Cooper Laboratories, Inc. v. Commissioner, Federal Food and Drug Administration

• Decision Date: 26 June 1974
• Docket Number: No. 72-1866,72-1866
• Citation: 163 U.S.App.D.C. 212,501 F.2d 772
• Parties: COOPER LABORATORIES, INC., Petitioner, v. COMMISSIONER, FEDERAL FOOD AND DRUG ADMINISTRATION, Respondent.
• Court: U.S. Court of Appeals — District of Columbia Circuit

Page 772

501 F.2d 772

163 U.S.App.D.C. 212

COOPER LABORATORIES, INC., Petitioner, v. COMMISSIONER, FEDERAL FOOD AND DRUG ADMINISTRATION, Respondent.

No. 72-1866.

United States Court of Appeals, District of Columbia Circuit.

Argued Oct. 18, 1973.

Decided April 19, 1974, Rehearing Denied June 26, 1974.

William R. Pendergast, Washington, D.C., for petitioner.

Howard S. Epstein, Atty., Dept. of Justice, with whom Peter Barton Hutt, Asst. Gen. Counsel, Food, Drugs and Product Safety Division, Food and Drug Administration, Joanne S. Sisk, Chief, Appellate and Special Proceedings Branch, Food and Drug Administration, and Jay H. Geller, Atty., Dept. of Health, Education and Welfare, were on the brief, for respondent.

Before WRIGHT and LEVENTHAL, Circuit Judges, and MATTHEWS, ^* Senior District Judge.

J. SKELLY WRIGHT, Circuit Judge:

To be marketed in interstate commerce under the Food, Drug and Cosmetic Act, a drug must generally be covered by a 'new drug application' (NDA) approved by the Food and Drug Administration (FDA). ¹ In 1944 the FDA approved an NDA for Protamide, an injectible colloidal solution of denatured proteolytic enzyme, upon a finding that the drug was safe for human use, and Protamide was thereafter marketed for symptomatic treatment of herpes zoster (popularly known as shingles), ophthalmic herpes zoster, tabes dorsalis, and neuritis. ² The 1962 amendments to the Act ³ required the FDA to withdraw approval from any NDA where 'substantial evidence' of the drug's effectiveness was lacking, 21 U.S.C. 355(e)(3) (Supp. II 1972), and placed the burden of coming forward with such evidence on the drug companies. ⁴ After several FDA requests, Cooper Laboratories, the maker of Protamide, submitted various documents purporting to establish the drug's effectiveness. Having analyzed this submission, the FDA on August 25, 1972 withdrew approval from Cooper's NDA, finding that the proffered materials did not constitute substantial evidence of efficacy. ⁵ On appeal Cooper asserts that the Administration should have granted it a hearing before acting.

The 1962 amendments define 'substantial evidence' as 'consisting of adequate and well-controlled investigations, including clinical investigations,' 21 U.S.C. 355(d) (1970), a standard explicated in considerable detail by FDA regulations promulgated in 1970, 21 C.F.R. 130.12(a)(5) (April 1, 1973). While the amendments speak of FDA action 'after due notice and opportunity for hearing,' 21 U.S.C. 355(e), the Administration has established summary procedures for finding a drug ineffective where the applicant's proffered evidence clearly does not include 'adequate and well-controlled investigations' and thus does not raise a 'genuine and substantial issue of fact' requiring a hearing. ⁶ The Supreme Court has recently construed these procedural regulations and declared them lawful. ⁷ The narrow question before us is whether the FDA's recourse to summary procedures was proper, given the evidence submitted to the Administration by Cooper. We find that it was and affirm the FDA's order of August 25, 1972 in all respects.

I. ADMINISTRATIVE HISTORY OF THE CASE

The 1962 amendments required the FDA to reevaluate more than 4,000 outstanding NDAs which had been approved solely on safety grounds since the passage of the Food, Drug and Cosmetic Act in 1938. ⁸ To simplify this task, the Administration engaged the National Academy of Science-- National Research Council in 1966 to create expert panels for preliminary screening of the effectiveness of these drugs; holders of NDAs were invited to submit data supporting the efficacy of their drugs. ⁹ Protamide was evaluated by three such panels, which reported their conclusions in 1969. The Panel on Neurological Drugs found Protamide 'ineffective' for neuritis and herpes zoster; the Panel on Drugs Used in Dermatology III found the drug 'ineffective' for herpes zoster; and the Panel on Drugs Used in Ophthalmology found the drug 'possibly effective' for treatment of ophthalmic herpes zoster. ¹⁰

Citing these findings, the FDA in March 1969 required the maker of Protamide to delete label 'indications (for) neuritis, herpes zoster, and tabes dorsalis,' and to provide, within six months, 'substantial evidence of effectiveness of the drug for use in ophthalmic herpes zoster.' 34 Fed.Reg. 5753 (March 27, 1969). ¹¹ Receiving no reply, the FDA in December 1969 notified the maker of Protamide that withdrawal proceedings would be initiated. 35 Fed.Reg. 11535 (July 17, 1970). It gave Cooper 30 days to request a hearing and to submit evidence of efficacy, warning that a hearing would be denied if Cooper's submission revealed 'no genuine and substantial issue of fact.'

Cooper made a timely request for a hearing and submitted three types of evidence to show Protamide's efficacy in treating various illnesses.

(1) By sworn affidavits, similarly worded, five licensed physicians testified that they had found Protamide effective in treating herpes zoster in their clinical practices. They further stated that the clinical experience of specialized physicians was peculiarly important in judging this drug's effectiveness because herpes zoster is difficult to diagnose, runs a variable course in patients, and produces a symptom-- pain-- which is highly subjective and thus resistant to objective means of detection and measurement.

(2) In letters responding to a written request by Cooper for information, 15 practicing doctors declared their belief that Protamide is more effective than any other regimen in treating herpes zoster and related ailments.

(3) Cooper also introduced nine clinical studies, printed in various medical journals, on Protamide's efficacy in treating herpes zoster and related illnesses. Eight of the studies, published between 1947 and 1960, concluded that the drug provided beneficial treatment; the ninth study, published in 1968, concluded that Protamide had no effect on herpes zoster.

There ensued, in the FDA's language, 'an extensive exchange of letters and numerous conferences' between Cooper and the Administration to explore 'methods of establishing the effectiveness of Protamide.' ¹² Two years of such discussions did not result in supplementation of Cooper's evidentiary submission. On August 25, 1972, pursuant to an analysis of this submission, the FDA simultaneously denied Cooper's request for a hearing and withdrew approval from the NDA for Protamide, explaining in an item-by-item critique of Cooper's evidence that none of the materials indicating efficacy constituted 'adequate and well-controlled investigations' as required by 21 U.S.C. 355(d) and (e) and defined by 21 C.F.R. 130.12(a)(5). ¹³

II. THE IMPACT OF Hynson

After this appeal was filed, the Supreme Court decided Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609, 93 S.Ct. 2469, 37 L.Ed.2d 207 (1973), which, as both parties concede, governs the instant case. In Hynson, as here, the FDA had withdrawn approval from an outstanding NDA without a hearing on a finding that the applicant's evidence of efficacy did not consist of 'adequate and well-controlled investigations.' The Court affirmed the Fourth Circuit's conclusion that Hynson's particular evidentiary submission was sufficient to require a hearing, but the opinion also set out three general principles which went beyond the facts of the case and are thus pertinent to this appeal. ¹⁴

(1) The Court upheld the validity of the FDA's regulatory criteria for 'adequate and well-controlled investigations,' 21 C.F.R. 130.12(a)(5).

It is not disputed here that they express well-established principles of scientific investigation. Moreover, their strict and demanding standards, barring anecdotal evidence indicating that doctors 'believe' in the efficacy of a drug, is amply justified by the legislative history. The hearings underlying the 1962 Act showed a marked concern that impressions or beliefs of physicians, no matter how fervently held, are treacherous.

412 U.S. at 618-619, 93 S.Ct. at 2777.

(2) The Court upheld the validity of the FDA's regulations allowing summary withdrawal of approval from NDAs, 21 C.F.R. 130.14(b) (April 1, 1973). Summary action was deemed proper

where it is apparent at the threshold that the applicant has not tendered any evidence which on its face meets the statutory standards as particularized by the regulations. There can be no question that to prevail at a hearing an applicant must furnish evidence stemming from 'adequate and well-controlled investigations.' We cannot impute to Congress the design of requiring, nor does due process demand, a hearing when it appears conclusively from the applicant's 'pleadings' that it cannot succeed.

412 U.S. at 620-621, 93 S.Ct. at 2478. A footnote qualified this statement to apply 'only to those regulations that are precise' and indicated that 'it might not be proper to deny a hearing (on) the grounds that (a) study did not comply' with regulatory standards which 'do not lend themselves to clear-cut definition.' 412 U.S. at 621 n. 17, 93, S.Ct. at 2479.

(3) Courts of Appeals were instructed, in reviewing a hearing denial, to

determine whether the Commissioner's findings accurately reflect the study in question and if they do, whether the deficiencies he finds conclusively render the study inadequate or uncontrolled in light of the pertinent regulations.

412 U.S. at 622, 93 S.Ct. at 2479.

With these parameters in mind, we move directly to consider Cooper's claims that its evidentiary submission was sufficient to require a hearing.

III. COOPER'S CLAIMS FOR A HEARING

Cooper argues that its evidence raised two broad issues of fact which the FDA could not lawfully resolve in summary fashion. First, Cooper contends that its five doctors' affidavits concerning the nature of herpes zoster raise the 'factual' question whether Protamide's efficacy can fairly be determined by the 'objective' methods prescribed in the FDA regulations...