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

Filing 21

RULE 56.1 STATEMENT. Document filed by Center For Science In The Public Interest, Food Animal Concerns Trust, Natural Resources Defense Council, Inc., Public Citizen, Inc., Union Of Concerned Scientists, Inc.. (Sorenson, Jennifer)

IN THE UNITED STATES DISTRICT 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.,

)
)
)
)
)
)
)
Plaintiffs,
)
)
v.
)
)
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.
)

11 CIV 3562 (THK)
ECF Case

PLAINTIFFS’ STATEMENT OF UNDISPUTED MATERIAL FACTS IN SUPPORT OF
MOTION FOR SUMMARY JUDGMENT
Plaintiffs Natural Resources Defense Council, Center for Science in the Public Interest
(CSPI), Food Animal Concerns Trust (FACT), Public Citizen, and Union of Concerned
Scientists (UCS) respectfully submit this Statement of Undisputed Material Facts in support of
their Motion for Summary Judgment. This statement is based on the Answer of Defendants
United States Food and Drug Administration (FDA); Margaret Hamburg, in her official capacity
as Commissioner, FDA; Center for Veterinary Medicine (CVM); Bernadette Dunham, in her

official capacity as Director, CVM; United States Department of Health and Human Services
(HHS); and Kathleen Sebelius, in her official capacity as Secretary, HHS; the concurrently filed
Declaration of Jennifer A. Sorenson (Sorenson Decl.); and accompanying exhibits.
Pursuant to Federal Rule of Civil Procedure 56 and this Court’s Local Civil Rule 56.1,
there is no genuine issue as to the following facts:
Antibiotic Resistance
1.

“Antibiotics are drugs used for treating infections caused by bacteria. Also known

as antimicrobial drugs, antibiotics have saved countless lives. Misuse and overuse of these drugs,
however, have contributed to a phenomenon known as antibiotic resistance. This resistance
develops when potentially harmful bacteria change in a way that reduces or eliminates the
effectiveness of antibiotics.” Decl. of Jennifer A. Sorenson (Sorenson Decl.) Ex. S, at 1;
Answer ¶ 1.
2.

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. Amended
Complaint ¶ 35; Answer ¶ 35; Sorenson Decl. Ex. X, at 2.
3.

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

classes of antibiotics. For example, the use of any one drug may select for groups of genes that
provide resistance not only to the original drug but also to other chemically related drugs.
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. Amended Complaint ¶ 36; Answer ¶ 36; Sorenson Decl. Ex. T, at 1.

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4.

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. Amended Complaint ¶ 38; Answer ¶ 38; Sorenson Decl. Ex. T,
at 1. According to FDA, “[w]hen a person is infected with an antibiotic-resistant bacterium, not
only is treatment of that patient more difficult, but the antibiotic-resistant bacterium may spread
to other people.” Sorenson Decl. Ex. S, at 1.
5.

In 2009, Cook County Hospital and the Alliance for the Prudent Use of

Antibiotics estimated that antibiotic-resistant infections from all sources cost Americans between
$16.6 and $26 billion every year. Amended Complaint ¶ 38; Answer ¶ 38.
6.

FDA considers antibiotic resistance “a serious public health threat” and “a

mounting public health problem of global significance.” Amended Complaint ¶ 38; Answer ¶ 38;
Sorenson Decl. Ex. O, at 3-4.
7.

According to FDA, “[p]reserving the effectiveness of current antimicrobials [or

antibiotics] . . . [is] vital to protecting human and animal health against infectious microbial
pathogens,” Sorenson Decl. Ex. R, at 1, and “[d]eveloping strategies for reducing antimicrobial
resistance is critically important for protecting both public and animal health.” Sorenson Decl.
Ex. O, at 3.
8.

Because the use of antibiotics “contributes to the emergence of drug resistant

organisms,” FDA has explained that “these important drugs must be used judiciously in both
animal and human medicine to slow the development of resistance. . . . Using these drugs
judiciously means that unnecessary or inappropriate use should be avoided.” Sorenson Decl. Ex.
O, at 3.

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9.

The Centers for Disease Control and Prevention (CDC), a division of HHS, names

antibiotic resistance as one of its “top concerns.” Sorenson Decl. Ex. X, at 2.
10.

Because antibiotic resistance “threatens our ability to treat disease and to protect

the advances made in global health in recent decades,” the World Health Organization (WHO)
urges that “[w]e must do everything in our power to preserve [antibiotics] for future
generations.” Sorenson Decl. Ex. BB, at 1.
11.

The Institute of Medicine of the National Academy of Sciences has warned that

“[t]he specter of untreatable infections—a regression to the pre-antibiotic era—is looming just
around the corner.” Amended Complaint ¶ 1; Answer ¶ 1; Sorenson Decl. Ex. Z, at 205.
Antibiotics in Livestock
12.

FDA reports that 13,067,100 kilograms of antibiotics were sold or distributed for

use in food-producing animals in the United States in 2009. Sorenson Decl. Ex. P, at 3. In
comparison, 3,316,906 kilograms of antibiotics were sold in the U.S. market for human use in
2009. Sorenson Decl. Ex. Q, enclosure, at 4. Thus, approximately 80 percent of the more than 16
million kilograms of antibiotics sold in the United States in 2009 went to livestock.
13.

Of the antibiotics sold for use in livestock, 11,766,613 kilograms, or 90 percent,

were sold for administration via animal feed or water, rather than by injection. Sorenson Decl.
Ex. Q, at 1.
14.

According to the Institute of Medicine, the majority of antibiotics used in animal

husbandry in the United States are used for growth promotion or preventive therapy in healthy
animals. Sorenson Decl. Ex. Z, at 207. These antibiotics are generally given to animals at
“subtherapeutic” levels, or in doses too low to treat disease. Sorenson Decl. Ex. H, at iii n.1;
Penicillin-Containing Premixes (Penicillin Notice), 42 Fed. Reg. 43,772, 43,773 (Aug. 30, 1977),
Ex. A to Sorenson Decl.
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15.

Since the 1950s, FDA has approved some antibiotics for growth promotion

indications in livestock. Some of the antibiotics that were originally approved for growth
promotion may be important to human medicine. Answer ¶ 3.
16.

Antibiotics used for growth promotion “are typically administered through the

feed or water on a herd- or flock-wide basis and are approved for such uses as increasing rate of
weight gain or improving feed efficiency.” Sorenson Decl. Ex. O, at 4. The approved dose of an
antibiotic for growth promotion is typically lower than the approved dose for a disease
indication. Answer ¶ 3; Penicillin Notice, 42 Fed. Reg. at 43,773.
17.

Administering medically important antimicrobial drugs to entire herds or flocks of

food-producing animals (e.g., for growth promotion) poses a qualitatively higher risk to public
health than administering such drugs to individual animals or targeted groups of animals.
Answer ¶ 34.
18.

Since the 1950s, FDA has approved some antibiotics for disease prevention in

livestock. Some of the antibiotics that were originally approved for disease prevention may be
important to human medicine. Answer ¶ 3.
19.

According to the Institute of Medicine, “it has been noted that subtherapeutic

antibiotics are most effective in animals under the stress of inadequate nutrition and suboptimal
sanitary conditions . . . ; therefore, improved hygiene and changes in animal husbandry practices
to control disease could potentially eliminate the need for growth promoters.” Sorenson Decl.
Ex. Z, at 208.
20.

According to FDA, 610,514 kilograms of penicillins were sold or distributed for

use in food-producing animals in the United States in 2009. Thus, penicillins accounted for
approximately 4.7 percent of all antibiotics sold for use in livestock. Sorenson Decl. Ex. P, at 3.

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21.

According to FDA, 4,611,892 kilograms of tetracyclines were sold or distributed

for use in food-producing animals in the United States in 2009. Thus, tetracyclines accounted for
approximately 35.3 percent of all antibiotics sold for use in livestock. Sorenson Decl. Ex. P, at 3.
Human Health Risks Posed by the Use of Antibiotics in Livestock
22.

FDA has classified penicillins and tetracyclines as “highly important” to human

medicine. Sorenson Decl. Ex. M, at 28-29, 30, 32.
23.

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. Amended Complaint ¶¶ 2, 74; Answer ¶¶ 2,
74; Sorenson Decl. Ex. Y, at 11, 17-23, 89; id. Ex. Z, at 207; id. Ex. W, cover letter, at 1;
Penicillin Notice, 42 Fed. Reg. at 43,776-78; Tetracycline (Chlortetracycline and
Oxytetracycline)-Containing Premixes (Tetracyclines Notice), 42 Fed. Reg. 56,264, 56,268-70
(Oct. 21, 1977), Ex. B to Sorenson Decl.
24.

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. Sorenson Decl. Ex. W, cover letter, at 1; Answer ¶ 41. These bacteria include
Salmonella, Campylobacter, and E. coli, all of which may cause foodborne illness in humans.
Sorenson Decl. Ex. Y, at 11, 17-23.
25.

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. Amended Complaint ¶ 73;
Answer ¶¶ 37, 73.

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26.

Data collected by the National Antimicrobial Resistance Monitoring System

(NARMS) in 2009 indicate that Salmonella was present on 21.0% of retail chicken breast
samples and 14.4% of retail ground turkey samples. Sorenson Decl. Ex. V, at 20 tbl.3. Nearly
half (48.4%) of the Salmonella on chicken breasts and more than a quarter (26.3%) of the
Salmonella from ground turkey was resistant to three or more classes of antibiotics. Id. at 8; 30
tbl.8. Tetracycline resistance was common among Salmonella isolates from chicken and turkey
products (59.9% and 65.3%, respectively), while resistance to ampicillin (an antibiotic in the
penicillin class), was only slightly less common, at 45.8% of chicken Salmonella and 57.9% of
turkey Salmonella. Id. at 23 tbl.5.
27.

The NARMS 2009 Retail Meat Report shows that Campylobacter, including the

Campylobacter jejuni and Campylobacter coli species, was present on 44.1% of retail chicken
breasts tested. Sorenson Decl. Ex. V, at 8, 20 tbl.3. Nearly half (46.2%) of the C. jejuni isolates
and more than a third (38.0%) of the C. coli isolates were resistant to tetracycline. Id. at 42
tbl.13.
28.

The 2009 NARMS report indicates that E. coli was highly prevalent on all retail

meat types tested: chicken breasts (87.5%); ground turkey (85.0%); ground beef (68.6%); and
pork chops (40.8%). Sorenson Decl. Ex. V, at 20 tbl.3. Multidrug resistance was most prevalent
among E. coli isolates from chicken breasts (37.5%) and ground turkey (66.3%). Id. at 70 tbl.24.
Approximately 56.2% of E. coli isolates from ground turkey were resistant to ampicillin, while
82.0% were resistant to tetracycline. Id. at 64 tbl.22.
29.

According to the U.S. Government Accountability Office (GAO), epidemiologic

studies suggest that antibiotic-resistant E. coli bacteria have been transferred from animals to
humans, and studies that include molecular subtyping demonstrate that antibiotic-resistant

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Salmonella and Campylobacter bacteria have been transferred from animals to humans through
the consumption or handling of contaminated meat. Sorenson Decl. Ex. Y, at 17-23.
30.

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. Amended
Complaint ¶ 45; Answer ¶ 45.
31.

According to GAO, “[r]esistant bacteria may . . . be spread to fruits, vegetables,

and fish products through soil, well water, and water runoff contaminated by waste material from
animals harboring these bacteria.” Sorenson Decl. Ex. Y, at 11.
32.

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. Amended Complaint ¶ 75; Answer ¶ 75.
33.

FDA has concluded that “the overall weight of evidence available to date supports

the conclusion that using medically important antimicrobial drugs for production purposes [in
livestock] is not in the interest of protecting and promoting the public health.” Sorenson Decl.
Ex. O, at 13; id. Ex. R, at 2.
34.

FDA recognizes that “[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.” Sorenson Decl. Ex. U, at 2;
Amended Complaint ¶ 40; Answer ¶ 40. “FDA believes it is critically important that
antimicrobial drugs be used as judiciously as possible in an effort to minimize resistance
development.” Sorenson Decl. Ex. U, at 2; Amended Complaint ¶ 40; Answer ¶ 40.

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35.

HHS has concluded that “there is a preponderance of evidence that the use of

antimicrobials in food-producing animals has adverse human consequences.” Sorenson Decl. Ex.
Y, at 89; Amended Complaint ¶ 39; Answer ¶ 39.
36.

In a 2004 report, 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.” Sorenson Decl.
Ex. Y, at 23; Amended Complaint ¶ 39; Answer ¶ 39.
37.

In its comments on the 2004 GAO report, HHS urged GAO to note that the only

article cited in the report as arguing that the risks were minimal was written by an advisory group
to the Animal Health Institute, an industry association representing pharmaceutical companies.
Sorenson Decl. Ex. Y, at 89; Amended Complaint ¶ 39; Answer ¶ 39.
38.

According to CDC, there is “strong scientific evidence of a link between

antibiotic use in food animals and antibiotic resistance in humans,” including “multiple North
American studies describing how: [u]se of antibiotics in animals results in resistant bacteria in
food animals; [r]esistant bacteria are present in the food supply and transmitted to humans; [and]
[r]esistant bacteria result in adverse human health consequences (such as increased
hospitalizations). . . . [T]here is a compelling body of evidence to demonstrate this link.”
Sorenson Decl. Ex. W, cover letter, at 1.
39.

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

antibiotics in livestock, such as WHO 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. Amended Complaint ¶ 46; Answer ¶ 46; Sorenson Decl. Ex. Z,

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at 209-11; id. Ex. AA, at 2. Eight years ago, the Institute of Medicine explained that “[t]he total
burden of human illness due to resistant bacteria that have been transferred from animals to
humans is unknown, but the guiding principle should be that we must do what the available
evidence suggests will help stem the tide of increasing resistance before it is too late,” and “[t]o
do nothing is, in effect, to allow the continued evolution of antimicrobial-resistant microbes,
which poses serious near- and long-term threats to global health.” Sorenson Decl. Ex. Z, at 209.
40.

According to the Institute of Medicine, the “main argument” against a ban on the

subtherapeutic use of antibiotics for growth promotion in the United States is an economic one.
Sorenson Decl. Ex. Z, at 208.
41.

The European Union, Australia, and New Zealand prohibit the use of penicillin

and tetracyclines for growth promotion indications, and Japan prohibits the use of penicillin for
growth promotion indications. Answer ¶ 46.
42.

Denmark discontinued 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. Amended Complaint ¶ 47; Answer ¶ 47;
Sorenson Decl. Ex. CC, at 40-41.
43.

According to CDC, “[i]n general, subtherapeutic use has been shown to lead to an

increase in resistant strains in animals. The European experience demonstrates that it is possible
to stop these uses, reduce overall use of antibiotics in animals, reduce resistant circulating
bacteria that can infect humans, and not have industry or consumers affected by decreased
production or increased costs.” Sorenson Decl. Ex. W, enclosure, at 3.

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FDA’s Failure to Withdraw Approvals for Penicillin and Tetracyclines in Animal Feed
44.

FDA approved the use of penicillin as an animal feed additive in the 1950s.

Today, penicillin may be used for growth promotion in chickens, turkeys, and swine. 21
C.F.R. § 558.460; Amended Complaint ¶ 48; Answer ¶ 48.
45.

FDA approved the use of chlortetracycline and oxytetracycline as an animal feed

additive in the 1950s. Currently, chlortetracycline and oxytetracycline are approved as growth
promoters in chickens, turkeys, swine, cattle, and sheep. 21 C.F.R. §§ 558.128, 558.450;
Amended Complaint ¶ 49; Answer ¶ 49.
46.

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, CDC, universities, and industry. See
New Animal Drugs; Removal of Obsolete and Redundant Regulations, 68 Fed. Reg. 47,272,
47,273 (Aug. 8, 2003), Ex. E to Sorenson Decl.; Antibiotic and Sulfonamide Drugs in Animal
Feeds, 37 Fed. Reg. 2444, 2444 (Feb. 1, 1972), Ex. C to Sorenson Decl.; Amended
Complaint ¶ 50; Answer ¶ 50.
47.

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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48.

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.
49.

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. 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), Ex.
D to Sorenson Decl.
50.

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 Notice, 42 Fed. Reg. at 43,774-75.
51.

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
safe. Accordingly, the Director of FDA’s Bureau of Veterinary Medicine (now CVM) issued
notices of opportunity for hearing on proposals to withdraw approvals for all uses of penicillin in

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animal feed, see Penicillin Notice, 42 Fed. Reg. at 43,772, and, with limited exceptions, all
subtherapeutic uses of tetracyclines in animal feed, see Tetracyclines Notice, 42 Fed. Reg. at
56,264.
The Penicillin Notice
52.

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, 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. See id. at 43,781.
53.

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-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
54.

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

Tetracyclines Notice. For purposes of the notice, FDA treated chlortetracycline, oxytetracycline,
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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.
55.

With limited exceptions, the Director proposed to withdraw “all approvals for

tetracycline-containing premix products intended for subtherapeutic uses in animal feed . . . on
the grounds that they have not been shown to be safe.” Tetracyclines Notice, 42 Fed. Reg. at
56,288. The Director carved out limited exceptions related to “unique, essential” drug uses,
primarily for the control of specific diseases. Id. at 56, 287.
Further Research
56.

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).
57.

In response, FDA contracted with the National Academy of Sciences 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. 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. Sorenson Decl. Ex. F, at 53; Amended Complaint ¶ 61; Answer ¶ 61.
58.

Soon thereafter, the House Committee on Appropriations requested that FDA

undertake additional research in response to the 1980 report of the National Academy, and that in
the meantime FDA continue to hold its penicillin and tetracyclines proposals in abeyance. See

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H.R. Rep. No. 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).
59.

FDA contracted with the Seattle-King County Department of Public Health and

the Institute of Medicine for further research. 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 transfer
resistance genes to other bacteria. Sorenson Decl. Ex. G, at 3, 169.
60.

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.”
Sorenson Decl. Ex. H, at 194.
61.

FDA has not concluded that the subtherapeutic use of penicillin and tetracyclines

in animal feed is safe. Removal of Obsolete Regulations, 68 Fed. Reg. at 47,275; Answer ¶ 65.
62.

FDA has never revoked the 1977 notices of opportunity for hearing containing the

agency’s findings that subtherapeutic uses of penicillin and tetracyclines in animal feed are not
shown to be safe. Amended Complaint ¶ 66; Answer ¶ 66.
63.

FDA’s 1977 Penicillin and Tetracyclines Notices are still pending. Answer ¶ 68.

64.

FDA has not withdrawn approvals for penicillin and tetracyclines as proposed in

the 1977 notices of opportunity for hearing. Answer ¶ 4.

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65.

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.” Sorenson
Decl. Ex. N, at 1-2. 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. Id. at 3.
Nonbinding Guidance
66.

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.” Sorenson Decl. Ex. M, at 2.
67.

In 2007, the House Committee on Appropriations expressed concern that FDA’s

Guidance No. 152 “does not assign enough weight to the impact of microbial resistance to drugs
that are highly important to human medicine but are not used to treat foodborne illnesses,”
because “[t]ransferred resistance from antimicrobials used in animals produced for food can also
render critically important human antibiotics ineffective.” H.R. Rep. No. 110-258, at 98-99
(2007). Because the Committee was “concerned that simply satisfying the requirements of the
guidance document is not adequate to protect human health,” the Committee “directed FDA to
reevaluate the basis on which it makes such decisions and to provide a report to the Committee
by November 1, 2007.” Id. at 99.

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68.

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.” Sorenson Decl. Ex. O, at 13. The Draft Guidance
recommends that medically important antibiotics be used in food-producing animals (1) only
when necessary to ensure the animals’ health, and not to promote growth or improve feed
efficiency, and (2) only with veterinary oversight. Id. at 16-17. Like other FDA guidance
documents, Draft Guidance No. 209 does “not establish legally enforceable responsibilities.” Id.
at 2.
69.

In 2011, the Senate Committee on Appropriations recommended that “FDA

examine medically important antimicrobial drugs currently approved for use in food-producing
animals and take steps to assure that such products are aligned with current safety standards.” S.
Rep. No. 112-73, at 80 (2011).
Citizen Petitions Filed with FDA in 1999 and 2005
70.

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.” Sorenson Decl. Ex. I, at 1-2.
71.

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.
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g. Expert committees and leading scientists support a phase-out of
subtherapeutic antibiotic use in livestock.
h. Authoritative scientific bodies such as CDC and WHO 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. Id. at 9-25.
72.

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
$9.72 a year in higher costs for consumers. Sorenson Decl. Ex. I, at 33. The petition also pointed
to the experiences of countries such as Sweden and Denmark, which have successfully
eliminated some uses of antibiotics in livestock. Id. at 33-34.
73.

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

petition requested that the FDA Commissioner “withdraw approvals for herdwide/flockwide uses
of [specific] antibiotics in chicken, swine, and beef cattle for purposes of growth promotion
(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).” Sorenson
Decl. Ex. K, at 1. The petition covered penicillins, tetracyclines, aminoglycosides,
streptogramins, macrolides, lincomycin, and sulfonamides. Id. It did not cover any uses of those
drugs to treat disease in animals. Id. at 2.
74.

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. Id. at 10-16.

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75.

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

Amended Complaint ¶ 87; Answer ¶ 87.
76.

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

tentative response, dated February 28, 2001, acknowledged concern about “the role that
antimicrobial drug use in food-producing animals plays in the emergence of antimicrobial drug
resistant bacteria,” and asserted that, “[t]o address these issues, the FDA is undertaking an
extensive process to evaluate issues related to the use of antimicrobial drugs in both humans and
animals, and to develop policies that protect public health.” Sorenson Decl. Ex. J, at 3. The
agency cited its efforts to develop guidance documents for industry. Id.
77.

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

agency again recognized “the need to address concerns related to the role that antimicrobial drug
use in food-producing animals plays in the emergence and selection of antimicrobial drug
resistant bacteria,” and explained that, “[t]o address these public health concerns, the FDA has
developed a regulatory strategy that includes Guidance #152 . . . . Like all FDA guidance
documents, Guidance #152 does not establish legally enforceable responsibilities.” Sorenson
Decl. Ex. L, at 2.

Dated: October 6, 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)

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s/ Jennifer A. Sorenson
Avinash Kar, admitted pro hac vice
Jennifer A. Sorenson, admitted pro hac vice
Natural Resources Defense Council, Inc.
111 Sutter Street, 20th Floor
San Francisco, California 94104
[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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