Smithkline Corp. v. Food and Drug Administration, 76-1942

• Decision Date: 22 June 1978
• Docket Number: No. 76-1942,76-1942
• Citation: 190 U.S.App.D.C. 210,587 F.2d 1107
• Parties: SMITHKLINE CORPORATION, Petitioner, v. FOOD AND DRUG ADMINISTRATION, and Donald Kennedy, Commissioner, Department of Health, Education and Welfare, and Joseph A. Califano, Jr., Respondents.
• Court: U.S. Court of Appeals — District of Columbia Circuit

Page 1107

587 F.2d 1107

190 U.S.App.D.C. 210

SMITHKLINE CORPORATION, Petitioner, v. FOOD AND DRUG ADMINISTRATION, and Donald Kennedy,

Commissioner, Department of Health, Education and

Welfare, and Joseph A. Califano, Jr., Respondents.

No. 76-1942.

United States Court of Appeals, District of Columbia Circuit.

Argued Jan. 11, 1978.

Decided June 22, 1978.

Stanley L. Temko, Washington, D. C., with whom Herbert Dym and Coleman S. Hicks, Washington, D. C., were on the brief, for petitioner.

Margaret A. Cotter, Asst. Chief, Consumer Affairs, Dept. of Justice, Washington, D. C., with whom Eric M. Blumberg, Associate Chief Counsel for Enforcement, Food and Drug Administration, Rockville, Md., was on the brief, for respondents.

Before BAZELON, McGOWAN and MacKINNON, Circuit Judges.

Opinion for the Court filed by BAZELON, Circuit Judge.

Opinion filed by McGOWAN, Circuit Judge, concurring in part and dissenting in part.

BAZELON, Circuit Judge:

Smith, Kline & French Laboratories (SKF), a Division of SmithKline Corporation, has since 1950 produced and marketed Dexamyl, ¹ a prescription drug used as an anorectic in the treatment of obesity. Dexamyl is a combination drug containing Dexedrine (dextroamphetamine sulfate), an appetite suppressant, and amobarbital, a barbituate designed to reduce the possible adverse side effects of Dexedrine. On August 24, 1976, the Acting Commissioner of Food and Drugs published an order denying SKF a hearing and refusing to approve the pending new drug applications (NDAs) for Dexamyl. 41 Fed.Reg. 35741 (1976). SKF petitions this court to reverse the Acting Commissioner's summary judgment order and to remand to the Food and Drug Administration (FDA) for an evidentiary hearing pursuant to 21 U.S.C. § 355(c). ² See id. at § 355(h).

I. BACKGROUND

A. The Statutory and Regulatory Framework

The Federal Food, Drug, and Cosmetic Act (the Act) prohibits the marketing in interstate commerce of any "new drug" unless an NDA for the drug has been approved. See 21 U.S.C. § 355(a). In 1962 the Act was amended to define "new drug" to mean any drug not generally recognized as safe and effective for its intended use. See 76 Stat. 781, 21 U.S.C. § 321(p). The Amendments provided that an NDA would not be approved if it were found, "after due notice to the applicant . . . and giving him an opportunity for a hearing," 21 U.S.C. § 355(d), that there was a lack of "substantial evidence" that the drug was effective for its intended use. Id. Substantial evidence was defined to mean:

evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the drug involved, on the basis of which it could fairly and responsibly be concluded by such experts that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.

Id. The Amendments exempted certain drugs from the requirement of providing substantial evidence as to their effectiveness. A "grandfather" clause provided:

In the case of any drug which, on the first day immediately preceding the enactment date, (A) was commercially used or sold in the United States, (B) was not a new drug as defined by section 201(p) of the basic Act as then in force, and (C) was not covered by an effective application under section 505 of that Act (21 U.S.C. § 355), the amendments to section 201(p) (21 U.S.C. § 321(p)) made by this Act shall not apply to such drug when intended solely for use under conditions prescribed, recommended, or suggested in labeling with respect to such drug on that day.

Section 107(c)(4), 76 Stat. 789 (1962).

FDA has promulgated regulations implementing this statutory scheme. See 21 U.S.C. § 371(a). It has required that for a fixed combination prescription drug such as Dexamyl substantial evidence must be presented both that the drug is effective for its intended use and that each constituent component contributes to the claimed effects. 21 C.F.R. § 300.50(a) (1977). In addition, FDA has specified criteria for the "adequate and well-controlled investigations" acceptable as substantial evidence of effectiveness. ³ Although the Act appears to contemplate a hearing if FDA does not approve an NDA, See 21 U.S.C. §§ 355(c), 355(d), Supra note 2, FDA has developed summary judgment procedures in cases where an applicant has failed to submit substantial evidence of drug efficacy sufficient to meet regulatory standards. ⁴ The Supreme Court has in principle approved such procedures, stating that, "(w)e 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 the application cannot succeed." Weinberger v. Hynson, Wescott & Dunning, Inc., 412 U.S. 609, 621, 93 S.Ct. 2469, 2479, 37 L.Ed.2d 207 (1973).

B. Proceedings Before FDA

When SKF decided to market Dexamyl tablets in 1949, it advised FDA of its position that the drug was not a "new drug" under the Federal Food, Drug and Cosmetic Act. ⁵ See Appendix B at 1b-2b. ⁶ FDA agreed and informed SKF of its conclusion that Dexamyl was not a new drug. ⁷ Id. at 5b. Thus no NDA was ever filed for Dexamyl. ⁸

When the 1962 Amendments changed the statutory definition of a "new drug" to designate one not generally recognized by experts as safe and effective for its intended use and in addition required substantial evidence of efficacy, FDA was faced with the massive task of reevaluating almost all marketed drugs. ⁹ For assistance in this task, FDA retained the National Academy of Sciences- National Research Council (NAS-NRC) to create expert panels to review the efficacy of drugs by class. One such expert panel studied certain amphetamine combination products. On August 18, 1970, the Commissioner of Food and Drugs announced his concurrence with the panel's finding that these products were only "possibly effective" for their claimed anorectic effects. ¹⁰ 35 Fed.Reg. 12678 (1970). The Commissioner invited those who held NDAs for these products and "persons marketing any of these drugs without approval" to "submit in a supplemental or original new-drug application data to provide substantial evidence of effectiveness . . . ." Id. at 12679.

On August 6, 1971, SKF submitted NDAs for Dexamyl, together with a letter stating its position that Dexamyl was covered by the "grandfather clause" of the 1962 Amendments and was thus not subject to the efficacy requirement. Joint Appendix (J.A.) at 3-6. FDA informed SKF by letter on January 15, 1973, that these NDAs were not approvable because "(t)he studies submitted fail to demonstrate the contribution of the sedative-tranquilizer constituent to the total effect of the drug." J.A. at 15. Under FDA regulations, SKF was given 30 days to make a "written request to file the application over protest." 21 C.F.R. § 130.5(d) (1973). ¹¹ Within the 30-day period, on February 12, 1973, SKF requested that its Dexamyl NDAs be filed over protest, again noting its position that Dexamyl was grandfathered under the 1962 Amendments. J.A. at 17-18.

On the same day, February 12, 1973, FDA published in the Federal Register an "Opportunity for Hearing on Proposal to Withdraw Approval of New Drug Applications," in which FDA stated that information concerning the efficacy of combination anorectic drugs that had been submitted in response to its August 8, 1970 notice was "found not to provide substantial evidence that the drugs are effective as fixed combinations for their claimed uses." 38 Fed.Reg. 4279 (1973). FDA proposed to withdraw approval of the listed NDAs and stated that "(a)ll identical, related, or similar products, not the subject of an approved new drug application, are covered by the new drug application(s) reviewed." ¹² Id. An NDA holder "or any other interested person" could request an evidentiary hearing on the issues involved. Id. at 4280.

SKF responded to the February 12, 1973 notice although the notice had not mentioned Dexamyl by name. J.A. at 21-26. SKF stated, first, that Dexamyl was not covered by the NDAs reviewed in the notice. ¹³ SKF went on to argue, however, that, assuming that Dexamyl was so covered, SKF had presented sufficient evidence in its previous submissions to require a full evidentiary hearing. On March 30, 1973, FDA approved the continued marketing of Dexamyl pending a ruling on SKF's request for a hearing. 38 Fed.Reg. 8290 (1973).

On July 11, 1973, SKF submitted to FDA the results of five, new, double-blind, clinical trials testing the efficacy of Dexamyl (multi-investigator clinical trials). J.A. at 27-31. Two weeks later, on July 27, 1973, FDA informed SKF by letter that the record regarding Dexamyl was closed as of that date, and that no further data would be accepted from SKF. J.A. at 85.

Three years later, on August 24, 1976, FDA published an order denying a hearing and refusing to approve the pending NDAs for Dexamyl. 41 Fed.Reg. 35741 (1976). The Acting Commissioner of Food and Drugs stated:

that (1) there is a lack of substantial evidence that Dexamyl products have the effects they are represented to have under the conditions of use recommended, suggested or prescribed in their labeling and (2) there is a lack of substantial evidence that each component of the combination products contributes to the total effects claimed.

Smith, Kline and French has failed to offer any data or legal reason to demonstrate the existence of a genuine and substantial issue of fact requiring a hearing.

Id. at 35754. The Acting Commissioner based his holding on the fact that none of the evidence submitted by SKF met the regulatory standards for adequate and well-controlled clinical studies. The Acting Commissioner also concluded that Dexamyl was covered by the NDAs of the drugs named in the February 12, 1973 order, ¹⁴ and that...