Source: https://supreme.justia.com/cases/federal/us/412/655/
Timestamp: 2019-04-19 04:25:57+00:00

Document:
it became effective, that the drugs were "covered by an effective application," and that, although "me-too" drugs (similar drugs) of other manufacturers would be exempt, petitioner's "me-too's" were not exempt.
1. "Any drug" is used in § 107(c)(4) in the generic sense, which means that the "me-too's," whether the products of the same or of different manufacturers "covered" by an "effective" NDA, are not exempt from the efficacy requirement of § 201(p). Pp. 412 U. S. 663-665.
2. Prescription drugs on the market are subject to the 1962 efficacy requirements, for if the 1962 amendments are to be comprehensively meaningful, § 107(c)(4) cannot be read so as to provide a loophole to permit the marketing of drugs previously subject to new drug regulation without demonstrating by the new statutory standards that they have the claimed efficacy. Pp. 412 U. S. 665-666.
3. The congressional purpose was to exempt only those drugs that never had been subject to the new drug regulation, and therefore any drug for which an NDA had once been effective does not fall within the exempt category. Pp. 412 U. S. 666-668.
Petitioner sells a line of drugs containing, as a principal active ingredient, citrus bioflavonoid, which is an extract from fruit skins. The drugs are sold in capsules, syrup, and tablets. In the 1950's, new drug applications (NDA's) were filed and became effective for seven of them; two, however, were sold without any NDA. In 1961, the Food and Drug Administration (FDA) advised petitioner that two of the products, when distributed under the existing labels, were not new drugs. These drugs were recommended for a wide variety of ailments, from bleeding, to hypertension, to ulcerative colitis. After the 1962 amendments to the Federal Food, Drug, and Cosmetic Act of 1938, 52 Stat. 1040, as amended, 76 Stat. 780 these products, together with a large number of other bioflavonoid products, were examined by FDA for drug effectiveness. The National Academy of Sciences-National Research Council (NAS-NRC) panels reviewed them. One panel on metabolic disorders concluded that the "use of these materials as hemostatic agents for capillary fragility is felt to be unjustifiable, and not proved." A panel on hematologic disorders found there was no proof that these products were efficacious for any medical use.
§ 107(c)(4). The administrative proceedings went forward, FDA refusing a stay pending the judicial proceedings. Petitioner submitted no evidence of "adequate and well controlled investigations" as required by § 505(d) of the Act, 21 U.S.C. § 355(d), to support its claims of effectiveness. The Commissioner made findings and withdrew petitioner's NDA's.
if there is "a lack of substantial evidence that the drug will have the effect it purports or is represented to have." Section 505(e) was amended to require that any previous approval of an application be withdrawn whenever it appears from new information or otherwise that there is a lack of substantial evidence of the drug's effectiveness.
necessity to review and approve every application already on file.
Section 107(c)(3) provides that drugs covered by NDA's already on file whose labeling remains unchanged are not affected by the amended provisions of § 505(b) or by approvals or refusals under § 505(d) insofar as the effectiveness of the drugs is concerned, so long as the application is not withdrawn or suspended under § 505(e). It also provides that the new effectiveness requirement in the withdrawal provision would not apply until two years after the amendments were adopted, or until the NDA approval were withdrawn for reasons other than lack of the drug's effectiveness, whichever came first. It seems apparent that, by reason of § 107(c)(3), the industry was assured it could continue to market previously approved NDA's unless and until the NDA was withdrawn, and that, before such withdrawal, they would be given a minimum of two years within which to submit "substantial evidence" to support the claims for their products.
Section 107(c)(4) exempted drugs from the new effectiveness requirements so long as their composition and labeling remained unchanged. This exemption, however, applies only to a product that, on the day before the 1962 amendments became effective, (A) was used or sold commercially in the United States, (B) was generally recognized by the experts as safe; and (C) was not "covered" by an "effective" application.
"Established drugs which have never been required to go through new drug procedures will not be affected by the new effectiveness test insofar as their existing clauses are concerned. [Footnote 6]"
"Effectiveness, as well as safety, should apply to new proprietary drugs, but proprietaries now on the market are not to be subject under the present bill to the provisions requiring them, upon notice by the FOA [sic], to support their claims for effectiveness. I think they should be so required. That is a matter which can be remedied in conference or by other legislation. [Footnote 9]"
It can be inferred from this statement that prescription drugs on the market were to be subjected to the efficacy requirements. If the 1962 amendments are to be comprehensively meaningful, we decline to read § 107(c)(4) so as to provide a loophole so that the manufacturers can go on marketing drugs previously subject to new drug regulation without demonstrating by the new statutory standards that they are effective as claimed.
withdraw the NDA's and to bring its products within the exemption.
Initially, we repeat that the legislative history indicates that it was Congress' purpose to exempt only those drugs that never had been subject to the new drug regulation. [Footnote 10] Quite obviously, any drug for which an NDA once had been effective does not fall within that category.
an intention to Congress and, accordingly, cannot agree with petitioner that its NDA's had been withdrawn prior to 1962 so that its bioflavonoid products were no longer "covered by an effective application."
Unlike the situation in CIBA Corp. v. Weinberger, ante, p. 412 U. S. 640, the order of the Commissioner withdrawing petitioner's NDA's had not become final prior to the District Court's assuming jurisdiction. In fact, the Court of Appeals for the District of Columbia Circuit reversed the Commissioner's decision, 151 U.S.App.D.C. 284, 466 F.2d 455, and the proceedings on remand are now pending before the Commission. Thus, petitioner was not barred from proceeding in the District Court. Cf. CIBA Corp. v. Weinberger, supra. Our decision today is not meant to indicate that the District Court, had it concluded that its jurisdiction was concurrent with that of FDA, would not have abused its discretion in refusing to stay this action pending the outcome of administrative proceedings. Cf. Weinberger v. Bentex Pharmaceuticals, Inc., ante, p. 412 U. S. 645. The Court of Appeals below found it unnecessary to consider whether petitioner had failed to exhaust its administrative remedies. 461 F.2d at 226.
There lurks in the case a question whether a drug could have been unsafe prior to the 1962 amendments because it was ineffective in treating the conditions for which its use was recommended by the label. That question, however, was not presented in the petition for certiorari.
"The term 'new drug' means --"
"Within one hundred and eighty days after the filing of an application under this subsection, or such additional period as may be agreed upon by the Secretary and the applicant, the Secretary shall either --"
"(1) approve the application if he then finds that none of the grounds for denying approval specified in subsection (d) applies, or"
"(2) give the applicant notice of an opportunity for a hearing before the Secretary under subsection (d). . . on the question whether such application is approvable. If the applicant elects to accept the opportunity for hearing by written request within thirty days after such notice, such hearing shall commence not more than ninety days after the expiration of such thirty days unless the Secretary and the applicant otherwise agree. Any such hearing shall thereafter be conducted on an expedited basis and the Secretary's order thereon shall be issued within ninety days after the date fixed by the Secretary for filing final briefs."
"If the Secretary finds, after due notice to the applicant in accordance with subsection (c). . . and giving him an opportunity for a hearing, in accordance with said subsection, that (1) the investigations, reports of which are required to be submitted to the Secretary pursuant to subsection (b) . . . do not include adequate tests by all methods reasonably applicable to show whether or not such drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling thereof; (2) the results of such tests show that such drug is unsafe for use under such conditions or do not show that such drug is safe for use under such conditions; (3) the methods used in, and the facilities and controls used for, the manufacture, processing, and packing of such drug are inadequate to preserve its identity, strength, quality, and purity; (4) upon the basis of the information submitted to him as part of the application, or upon the basis of any other information before him with respect to such drug, he has insufficient information to determine whether such drug is safe for use under such conditions; or (5) evaluated on the basis of the information submitted to him as part of the application and any other information before him with respect to such drug, 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 proposed labeling thereof; or (6) based on a fair evaluation of all material facts, such labeling is false or misleading in any particular; he shall issue an order refusing to approve the application. If, after such notice and opportunity for hearing, the Secretary finds that clauses (1) through (6) do not apply, he shall issue an order approving the application. As used in this subsection and subsection (e) . . . , 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."
H.R.Rep. No. 2464, 87th Cong., 2d Sess., p. 3.
"because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, is not safe for use except under the supervision of a practitioner licensed by law to administer such drug;"
or (C) is limited to prescription use in the application under § 505.
See S.Rep. No. 1744, 87th Cong., 2d Sess., pt.. 2, p. 8; H.R.Rep. No. 2464, 87th Cong., 2d Sess., 12; H.R.Rep. No. 2526, 87th Cong., 2d Sess., 22-23; 108 Cong.Rec. 17366.

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