# Cooper Laboratories, Inc. v. Commissioner, Federal Food and Drug Administration

> Court of Appeals for the D.C. Circuit · June 26, 1974 · 501 F.2d 772

URL: https://www.frixlaw.com/law-library/cases/9460922

## Case

- **Full name:** COOPER LABORATORIES, INC., Petitioner, v. COMMISSIONER, FEDERAL FOOD AND DRUG ADMINISTRATION, Respondent
- **Court:** Court of Appeals for the D.C. Circuit
- **Decided:** June 26, 1974
- **Citations:** 501 F.2d 772; 163 U.S. App. D.C. 212; 1974 U.S. App. LEXIS 7947
- **Precedential status:** Published
- **Opinion:** Dissent by Leventhal
- **Judges:** Wright, Leventhal, Matthews
- **Cited by:** 20 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/9460922

## How later opinions describe it (automated extraction)

- rejecting argument that controlled tests are impossible for drug designed to relieve pain

## Opinion text

LEVENTHAL, Circuit Judge,
dissenting:
This case gives the court its first opportunity to consider and apply the principles announced by the Supreme Court in Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609 , 93 S.Ct. 2469 , 37 L.Ed.2d 207 (1973). Because I believe the majority has applied Hynson improperly and has misperceived the nature of the relationship between this court and the FDA, I respectfully dissent. I take this course reluctantly, being wary that the claim advanced by petitioners may reflect a legal tactic more than a genuine controversy posed by a member of a regulated industry. However, I think the larger view of the public interest requires a ruling on the inadequacy of the FDA’s approach. If petitioners have gained a litigating advantage, it will be only temporary, for if the FDA does its task correctly, it can proceed expeditiously and effectively in the public interest without undue sacrifice of interests of regulated companies.
I. GENERAL DISCUSSION OF ROLE OF COURTS ON FDA WITHDRAWAL OR APPROVAL OF NDA’s
In the Drug Amendments of 1962, 76 Stat. 780 , amending 21 U.S.C. § 301 et seq., Congress required the FDA to withdraw its approval of all ineffective prescription drugs. Because it required re-evaluation of the large number of approved drugs already in the market, the statute placed a heavy burden on the FDA. To discharge this burden, the agency has evolved certain innovative procedures, principal among which is the summary judgment technique validated in Hynson. That ruling is not to be applied grudgingly, for it is both sound in concept and necessary in practical administration. Yet Hynson imposes a limitation on FDA use of summary procedures : the agency must act on the basis of particularized regulations, and it cannot deny a hearing for failure to comply with qualitative regulatory standards that so lack clear-cut definition that it cannot be ascertained from the face of a study whether the standard has been met. See 412 U.S. at 620 , 621 n. 17, 93 S.Ct. at 2479 n. 17. The significance of this limitation is apparent from the statutory and administrative context of the summary judgment procedure.
A. Statutory Background.
The Food and Drug Act requires “due notice and opportunity for hearing to the applicant” before FDA can withdraw approval of an existing New Drug *788 Application. 1 However, no evidentiary hearing need be held unless the manufacturer can demonstrate it would have a purpose. A hearing may be denied to an applicant who, having been given notice of a proposed withdrawal of and NDA for an allegedly ineffective drug, fails to present, in the words of the FDA regulation, a “well-organized and full factual analysis of the clinical and other investigational data he is prepared to prove in support of his opposition”— and his claim of effectiveness. See Hynson, 412 U.S. at 620 , 93 S.Ct. at 2478 .
The Supreme Court has predicated latitude in summary dispositions upon the FDA’s having first issued clear-cut regulations that particularize the statutory standards. Regulations defining the content of “adequate and well-controlled studies” are necessary for the “due notice” to drug manufacturers of what the manufacturers must provide to demonstrate that there are matters requiring a hearing. Absent such “due notice” to inform the manufacturers’ submissions, the agency cannot provide for “barring at the threshold those who neither measure up [to the statutory standards] nor show reasons why in the public interest the rule should be waived.” FPC v. Texaco, 377 U.S. 33, 39 , 84 S.Ct. 1105 , 12 L.Ed.2d 112 (1964), quoted in Hynson, 412 U.S. at 620 , 93 S.Ct. at 2478 .
Even with particularized regulations, the FDA cannot deny a hearing for failure to comply with the regulations unless the study or analysis proffered is “totally deficient” in compliance. Hyn-son, 412 U.S. at 621 n. 17, 93 S.Ct. 2479 n. 17.
B. Role of Reviewing Court
The Supreme Court charges the courts of appeals to monitor the FDA’s application of its regulations to deny a hearing. It seems plain, as the FDA brief puts it, that the Supreme Court did not intend us to undertake a de novo review of the evidence upon which the Commission acted to deny a hearing. Certainly there is need to take into account the FDA’s expertise. 2 Indeed, it is often not possible to understand, much less apply, the drug law and regulations without the benefit of technical knowledge that is not part of this court’s working kit. 3
When the court is asked to review the substantive determination of an agency, the test that defines its review — both its supervisory aspect, and its obligation of restraint — calls for affirmance if the agency’s determination has a reasonable basis and has not been shown to be arbitrary or capricious.
While the court of appeals does not engage in technical dialogue with the agency, it does ensure that the agency has followed procedures conducive to a full airing of technical issues, and has “genuinely engaged in reasoned decision-making.” See Greater Boston Television Corp. v. FCC, 143 U.S.App.D.C. 383, 393-394 , 444 F.2d 841, 851-852 (1970), cert. denied, 403 U.S. 923 , 91 S.Ct. 2229 , 2233, 29 L.Ed.2d 701 (1971). The requirement of reasoned decision-making is usually articulated for decisions rendered after an evidentiary hearing, but it also has vitality for the decision rendered without a hearing. Indeed, that decision requires reasons not only for the disposition of the matters under consideration, but also for the conclusion *789 that the applicant’s contrary position does not even present a genuine and substantial issue.
In its reviewing capacity the court is not to be hostile to the agency, but is rather to proceed in the context of a “partnership” between court and agency in furtherance of the public interest. 4 This is the model of the relationship envisioned in Hynson. In these drug efficacy cases the agency is permitted to adjudicate substantial rights in summary fashion, provided the court has assured itself the necessary preconditions exist: First, that the agency’s regulations — its “articulated standards” — are sufficiently clear-cut to provide the “due notice” needed for a summary disposition. Second, that the agency’s application of the regulations, and its determination that the study proffered as compliance is totally deficient, reflects “reasoned decision-making.”
II. PARTICULAR APPLICATION OF GENERAL PRINCIPLES: THE SUMMARY WITHDRAWAL OF APPROVAL OF THE NDA FOR PROTAMIDE
Examining Cooper’s submissions to the FDA and the FDA’s disposition of them, I do not feel that the agency’s summary disposition comports with Hynson. In affirming the FDA, the majority, in my view, has exceeded the bounds of a court’s role. To highlight my differences, I shall focus on the Baker study discussed in the majority opinion.
The matter before us is a new drug application for Protamide, for use with herpes zoster. In his study, “Use of Protamide in the Treatment of Herpes Zoster,” published in the Pennsylvania Medical Journal (63 Penn.Med.J. 697 (May, I960)), Dr. Baker obtained dramatic evidence of Protamide’s efficacy. Baker treated 44 patients suffering from herpes zoster, administering Pro-tamide to 34 of the patients (30 adults and 4 children) and vitamin B-12 to the remaining 10 (adults). Therapy began as soon after the onset of herpes zoster as possible — some patients having sought treatment with more advanced symptoms than others — and continued for five to sixteen days, varying with the severity of the infection, with follow-ups for six months. Baker found that 94% of the patients receiving Pro-tamide obtained “good to excellent” results, including symptom relief and shortening of the course of the infection. None of these patients suffered post-herpetic pain. By contrast, none of the control group receiving vitamin B-12 responded well to the therapy, and seven of the ten suffered some post-her-petic neuralgia. From these results, Baker concluded that Protamide had “marked therapeutic benefit” when administered prior to or at the time when lesions appeared in patients suffering from herpes zoster.
1. In dismissing the Baker study as “not well-controlled,” the FDA gives only two reasons for its finding: (1) “the size of the control group is statistically inadequate;” and (2) “there is no raw data provided upon which a comparison of the test and control groups can be made.” The first reason, as Judge Wright concludes, has no basis in current regulations, and therefore cannot trigger a summary disposition. This conclusion accords with the teaching of Hynson.
2. As to the second reason, the FDA rejected the Baker study because it lacks *790 raw data, even though existing regulations contain no requirement that a petitioner submit raw data as part of his study. Under Hynson this summary rejection is impermissible because it is not based upon a promulgated regulation. Petitioners point out that another study approved by the FDA as adequate and well-controlled (the Boundy study) was also lacking in “raw data.” Judge Wright acknowledges this, but in effect drafts a “raw data” requirement that contains an exception which would justify both FDA rulings. He asserts that a petitioner must either describe the selection process whereby test and control groups were formed, or must submit sufficient raw data to allow the agency to decide whether the test complies with its conception of an adequate and well-controlled investigation. The difficulty, however, is that FDA has not promulgated a particularized regulation containing the requirement developed by Judge Wright. And summary judgment is only proper, under Hynson, when the petitioner has failed to present material required by a regulation it was on notice to satisfy.
3. To remand to the FDA for compliance with the Hynson guidelines is not to “exalt form over substance,” as Judge Wright says, but is to insist on fair process. A court does not skimp fair process because of its view of the merits. We would all agree that if the issue were one of due process in a criminal trial, we would not skimp fair procedure merely because the evidence clearly showed the defendant was guilty. The values involved in an administrative agency proceeding are different, of course, but the need for process that is fair is too important to water down.
4. Judge Wright’s misapprehension of the judicial role is highlighted by his ruling — notwithstanding a total lack of any FDA comment on Baker’s use of vitamin B-12 as a control substance — that FDA’s Order “plainly implies disapproval” of that usage. The sole basis for this ruling is the FDA’s use of “disparaging” quotation marks around the word “control.”
This exercise reverses the roles of agencies and courts. It is the agency’s job to decide whether a study is adequate or not and, if not, to state the reasons. When there is no hearing, and the agency’s stated reasons are not satisfactory, a court cannot sustain an order by conjecturing about unstated inferences. Ultimately the court lacks the capacity to develop its own analysis concerning the adequacy of the study.
Thus, notwithstanding Judge Wright’s reconstruction, the FDA’s placing of “control” in quotation marks seems to me entirely consistent with the two reasons expressly given in the Order, statistical inadequacy (rejected by Judge Wright) and lack of raw data (discussed above).
There are good reasons why a court should confine itself to a review of the reasons the agency itself gives for the actions it takes. Agencies are weakened, not strengthened, if they can bypass their responsibilities and look to a sympathetic reviewing court to shoulder them. There is also the danger that the court’s inferences, and construction of regulations, will differ from the agency’s. When this happens, even clear-cut regulations become fuzzy, and their utility as “due notice” may be vitiated. Judge Wright’s treatment of vitamin B-12 brings us to this potential problem.
Judge Wright attributes to FDA a reason not stated in the Order, that B-12 was an inappropriate control, in view of the regulation stating, inter alia, that a control substance must be either “an inactive preparation” 5 or “[a]n effective regiment [sic] of therapy.” 6 Judge Wright concludes that vitamin B-12 fits neither description because Baker originally felt it might be somewhat helpful, a category different from those described in the regulation. Although Baker later decided that vitamin B-12 was in fact ineffective against herpes zoster, Judge Wright asserts that *791 “this limited experience hardly renders the substance a known inactive preparation. . . . ” But the regulations do not specify a requirement of prior knowledge of some specified experimental data on which to base the required designation of inactivity.
The dangers of judicial interjection are not mere word play. Indeed, it is my own intuition — for neither Judge Wright nor I have the material for a reasoned inference — that the FDA carefully avoided resting its decision on the ground that B-12 was an inadequate control within the meaning of the regulations cited by Judge Wright. The FDA may have been of the view that B-12 was an inactive preparation in present context, for all practical purposes, or it may have concluded that for study purposes it was not necessary to resolve whether B-12 was (a) inactive, as Baker finally concluded, or (b) helpful, as he at first premised, because the utility of B-12 as an adequate control was sufficiently established by the high probability that it was not a harmful substance.
Alternatively, the FDA may have concluded that any technical problems associated with use of a B-12 control could not fairly be used as the basis of decision because it was unlikely to account for the dramatic benefit shown by the Baker study in favor of petitioner’s product in comparison with B-12. The nature of the results may have a bearing on the adequacy of a study. The dramatic results obtained by Dr. James Lind with administration of citrus fruit to only two scurvy-ridden sailors, out of a group of twelve, established this classic medical study of the 1740’s. FDA’s silence may well betoken the view that use of a beneficial substance, though not strictly “inactive,” would not realistically undercut the validity of Baker’s experiment.
The natural question that occurs to me — and I must think about this without the benefit of any reasoning from the FDA — is why a study is plainly not “adequate,” is too insubstantial for serious consideration, merely because the “control” used is a preparation that may be generally productive of well being, even though it is neither an inert placebo nor an “effective regimen of therapy.” I don’t think this is the time or place to debate the validity of the FDA’s regulation as such, but I can see good reasons why the FDA would hesitate to lay it on the line in a case involving B-12.
I see particular problems for the FDA, in any rigidity concerning the requirement for an inert control substance, when the drug being tested is designed to relieve pain, as is Protamide, in view of striking analgesic effect assigned by authoritative medical research to placebos. A much-cited work reviewing pertinent studies concludes that in one-third of a patient population, a placebo will relieve severe pain as well as either morphine or aspirin, an impressive statistic, especially alongside the fact that one-fourth of that same population will obtain no relief from either the drug or the placebo. 7 To avoid misunderstanding, I am not suggesting that FDA must or should forgo attempts to ascertain the efficacy of purported analgesic drugs, or that the “placebo effect” necessarily vitiates the validity of the FDA regulation here in question. The point is that the methodological complexity of the various medical research issues involved in drug testing should make the courts hesitant in venturing judicial reconstruction of reasoning which FDA omitted, or in supposing, without benefit of any expertise, that the underlying principles of drug testing are so well-settled, widely known and agreed upon that the FDA’s conclusory statement of a deficiency reflects a pal *792 pable shortfall that does not merit a hearing of any kind.
5. In sum, I find no reason in the FDA’s Final Order rejecting the Baker study which satisfies the guidelines announced in Hynson. As to the case at hand, the FDA is not powerless to act; what is required is that it act after opportunity to explore the adequacy of Baker’s methodology. Even without a particularized regulation, the FDA can structure a hearing that requires petitioner to produce Baker’s raw data, and to offer evidence on the issue whether his study is “adequate and well-controlled.”
III. OPPORTUNITY FOR RESPONSIVE RECONSIDERATION
As a court, we are charged to oversee FDA’s use of a summary procedure so as to be responsive to the agency’s need for expedition, yet avoid deprivation of substantial rights without hearing. While we must defer substantially to the agency’s exercise of technical judgment, we must have assurance that the agency is following a procedure that guards against abusive use of its power, and assures full access and input.
In my view, modest changes in current FDA procedures would allow us to defer to agency expertise while receiving the assurance we require. These changes would also recognize the difficulty of constructing regulations particularized enough to meet the Hynson standard, yet broad enough to be generally applicable. As matters now stand, the FDA notifies an NDA holder that his product has been found “ineffective or possibly ineffective.” This notification is quite summary in nature, and is generally the product of a concise ultimate finding by the NAS-NRC review panel. Thereafter, the manufacturer must submit “substantial evidence” consisting of “adequate and well-controlled studies” in order to overcome the presumption of ineffectiveness established by the FDA and NAS-NRC findings. The FDA then responds to these studies with its final declaration. Often this is a bare conclusion that the submitted studies are not adequate and well-controlled, that no material issue of fact has been raised, and that a hearing is denied and approval of the NDA is withdrawn.
A central difficulty is that FDA is engaged in fleshing out general regulations with concrete applications. This is fair enough. What may not be fair is a system of particularization without hearings, letting applicants know after the fact that they were in default all along for failure to observe a requirement that had not yet been spelled out. And when FDA is administering regulations that are in some measure “imprecise,” “subjective,” or lacking in “clear-cut definition,” there are elements that militate against disposition without a hearing. Hynson, 412 U.S. at 421 n.17, 93 S.Ct. 2479 n. 17.
The first move toward untying the tangle could be taken if the FDA allowed the petitioners an opportunity for at least a written response to the determination that is now issued as the FDA’s final order, but which, under a change in procedure to cope with the problem, would become a proposed disposition. At that time, NDA holders would, for the first time, have the FDA’s declared approach for rejection of the study, and have a genuine opportunity to respond to that approach. Such a procedure would open up the process toward a reasoned decision based on fair opportunity for input. Perhaps petitioners could supplement the studies, say, by provision of raw data, if that were identified as a need. Or perhaps they could point out flaws in the FDA’s approach.
It may be that such a response by the applicant would lead FDA to schedule a hearing. This is not an unthinkable calamity. We are not discussing a situation where the applicant is relying merely on subjective presentations that amount in essence to mere “anecdotal evidence indicating that doctors ‘believe’ in the efficacy of a drug” — a submission that would confute the legislative *793 approach that mere “impressions or beliefs of physicians, no matter how fervently held, are treacherous.” 8 Such subjective presentations have no serious claim to consideration as substantial evidence of a controlled study. But when we come to what purport on their face to be studies with a control element, conducted by persons who have at least a prima facie claim to expertise, then we have a matter that calls for resolution after hearing. The “hearing” appropriate for such cases need not borrow the characteristics of conventional courtroom controversy, burdened with the impedimenta of the kind of arcane questions with which lawyers often bedevil expert witnesses. Marine Space Enclosures v. FMC, 137 U.S.App.D.C. 9 , 420 F.2d 577 (1969).
As Marine Space Enclosures points out, even when statutes contemplate an adjudicatory hearing baseline, a particular case may involve the kind of issue that calls for an oral argument rather than an evidentiary hearing 9 or for a legislative rather than an adjudicative hearing. 10 These comments are highly pertinent when what is at issue are technical questions of methodology. Indeed, in such a case the reality of technical dialogue and interchange of view can perhaps best be provided by an on the record conference-hearing procedure, modeled on conference discussions between lawyers and experts. 11 The law does not require a bog-down at the agency level, it seeks only an opportunity for reasonable give and take. If the hearing officer is worth his salt, he can keep counsel and experts to the business at hand in a straight-forward way.
If the applicant’s response to the proposed disposition, in the procedure outlined above, is thought by the FDA to be so palpably shallow as to permit the agency to take final action without any further proceeding, the agency would at least have the benefit of a more focused record which, hopefully, would foster reasoned findings in place of bare con-clusory statements. And there would be generated the kind of record that makes minimum judical review, without a de novo inquiry, a meaningful assurance.
In my view, there should be a remand to require that petitioners be given such an opportunity to make a presentation at the administrative level.
. Section 505(e), as amended, 21 U.S.C. § 355 (e), provides in relevant part:
“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
. See Pfizer, Inc. v. Richardson, 434 F.2d 536, 546-547 (2d Cir. 1970), cited in Hyn-son, 412 U.S. at 622 n. 19, 93 S.Ct. 2479 n. 19.
. See Bradley v. Weinberger, 483 F.2d 410 (1st Cir. 1973).
. See Greater Boston Television Corp. v. FCC, 143 U.S.App.D.C. at 393-394 , 444 F.2d at 851 -852:
The process thus combines judicial supervision with a salutary principle of judicial restraint, an awareness that agencies and courts together constitute a “partnership” in furtherance of the public interest, and are “collaborative instrumentalities of justice.” The court is in a real sense part of the total administrative process, and not a hostile stranger to the office of first instance. This collaborative spirit does not undercut, it rather underlines the court’s rigorous insistence on the need for conjunction of articulated standards and reflective findings, in furtherance of evenhanded application of law, rather than impermissible whim, improper influence, or misplaced zeal. (Footnotes omitted).
. 21 C.EYR. § 130.12(a) (5) (ii) (a) (4) (ii).
. 21 CJBYR. § 130.12(a) (5) (ii) (a) (4) (iii).
. H. Beecher, Measurement of Subjective Responses 65-72 (Oxford University Press, 1959). Beecher points out that experimental designs can and should take account of the “placebo effect,” but this court is certainly not the proper forum for a cíe novo consideration of experiment-design issues, or their imjdications for the Baker study.
. Hynson, supra, 412 U.S. at 619 , 93 S.Ct. at 2478 .
. 137 U.S.App.D.C. at 21 , 420 F.2d at 589 .
. Id. at 22, 420 F.2d at 590 ; see also Holm v. Hardin, 145 U.S.App.D.C. 347 , 449 F.2d 1009 (1971).
. American Airlines, Inc. v. CAB, 123 U.S.App.D.C. 310 , 316 n. 18, 359 F.2d 624 , 630 n. 18, cert. denied, 385 U.S. 843 , 87 S.Ct. 73 , 17 L.Ed.2d 75 (1966).

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Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/9460922. Public record. Not legal advice.