDA finds that the drug

is not shown to be safe for the uses for which it was approved. In 1977, FDA found that certain
subtherapeutic uses of penicillin and tetracyclines in animal feed were not shown to be safe. The
agency found that these drug uses were contributing to the development of antibiotic-resistant
bacteria that could be transferred to humans, a conclusion that later research has reinforced. FDA
has never reversed or retracted this conclusion. Instead, it has reiterated its findings in
subsequent decades. Nonetheless, despite the statutory requirement that it do so, and the steady
accumulation of scientific research establishing the risks posed by the routine, nontherapeutic
2

use of antibiotics in livestock, FDA has never withdrawn its approvals for subtherapeutic uses of
penicillin and tetracyclines.
5.

FDA's failure to withdraw approvals for subtherapeutic uses of penicillin and

tetracyclines in animal feed constitutes an agency action unlawfully withheld in violation of the
Administrative Procedure Act (APA), 5 U.S.c. § 706(1), and the Food and Drug Act, 21 U.S.C.
§ 360b(e)(l).

6.

In 1999 and 2005, Plaintiffs Center for Science in the Public Interest (CSPI),

Food Animal Concerns Trust (FACT), Public Citizen, and Union of Concerned Scientists (UCS)
submitted citizen petitions ("the Petitions") to FDA requesting that the agency withdraw
approvals for nontherapeutic uses of antibiotics in livestock if those antibiotics are also important
in human medicine. FDA has never issued a final response to either petition.
7.

FDA has unreasonably delayed ruling on the Petitions, in violation of the APA, 5

U.S.c. § 706(1), and the Food and Drug Act's implementing regulations, 21 C.F.R.
§ 1O.30(e)(1).

8.

Plaintiffs Natural Resources Defense Council (NRDC), CSPI, FACT, Public
,

Citizen, and UCS seek a judgment declaring that FDA's (1) failure to withdraw approval of
subtherapeutic uses of penicillin and tetracyclines in animal feed, and (2) delay in issuing a final
response to the Petitions, violate the APA and the Food and Drug Act. Plaintiffs also seek an
order compelling FDA to withdraw approval for subtherapeutic uses of penicillin and
tetracyclines, unless FDA's findings are reversed in new administrative proceedings, and to
respond to the Petitions, all by specific deadlines.
JURISDICTION AND VENUE
9.

This Court has jurisdiction pursuant to 28 U.S.C. § 1331.
3

10.

Venue is proper in this Court pursuant to 28 U.S.C. § 1391(e)(3), because

Plaintiff NRDC resides and has its principal place of business in this judicial district.
11.

This Court may award Plaintiffs all necessary injunctive relief pursuant to the

APA, 5 U.S.c. § 706(1), and may award declaratory relief pursuant to the Declaratory Judgment
Act, 28 U.S.c. §§ 2201-02.
THE PARTIES
12.

Plaintiff NRDC is a nonprofit environmental and public health advocacy

organization headquartered in New York, New York, with a national membership of more than
400,000. NRDC engages in research, advocacy, and litigation to improve the regulation of
harmful substances in food and consumer products, including drug-resistant bacteria engendered
by the misuse and overuse of antibiotics and other antibacterial products. NRDC also works to
promote sustainable agricultural practices.
13.

Plaintiff CSPI is a science-based nonprofit organization that focuses on nutrition

and food safety issues. It is based in Washington, DC. CSPI is supported by about 750,000
American subscribers-members. For more than a decade, CSPI has published reports and articles
about the risks of antibiotic use in farm animals.
14.

Plaintiff FACT is a nonprofit organization located in Chicago, lllinois, and

dedicated to improving the welfare of farm animals, addressing public health problems that come
from the production of meat, milk, and eggs, and broadening opportunities for family farmers.
FACT conducts on-farm research projects and makes science-based recommendations to
agricultural, public health, and environmental organizations and to federal regulatory agencies.
Phasing out the routine, nontherapeutic use of medically important antibiotics in livestock has
been one of FACT's top priorities for more than a decade.
4

15.

Plaintiff Public Citizen is a national, nonprofit, public interest organization,

headquartered in Washington, DC, with approximately 225,000 members and supporters. Since
its founding in 1971, Public Citizen has worked before Congress, regulatory agencies, and in the
courts to advance the interests of its members on a wide range of consumer protection issues. In
particular, Public Citizen's Health Research Group (HRG) promotes research-based, systemwide changes in health care policy and provides oversight concerning drugs, medical devices,
doctors, hospitals, and occupational health. HRG works to ban or relabel unsafe or ineffective
drugs, and publishes "Worst Pills, Best Pills News," a consumer guide to avoiding drug-induced
death or illness. "Worst Pills, Best Pills News" has about 160,000 subscribers.
16.

Plaintiff UCS is a science-based nonprofit organization headquartered in

Cambridge, Massachusetts, with a national membership of about 79,000. Established in 1969,
UCS combines rigorous scientific analysis, innovative policy development, and effective citizen
advocacy to achieve practical environmental solutions. Ensuring that all people have food that is
produced in a safe and sustainable manner is central to UCS's mission. For over a decade, UCS
has worked to eliminate routine, nontherapeutic uses of medically important antibiotics in
livestock.
17.

Plaintiffs NRDC, CSPI, Public Citizen, and UCS bring this action on their own

behalf and on behalf of their members. NRDC's, CSPI's, Public Citizen's, and UCS' s
memberships include consumers who are concerned about health risks from their exposure to
antibiotic-resistant bacteria in meat and poultry products. FDA's failure to withdraw approval for
subtherapeutic uses of penicillin and tetracyclines in animal feed increases the likelihood that
these members will be exposed to antibiotic-resistant bacteria. These bacteria may cause
infections that are difficult or impossible to treat, or they may transfer resistance traits to other,

5

more dangerous bacteria. At least one of Plaintiffs' members has already suffered from an
antibiotic-resistant infection that was difficult to treat and required a prolonged hospital stay.
18.

Plaintiff FACT brings this action on its own behalf. Plaintiffs CSPI, FACT,

Public Citizen, and UCS have been injured by FDA's unreasonable delay in issuing a final
response to the Petitions filed with the agency in 1999 and 2005. FDA's long delay has deprived
CSPI, FACT, Public Citizen, and UCS of (1) a decision on the merits of the Petitions and (2) the
opportunity to seek judicial review of that decision, if necessary.
19.

Defendants FDA and Margaret Hamburg, in her official capacity as

Commissioner of FDA, are charged by the Food and Drug Act with protecting the public health
by ensuring that veterinary drugs are safe. The Food and Drug Act requires FDA to withdraw
approval of new animal drugs that are not shown to be safe.
20.

Food and Drug Act implementing regulations and the APA require Defendants

FDA and Hamburg to rule on citizen petitions within a reasonable period of time.
21.

Defendants Center for Veterinary Medicine (CVM) and Bernadette Dunham, in

her official capacity as Director of CVM, are charged by the Food and Drug Act and its
implementing regulations with withdrawing approval of new animal drugs that are not shown to
be safe.
22.

Defendants United States Department of Health and Human Services (HHS) and

Kathleen Sebelius, in her official capacity as Secretary of HHS, are charged with responsibility
for the implementation and administration of relevant provisions of the Food and Drug Act.
23.

For the purposes of this Complaint, Defendants FDA, Margaret Hamburg, CVM,

Bernadette Dunham, HHS, and Kathleen Sebelius shall individually and collectively be referred
to as "FDA."

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STATUTORY AND REGULATORY FRAMEWORK
Withdrawal of New Animal Drug Applications
24.

The Secretary ofHHS, "through the Commissioner" of FDA, 21 U.S.c.

§ 393(d)(2), regulates antibiotics in animal feed as "new animal drugs" under section 512 of the

Food and Drug Act, 21 U.S.C. § 360b.
25.

FDA is required to withdraw its existing approval of a new animal drug

application if new information shows that the drug is not shown to be safe:
The Secretary shall, after due notice and opportunity for hearing to the
applicant, issue an order withdrawing approval of an application ... if the
Secretary finds ... that experience or scientific data show that such drug is
unsafe for use under the conditions of use upon the basis of which the
application was approved ... ; [or] that new evidence not contained in
such application ... evaluated together with the evidence available to the
Secretary when the application was approved, shows that such drug is not
shown to be safe for use under the conditions of use upon the basis of
which the application was approved ....
21 U.s.c. § 360b(e)(1) (emphasis added).
26.

The Commissioner of FDA has delegated several responsibilities under 21 U.S.C.

§ 360b to the Director ofCVM, formerly known as the Bureau of Veterinary Medicine. As of

1977, the Commissioner had delegated to the Director the authority to "issue notices of an
opportunity for a hearing on proposals to refuse approval or to withdraw approval of new animal
drug applications." 21 c.F.R. § 5.84 (1977). This delegation is now contained in FDA's Staff
Manual Guides. See FDA, Staff Manual Guides § 1410.503 (2011).
Citizen Petitions
27.

FDA's regulations allow citizens to petition FDA to "issue, amend, or revoke a

regulation or order, or to take or refrain from taking any other form of administrative action." 21
C.F.R. § 10.25.
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28.

FDA must rule on each petition filed. 21 C.F.R. § 1O.30(e)(1); see id.

§ 1O.30(e)(2)(iii); id. § 1O.30(e)(3).

29.

The Commissioner must respond within 180 days of receipt of the petition by

approving, denying, or providing a tentative response to the petition, indicating why the agency
has not yet been able to reach a decision on the petition. 21 C.F.R. § 1O.30(e)(2). In a tentative
response, the Commissioner "may also indicate the likely ultimate agency response, and may
specify when a final response may be furnished." [d. § 1O.30(e)(2)(iii).
30.

The Commissioner "may grant or deny such a petition, in whole or in part, and

may grant such other relief or take other action as the petition warrants." 21 c.F.R. § 1O.30(e)(3).
The petitioner must be "notified in writing of the Commissioner's decision." [d.
THE FACTS
Human Health Risks Posed by Antibiotics in Animal Feed
31.

Livestock producers have been adding low doses of antibiotics to the feed of

healthy animals since the 1950s. One reason they do so is that subtherapeutic doses of antibiotics
appear to promote faster animal growth on less feed.
32.

Another reason livestock producers give subtherapeutic doses of antibiotics to

herds of healthy animals is to prevent diseases that tend to occur when animals are kept in
cramped, unsanitary conditions. Researchers have observed that the beneficial effects of the
subtherapeutic use of antibiotics in livestock are less pronounced in clean, healthful, and stressfree environments.
33.

Today, approximately 80 percent of all antibiotics used in the United States are

used in livestock.

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34.

The majority of the antibiotics used in livestock-according to the best estimates,

about 83 percent-are administered flock- or herdwide at low levels for nontherapeutic purposes,
such as growth promotion and routine disease prevention. According to FDA, the use of
antibiotics in entire herds or flocks of animals over extended periods of time poses a qualitatively
higher risk to public health than the short-term use of such drugs in individual animals or
targeted groups of animals. This litigation does not concern targeted, short-term uses of
antibiotics to treat animals that are already sick.
35.

It has long been understood that bacteria are capable of developing resistance to

antibiotics. Natural selection plays an important role in the development of antibiotic resistance.
When an antibiotic drug is introduced to a population of bacteria, the bacteria that are susceptible
to the drug die off, but bacteria that are resistant to the drug survive and reproduce, increasing
the proportion of resistant bacteria in the population.
36.

Through a variety of mechanisms, bacteria may become resistant to multiple

classes of antibiotics. For example, the use of anyone drug may select for groups of genes that
provide resistance not only to the original drug but to other chemically related drugs as well.
Bacteria can also transfer resistance traits to other bacteria, allowing bacteria that have never
been exposed to antibiotics to become resistant to them. Bacteria can transfer resistance genes to
bacteria in different species and genera, and from bacteria that do not cause human illness to
bacteria that do.
37.

Studies have shown, for example, that the use of tetracycline in swine may

promote increased bacterial resistance not only to tetracycline but also to other medically
important drugs, including penicillins, cephalosporins, and arninoglycosides. The use of
penicillins, such as amoxici11in and ampicillin, has been shown to promote bacterial resistance to
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cephalosporins (in a study of swine) and aminoglycosides and fluoroquinolones (in a laboratory
study). Aminoglycosides, cephalosporins, and fluoroquinolones are among the few treatments
available for serious human infections caused by bacteria that can be transferred from animals to
humans.
38.

According to FDA, "[a]ntimicrobial [or antibiotic] resistance, and the resulting

failure of antimicrobial therapies in humans, is a mounting public health problem of global
significance." Draft Guidance No. 209, at 4 (2010). People who contract antibiotic-resistant
infections are more likely to have longer hospital stays, may be treated with less effective and
more toxic drugs, and may be more likely to die as a result of the infection. In 2009, Cook
County Hospital and the Alliance for the Prudent Use of Antibiotics estimated that antibioticresistant infections from all sources cost Americans between $16.6 and $26 billion every year.
39.

It is widely agreed that the overuse of antibiotics in livestock is helping fuel the

rapid proliferation of antibiotic-resistant bacteria in animals and humans. HHS has concluded
that "there is a preponderance of evidence that the use of antimicrobials in food-producing
animals has adverse human consequences." In a 2004 report, the U.S. General Accounting Office
(GAO) observed that "[m]any studies have found that the use of antibiotics in animals poses
significant risks for human health, and some researchers contend that the potential risk of the
transference is great for vulnerable popUlations," while only a "small number of studies contend
that the health risks of the transference are minimal." In its comments on the report, HHS urged
GAO to note that the only article cited in the report as arguing that the risks were miniIllal was
written by an advisory group to the Animal Health Institute, an industry association representing
pharmaceutical companies.

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40.

As FDA has explained, "[a]ntimicrobial use in animals can contribute to the

emergence of antimicrobial resistance which may be transferred to humans, thereby reducing the
effectiveness of antimicrobial drugs for treating human disease." For this reason, "FDA believes
it is critically important that antimicrobial drugs be used as judiciously as possible in an effort to
minimize resistance development."
41.

Studies show that the use of antibiotics in livestock, including nontherapeutic uses

in feed, leads to the development of antibiotic-resistant bacteria in the animals receiving the
antibiotics. These bacteria include common sources of foodbome illness in humans, such as

Salmonella, Campylobacter, and E. coli. It is well documented that antibiotic-resistant bacteria,
including Salmonella, Campylobacter, and E. coli, have been transferred from animals to people.
42.

Although the nontherapeutic use of antibiotics in livestock may present risks to

animal health as well as human health, this Complaint focuses exclusively on risks to human
health.
43.

Researchers have focused most often on the transfer of antibiotic-resistant

bacteria from animals to humans through the consumption or handling of contaminated meat.
Data collected by the National Antimicrobial Resistance Monitoring System indicate that retail
meat products are frequently contaminated by Salmonella, Campylobacter, E. coli, and other
bacteria that are resistant to multiple classes of antibiotics. Various epidemiological studies have
confirmed that these bacteria have been transferred to humans.
44.

A study published earlier this year reported that nearly half of the meat and

poultry products sampled in five U.S. cities contained drug-resistant strains of Staphylococcus

aureus, the type of bacteria that commonly causes staph infections. More than half of those
bacteria were resistant to multiple classes of antibiotics. Research has shown that veal calves

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treated with antibiotics are more likely to carry methicillin-resistant S. aureus than calves not
treated.
45.

Humans can also be exposed to antibiotic-resistant bacteria from animals in other

ways. For example, there are several documented cases of the transfer of drug-resistant bacteria
from livestock to farmworkers and others who came in contact with the animals. There may also
be environmental exposure pathways: a recent study found that bacteria collected in waterways
downstream of concentrated animal feeding operations were more than twice as likely to be
resistant to multiple antibiotics than bacteria in waterways that were not agriculturally impaired.
46.

Many organizations that have studied the human health risks linked to the use of

antibiotics in livestock, such as the World Health Organization and the Institute of Medicine,
have recommended that livestock producers be prohibited from using antibiotics for growth
promotion if those antibiotics are also used in human medicine. Other nations have already acted
on these recommendations: In Australia and Japan, penicillins and tetracyclines cannot be used
for growth promotion. New Zealand prohibits using antibiotics for growth promotion if they are
related to antibiotics used in human medicine. The European Union has banned the use of all
antibiotics for growth promotion since 2006.
47.

Denmark banned the use of antibiotics for growth promotion in broiler chickens

and adult swine in 1998, and in young swine in 1999. Danish government and industry data
collected since then show that antibiotic-resistant bacteria in livestock and in meat products have
declined, and livestock production has increased.

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FDA's Failure to Withdraw Approval of
Penicillin and Tetracyclines in Animal Feed
48.

FDA first approved the use of penicillin as an animal feed additive in 1951.

Today, penicillin maybe used for growth promotion in chickens, turkeys, and swine. 21 c.F.R.
§ 558.460.

49.

FDA first approved the use of chlortetracycline as an animal feed additive in

1951, and it approved such use of oxytetracycline as early as 1954. Currently, chlortetracycline
and oxytetracycline are approved as growth promoters in chickens, turkeys, swine, cattle, and
sheep. 21 C.F.R. §§ 558.128, 558.450.
50.

In the mid-1960s, FDA became concerned that the long-term uSe of antibiotics in

animals might pose threats to human and animal health. In 1970, the agency convened a Task
Force to study the issue; it staffed the Task Force with scientists from FDA, the National
Institutes of Health, the U.S. Department of Agriculture, the Center for Disease Control,
universities, and industry. See Removal of Obsolete Regulations, 68 Fed. Reg. 47,272, 47,273
(Aug. 8, 2003); Antibiotic and Sulfonamide Drugs in Animal Feeds, 37 Fed. Reg. 2444, 2444
(Feb. 1, 1972).
51.

The Task Force concluded that (1) the use of antibiotics in animal feed, especially

at subtherapeutic levels, favors the development of antibiotic-resistant bacteria; (2) animals
receiving antibiotics in their feed may serve as a reservoir of antibiotic-resistant pathogens,
which can produce human infections; (3) the prevalence of bacteria carrying transferable
resistance genes for multiple antibiotics had increased in animals, and the increase was related to
the use of antibiotics; (4) antibiotic-resistant bacteria had been found on meat and meat products;
and (5) the prevalence of antibiotic-resistant bacteria in humans had increased. See Antibiotic
and Sulfonamide Drugs in Animal Feeds, 37 Fed. Reg. at 2444-45.
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52.

The Task Force recommended, inter alia, that (1) antibiotics used in human

medicine be prohibited from use in animal feed unless they met safety criteria established by
FDA and (2) several specific drugs, including tetracycline and penicillins, be reserved for
therapy unless they met safety criteria for subtherapeutic use. See id. at 2445.
53.

In response to the "significant questions" raised by the Task Force's findings, in

1973 FDA issued a regulation providing that the agency would propose to withdraw all
approvals for subtherapeutic uses of antibiotics in animal feed unless drug sponsors and other
interested parties submitted data within the next two years "which resolve[d] conclusively the
issues concerning [the drugs'] safety to man and animals ... under specific criteria" established
by FDA. See Antibiotic and Sulfonamide Drugs in the Feed of Animals, 38 Fed. Reg. 9811, 9813
(Apr. 20, 1973) (codified at former 21 C.F.R. § 135.109; renumbered as 21 c.F.R. § 558.15).
54.

One of the "most important" of the human and animal health safety criteria that

FDA established for drug safety evaluations under the regulation dealt with the transfer of drug
resistance: "An antibacterial drug fed at subtherapeutic levels to animals must be shown not to
promote increased resistance to antibacterials used in human medicine. Specifically, increased
mUltiple resistance capable of being transferred to other bacteria in animals or man should not
occur." Penicillin-Containing Premixes ("Penicillin Notice"), 42 Fed. Reg. 43,772,43,774-75
(Aug. 30, 1977). Additional criteria focused on the effects of subtherapeutic antibiotics on the

Salmonella reservoir in livestock, whether antibiotic use increases the pathogenicity of bacteria,
and the presence of antibiotic residues in food products. See id. at 43,774.
55.

After evaluating the information collected under 21 C.F.R. § 558.15, FDA

concluded that, at least with respect to penicillin and certain uses of tetracyclines, the drug
sponsors had failed to demonstrate that using the drugs subtherapeutically in animal feed was
14

safe. Accordingly, the Director of FDA's Bureau of Veterinary Medicine issued notices of
opportunity for hearing on proposals to withdraw all uses of penicillin in animal feed, see
Penicillin Notice, 42 Fed. Reg. at 43,772, and nearly all subtherapeutic uses of tetracyclines in
animal feed, with limited exceptions, see Tetracycline (Chlortetracycline and Oxytetracycline)Containing Premixes ("Tetracyclines Notice"), 42 Fed. Reg. 56,264, 56,264 (Oct. 21, 1977).
The Penicillin Notice
56.

In the Penicillin Notice, the Director reported that "[n]one of the specified human

and animal health safety criteria [for the sUbtherapeutic use of penicillin] have been satisfied." 42
Fed. Reg. at 43,775. With respect to the criterion dealing with the transfer of drug resistance, for
example, the Director surveyed the available data and found that (1) the pool of bacteria carrying
transferable resistance genes was increasing; (2) the increase was due in part to the
subtherapeutic use of penicillin in animal feed; and (3) antibiotic-resistant bacteria were
transferred from animals to humans as a result of direct human-animal contact, the consumption
of contaminated food, and the widespread presence of resistant bacteria in the environment.
Studies submitted by or on behalf of the drug sponsors failed to rebut these findings. [d. at
43,781.
57.

Following an extensive analysis, the Director indicated that he was "unaware of

evidence that satisfies the requirements for the safety of penicillin-containing premixes [i.e., feed
supplements] as required by section 512 of the Federal Food, Drug. and Cosmetic Act and

§ 558.15 of the agency's regulations." Penicillin Notice, 42 Fed. Reg. at 43,792. He proposed to
"withdraw approval of new animal drug applications ... for all penicillin-containing premixes
intended for use in animal feed on the grounds that ... new evidence shows that the penicillin-

15

containing products have not been shown to [be] safe for subtherapeutic use" as required by the
Food and Drug Act. Id. at 43,772.
The Tetracyclines Notice
58.

The Director undertook a similar analysis, and reached similar conclusions, in the

Tetracyclines Notice. For purposes of the notice, FDA treated chlortetracycline, oxytetracycline,
and tetracycline identically because it concluded there was no scientific basis for treating them
otherwise. See Tetracyclines Notice, 42 Fed. Reg. at 56,266. The Director found that "the results
of the studies submitted and the data available are clear-the affected parties have failed to show
that extensive subtherapeutic use of the tetracyclines is safe." Id. at 56,267.
59.

The Director proposed retaining seven limited sUbtherapeutic uses of tetracyclines

then considered "unique" and "essential," primarily for the control of specific diseases.
Tetracyclines Notice, 42 Fed. Reg. at 56,287. He then proposed to withdraw "all approvals for
tetracycline-containing premix products intended for subtherapeutic uses in animal feed, other
than those cited, ... on the grounds that they have not been shown to be safe." Id. at 56,288.
Further Research
60.

Shortly after FDA issued the two notices of opportunity for hearing, the House

Committee on Appropriations requested that FDA, before taking action on its withdrawal
proposals, conduct further research on the question whether the subtherapeutic use of antibiotics
in animal feed presents a threat to human health. See H.R. Rep. No. 95-1290, at 99-100 (1978).
In response, FDA contracted with the National Academy of Sciences (the "National Academy")

to assess the human health consequences of the subtherapeutic use of penicillin and tetracyclines
in animal feeds by evaluating existing data, and to recommend areas for additional research.

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61.

The resulting report by the National Academy, published in 1980, did not

conclude that using antibiotics subtherapeutically in animal feed was safe. The Academy
recommended additional epidemiological studies.
62.

Soon thereafter, the House Committee on Appropriations requested that FDA

undertake additional research in response to the 1980 report ofthe National Academy, and that in
the meantime FDA continue to hold its penicillin and tetracyclines proposals in abeyance. See
H.R. Rep. 96-1095, at 105-06 (1980). The following year, the Senate Committee on
Appropriations made the same request. See S. Rep. No. 97-248, at 79 (1981). FDA contracted
with the Seattle-King County Department of Public Health and the Institute of Medicine for
further research.
63.

The Seattle-King County study, published in 1984, contained several important

findings that supported FDA's concerns about the risks posed by antibiotics in animal feed. For
example, the study found that Campylobacter bacteria were likely transferred from chickens to
humans through the consumption of poultry products; that samples of such bacteria taken from
pOUltry products and humans exhibited "surprisingly high" and "similar" patterns of tetracycline
resistance;·and that drug-resistant Campylobacter could likely transfer resistance genes to other
bacteria.
64.

The 1988 report of the Institute of Medicine, like the studies before it, could not

conclude that the subtherapeutic use of antibiotics in animal feed was safe. The Institute found
several sources of "indirect evidence implicating sUbtherapeutic use of antimicrobials in
producing resistance in infectious bacteria that causes a potential human health hazard."
65.

By 1988, FDA had completed the research requested by the congressional

appropriations committees. As a result of that research, FDA "did not conclude that the
17

continued subtherapeutic use of penicillin and the tetracycylines [sic] in animal feed is safe."
Removal of Obsolete Regulations, 68 Fed. Reg. at 47,275.
66.

FDA has never rescinded or altered its 1977 findings that subtherapeutic uses of

penicillin and tetracyclines in animal feed are not shown to be safe. As recently as 2003, FDA
confirmed that the 1977 Penicillin and Tetracyclines Notices "remain pending." Id. In 1983,
FDA denied a request by drug sponsors that it withdraw the penicillin and tetracyclines
proposals. The agency explained that "[t]he Director has not changed his earlier conclusion that
the available scientific information warrants the proposed actions .... The notices of opportunity
for hearing represent the Director's formal position that use of the drugs is not shown to be safe."
Penicillin and Tetracycline in Animal Feeds, 48 Fed. Reg. 4554, 4555-56 (Feb. 1, 1983)
(emphasis added).
67.

In 2004, FDA sent letters to several manufacturers of approved animal feed

products containing penicillin and tetracyclines, explaining that the administrative record did not
contain sufficient information to alleviate FDA's concerns about "the use of these products and
their possible role in the emergence and dissemination of antimicrobial resistance." FDA
reported that it had conducted a qualitative risk assessment and concluded that the products fell
into "Category 1," or "high" risk, and use of the products for growth promotion was therefore not
appropriate. FDA invited the manufacturers to meet with the agency to discuss its findings.
Nonbinding Guidance
68.

Rather than act on its 1977 findings and withdraw approval of sUbtherapeutic uses

of penicillin and tetracyclines in animal feeds, FDA has issued a series of nonbinding guidance
documents.

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69.

In 2003, FDA issued Guidance for Industry No. 152. The guidance recommended

a risk assessment approach that drug sponsors could use to evaluate the safety of antimicrobial
new animal drugs with regard to their microbiological effects on bacteria of human health
concern. Guidance No. 152 made clear that "FDA's guidance documents, including this
guidance, do not establish legally enforceable responsibilities." Guidance No. 152, at 2.
70.

In 2010, FDA issued Draft Guidance No. 209, expected to be finalized in 2011,

which concludes that "using medically important antimicrobial drugs for production purposes
[i.e., increasing rate of weight gain or improving feed efficiency] is not in the interest of
protecting and promoting the public health." Draft Guidance No. 209, at 13. The guidance
recommends that medically important antibiotics be used in food-producing animals (1) only
when necessary to ensure the animals' health and (2) only with veterinary oversight. See id. at
16-17. Like other FDA guidance documents, Draft Guidance No. 209 does "not establish legally
enforceable responsibilities." Id. at 2.
71.

Today, the science supporting FDA's 1977 findings is stronger than ever. In

recognition of the "[m]ounting evidence suggest[ing] a relationship between antimicrobial use in
animal husbandry and an increase in bacterial resistance in humans," the Institute of Medicine
now recommends that FDA "ban the use of antimicrobials for growth promotion in animals if
those classes of antimicrobials are also used in humans." FDA has not done so.
Harm to Plaintiffs from FDA's Failure to Withdraw
Approval of Penicillin and Tetracyclines in Animal Feed
72.

According to figures released by FDA in 2010, penicillins now account for

approximately 4.7 percent of total antibiotic use in U.S. livestock, and tetracyclines account for
approximately 35.3 percent. Most of this use is nontherapeutic.

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73.

The use of penicillin and tetracyclines in animal feed promotes the development

of antibiotic-resistant bacteria in livestock. These bacteria may be resistant not only to penicillin
or tetracyclines but also to other medically important drugs.
74.

Antibiotic-resistant bacteria may be transferred from animals to humans through

the consumption and handling of contaminated meat products. Data collected by the National
Antimicrobial Resistance Monitoring System demonstrate that Salmonella, Enterococcus, and E.
coli bacteria collected from retail meat and poultry samples are frequently resistant to penicillins
and tetracyclines, and Campylobacter bacteria so collected is often resistant to tetracyclines.
75.

Antibiotic-resistant bacteria that have been transferred from animals to humans

may cause drug-resistant infections, or they may transfer resistance traits to other bacteria that
can cause infections.
76.

The health of Plaintiffs' members is continually threatened by their exposure to

meat and poultry products contaminated with bacteria resistant to penicillins, tetracyclines, and
other antibiotics, including aminoglycosides and cephalosporins.
77.

The risk that Plaintiffs' members will be exposed to bacteria resistant to

penicillins, tetracyclines, or other antibiotics through the consumption or handling of
contaminated meat products is traceable to FDA's failure to comply with its statutory duty to
withdraw approval for sUbtherapeutic uses of penicillin and tetracyclines in animal feed.
78.

If FDA were to withdraw approval for subtherapeutic uses of penicillin and

tetracyclines in animal feed, the prevalence of bacteria in livestock with resistance to those drugs
would stop increasing, and would likely decrease. As a result, Plaintiffs' members would face a
reduced risk of contracting a drug-resistant infection from consuming or handling meat products.

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Citizen Petitions Filed with FDA in 1999 and 2005
79.

On March 9, 1999, CSPI, FACT, Public Citizen, and UCS submitted a petition to

FDA requesting that the agency "rescind approvals for sUbtherapeutic uses in livestock of any
antibiotic used in (or related to those used in) human medicine."
80.

The petition summarized the supporting science, and explained that:
(A) Subtherapeutic antibiotics are used widely in livestock.
(B) Subtherapeutic antibiotic use in livestock leads to the selection of
antibiotic-resistant bacteria.
(C) Antibiotic-resistant bacteria can be transferred between animals
and from animals to people.
(D) Antibiotic-resistant bacteria may transfer resistance genes to other
bacteria.
(E) Subtherapeutic antibiotic use may select for multi-drug-resistant
bacteria that can cause infections that are difficult to treat.
(F) Subtherapeutic antibiotic use jeopardizes therapeutic options in
veterinary and human medicine.
(G) Expert committees and leading scientists support a phase-out of
subtherapeutic antibiotic use in livestock.
(H) Authoritative scientific bodies such as the U.S. Centers for Disease
Control and Prevention and the WorId Health Organization
consider it a human health risk to permit subtherapeutic use in
livestock of antibiotics that are used in (or related to those used in)
human medicine.

81.

The petition also addressed the modest economic and environmental impacts of

the proposed withdrawals. As evidence, the petition cited the National Academy's estimate that
elimination of all subtherapeutic use of antibiotics in livestock would lead to approximately
$4.84 to $9.72 a year in higher costs for consumers. The petition also pointed to the experiences
of countries such as Sweden and Denmark, which have successfully eliminated some uses of
antibiotics in livestock.
82.

On April 7, 2005, FACT and UCS submitted a second petition to FDA. The

petition requested that the FDA Commissioner "withdraw approvals for herdwidelflockwide uses
of [specific] antibiotics in chicken, swine, and beef cattle for purposes of growth promotion
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(including weight gain and feed efficiency) and disease prevention and control (except for nonroutine use where a bacterial infection has been diagnosed within a herd or flock)." The petition
covered penicillins, tetracyclines, aminoglycosides, streptogramins, macrolides, lincomycin, and
sulfonamides. It did not cover any uses of those drugs for disease treatment.
83.

The second petition analyzed the listed antibiotics under the risk assessment

approach developed by FDA in Guidance No. 152. The petition demonstrated that herdwide or
flockwide uses of the listed drugs-all of which were classified by FDA as "critically important"
or "highly important" for human health-were inconsistent with the agency's own risk
management criteria.
84.

FDA has never issued a final response to either the 1999 or 2005 petition.

85.

The agency issued tentative responses to the 1999 petition in 1999 and 2001. The

second tentative response, dated February 28, 200 1, explained that FDA "cannot yet issue a final
response" to the petition because the withdrawal of a new animal drug application involves
multiple steps, and agency resources are limited.
86.

FDA issued a tentative response to the 2005 petition on October 4,2005. The

agency essentially reiterated its response to the 1999 petition, and also mentioned its
development of nonbinding guidance for evaluating the safety of antimicrobial drug use in foodproducing animals.
87.

FDA is required by Food and Drug Act implementing regulations to make a final

decision on all citizen petitions. FDA's long delay in ruling on the Petitions is unreasonable.
Harm to Plaintiffs from FDA's Delay in Issuing
a Final Response to the Citizen Petitions
88.

In over twelve years, CSPI, FACT, Public Citizen, and UCS have not received a

final response to their 1999 petition. FACT and UCS have waited more than six years for a final
22

'.
response to their 2005 petition. FDA's delay has injured CSPI, FACT, Public Citizen, and UCS
by depriving them of (1) a decision on the merits of the Petitions and (2) the opportunity to seek
judicial review of that decision, if necessary.
89.

While CSPI, FACT, Public Citizen, and UCS await a final decision on tlie

Petitions, the health of CSPI's, Public Citizen's, and UCS's members is continually threatened
by their exposure to meat and poultry products contaminated with bacteria resistant to medically
important antibiotics.
90.

A final response either granting or denying the Petitions would redress CSPI,

FACT, Public Citizen, and UCS's injuries by either (1) granting them the relief they seek or (2)
giving them an opportunity to seek judicial review of a denial of the Petitions.
ARSTCLAUMFORRELffiF
91.

Plaintiffs incorporate by reference all preceding paragraphs.

92.

The Food and Drug Act requires FDA to withdraw approval of a new animal drug

application if it finds that new evidence shows that the drug is not shown to be safe for the uses
for which it was approved. See 21 U.S.C. § 360b(e)(1).
93.

FDA found in 1977 that all subtherapeutic uses of penicillin in animal feed, and

certain sUbtherapeutic uses of tetracyclines, have not been shown to be safe. FDA has never
retracted those findings, it has reaffirmed them, and the scientific evidence supporting them is
stronger now than ever.
94.

For more than thirty years, FDA has failed to comply with its statutory duty, after

notice and opportunity for hearing, to withdraw approval of subtherapeutic uses of penicillin and
tetracyclines in animal feed.

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95.

FDA's failure to withdraw approval constitutes an agency action unlawfully

withheld in violation of the APA, 5 U.S.c. § 706(1), and the Food and Drug Act, 21 U.S.C.
§ 360b(e)(1).

SECOND CLAIM FOR RELIEF
96.

Plaintiffs incorporate by reference all preceding paragraphs.

97.

FDA has delayed unreasonably in issuing a final response to the Petitions

submitted in 1999 and 2005.
98.

FDA's failure to issue a final response constitutes an agency action unreasonably

delayed in violation of the APA, 5 U.S.C. § 706(1), and the Food and Drug Act's implementing
regulations, 21 c.F.R. § 10.30(e)(1).
REQUEST FOR RELIEF
Plaintiffs request that this Court enter judgment against FDA as follows:
A.

Declaring that FDA's failure to withdraw approval of subtherapeutic uses of

penicillin and tetracyclines in animal feed is unlawful, pursuant to the APA, 5 U.S.C. § 706(1),
and the Food and Drug Act, 21 U.S.C. § 360b(e)(1);
B.

Declaring that FDA's delay in issuing a final response to the Petitions is

unreasonable and not in accordance with law, pursuant to the APA, 5 U.S.c. § 706(1), and the
Food and Drug Act's implementing regulations, 21 C.F.R. § 1O.30(e)(l);
C.

Compelling FDA to withdraw approval for subtherapeutic uses of penicillin and

tetracyclines in animal feed, unless FDA's findings are overturned in new administrative
proceedings, by a Court-ordered deadline;
D.

Compelling FDA to issue a final response to the Petitions, by a Court-ordered

deadline;
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.,

E.

Awarding Plaintiffs their reasonable costs and attorneys' fees; and

F.

Granting such other and further relief as the Court deems just and proper.

Dated: New York, New York
May 25, 2011
Respectfully submitted,

Mitchell S. Bernard (MB 5823)
Natural Resources Defense Council, Inc.
40 West 20th Street
New York, New York 10011
[phone]
[phone] (fax)
Counsel for Plaintiffs

Of Counsel for Plaintiff Center for Science
in the Public Interest:
Stephen Gardner (SG 3964)
Center for Science in the Public Interest
5646 Milton Street, Suite 211
Dallas, Texas 75206
[phone]
[phone] (fax)

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