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

Filing 50

MEMORANDUM OF LAW in Opposition re: 40 MOTION for Summary Judgment. and reply in support of 19 Pls. MOTION for Summary Judgment. 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.,

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Plaintiffs,
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v.
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UNITED STATES FOOD AND DRUG
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ADMINISTRATION; MARGARET
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HAMBURG, in her official capacity as
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Commissioner, United States Food and Drug )
Administration; CENTER FOR
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VETERINARY MEDICINE; BERNADETTE )
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DUNHAM, in her official capacity as
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Director, Center for Veterinary Medicine;
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UNITED STATES DEPARTMENT OF
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HEALTH AND HUMAN SERVICES; and
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KATHLEEN SEBELIUS, in her official
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capacity as Secretary, United States
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Department of Health and Human Services,
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Defendants.
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11 CIV 3562 (THK)
ECF Case

OPPOSITION TO THE GOVERNMENT’S MOTION FOR SUMMARY JUDGMENT
AND REPLY IN SUPPORT OF PLAINTIFFS’ MOTION FOR SUMMARY JUDGMENT
Mitchell S. Bernard (MB 5823)
Natural Resources Defense Council, Inc.
40 West 20th Street
New York, New York 10011
[phone]
[phone] (fax)
[e-mail]

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)
[e-mail]; [e-mail]
Counsel for Plaintiffs

Dated: January 31, 2012

TABLE OF CONTENTS
TABLE OF AUTHORITIES ......................................................................................................... iii
INTRODUCTION .......................................................................................................................... 1
ARGUMENT .................................................................................................................................. 2
I.

FDA Is Required to Withdraw Approval for Penicillin and Tetracyclines Unless
the Agency’s 1977 Findings Are Reversed in Administrative Hearings .............................2
A.

The Government’s Interpretation Strains the Text and Logic of the Statute .......... 3

B.

The Government’s Interpretation Contradicts FDA’s Own Regulations ............... 5

C.

FDA’s 1977 Findings Are Sufficient to Compel Withdrawal ................................ 6
1.
2.

II.

BVM Was Authorized to Make Findings Requiring Withdrawal ............ 10

3.
D.

Once FDA Finds that a Drug Is Not Shown to Be Safe, the Burden
Shifts to the Drug Sponsor to Prove Safety ................................................ 7

The Commissioner of Food and Drugs Has Endorsed BVM’s
1977 Findings............................................................................................ 11

The Government’s Litigation Position Is Not Entitled to Chevron
Deference .............................................................................................................. 14

FDA’s Withdrawal of the 1977 Notices of Opportunity for a Hearing Does Not
Alter Its Statutory Duty to Act on Its Unrecanted Findings ..............................................16
A.

Withdrawal of the Notices of Opportunity for a Hearing Does Not Moot
Plaintiffs’ Claim that FDA Has Unlawfully Withheld Agency Action ................ 16

B.

FDA’s Stated Reasons for Withdrawing the Notices of Opportunity for a
Hearing Do Not Excuse FDA’s Failure to Act ..................................................... 17
1.
2.

Updating the Notices Is Not a Significant Hurdle .................................... 20

3.
C.

Nonbinding Recommendations Cannot Substitute for Withdrawal.......... 18

The Need to Prioritize the Withdrawal of Approvals Does Not
Excuse FDA’s Failure to Withdraw Any Approvals ................................. 20

The Court Should Not Countenance FDA’s Attempts to Avoid Its
Statutory Duty ....................................................................................................... 21

i

III.

Plaintiffs Seek Limited Judicial Relief ..............................................................................22

CONCLUSION ............................................................................................................................. 22

ii

TABLE OF AUTHORITIES
CASES
Bloate v. United States,
130 S. Ct. 1345 (2010) .........................................................................................................3
Bowen v. Georgetown Univ. Hosp.,
488 U.S. 204 (1988) ..........................................................................................................14
Christensen v. Harris County,
529 U.S. 576 (2000) ...........................................................................................................15
Clark v. Astrue,
602 F.3d 140 (2d Cir. 2010)...............................................................................................14
Cutler v. Hayes,
818 F.2d 879 (D.C. Cir. 1987) .............................................................................................2
Defenders of Wildlife v. Norton,
258 F.3d 1136 (9th Cir. 2001) ...........................................................................................16
NRDC v. Abraham,
355 F.3d 179 (2d Cir. 2004) ..............................................................................................16
NRDC v. EPA,
595 F. Supp. 1255 (S.D.N.Y. 1984)...................................................................................19
Pub. Citizen v. Nuclear Reg. Comm’n,
901 F.2d 147 (D.C. Cir. 1990) ...........................................................................................19
Pub. Citizen, Inc. v. Nat’l Highway Traffic Safety Admin.,
374 F.3d 1251 (D.C. Cir. 2004) .........................................................................................18
Rhone-Poulenc, Inc. v. FDA,
636 F.2d 750 (D.C. Cir. 1980) .........................................................................................2, 9
W. Harlem Envtl. Action v. EPA,
380 F. Supp. 2d 289 (S.D.N.Y. 2005)................................................................................19
ADMINISTRATIVE ADJUDICATIONS
Enrofloxacin in Poultry, No. 2000N-1571 (FDA July 27, 2005) ....................................7, 8, 11, 14

iii

STATUTES AND REGULATIONS
21 C.F.R. § 5.84 (1977) .................................................................................................................10
21 C.F.R. pt. 12 ..............................................................................................................................11
21 C.F.R. § 514.115(b)(3)..........................................................................................................5, 15
21 C.F.R. § 514.200 .................................................................................................................10, 11
21 C.F.R. § 514.201 ...................................................................................................................... 11
21 C.F.R. § 558.15 .........................................................................................................................12
21 U.S.C. § 360b(b)(1) ....................................................................................................................9
21 U.S.C. § 360b(c) ...............................................................................................................5, 9, 10
21 U.S.C. § 360b(d)(1) ....................................................................................................................9
21 U.S.C. § 360b(e)(1) ........................................................................................................... passim
OTHER AUTHORITIES
37 Fed. Reg. 2444 (Feb. 1, 1972) .................................................................................................12
38 Fed. Reg. 9811 (Apr. 20, 1973) ...............................................................................................12
42 Fed. Reg. 43,772 (Aug. 30, 1977)...................................................................................2, 10, 12
42 Fed. Reg. 56,264 (Oct. 21, 1977) ...................................................................................2, 10, 12
44 Fed. Reg. 54,852 (Sept. 21, 1979) .......................................................................................9, 11
48 Fed. Reg. 4554 (Feb. 1, 1983) .................................................................................................13
56 Fed. Reg. 41,902 (Aug. 23, 1991).....................................................................................8, 9, 11
76 Fed. Reg. 79,697 (Dec. 22, 2011) ..................................................................................... passim
FDA Staff Manual Guides § 1410.503 (2011).........................................................................10, 11
William Strunk, Jr. & E.B. White, The Elements of Style (Macmillan Paperbacks ed. 1962) ........4

iv

INTRODUCTION
The Government’s response to this lawsuit is striking for what it omits: not once has the
U.S. Food and Drug Administration (FDA) recanted or even cast doubt upon its own 1977
findings that subtherapeutic uses of penicillin and tetracyclines in animal feed are not shown to
be safe for human health. It has not done so in the papers filed in this Court, nor in the notice the
agency published in the Federal Register last month, withdrawing its 1977 notices of opportunity
for a hearing. On the contrary, consistent with its repeated pronouncements over the last three
decades, FDA continues to highlight the human health risks posed by nontherapeutic uses of
medically important antibiotics in farm animals.
FDA’s unrecanted findings trigger mandatory actions under the Federal Food, Drug, and
Cosmetics Act (Food and Drug Act) to protect public health. FDA must withdraw approval for
drug uses not shown to be safe unless a drug sponsor proves at a hearing that the uses are safe.
FDA asserts that its findings do not compel agency action because they were made before, not
after, a hearing, and not by a particular official. This litigation position defies the plain meaning
of the Food and Drug Act and contradicts FDA’s own implementing regulations.
The question at the core of the case is this: Can FDA, over the course of more than three
decades, repeatedly express serious concerns about the safety of previously approved drugs, and
yet allow those drugs to remain on the market all that time, without ever requiring the drug
sponsors to prove their safety? For the reasons set forth in Plaintiffs’ opening brief and below,
the answer is no. Plaintiffs request an order directing FDA to withdraw approval for penicillin
and tetracyclines in animal feed within one year, unless the agency’s findings are overturned in
formal hearings.

1

ARGUMENT
I.

FDA Is Required to Withdraw Approval for Penicillin and Tetracyclines Unless the
Agency’s 1977 Findings Are Reversed in Administrative Hearings
The Food and Drug Act mandates that FDA “shall, after due notice and opportunity for

hearing to the applicant, issue an order withdrawing approval” of a previously approved animal
drug if the agency “finds . . . that new evidence . . . shows that such drug is not shown to be
safe.” 21 U.S.C. § 360b(e)(1)(B) (emphasis added). The Government admits that if FDA makes
the finding contemplated by the statute, then it is “required to withdraw approval” for the drug
not shown to be safe. Mem. in Supp. of the Government’s Mot. for Summ. J. and in Opp’n to
Pls.’ Mot. for Summ. J. (Gov’t Opp’n Br.) 19 (Dkt. 41) (emphasis added); see Rhone-Poulenc,
Inc. v. FDA, 636 F.2d 750, 752 (D.C. Cir. 1980); cf. Cutler v. Hayes, 818 F.2d 879, 893
n.116 (D.C. Cir. 1987). The only question, then, is whether FDA has made the requisite findings
with respect to penicillin and tetracyclines in animal feed. It has. See Tetracycline
(Chlortetracycline and Oxytetracycline)-Containing Premixes (Tetracyclines Notice), 42 Fed.
Reg. 56,264, 56,288 (Oct. 21, 1977) (proposing, with limited exceptions, to “withdraw all
approvals for tetracycline-containing premix products [i.e., feed supplements] intended for
subtherapeutic uses in animal feed . . . on the grounds that they have not been shown to be safe”),
Ex. B to Decl. of Jennifer A. Sorenson, Oct. 5, 2011 (Sorenson Decl.) (Dkt. 33-2); PenicillinContaining Premixes (Penicillin Notice), 42 Fed. Reg. 43,772, 43,772 (Aug. 30, 1977)
(proposing to withdraw approvals 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”), Sorenson Decl. Ex. A (Dkt. 33-1).
The Government contends that the statute mandates withdrawal only on a finding by the
Commissioner of Food and Drugs, made after the drug sponsor has been provided with notice
2

and opportunity for a hearing. Because FDA’s 1977 findings on penicillin and tetracyclines were
made by the Director of the Bureau of Veterinary Medicine (BVM, now known as the Center for
Veterinary Medicine or CVM), and because hearings were never held on the agency’s proposal
to withdraw approval for penicillin and tetracyclines, the Government argues that FDA is free to
leave the drugs on the market.
Plaintiffs recognize that the law requires FDA to provide notice and opportunity for a
hearing so that a drug sponsor can try to prove the safety of a drug FDA has proposed to prohibit.
But that procedural requirement does not diminish FDA’s statutory obligation to withdraw
approval for a drug that is not shown to be safe. Rather, a “not shown to be safe” finding has two
procedural consequences: it sets in motion mandatory withdrawal proceedings, and it shifts to the
drug sponsor the burden of proving the drug’s safety. If the drug sponsor fails to carry its burden
in a formal administrative hearing, then FDA must withdraw approval for the drug.
FDA’s own regulations and rulings support Plaintiffs’ understanding of the procedures
prescribed by law. The agency’s regulations also demonstrate that BVM was authorized to make
findings triggering the agency’s duty to act. Moreover, the history of FDA’s pronouncements on
penicillin and tetracyclines in animal feed reveals that the Commissioner himself endorsed
BVM’s findings that the drugs were not shown to be safe. To this day, the agency’s statements
continue to reinforce the conclusion that approval for the drugs must be withdrawn, absent proof
of safety.
A.

The Government’s Interpretation Strains the Text and Logic of the Statute

Statutory construction must take into account the “structure and grammar” of a provision.
Bloate v. United States, 130 S. Ct. 1345, 1354 (2010). The Food and Drug Act directs that “[t]he
Secretary shall, after due notice and opportunity for hearing to the applicant, issue an order
withdrawing approval of an [animal drug] . . . if the Secretary finds . . . that new evidence . . .
3

shows that such drug is not shown to be safe . . . .” 21 U.S.C. § 360b(e)(1)(B) (emphasis added).
The plain meaning of the provision is this: If FDA finds that a drug is not shown to be safe, it
must withdraw its approval for the drug. Before it can issue the withdrawal order, the agency
must provide notice and opportunity for a hearing. Unless FDA’s findings are reversed in a
hearing, the withdrawal order must issue. The Government’s contention that FDA’s duty to
withdraw approval for a drug not shown to be safe is triggered only by a finding made after a
hearing strains both the text and logic of the statute.
“The position of the words in a sentence is the principal means of showing their
relationship. . . . Modifiers should come, if possible, next to the word they modify.” William
Strunk, Jr. & E.B. White, The Elements of Style 22, 24 (Macmillan Paperbacks ed. 1962). Here,
Congress interposed the phrase “after due notice and opportunity for hearing to the applicant”
between the words “shall” and “issue an order,” indicating that the phrase modifies these words.
That is, the event that may take place only after notice and opportunity for a hearing is the
issuance of an order withdrawing approval for a drug.
Congress could have placed the phrase “after due notice and opportunity for hearing”
after the words “if the Secretary finds,” like so: “The Secretary shall issue an order withdrawing
approval of an [animal drug] . . . if the Secretary finds, after due notice and opportunity for
hearing to the applicant, . . . that new evidence . . . shows that such drug is not shown to be
safe . . . .” That would have indicated that the agency could not make a finding compelling
withdrawal until after notice and opportunity for a hearing. Or, if Congress had intended the
phrase “after due notice and opportunity for hearing” to modify the entire provision, it could
have put those words at the beginning of the sentence: “After due notice and opportunity for
hearing to the applicant, the Secretary shall issue an order withdrawing approval of an [animal

4

drug] . . . if the Secretary finds . . . that new evidence . . . shows that such drug is not shown to be
safe . . . .” But Congress did neither of these things. Instead, it placed the phrase “after due notice
and opportunity for hearing” as close as possible to the words “shall issue an order,” even
interrupting a compound verb to do so. This drafting decision supports Plaintiffs’ natural reading
of the provision.
Far from dispensing with the procedural requirement of providing notice and opportunity
for a hearing, see Gov’t Opp’n Br. 13-15, Plaintiffs’ reading explains when FDA must issue a
notice of opportunity for a hearing in the first place. Unlike the Government’s interpretation, this
reading also accounts for the situation in which a drug sponsor receives notice of opportunity for
a hearing and waives a hearing. In that case, there would be no hearing and necessarily no posthearing findings. But surely FDA would still have both the authority and the obligation to
withdraw approval for the drug, based on the agency’s pre-hearing findings that the drug was not
shown to be safe.
B.

The Government’s Interpretation Contradicts FDA’s Own Regulations

The interpretation of the withdrawal provision advanced by the Government in this
litigation contradicts FDA’s own regulations implementing that provision. The Government all
but concedes this contradiction, acknowledging that “an FDA regulation appears on its face to
predicate the issuance of a notice of opportunity for hearing upon a finding that a drug is unsafe
or not shown to be safe.” See id. at 18 n.16. The regulation states: “The Commissioner shall
notify in writing the person holding an [animal drug] application approved pursuant to [21
U.S.C. § 360b(c)] and afford an opportunity for a hearing on a proposal to withdraw approval of
such application if he finds . . . [t]hat . . . [n]ew evidence . . . shows that such drug is not shown
to be safe . . . .” 21 C.F.R. § 514.115(b)(3)(ii) (emphasis added).

5

The “not shown to be safe” finding is the legal predicate to the notice. Once the
Commissioner finds that a drug is not shown to be safe, she is required to initiate the statutorily
mandated withdrawal proceedings by providing notice and opportunity for a hearing on a
proposal to withdraw approval for the drug. See id. Unless the drug sponsor proves the drug’s
safety, these proceedings must end in withdrawal. See 21 U.S.C. § 360b(e)(1)(B). As discussed
in Part II, below, FDA cannot avoid its duty to withdraw approval for penicillin and tetracyclines
in animal feed by withdrawing its notices of opportunity for a hearing, when it has not recanted
the findings themselves.
C.

FDA’s 1977 Findings Are Sufficient to Compel Withdrawal

The Government attempts to explain away the contradiction between its statutory
interpretation and FDA’s own regulations by inventing a distinction between so-called
“preliminary,” pre-hearing findings and “final,” post-hearing findings that a drug is not shown to
be safe. Gov’t Opp’n Br. 12. The Government argues that BVM’s 1977 findings that penicillin
and tetracyclines have not been shown to be safe are insufficient to compel withdrawal because
BVM was authorized only to make preliminary findings, which do not obligate FDA to take any
action. See Gov’t Opp’n Br. 15-18. These arguments fail for three reasons: First, neither the
statute nor the implementing regulations mention, much less require, two sets of findings
meeting two different standards. Second, BVM was authorized to make findings compelling
withdrawal of approval for animal drugs not shown to be safe. Third, the Commissioner of Food
and Drugs has endorsed BVM’s 1977 findings that penicillin and tetracyclines in animal feed
have not been shown to be safe.

6

1.

Once FDA Finds that a Drug Is Not Shown to Be Safe, the Burden
Shifts to the Drug Sponsor to Prove Safety

The Government misreads several of FDA’s own administrative adjudications to suggest
that the agency must meet a higher standard of proof when it actually withdraws approval for a
drug, after a hearing, than when it proposes to withdraw approval for a drug, before a hearing.
Gov’t Opp’n Br. 17-18. An attentive reading of these adjudications, and the case law on which
they rely, demonstrates that FDA bears only an initial burden of showing that a drug is not
shown to be safe. It is the drug sponsor, not FDA, who carries the burden of persuasion. Once
FDA has found that a drug is not shown to be safe, the burden shifts to the drug sponsor to prove
otherwise. If the drug sponsor fails to do so, then FDA must withdraw approval for the drug.
In the Enrofloxacin Decision, on which the Government primarily relies, the
Commissioner explains that the withdrawal of approval for an animal drug involves a two-step
inquiry: “CVM, as the proponent of withdrawal of approval of [the drug], has the burden of
making the first showing; in other words, CVM has the initial burden of production.”
Enrofloxacin in Poultry (Enrofloxacin Decision), No. 2000N-1571, at 7 (FDA July 27, 2005),
Ex. N to Decl. of Amy A. Barcelo, Jan. 9, 2012 (Barcelo Decl.) (Dkt. 44-14). To meet this
burden, CVM “must provide a reasonable basis from which serious questions about the ultimate
safety of [the drug] . . . may be inferred.” Id. (alteration in original; internal quotation marks
omitted). “If CVM carries its burden of production, . . . the drug’s sponsor[] has the burden of
persuasion on the ultimate question of whether [the drug] is shown to be safe.” Id. at 9. That is,
the drug sponsor “must come forward with evidence that is sufficient to address CVM’s safety
questions.” Id. at 8. As the “fact finder,” the Commissioner determines whether the drug sponsor
has carried its burden of proving the drug’s safety. Id. at 9. If not, CVM’s findings stand, and
approval for the drug must be withdrawn.
7

Without analysis, the Government asserts that the “serious questions” standard “is lower
than the standard for withdrawal contained in section 360b(e)(1), which requires an actual
determination that the drugs at issue are ‘unsafe’ or not ‘shown to be safe.’” Gov’t Opp’n Br. 17.
But the Enrofloxacin Decision makes clear that the “serious questions” standard is the same as
the “not shown to be safe” standard: the Commissioner explains that “the relevant statutory
question is whether the animal drug ‘has been shown to be safe,’ 21 U.S.C. § 360b(e)(1), which,
as explained earlier, has been interpreted to require that CVM show that there are serious
questions about the safety of [the drug].” Enrofloxacin Decision 45. In other words, FDA has
concluded that a drug is “not shown to be safe” when there are “serious questions” about its
safety.
Once FDA has found that a drug is not shown to be safe—that is, that there are “serious
questions” about the drug’s safety—it is up to the drug sponsor to prove otherwise. If the drug
sponsor fails to do so, then the inquiry is over, and approval for the drug must be withdrawn.
There is no statutory or regulatory requirement that FDA make an additional, “final” finding
meeting some higher standard.
The administrative adjudications cited by the Government confirm this two-step
sequence. Like the Enrofloxacin Decision, the Nitrofurans Decision explains that “[t]he
proponent of withdrawal, [CVM], has the burden of making the first showing (i.e., that the drug
is no longer shown to be safe). . . . Once the limited threshold burden has been satisfied, of
course, the burden passes to the sponsors to demonstrate safety.” Nitrofurans (Nitrofurans
Decision), 56 Fed. Reg. 41,902, 41,903 (Aug. 23, 1991), Ex. A to Supplemental Decl. of Jennifer
A. Sorenson, Jan. 31, 2012 (emphasis added). Similarly, the DES Decision states, “Because the
Bureaus are the proponents of withdrawal, . . . they have the burden of proving that the first

8

‘showing’ (i.e., a showing that the drug is no longer shown to be safe) has been made . . . . In
other words, the Bureaus must provide a reasonable basis from which serious questions about the
ultimate safety of [the drug] . . . may be inferred.” Diethylstilbestrol (DES Decision), 44 Fed.
Reg. 54,852, 54,861 (Sept. 21, 1979), Barcelo Decl. Ex. P (Dkt. 44-16) (internal quotation marks
omitted). In both cases, the Commissioner ordered withdrawal after concluding that CVM/BVM
had carried its burden and the drug sponsors had not carried theirs. Nitrofurans Decision, 56 Fed.
Reg. at 41,911-12; DES Decision, 44 Fed. Reg. at 54,900.
The case law cited in these adjudications likewise demonstrates that once FDA has found
that a drug is not shown to be safe, the burden shifts to the drug sponsor to prove safety.
Evaluating a finding made by the Commissioner after a hearing, the D.C. Circuit held that “the
Commissioner has met his initial burden of coming forward with some evidence of the
relationship between the residue and safety . . . . This evidence is sufficient to shift the burden of
showing the safety of DES to the manufacturers.” Rhone-Poulenc, 636 F.2d at 753 (emphasis
added) (internal citations and quotation marks omitted). The Court referred to FDA’s burden as
“initial” not because the agency was later required to meet some higher standard, but because the
only burden FDA bore was an initial one: once it had been met, the burden shifted to the drug
sponsors to prove safety. Because the Commissioner’s determination that the drug sponsors “had
not sustained their burden” was supported by substantial evidence, the Court upheld FDA’s
withdrawal of approval for DES. Id.
This interpretation of FDA’s burden is the only sensible one. The Food and Drug Act
places squarely on drug sponsors the burden of proving that a drug is safe: they must prove
safety if a drug is to be approved in the first instance, 21 U.S.C. §§ 360b(b)(1)(A), (c)(1) &
(d)(1)(A), and if serious questions later arise about the safety of a previously approved drug, they

9

must put those questions to rest. FDA cannot evade its statutory duty to protect the public from
potentially unsafe drugs by labeling its 1977 findings “preliminary.” Once FDA has found that a
drug has “not been shown to be safe,” Tetracyclines Notice, 42 Fed. Reg. at 56,288; Penicillin
Notice, 42 Fed. Reg. at 43,772, it is both illegal and irresponsible for the agency to allow the
drug to remain on the market indefinitely, without ever requiring the drug sponsor to prove its
safety. That is what FDA is doing here.
2.

BVM Was Authorized to Make Findings Requiring Withdrawal

The Government’s contention that BVM was not authorized to make findings requiring
withdrawal is baseless. FDA’s own regulations provide that “[t]he Commissioner shall notify in
writing the person holding an application approved pursuant to [21 U.S.C. § 360b(c)] and afford
an opportunity for a hearing on a proposal to withdraw approval of such application if he
finds . . . [t]hat . . . [n]ew evidence . . . shows that such drug is not shown to be safe.” 21 C.F.R.
§ 514.115(b)(3)(ii). The Commissioner has delegated this duty to BVM (and now CVM): as of
1977, the Director of BVM was “authorized to issue notices of an opportunity for a hearing on
proposals . . . to withdraw approval of new animal drug applications.” 21 C.F.R. § 5.84 (1977),
Barcelo Decl. Ex. M (Dkt. 44-13); see also FDA, Staff Manual Guides § 1410.503 (2011),
Barcelo Decl. Ex. A (Dkt. 44-1).
The delegation to “issue notices of an opportunity for a hearing on proposals . . . to
withdraw approval of new animal drug applications” necessarily encompasses the authority to
make findings that an animal drug is not shown to be safe. The notice could not issue absent such
a finding. Any notice issued must “specify the grounds upon which” the proposal is based. 21
C.F.R. § 514.200(a). If, upon receiving notice, a drug sponsor elects to waive its opportunity for
a hearing, then the Commissioner never gets involved at all: BVM is authorized to issue an order
withdrawing approval of the drug. 21 C.F.R. § 5.84 (1977); see also FDA, Staff Manual
10

Guides § 1410.503, ¶ 1.A.2 (2011). Thus, BVM must have the authority to issue a finding
sufficient to compel withdrawal under 21 U.S.C. § 360b(e)(1).
If the sponsor requests a hearing, then FDA’s formal hearing procedures come into play.
See 21 C.F.R. §§ 514.200, 514.201 & pt. 12. The officer presiding over the hearing makes an
initial decision as to whether the drug sponsor has proved the drug’s safety; if the sponsor
appeals, the Commissioner makes a final decision. Id. §§ 12.120-.130. But the involvement of
the Commissioner does not diminish the legal significance of BVM’s findings. These findings
still trigger the statutorily mandated withdrawal proceedings, which must end in withdrawal if
the drug sponsor cannot prove the drug safe. Moreover, as explained in the administrative
adjudications discussed in the previous section, it is BVM, as the “proponent of withdrawal,”
that makes the showing that a drug is not shown to be safe or, in other words, that there are
“serious questions” about the drug’s safety. Enrofloxacin Decision 7; Nitrofurans Decision, 56
Fed. Reg. at 41,903; DES Decision, 44 Fed. Reg. at 54,861. Nothing about this scheme suggests
that BVM lacks the authority to make findings compelling withdrawal under the Food and Drug
Act.
3.

The Commissioner of Food and Drugs Has Endorsed BVM’s
1977 Findings

In this case, the question whether BVM, rather than the Commissioner, was authorized to
make findings compelling withdrawal is academic. As the history of FDA’s statements on
penicillin and tetracyclines in animal feed shows, the Commissioner of Food and Drugs has
endorsed BVM’s 1977 findings. Moreover, those findings were not written on a blank slate: the
drug sponsors had already submitted data to FDA that failed to prove the drugs’ safety.
In 1970, the Commissioner established a Task Force to evaluate the potential human
health threats posed by the long-term use of antibiotics in animals. See Antibiotic and
11

Sulfonamide Drugs in Animal Feeds, 37 Fed. Reg. 2444, 2444 (Feb. 1, 1972), Sorenson Decl.
Ex. C (Dkt. 33-3). The Commissioner concluded that the Task Force’s findings raised “sufficient
question” about potential human health hazards to require drug sponsors to prove that the drugs
were safe. Antibiotic and Sulfonamide Drugs in the Feed of Animals, 38 Fed. Reg. 9811, 9813
(Apr. 20, 1973), Sorenson Decl. Ex. D (Dkt. 33-4). He ordered drug sponsors and other
interested parties to submit data within the next two years “which resolve conclusively the issues
concerning [the drugs’] safety to man and animals . . . under specific criteria” established by
FDA, or the agency would propose to withdraw all approvals for subtherapeutic uses of
antibiotics in animal feed. Id. (codified at former 21 C.F.R. § 135.109; renumbered as 21 C.F.R.
§ 558.15).
Evaluating the information submitted by drug sponsors and others, the Director of BVM
concluded that “the affected parties have failed to answer the safety questions raised” about
penicillin, Penicillin Notice, 42 Fed. Reg. at 43,774, and “the affected parties have failed to show
that extensive subtherapeutic use of the tetracyclines is safe.” Tetracyclines Notice, 42 Fed. Reg.
at 56,267. Finding that the drugs had “not been shown to be safe” for the uses for which they
were approved, the Director issued notices of opportunity for a hearing on proposals to withdraw
all subtherapeutic uses of penicillin and most subtherapeutic uses of tetracyclines in animal feed.
Penicillin Notice, 42 Fed. Reg. at 43,772; Tetracyclines Notice, 42 Fed. Reg. at 56,288.
In 1983, the Commissioner denied a request by drug sponsors that FDA withdraw the
notices of opportunity for a hearing regarding penicillin and tetracyclines. The Commissioner
explained that “[t]he Director [of BVM] 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

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and Tetracycline in Animal Feeds, 48 Fed. Reg. 4554, 4555-56 (Feb. 1, 1983), Sorenson Decl.
Ex. DD (Dkt. 33-30). For these reasons, the Director did not wish to withdraw the notices of
opportunity for a hearing. The Commissioner stated that he had “reviewed the Director’s
decision and concur[red] with it.” Id. at 4556. The sole regulatory basis for the notices, and thus
for the Commissioner’s concurrence, was the substantive finding that the animal drug uses were
not shown to be safe.
Recent statements by FDA continue to confirm the substance of the agency’s 1977
findings. It is undisputed that in 2010, FDA 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.” Gov’t Resp. to Pls.’ Statement of Facts ¶ 33 (Dkt. 45) (alterations in original) (internal
quotation marks omitted). FDA reached that conclusion after reviewing forty years’ worth of
scientific reports issued by leading authorities around the world. See FDA, Draft Guidance No.
209, The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals
4-13 (2010), Sorenson Decl. Ex. O (Dkt. 33-15). In its review, FDA quoted the 2004 comments
of its parent agency, the Department of Health and Human Services (HHS): “‘We believe that
there is a preponderance of evidence that the use of antimicrobials in food-producing animals has
adverse human consequences. . . . There is little evidence to the contrary.’” Id. at 12. Since FDA
published its review, the Centers for Disease Control and Prevention, another division of HHS,
has stated that there is “strong scientific evidence of a link between antibiotic use in food animals
and antibiotic resistance in humans,” resulting in “adverse human health consequences.” Gov’t
Resp. to Pls.’ Statement of Facts ¶ 38 (internal quotation marks omitted). Last month, in
withdrawing the 1977 notices of opportunity for a hearing, FDA reiterated that it “remains

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concerned about” antimicrobial resistance and “continues to view [it] as a significant public
health issue.” Withdrawal of Notices of Opportunity for a Hearing, 76 Fed. Reg. 79,697, 79,698,
79,700 (Dec. 22, 2011), Barcelo Decl. Ex. L (Dkt. 44-12).
Against this backdrop, the Government’s contention that BVM lacked authority to make
findings compelling withdrawal is specious. FDA has repeatedly identified serious questions
about the safety of penicillin and tetracyclines in animal feed, and has made formal findings that
the drugs “have not been shown to be safe.” The Food and Drug Act dictates what the agency
must do in this situation: it must withdraw approval for the drugs, after notice and opportunity
for a hearing. FDA has made clear that it has no intention of complying with this statutory
mandate. It is up to this Court to enforce the law.
D.

The Government’s Litigation Position Is Not Entitled to Chevron Deference

The Government contends that its interpretation of the withdrawal provision, 21 U.S.C.
§ 360b(e)(1), is “long-standing” and therefore entitled to Chevron deference. Gov’t Opp’n Br.
16. Where, as here, the statutory language is “unambiguous,” the Court “must give effect to the
unambiguously expressed intent of Congress.” Clark v. Astrue, 602 F.3d 140, 147 (2d Cir. 2010)
(internal quotation marks omitted). Even if the withdrawal provision were ambiguous, however,
the Government’s claim for deference would fail, because the agency documents it offers in
support of its position do not embody the statutory interpretation it advances in this litigation.
Courts do not defer to “agency litigating positions that are wholly unsupported by regulations,
rulings, or administrative practice.” Bowen v. Georgetown Univ. Hosp., 488 U.S. 204, 212
(1988).
As evidence of its “consistent[]” interpretation of the withdrawal provision, the
Government points to two sources: the Commissioner’s delegations of authority to the Director
of BVM, and FDA’s administrative adjudications in the Enrofloxacin, Nitrofurans, and DES
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cases. Gov’t Opp’n Br. 16-17. None of these documents explicitly states that only a post-hearing
finding that a drug is not shown to be safe requires FDA to withdraw approval for the drug. The
Government contends, instead, that the documents imply that position by drawing a distinction
between preliminary findings by BVM, meeting a “lower . . . standard” of proof, and final
findings by the Commissioner, meeting the “high standard of section 360b(e)(1).” Gov’t Opp’n
Br. 17-18. As demonstrated in the previous sections, however, the documents do not draw any
such distinction. See supra pp. 7-11. The Commissioner’s delegations authorized the Director of
BVM to make findings legally sufficient to compel withdrawal under 21 U.S.C. § 360b(e)(1).
And FDA’s administrative adjudications make clear that FDA is not required to make two
separate showings, meeting two separate standards. These agency documents support Plaintiffs’
reading of the withdrawal provision, rather than the interpretation now advanced by the
Government.
If this Court defers to FDA at all, it should defer to FDA’s own regulation implementing
the withdrawal provision, on which, notably, the Government does not rely. See 21 C.F.R.
§ 514.115(b)(3)(ii). As discussed above, this regulation makes clear that a pre-hearing finding by
FDA that a drug is “not shown to be safe” obligates the agency to pursue withdrawal
proceedings. Id. The Government argues that this regulation does not mean what it says, and for
support it points again to FDA’s administrative adjudications. See Gov’t Opp’n Br. 18 n.16.
Again, the Court should not credit this litigation position.
Deference to an agency’s interpretation of its own regulation “is warranted only when the
language of the regulation is ambiguous.” Christensen v. Harris County, 529 U.S. 576, 588
(2000). The Government concedes that the language of the regulation is plain: it “appears on its
face to predicate the issuance of a notice of opportunity for hearing upon a finding that a drug is

15

unsafe or not shown to be safe.” Gov’t Opp’n Br. 18 n.16 (emphasis added). Moreover, as
demonstrated above, the administrative adjudications cited by the Government cannot bear the
reading the Government now imposes on them. See supra pp. 7-10. This Court should read the
implementing regulation as it is written and defer to it, rather than to a Government position
“newly minted, it seems, for this lawsuit.” NRDC v. Abraham, 355 F.3d 179, 201 (2d Cir. 2004)
(quoting Defenders of Wildlife v. Norton, 258 F.3d 1136, 1145-46 n.11 (9th Cir. 2001)).
II.

FDA’s Withdrawal of the 1977 Notices of Opportunity for a Hearing Does Not Alter
Its Statutory Duty to Act on Its Unrecanted Findings
A.

Withdrawal of the Notices of Opportunity for a Hearing Does Not Moot
Plaintiffs’ Claim that FDA Has Unlawfully Withheld Agency Action

Contrary to the Government’s representation when it requested and received an extension
of the briefing schedule, see Letter from Amy A. Barcelo to the Hon. Theodore H. Katz, at 2
(Nov. 7, 2011), the Government does not now argue that FDA’s recent withdrawal of the 1977
notices of opportunity for a hearing moots Plaintiffs’ claim that FDA has unlawfully withheld
agency action. Plaintiffs’ claim cannot be moot because FDA has never recanted its findings that
penicillin and tetracyclines in animal feed are not shown to be safe for human health. In fact,
FDA’s notice withdrawing the 1977 notices reinforces the science underlying the agency’s
earlier findings, lending additional support to Plaintiffs’ claim.
FDA’s December 22, 2011, notice acknowledges that the agency “remains concerned
about” antimicrobial resistance and “continues to view [it] as a significant public health issue.”
Withdrawal of Notices of Opportunity for a Hearing, 76 Fed. Reg. at 79,698, 79,700. The notice
explicitly states that the withdrawal of the 1977 notices “should not be interpreted as a sign that
FDA no longer has safety concerns about the use of medically important antibiotics in food
producing animals or that FDA will not consider re-proposing withdrawal proceedings in the
future.” Id. at 79,700-01. FDA also acknowledges that the scientific evidence supporting
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withdrawal of approval of penicillin and tetracyclines has increased since 1977: the agency
explains that, were it to re-propose withdrawal proceedings, it would issue new notices of
opportunity for a hearing because “the body of scientific information relevant to the use of
penicillins and tetracyclines in animal feeds has grown since 1977,” and “FDA would need to
provide notice to the sponsors that the information available since 1977 would be used to support
the proposal to withdraw the approved uses of the drugs.” Id. at 79,700.
FDA’s December 2011 notice demonstrates why this Court must compel FDA to act by
withdrawing approval for penicillin and tetracyclines in animal feed, unless the agency’s
findings are reversed in a hearing. For more than three decades, the agency has acknowledged
that it has serious concerns about the safety of these drugs. The December notice reiterates these
concerns. Yet FDA continues to shirk its statutory and regulatory duty to remove the drugs from
the market absent proof of safety. The Court should compel FDA to withdraw the approvals
unless the drug sponsors can prove in a hearing that the drug uses are safe.
B.

FDA’s Stated Reasons for Withdrawing the Notices of Opportunity for a
Hearing Do Not Excuse FDA’s Failure to Act

In its December 2011 notice, FDA offered three justifications for withdrawing the 1977
notices of opportunity for a hearing. First, the agency would prefer to address the mounting
problem of antibiotic resistance by “promoting voluntary reform and the judicious use of
antimicrobials.” Id. at 79,701. Second, if FDA were to withdraw approval for penicillin and
tetracyclines in animal feed, it would “update” the notices of opportunity for a hearing “to reflect
current data, information, and policies.” Id. Third, if FDA were to withdraw approval for any
animal drugs, it would need to prioritize the withdrawal proceedings to “take into account which
withdrawal(s) would likely have the most significant impact on the public health.” Id. None of

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these justifications relieves FDA of its statutory duty to withdraw approval of penicillin and
tetracyclines in animal feed.
1.

Nonbinding Recommendations Cannot Substitute for Withdrawal

Rather than withdraw approval for penicillin and tetracyclines in animal feed, FDA has
issued a nonbinding, draft guidance document that discourages the use of medically important
antibiotics in livestock for “production” purposes, such as “promoting faster weight gain or
improving feed efficiency.” Id. at 79,699 (discussing Draft Guidance No. 209). The agency
“believes” that Draft Guidance No. 209 “represents another pathway to achieving the same goals
contemplated by the 1977 [notices of opportunity for a hearing].” Id. In lieu of evidence that a
nonbinding guidance will protect human health, the agency offers its “belie[f] that the animal
pharmaceutical industry is generally responsive to the prospect of working cooperatively with
the Agency,” and says it “intends to work with sponsors who approach FDA and are interested in
working cooperatively with the Agency to phase out production uses of medically important
antimicrobials.” Id. (emphasis added). FDA “believes” that by pursuing voluntary reform, “it
will achieve its goal of promoting the judicious use of antimicrobial drugs in a more timely and
resource-efficient manner than could be accomplished otherwise.” Id. at 79,699-700. FDA has
presented not a scrap of evidence (in the notice or to this Court) to support its counterintuitive
belief in the efficacy of voluntary measures, and the degree of equivocation in the agency’s own
language effectively refutes any professed confidence in such measures.
Moreover, as a matter of law, FDA’s issuance of nonbinding recommendations cannot
excuse its failure to withdraw approval for animal drugs that are not shown to be safe. “[A]n
agency ordered by Congress to promulgate binding regulatory requirements may not issue a nonbinding policy statement that encourages but does not compel action.” Pub. Citizen, Inc. v. Nat’l
Highway Traffic Safety Admin., 374 F.3d 1251, 1261 (D.C. Cir. 2004) (summarizing the holding
18

of Pub. Citizen v. Nuclear Reg. Comm’n, 901 F.2d 147, 157 (D.C. Cir. 1990)). As the D.C.
Circuit has explained, for example, when Congress provided that the Secretary of Labor “shall
establish minimum requirements” for firefighting equipment in coal mines, “[o]ne would hardly
surmise . . . that Congress wanted the Secretary merely to exhort coal mine operators to have
minimally suitable firefighting equipment on hand.” Pub. Citizen v. Nuclear Reg. Comm’n, 901
F.2d at 155. Similarly, where the Environmental Protection Agency (EPA) had made de facto
findings that certain chemicals were subject to a mandatory testing regime under the Toxic
Substances Control Act, the court rejected EPA’s “negotiation and acceptance of voluntary
testing agreements by the manufacturers.” NRDC v. EPA, 595 F. Supp. 1255, 1261 (S.D.N.Y.
1984). Finding “no support for EPA’s decision to utilize negotiated testing agreements instead of
the statutorily-prescribed initiation of rulemaking proceedings either on the face of the statute or
based on some vague assertion of agency discretion,” the court explained that “[t]he agency
charged with implementing the statute is not free to evade the unambiguous directions of the law
merely for administrative convenience.” Id. (internal quotation marks omitted).
Here, the Food and Drug Act commands FDA to take binding action if a previously
approved animal drug is no longer shown to be safe: the agency must “issue an order
withdrawing approval” for the drug. 21 U.S.C. § 360b(e)(1). FDA is not free to substitute an
improvised, unenforceable program for the mandatory regime devised by Congress. The agency
“is not in the business of reaching consensus with the ‘stakeholders’ it regulates.” W. Harlem
Envtl. Action v. EPA, 380 F. Supp. 2d 289, 296 (S.D.N.Y. 2005). FDA does not point to any
statutory authorization for its voluntary approach, nor is there any. The agency must withdraw
approval for penicillin and tetracyclines in animal feed, as the Food and Drug Act requires,
unless the drug sponsors can prove that the drug uses are safe.

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2.

Updating the Notices Is Not a Significant Hurdle

The need to update the 1977 notices of opportunity for a hearing to reflect the growing
body of scientific knowledge underscoring the dangers of antibiotic resistance does not relieve
FDA of its duty to act on its findings that penicillin and tetracyclines in animal feed are not
shown to be safe. As discussed above, FDA has confirmed the substance of these findings. If the
agency needs to update the notices of opportunity for a hearing to incorporate new scientific
information such as “advances in our understanding of the genetics of resistance,” then it must
do so. Withdrawal of Notices of Opportunity for a Hearing, 76 Fed. Reg. at 79,700. Updating the
notices presents no real impediment to FDA’s prosecution of withdrawal proceedings for
penicillin and tetracyclines. FDA has been actively reviewing the available scientific knowledge
on antibiotic resistance, as its Draft Guidance demonstrates. See Draft Guidance No. 209, at 413. Moreover, it is undisputed that, in 2004, FDA sent letters to several manufacturers of
approved animal feed products containing penicillin and tetracyclines, reporting that the agency
had conducted a qualitative risk assessment and concluded that the products fell into a “high”
risk category. Gov’t Resp. to Pls.’ Statement of Facts ¶ 65. FDA has had ample time to update
the notices with the results of its analyses.
3.

The Need to Prioritize the Withdrawal of Approvals Does Not Excuse
FDA’s Failure to Withdraw Any Approvals

FDA’s contention that it would need to prioritize which withdrawals to propose, were it
to withdraw approval for any animal drugs, is irrelevant. The agency has made clear that it does
not intend to pursue any withdrawals: “for now, FDA’s efforts will focus on promoting voluntary
reform and the judicious use of antimicrobials.” Withdrawal of Notices of Opportunity for a
Hearing, 76 Fed. Reg. at 79,701. Nor is there evidence that FDA has made any attempt to set
priorities for the necessary withdrawals. FDA made it known in 1977 that penicillin and
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tetracyclines in animal feed are not shown to be safe for human health. For all that time, the
agency has been under a statutory obligation to withdraw approval for these drugs. FDA has no
excuse for allowing the drugs to linger on the market for more than three decades, when public
health is at stake. The Food and Drug Act demands that the agency act.
C.

The Court Should Not Countenance FDA’s Attempts to Avoid Its
Statutory Duty

FDA has not discharged its statutory duty to withdraw approval for subtherapeutic uses
of penicillin and tetracyclines in animal feed absent proof of safety. As the existing science
required, the agency found in 1977 that these animal drug uses were not shown to be safe. FDA
notified the drug sponsors of their opportunity to prove otherwise at a hearing. FDA has never
held those hearings or withdrawn the approvals, even though subsequent science has reinforced
the validity of the agency’s 1977 findings.
When Plaintiffs sued and moved for summary judgment, suddenly FDA withdrew the
notices that flowed from the 1977 findings. It did not retract the findings themselves, and could
not have done so given the mounting scientific evidence, confirmed by the agency, of the serious
threat that antibiotic overuse in animal feed poses to human health. In Plaintiffs’ view, FDA’s
withdrawal of the notices was a litigation maneuver designed to avoid a judicial reckoning with
its unlawful conduct. The agency’s purported justification for aborting the withdrawal process is
an untested voluntary guidance that cannot substitute for the prohibition the statute prescribes.
This is not a game. FDA’s principal purpose is to protect public health. For decades it has
been clear to FDA that the overuse in animal feed of antibiotics that are also used to treat human
infections jeopardizes public health. Yet the agency has refused to act as the law requires. When
confronted with that failure, the agency has continued to evade its responsibilities. All the while,

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the efficacy of antibiotics to treat human disease diminishes. The Court should not countenance
the agency’s persistent, harmful refusal to act.
III.

Plaintiffs Seek Limited Judicial Relief
Because an updated notice will be required, followed by a hearing if drug sponsors

request one, Plaintiffs do not seek an order compelling FDA to withdraw its approval for
penicillin and tetracyclines in animal feed immediately. Instead, Plaintiffs request an order
directing FDA to withdraw approval for these drug uses within one year, unless the agency’s
findings are overturned in formal hearings. See Am. Compl., Request for Relief ¶ C. This is the
primary injunctive relief Plaintiffs seek, not an “alternative” request, as suggested by the
Government. Gov’t Opp’n Br. 23. It is the appropriate relief if Plaintiffs prevail on their claim
that FDA has unlawfully withheld agency action, because it would compel the agency to take the
action it is required by statute to take. It is also modest relief: Plaintiffs do not ask this Court to
prejudge the outcome of any hearing that FDA may hold. They ask only that this Court enforce
the Food and Drug Act by compelling FDA expeditiously to remove from the market drugs that
are not shown to be safe, unless the drug sponsors can prove their safety. This is what the Food
and Drug Act requires.
CONCLUSION
For these reasons, and those set forth in their opening papers, Plaintiffs respectfully
request that this Court grant their motion for summary judgment; deny the Government’s motion
for summary judgment; and order FDA to withdraw approval for penicillin and tetracyclines in
animal feed within one year, unless FDA’s findings are reversed in a formal hearing.
//
//
//
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Dated: January 31, 2012

Respectfully submitted,
Mitchell S. Bernard (MB 5823)
Natural Resources Defense Council, Inc.
40 West 20th Street
New York, New York 10011
[phone]
[phone] (fax)
[e-mail]
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)
[e-mail]; [e-mail]
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)
[e-mail]

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