Legal Document

412 U.S. 609 93 Supreme Court Reporter 2469 37 United States Reports Lawyer’s Edition 2d Series KF101.8 U54 207 Caspar W. WEINBERGER, Secretary of Health, Education, and Welfare, et al. Petitioners,v.HYNSON, WESTCOTT AND DUNNING, INCORPORATED. HYNSON, INCORPORATED, Petitioner, versus Nos. 72—394, 72—414. Argued April 17, 1973. Decided June 18, Syllabus The Federal Food, Drug, Cosmetic Act 1938, as amended in 1962, establishes a system premarketing clearance for drugs prohibits § 505 (a) the introduction into commerce any 'new drug' unless new drug application (NDA) filed with Food Drug Administration (FDA) was effective respect to such drug. Under procedures were established filing applications not only safety but their efficacy well. Standards provided under which, after notice hearing, FDA could refuse allow an Non-Disclosure Agreement become effective, or suspend effect on basis evidence that effective. is directed approval withdraw prior if 'substantial evidence' (§ 505(d)) its intended use lacking. All NDA's 'effective' 1962 deemed 'approved' manufacturers given two years develop substantial effectiveness during which previously approved be withdrawn by drug's lack effectiveness. also contained 'grandfather' clause exempting from requirements day proceeding enactment (1) commercially used sold States, (2) defined 1938 Act, (3) 'was covered application' Act. had permitted more than 9,000 between some 4,000 still market. Additionally, have marketed thousands 'me-too' without applying clearance, similar identical NDA's, reliance 'pioneer' FDA. To aid it fulfilling statutory mandate review all drugs, whether approved, efficacy, retained National Academy Sciences-National Research Council (NAS—NRC) create expert panels class each Holders invited furnish best available data establish announced would apply NAS—NRC findings including drugs. Respondent Number 72—394 (Hynson) called Lutrexin informed Hynson studies submitted sufficiently well controlled justify claims effectiveness, allowed since evaluation solely safety. When amendments became drug, panel reported satisfied requirements. Notice intention covering Commissioner Drugs. Before brought suit District declaratory judgment exempt provisions there no efficacy. Petitioners' motion dismiss granted. While litigation pending, denied Hynson's request hearing based Lutrexin's withdrew ruling adequate Appeals reversed, holding while exempt, entitled substantial-evidence issue. 72 414 cross-petition Appeals, suggested district court has authority determine drug.' agrees status proceedings product's NDA, manufacturers, parties other suits this group cases, advance contrary view. Held: 1. regulations issued thereunder, express well-established principles scientific investigation, reduction standard detailed guidelines protection public, make FDA's so-called administrative summary procedure appropriate. Pp. 617—619. 2. procedure, whereby will provide formal when apparent at threshold applicant tendered face meets standards particularized regulations, valid. Storer Broadcasting Co., 351 192, 76 763, 100 L.Ed. 1081; FPC Texaco, Inc., 377 33, 84 1105, 12 112. 620—622. 3. In Appeals' submission burden providing affirmed. 622—623. 4. heart grant primary jurisdiction FDA, subject judicial remedies are exhausted. 623—627. 5. Although can 'generally recognized' experts within meaning consensus founded upon evidence,' premature, must await outcome held (item 3, supra). 628—632. 6. construction accords legislative history suggests exemption afforded never been regulation. 632—634. 461 Reporter, 2nd 215, affirmed modified. Opening statement Daniel M. Friedman, Washington, D.C., Weinberger, Secretary, HEW, five cases. Andrew L. Frey, others. Edward Brown Williams, Hynson, Westcott Dunning, Incorporated. Mr. Justice DOUGLAS delivered opinion Court. 1 These together Weinberger Bentex Pharmaceuticals, 645, 2488, 235; CIBA Corporation 640, 2495, 230, USV Pharmaceutical 655, 2498, 244, here certiorari, raise series questions amendments1 1938. 52 Statutes-at-Large 1040. prohibited (FDA)2 505(a), 1052. one generally recognized qualified safe use. 201(p)(1). Government sue enjoin violations, prosecute criminally, seize condemn articles. §§ 301(d), 302(a), 303, 304. 505(b), 505(c) (d), unsafe. 505(e). Orders denying suspending reviewed record. 505(h). 2 201(p)(1) define among 21 Code KF62 321(p)(1). A now defined, may effect. evidence'3 355(d) (e). Thus, basic system, requiring before lawfully marketed, continued, except either approve disapprove 180 days. 355(c). (Under automatically disapproved.) Judicial transferred courts appeals. 355(h). 3 Since requires affirmative agency approval, definition, effectiveness.4 contain preceding (it being safe), Act.5 4 Between 9,457 Of these, addition, clearance. known 'me-toos,' manufacturer obtained advisory letter product safe. 5 task therapeutic drugs.6 FDA; January 23, 1968, policy related drugs.7 6 * & Lutrexin, recommended treatment premature labor, threatened habitual abortion, dysmenorrhea. urged represent useful abortion. But grounds again test safety, undertook appraise theretofore safe, list literature references, copy unpublished study, representative sample testimonial behalf Lutrexin. working relevant field inappropriate unwarranted absence further appropriate documentation. At invitation Drugs, additional data. concluded information inadequate published his offering opportunity prewithdrawal hearing. take place, question or, alternatively, Government's granted, failed exhaust remedies. 7 promulgated establishing minimal 'adequate well-controlled investigations' limiting right those applicants who proffer least meeting standards.8 maintained because initial predated issuance, renewed material claimed constituted He ruled question. 8 Section 505(e)9 directs fails carry showing evidence'10 respecting As says, substituted 'preponderance' evidence. F.2d, 220. Regulations, guidelines,11 9 general contours 505(d) include 'evidence consisting investigations, clinical training experience evaluate involved, fairly responsibly purports represented conditions prescribed, recommended, labeling proposed thereof.' 355(d). Acting pursuant 'authority promulgate efficient enforcement' 701(a), 371(a), 'principles . community essentials investigations. They determination thre support drugs' ..' Regulations 130.12(a)(5)(ii). 'plan protocol' setting forth objective study method selecting subjects,12 explaining methods observation steps taken minimize bias, comparison four 'recognized' results diagnosis control, summarizing analysis, statistical methods. Id., 130.12(a)(5)(ii)(a). No investigation considered 'standardized identity, strength, quality, purity, dosage form give significance investigation.' 130.12(a)(5)(ii)(b). Finally, regulation provides '(u)ncontrolled partially acceptable sole Such studies, carefully conducted documented, corroborative .. Isolated case reports, random experience, reports lacking details permit considered.' 130.12(a)(5)(ii)(c). 10 Lower upheld validity these regulations,13 disputed they investigation. Moreover, strict demanding standards, barring anecdotal indicating doctors 'believe' amply justified history. hearings underlying show marked concern impressions beliefs physicians, matter how fervently held, treacherous.14 Congress definition wrote requirement investigations.' Senate Report makes clear abrupt departure old norms marketing There mounting over we safety.15 stated:16 11 '(A) claim rejected found investigations 'adequate'; (b) 'well controlled'; (c) made; (d) conclusions drawn derived sure, 'due applicant' NDA. 505(e), 355(e). however, regulation, desires submit reasons 'why should withdrawn, well-organized full-factual analysis investigational he prepared prove opposition clearly appears factual genuine issue fact ., e.g., effectiveness,' deny enter order withdrawing 130.14(b). What said, then, where regulations. 13 propriety decided 205, 771, 1081, 39, 1109, We said Texaco: 14 '(T)he (of Natural Gas Act) does preclude Commission particularizing through rulemaking process neither measure up them nor why public interest rule waived.' Ibid. 15 prevail stemming cannot impute design requiring, due demand, conclusively applicant's 'pleadings' succeed.17 16 evaluated approximately 16,500 made 1962. Seventy percent supported 434 uses. If required hold whose questioned even though many exercise futility, doubt fulfill remove market do meet 17 involving trial jury Seventh Amendment, sharper limitations judgment,18 our decisions reveal. See, Adickes S. Haw. Hawai‘i KFH45 A2 Kress 398 144, 153—161, 90 1598, 1606—1610, 26 142; White Motor company 372 253, 83 696, 738. surely great leeway releasing miracles hand, merely easy money-making schemes fraudulent articles labeled mysterious dress. 'well-controlled protective designed ferret out affirmative, reliable full precise present sustain circumstances find unexceptionable constitutional ground. 18 Our conclusion valid end matter, argues burden. reviewing appeals Commissioner's accurately reflect do, deficiencies finds render uncontrolled light pertinent regulations.'19 contrariety concerning adequacy submission. majority view sufficient warrant affirm phase case. II 19 72—414 Appeals. This raises amendments. contends agrees, 20 Prior machinery commerce. 1906 34 768, adulterated misbranded narrowly criminal sanctions seizure libel condemnation. noted, regulatory suspension interests introduce fixed period refused finding existing shown 1041—1042, Any suspended testing showed 1053. reviewable record court. Marketing enjoined prosecution, seized condemnation proceedings. steady stream voluminous data.20 Many claiming illegally launched recognzied It estimated 1969 every Enormous problems created. Each about 30 volumes, stack feet high; 400 volumes 22 us power particular require public. indeed selected administer intelligently rationally what 201(p) grandfather 107(c)(4). 23 Regulatory agencies statutes usually proceeded case-by-case basis, giving person separate hearings. always reason done. example. rules Communications number broadcasting stations single individual might own, saying proper agency's 'rule-making necessary orderly conduct business.' 202, 770. comprehensive, rather individual, quick relief. See Permian Basin Area Rate Cases, 390 747, 88 1344, 312. generic drug—which unsafe and/or efficacy—may manufactured several persons manufacturers. against each, owner Black Acre condemned, delay health prompt action. heard constitutionally permissible measured procedural process. 24 maintains withdrawal covers For stated, challenged heard. 554 Administrative Procedure governing 554(e). That section prescribes follow 'in adjudication statute determined hearing.' 554(a). industry 554(e) avail common issue, argued, resolved 'on assumes individualized 554(e), place straitjacket. sound discretion, terminate controversy uncertainty.' termination often prime importance. age ever-expanding dockets leval. controls efficient, exercised dispatch. Only paralysis result battles way protect ineffective category put actions, inequities result. months eliminat Meanwhile, competitors selling same go scot-free until tedious laborious reached them. believe engaged futility enacted restore enforcement enjoyed primitive uncertainty Abbott Laboratories Gardner, 387 136, 87 1507, 681. 25 lawful purpose determining lawsuits file future. Yet another version tactics procrastination offers serve industry's needs. needs are, opposed paramount. accept decide withdrawn. Its is, course, reviewable. essential operation court's like power. Cf. Shipp, 203 563, 573, 27 165, 166, 51 319. final say, had, (except limited cases discuss), unbridled discretion pleases. satisfy rudiments fair play. relief argued empowered 28 'The term means—its NDA's. Some seeking Nevertheless, 505(h), 701—704; Citizens Preserve Overton Park Volpe, 401 402, 410, 91 814, 820, 136; supra, 139 148, 1510—1515. By analogy declaring commodity normally reviewable, Frozen Express 40, 569, 730. 29 then presented properly instance. indicated above, requesting asked amended, 321(p).21 'grandfathered' 107(c)(4) amendments.22 both claims. Finding 'there base conclude proven so uses.' 1953, thus 'covered 107(c)(4)(C). did discuss currently agree come 107(c)(4), vacated. thrust qualitative quantitative. nowhere defines constitutes 'general recognition' experts. 'lack applicable proof actual fall rely testimony physicians extant literature, characterized 'anecdotal.' scheme overriding compel hurdle supporting fortiori Act.23 31 first time gave scrutinize 505(d), Similarly, subsequently determines Evidence accepted consists involved indicates rigorous one. reflects Congress, hearings,24 practicing poorly experiments constitute underlies defining evidence': 'Uncontrolled 32 prospective only. Clearly, two-year moratorium adoption amendments, plainly contemplates thwarted recognition regardless used. But, construe deprive passed test. 'would paralyze hand sought promote other.' Clark Uebersee Finanz-Korp., 332 480, 489, 68 174, 178, 92 88. 33 interpretation consistent operates purely basis. subsection (2), transcend 'to extent time.' Yet, evidence.' Solicitor General argues, 'the market, mustered requisite scientifically long position drop active ceasing drug." interpreting most harmonious, comprehensive possible' purpose. U.S., 488, S.Ct., 178; see Article Bacto-Unidisk, 394 784, 798, 89 1410, 1418, 726. accordingly 505(d). Consequently, 35 virtue treated if, (B) force, (C) applicability turns 'covered' immediately longer drug,' ceased effective.25 36 argument draws support. mechanism once cease Indeed, 505(e) leads remains suspended. empowers whenever comes suggesting unsafe, interim. argument, recognized, superfluous. reasoning, (B)—i.e., safe—automatically (C). construction, therefore, offends well-settled parts statute, possible, e.G., Jarecki G. D. Searle 367 307, 81 1579, 1582, 859; Ginsberg Sons Popkin, 285 204, 208, 322, 323, 704. accorded operative limit blanket regulation.26 38 Except modification status, 39 Judgment 40 BRENNAN took part consideration decision 41 STEWART APPENDIX TO OPINION OF THE COURT Title 130.12(a)(5) provides: 42 (ii) following developed antibiotic 43 plan protocol report following: 44 objectives 45 selection subjects that— 46 (i) Provides assurance suitable purposes diagnostic criteria condition diagnosed, confirmatory laboratory tests appropriate, and, prophylactic agents, susceptibility exposure prophylaxis desired. 47 Assigns groups bias. 48 (iii) Assures comparability control variables, age, sex, severity, duration disease, 49 Explains recording results, variables measured, quantitation, assessment subject's response, bias observer. 50 (4) fashion quantitative evaluation. nature stated explanation observers analysts Level 'blinding,' used, documented. Geneally, types recognized: treatment: Where measurements placebo negligible, comparable untreated patients. Placebo control: Comparison entity inactive preparation resemble far possible. 53 Active An regimen therapy comparison, administration patient. 54 (iv) Historical certain circumstances, diseases high predictable mortality (acute leukemia childhood), signs symptoms severity (fever infections), prophylaxis, morbidity predictable, compared quantitatively historically adequately documented natural disease patients populations (therapeutic, diagnostic, prophylactic) established. 55 (5) 56 Provided, above waived whole part, completed Director Bureau Drugs specific investigation; petition waiver adversely affected reasonably alternative be, been, followed, yielded shall set concisely provision sought, procedures, any, employed, obtained, notwithstanding nonconformance requested. 57 standardized 58 Uncontrolled regarding yield valuable merits listed here, exception controls. considered. 59 POWELL, concurring part. 60 N Dec. Immigration Nationality Decisions concur Part Court's opinion, disposes issues raised (No. 72—414). I, addresses 394), state briefly sense conclusion. 61 Insofar today sustains below 'a fact' ultimate 130.14(b), am accord. presentation investigations,' 355(d), Commission's 130.12(a)(5). record, implications regulations—as construed applied case—are compatible Due Process Clause.1 squarely complied resolution unnecessary decision. 62 Were reach issues, serious specifications coupled restrictive beyond frustrate congressional 'opportunity where, case, construes medical profession decades, significant volume opinions qualifications questioned.2 63 important complex future briefed fully Amendments (Harris-Kefauver Act), 780, amending 301 seq. originally Agriculture, functions assigned Department Welfare (HEW), HEW delegated responsibilities 2.120. 'Substantial mean 107(c)(2) (c)(3)(B), 788, note 321. Fed.Reg. 9426. recently adopted manner Efficacy Study Implementation Notices Opportunity Hearing identical, related, pioneer 23185, adding 130.40 CFR. 7251, 130.14. 355(e), part: shall, applicant, him thereof n. supra. Appendix opinion. Subjects chosen 'suitable study,' terms 'pertinent 130.12(a)(5)(ii)(a)(2). Upjohn Finch, 422 944 (CA6); Manufacturers Association Richardson, 318 F.Supp. (D.C.Del.). enforcing September 19, 1969, 14596, ground 307 858 reissued current May 8, 1970. 7251. Hearings 1552 Subcommittee Antitrust Monopoly Committee Judiciary, 87th Cong., 1st Sess., pt. 1, Pages 195, 282, 411—412. Much aspect background enlightening detail Judge Latchum Assn. F.Supp., 306 S.Rep.No.1744, 2, Page U.S.Code Cong. Admin.News 2884. applies, precise. example, '(a) methods.' 130.12(a)(5)(ii)(a)(5). mere reading indicate totally deficient regard. precise, call subjective controlled. 130.12(a)(5)(ii)(a)(2)(i) study.' (Emphasis added.) 'adequate' 'suitable' lend themselves clear-cut possible tell met. comply Rules Civil party moving fact. 157, 1608, 142. reviews 556 557 'otherwise 706(2)(E). concerned involves statute. Pfizer, Incorporated 536, 546—547 (CA2). 1939 Annual 1941 Security Agency (1938—1952); (1953—1962). (hew means— '(1) animal feed bearing containing drug) composition ans thereof, chapter 30, 1906, representations use; '(2) conditions, not, otherwise conditions.' 'In date, (A) day.' follows Hearings, 14. 107(c)(2), 'An 505(b) date Act.' goes, 107(c)(2). shares thread 107(c)(4)—that persuasive offered upset transitionary (c)(3). affirmatively approving protected Without provision, continued 8; H.R.Rep.No.2464, 12; H.R.Rep.No.2526, Sess. 22—23; renders nugatory defeats that, class, consist primarily over-the-counter although universal old, ingredients came Fuentes Shevin, 407 67, 80, 1983, 1994, (1972), cited therein. question, adopt reasonable applied, property elementary doubt, language impose bar professions belief determinative arbitrary withholding action, especially vested official acts capacity, specifically two-fold: accordance process, utility effectiveness; retain efficacious. understandable zeal former, overlook proprietor protecting prevention, illness.

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