Pharmaceutical Manufacturers Ass'n v. Richardson, Civ. A. No. 3946.

• Decision Date: 20 October 1970
• Docket Number: Civ. A. No. 3946.
• Citation: 318 F. Supp. 301
• Parties: PHARMACEUTICAL MANUFACTURERS ASSOCIATION, Plaintiff, v. Elliot L. RICHARDSON, Secretary of Health, Education, and Welfare, and Charles C. Edwards, Commissioner of Food and Drugs, Defendants.
• Court: U.S. District Court — District of Delaware

318 F. Supp. 301

PHARMACEUTICAL MANUFACTURERS ASSOCIATION, Plaintiff, v. Elliot L. RICHARDSON, Secretary of Health, Education, and Welfare, and Charles C. Edwards, Commissioner of Food and Drugs, Defendants.

Civ. A. No. 3946.

United States District Court, D. Delaware.

October 20, 1970.

Alexander L. Nichols and David A. Drexler, of Morris, Nichols, Arsht & Tunnell, Wilmington, Del., Lloyd N. Cutler and Daniel Marcus, of Wilmer, Cutler & Pickering, Washington, D. C. and Bruce J. Brennan, Washington, D. C., of counsel, for plaintiff.

F. L. Peter Stone, U. S. Atty., Wilmington, Del., John J. Murphy, Chief Administrative Regulations Section, Howard S. Epstein, Atty. of the Dept. of Justice, Washington, D. C., and William W. Goodrich, Asst. Gen. Counsel, Joanne S. Sisk and Eugene M. Pfeiffer, Attys. of the Dept. of Health, Education and Welfare, Washington, D. C., of counsel, for defendants.

OPINION

LATCHUM, District Judge.

In this action for declaratory and injunctive relief, the Pharmaceutical Manufacturers Association ("PMA"), on behalf of its members, seeks a preliminary injunction restraining the Secretary of Health, Education and Welfare ("the Secretary") and the Commissioner of Food and Drugs ("the Commissioner") from taking any action in reliance upon the regulations promulgated in the Commissioner's Order of May 8, 1970 ("the May regulations"), 35 Fed.Reg. 7250. The defendants oppose the issuance of a preliminary injunction and also move for summary judgment of dismissal on the ground that the May regulations are clearly justified.

The May regulations establish standards of evidence necessary to demonstrate the effectiveness of drug products by defining the scientific content of adequate and well-controlled clinical investigations and also set forth the procedural requirements for obtaining an evidentiary hearing in any proceeding to amend the antibiotic certification regulations or to withdraw approval of a new drug application on the ground of lack of substantial evidence of effectiveness. The May regulations are a direct outgrowth of regulations previously issued by the Commissioner on September 19, 1969 ("the September regulations"), 34 Fed.Reg. 14596. In prior litigation in this Court between the same parties, the September regulations were held to be invalid on the ground that they had been issued without prior notice or an opportunity for interested parties to comment as required by section 4 of the Administrative Procedure Act, 5 U.S.C. § 553. Pharmaceutical Manufacturers Association v. Finch, 307 F.Supp. 858 (D. Del.1970).

Two purely legal questions are raised by the present action:¹ (1) May the Commissioner validly establish criteria for adequate and well-controlled clinical investigations necessary to demonstrate the effectiveness of drug products already on the market and (2) does the summary procedure specified in the May regulations comport with the Act and the requirements of due process?

The Court finds (a) that it has the jurisdictional power under 28 U.S.C. §§ 1331, 1337 and 2201 to examine the validity of the May regulations and (b) that the controversy is ripe for judicial determination because the regulations represent final agency action, the two issues raised are purely legal in nature, no genuine issue of material fact is in dispute, the regulations have a direct and immediate impact upon PMA's members and the challenge is not calculated to delay or impede the effective enforcement of the Act. Abbott Laboratories v. Gardner, 387 U.S. 136, 148-156, 87 S.Ct. 1507, 18 L.Ed.2d 681 (1967); Toilet Goods Ass'n v. Gardner, 387 U.S. 158, 87 S.Ct. 1520, 18 L.Ed.2d 697 (1967).

The Drug Amendments Of 1962

The relevant provisions of the Federal Food, Drug and Cosmetic Act ("the Act"), 21 U.S.C. § 301 et seq., governing the marketing of drug products may be summarized as follows:

Under section 505 of the Act, 21 U.S. C. § 355, a "new drug" can be marketed only if the Food and Drug Administration ("the FDA") has approved a new drug application covering that product. Most prescription drugs now on the market were new drugs when first developed and therefore are or have been the subject of approved new drug applications. Antibiotic drugs are marketed under a separate statutory scheme, embodied in section 507 of the Act, 21 U.S.C. § 357.

From 1938, when the Act was first enacted, until 1962, section 505 contained no requirement that a new drug be shown to be effective before a new drug application for the product was approved; only the safety of the drug had to be established by the drug company. Similarly, under section 505(e), an approved new drug application could be suspended, after notice and opportunity for hearing, on the ground that the drug had been shown to be unsafe, but not because it was ineffective. 52 Stat. 1052, 1053 (1938).

In 1962 Congress amended section 505 of the Act to require that any new drugs be shown to be effective as well as safe before being approved for marketing. That section also required claims of effectiveness for a drug to be supported by "substantial evidence." Thus, as a result of the 1962 amendments, approval of a new drug application may be refused, if after notice and opportunity for hearing, the FDA finds there is a "lack of substantial evidence" that the drug is effective for its recommended use. § 505(d), 21 U.S.C. § 355(d). Similarly, section 505(e), as amended, 21 U.S.C. § 355(e), authorizes the Secretary to withdraw approval of a new drug application (including those approved before the adoption of the 1962 amendments) if, after notice and an opportunity for hearing, he finds "on the basis of new information before him with respect to such drug, evaluated together with the evidence available to him when the application was approved, that there is a lack of substantial evidence 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 thereof. * * *"

The term "substantial evidence" is defined in section 505(d) of the Act, 21 U.S.C. § 355(d), 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."

Antibiotic drugs are marketed under a separate procedure provided in section 507 of the Act, 21 U.S.C. § 357. That section, which provides for batch certifications of certain antibiotic drugs, has contained a requirement of efficacy as well as safety since its original enactment in 1945. Before 1962, however, section 507 applied only to certain named antibiotics.² Before 1962, drug products containing other antibiotics were subject to the new drug provisions of section 505 which did not require a showing of effectiveness. When Congress amended section 507 in 1962 to cover all antibiotic drugs, antibiotics previously marketed under section 505 were "transferred" to section 507. Section 507(h), added by the 1962 amendments, directed that initial regulations for certification of such antibiotics be established without the need for an affirmative finding of efficacy. That subsection further provides, however, that the regulations for the certification of those drugs may subsequently be amended or repealed by the Secretary after he makes a finding on a basis similar to that required in section 505(e), discussed above, that there is lack of substantial evidence of the effectiveness of the antibiotic drug. The procedure to amend or repeal antibiotic regulations also provides for notice of the proposed action, an opportunity to present views and a hearing on objections stating "reasonable grounds" in opposition to any final order amending or repealing the regulation. § 507(f), 21 U.S.C. § 357(f).

The NAS-NRC Drug Efficacy Study

Pursuant to the 1962 amendments, the FDA determined to undertake a review of the claims of effectiveness for all drugs approved for marketing between 1938 and 1962. Because of the magnitude of the undertaking and the fact that the resources of the FDA were fully extended in keeping up with the evaluation of currently filed new drug applications,³ the FDA on June 17, 1966 entered into a contract with the National Academy of Sciences-National Research Council ("the NAS-NRC") for the conduct of such a review, and invited drug manufacturers to submit to the NAS-NRC data to support their claims of effectiveness. Thirty panels of physicians were selected by the NAS-NRC, each composed of six experts in a particular field of drug therapy, to review the claims. The review extended over a two-year period and some 4000 drug formulations marketed by 237 firms were examined and reports of the panel findings were made to the FDA. The panels found a considerable number of the drugs effective, about 7% ineffective or ineffective as fixed combinations, and the majority received varying findings of "probably effective", "possibly effective", "effective but", and effective for some of the numerous claims made in each drug's labeling.

The Commissioner's Actions

After reviewing the panel findings, the Commissioner has either concurred or disagreed and from time to time has published in the Federal Register on a product-by-product basis summaries of the conclusions of the NAS-NRC with respect to particular drugs. In several instances in the past on the basis of the conclusions of NAS-NRC panels, the FDA has initiated action to remove products from the market for lack of substantial evidence of effectiveness.

After setbacks in two separate efforts to remove from the market certain antibiotic drugs before acting on...