USV Pharmaceutical Corp. v. SECRETARY OF HEALTH, E. & W.

• Decision Date: 14 August 1972
• Docket Number: No. 24900.,24900.
• Citation: 466 F.2d 455
• Parties: USV PHARMACEUTICAL CORPORATION, Petitioner, v. SECRETARY OF HEALTH, EDUCATION & WELFARE and Commissioner of Food & Drugs, Respondents.
• Court: U.S. Court of Appeals — District of Columbia Circuit

466 F.2d 455 (1972)

USV PHARMACEUTICAL CORPORATION, Petitioner, v. SECRETARY OF HEALTH, EDUCATION & WELFARE and Commissioner of Food & Drugs, Respondents.

No. 24900.

United States Court of Appeals, District of Columbia Circuit.

Argued December 17, 1971.

Decided August 14, 1972.

Mr. Joel E. Hoffman, Washington, D. C., with whom Messrs. Robert L. Wald, Stephen M. Truitt and Miss Selma M. Levine, Washington, D. C., were on the brief, for petitioners.

Mr. Howard E. Epstein, Atty., Dept. of Justice, with whom Messrs. John L. Murphy, Chief, Administrative Regulations Section, Dept. of Justice, William W. Goodrich, Asst. Gen. Counsel, and Joanne S. Sisk, Atty., Dept. of Health, Education and Welfare, were on the brief, for respondent.

Before ROBINSON, ROBB and WILKEY, Circuit Judges.

ROBB, Circuit Judge:

The petitioner, USV Pharmaceutical Corporation (USV), is engaged in the manufacture and marketing of a line of citrus bioflavonoid drugs known as CVP.¹ The petitioner challenges an order of the Commissioner of Food and Drugs² withdrawing approval of three New Drug Applications held by USV for these drugs. The order was issued pursuant to section 505(e) of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 355(e) (1970), and its effect is to make the interstate distribution of the drug illegal. 21 U.S.C. §§ 331, 355. The Commissioner says that his order is supported by his finding that there is a lack of substantial evidence, as that term is defined in the Act, 21 U.S.C. § 355(d), that the drugs will have the effectiveness claimed for them. The petitioner counters that the order is invalid because of substantial defects in the proceedings upon which it is based. Reviewing the matter pursuant to 21 U.S.C. § 355(h), we are constrained to agree with the petitioner.

Under the statutory scheme the Commissioner approves or disapproves a drug upon the basis of what is known as a New Drug Application (NDA) submitted by the person proposing to introduce the drug into interstate commerce. In 1956 and 1957 three NDAs for the petitioner's CVP drugs were approved by the Commissioner pursuant to the Federal Food, Drug and Cosmetic Act of 1938, 52 Stat. 1041, 1052, 21 U.S.C.A. §§ 321(p), 355 (1961). Under this statute drug approval was granted if the sponsor submitted proof establishing that the drug was safe for its intended use. No determination of the drug's effectiveness for its prescribed uses was required. In 1962, however, the relevant sections of the statute were amended to require a showing by a drug sponsor that a drug was both safe and effective for its prescribed uses. Act of October 10, 1962, 76 Stat. 781-783, 784, 785, 21 U.S.C. § 355. Among other things the new Act provided that:

The Secretary shall, after due notice and opportunity for hearing to the applicant, withdraw approval of an application with respect to any drug under this section if the Secretary finds * * * (3) 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. . . . Any order under this subsection shall state the findings upon which it is based. 21 U.S.C. § 355(e).

The Act defined the term "substantial evidence" as follows:

As used in this subsection and subsection (e) of this section, the term "substantial evidence" means 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. 21 U.S.C. § 355(d).

The proceedings to withdraw approval of the petitioner's CVP drug applications were under 21 U.S.C. § 355(e).

By notice in the Federal Register on July 9, 1966 the Commissioner announced that the National Academy of Sciences—National Research Council (NAS-NRC) had "agreed to assist the Food and Drug Administration in its review of the claims of effectiveness for drugs cleared through the new-drug procedures from 1938 until October 10, 1962." 31 Fed.Reg. 9426. The notice directed holders of such approved new-drug applications to submit certain specified data and material to NAS-NRC, in order to

facilitate this review and a determination of whether there may be ground for invoking section 505(e) of the Federal Food, Drug, and Cosmetic Act, and to provide each holder of such an approved new-drug application an opportunity to present for the consideration of the reviewing experts the best data available to support the medical claims. . . .

Among the materials to be submitted were:

f. Current labels and package inserts (attach 10 copies of each to original of form; 1 copy of each to duplicate).

g. List of literature references most pertinent to an evaluation of the effectiveness of the drug for the purposes for which it is offered in the label, package insert, or brochure. Approximately 5 to 10 key references, if available (attach 10 copies of the list to original of form and 1 copy to duplicate).

h. Unpublished articles or other data pertinent to an evaluation of the claims (one copy only; attach to duplicate).

Responding to the Commissioner's notice of July 9, 1966 USV submitted two bibliographies, one containing nine references, the other sixteen. This submission was reviewed by two NAS-NRC panels which in due course reported to the Commissioner. The complete report of the Panel on Drugs Used in Hematologic Disorders was as follows:

C.V.P. with VITAMIN K NDA 9965 LOG 734 Panel on Drugs Used in Hematologic Disorders INDICATIONS I. As a supplementary source of bioflavonoids, ascorbic acid, and menadione. EVALUATION: Ineffective. COMMENTS: The label correctly states that the dietary need for these agents has not been established in agreement with Burns. DOCUMENTATION 1. Burns, J. J. Water-soluble vitamins; II. asscorbic acid (vitamin C), pp. 1673-1680. In L. S. Goodman and A. Gilman, Eds. The Pharmacological Basis of Therapeutics. (3rd ed.) New York: The MacMillan Co., 1965. Approved by William illegible Chairman

So far as material the report of the Panel on Drugs Used in Metabolic Disorders was as follows:

DUO-C.V.P. NDA 9965 LOG 733

Panel on Drugs Used in Metabolic Disorders

INDICATIONS None.

GENERAL COMMENTS

I. There is no package insert, but just a label indicating that this is a "supplementary source of bioflavonoids and ascorbic acid." There is no definite claim for therapeutic use and a statement on the label admits that "the need for bioflavonoids in human nutrition has not been established." However, the inference is that there is indeed a need for such a product. The references support this inference, in that everything from threatened abortion to bleeding gums is reported to have responded. The use of these materials as hemostatic agents for capillary fragility is felt to be unjustifiable and not proved. The Panel recommends that there should be a clear statement as to the use of this preparation.

II. The Panel finds that the term "minimum daily adult" requirement is meaningless because variations in nutritional needs depend on the health, sex, age, and physical activity of the individual. The term "dietary allowances" is preferred.

III. See the general statement on multiple-vitamin preparations.

Approved by D. H. Nelson Chairman

On January 23, 1968 the Commissioner announced that the Food and Drug Administration, having received the NAS-NRC report, "has considered the report and has concluded on the basis of the report and its own evaluations that there is no evidence that * * * bioflavonoids are effective for use in man for any condition." 33 Fed.Reg. 818. The Commissioner noted that lack of substantial evidence of effectiveness of a drug was a basis for withdrawing approval of a new-drug application, and that the Commissioner intended "to publish a notice of opportunity for a hearing on a proposal to withdraw approval" of new-drug applications for the bioflavonoids. The Commissioner stated, however, that before taking such action he invited all interested holders of new-drug applications to attend a meeting on January 31, 1968 "to discuss the procedural matters involved in the proposed action * * * and to attempt to identify and resolve problems that may be anticipated as a result of the actions to be taken." The meeting was held on January 31, 1968 at which time the Food and Drug Administration again invited the submission of additional scientific and medical information that might be pertinent to the question of the effectiveness of the drugs. In response, USV submitted certain additional information in the form of reports and reprints.

By notice published in the Federal Register on July 10, 1968, 33 Fed.Reg. 9908, the Commissioner announced that "the additional information received, considered together with other information available, did not provide substantial evidence of effectiveness of such drugs for use in man for any condition." Accordingly, the Commissioner gave notice that he proposed to withdraw approval on the ground that there was a lack of substantial evidence that any bioflavonoids had the effect which the drugs purported or were represented to have under the conditions for use prescribed, recommended or suggested in the labeling thereof, or that such articles alone, or as added components with other drugs, were effective for use in man in any condition. Continuing, the notice stated that "the Commissioner will give each applicant and any interested person who...