Plaintiff-appellee/cross-appellant Public Citizen Health Research Group ("Public Citizen") hereby opposes the motion of cross-appellees Food and Drug Administration ("FDA") and Hoechst Marion Roussel, Inc. ("HMR") for summary affirmance of the district court's decision denying Public Citizen access to information about an HMR experimental drug and denying Public Citizen's request for discovery. This motion should be denied because, as explained in detail below, the cross-appeal for which summary affirmance is sought raises issues central to the appeals filed by FDA and Schering Corporation ("Schering") which will be considered by a full merits panel, and is complex and thus, is not appropriate for summary consideration.
This case arises from a Freedom of Information Act ("FOIA") request for FDA records concerning experimental drugs that were being tested on humans as part of the FDA's Investigational New Drug Application ("IND") process. Public Citizen requested access to the safety and effectiveness data in INDs where the testing of the experimental drug was stopped because of health or safety concerns. HMR and Schering are sponsors of four of these experimental drugs and intervened in this case claiming that release of the records would cause them substantial competitive harm, even though human testing of the drugs was discontinued because the drugs posed unreasonable risks to the patients.
Based on a disclosure mandate in the Food, Drug, and Cosmetic Act ("FD&C Act") and agency regulations that require disclosure of safety and effectiveness data when a drug sponsor has abandoned its efforts to have an IND approved, the district court ordered release of information about the three Schering experimental drugs because Schering admitted it had no further plans to have its drugs approved for marketing in the United States. Public Citizen Health Research Group v. FDA, Civil Action No. 94-0018 (RCL), slip op. at 22-35 (D.D.C. March 11, 1998) (Public Citizen); 21 U.S.C. § 355(l)(1); 21 C.F.R. § 314.430(f)(1). The district court found that this disclosure mandate did not apply to HMR's IND because HMR claimed that it has not abandoned the pursuit of FDA approval for its drug, even though testing of the drug was stopped in 1990 and the drug application had been placed on inactive status for three years by the time cross-motions for summary judgment were filed. See Public Citizen, slip op. at 37-40. Moreover, the district court found that there would be substantial competitive harm to HMR from release of any information about its experimental drug, including even its name, and denied Public Citizen's request for discovery.
As demonstrated below, the motion for partial summary affirmance of this decision should be denied for two reasons. First, these cross-appeals present two questions of interpretation of a single statutory provision, and it would waste judicial resources for separate panels to decide these appeals in a piecemeal fashion. One is a question of first impression: What showing must FDA and a drug sponsor make in order to prevent disclosure of records concerning an abandoned drug application within the requirements of the FD&C Act? This Court will consider this question after full briefing and argument on FDA's and Schering's appeal (Nos. 98-5161, 98-5162). The related question, presented by this cross-appeal, is: What evidence is sufficient to show that a drug sponsor intends to continue development of an experimental drug when no work has been done to have a drug approved for several years? These two related questions should be considered at the same time by this Court when it reviews the language, history, and regulatory context of the statute.
Second, the district court erred when it granted defendants' motion for summary judgment on the HMR records. HMR's drug is currently being marketed in numerous countries abroad; therefore, as the district court recognized, competitors have access to substantial therapeutic and toxicological data on the drug in the published literature. However, the district court found that commercial harm was caused by release in the context of FDA's decision to prevent further testing of the drugs on patients. See Public Citizen, slip op. at 21-22. Although the fact of FDA's clinical hold would be of significant interest to the doctors prescribing and patients taking HMR's drug abroad and might reduce the use of the drug abroad, this is not the type of harm the law seeks to prevent.
Accordingly, this appeal is not appropriate for summary consideration, but should instead be heard in tandem with Schering's appeal.
A. The Regulatory and Statutory Framework
A new drug must be approved by the FDA before it may be marketed in the United States. See 21 U.S.C. § 355(a); 21 C.F.R. Part 314. The FDA will approve a new drug if, among other things, the drug has been shown to be safe and effective for its intended use on the basis of studies conducted in the laboratory, in animals, and in humans. See 21 U.S.C. § 355(d). Before the drug may be administered to humans, the sponsor must first submit an IND to the FDA. See 21 U.S.C. § 355(i).
The IND must include information about pharmacological and toxicological studies of the drug performed on laboratory animals or in vitro, on the basis of which the sponsor has concluded that it is reasonably safe to conduct the proposed studies on humans. See 21 C.F.R. § 312.23(a)(8). However, the FDA permits human testing to begin well before animal studies are concluded and evaluated to determine whether the drug poses long-term health problems. See Supplemental Declaration of Sidney M. Wolfe, M.D. ("Supp. Wolfe Dec."), filed June 10, 1997, ¶¶ 6-7; see also 62 Fed. Reg. 24319, 24320-22 (1997). As a result, human testing can be well underway when the animal tests reveal a serious health threat. When test results show that human subjects are or would be exposed to an unreasonable and significant risk of illness or injury, the testing is halted and an IND is placed on "clinical hold" by the FDA, 21 C.F.R. § 312.42(b)(1)(i), is terminated by the FDA, 21 C.F.R. § 312.44(b)(1)(i), or is withdrawn by the sponsor. 21 C.F.R. § 312.38(c).
Once health problems arise and when no work is being or will be done to have an IND approved, FDA regulations require the release of safety and effectiveness data to the public unless exceptional circumstances exist. See 21 C.F.R. § 314.340(f); Supplemental Declaration of Carolann W. Hooton ("Supp. Hooton Dec."), filed April 21, 1997, ¶ 16. The regulation recognizes that, under such circumstances, full safety and effectiveness reports will no longer be of competitive value to the drug's sponsor. See Id. As HMR's declarant aptly states, "[u]nder such circumstances, the [IND's] sponsor presumably no longer has any commercial interest in the drug and would not be harmed by a competitor's use of the information." Declaration of Elaine S. Waller ("Waller Dec."), filed April 18, 1997, ¶ 19. Congress codified FDA's regulations in 1984 as part of the Waxman-Hatch Amendments to the FD&C Act. See Public Citizen, slip op. at 6, 31-34; see also 21 U.S.C. § 355(l); Supp. Hooton Dec. ¶ 16.
This disclosure mandate serves the public interest in two important ways. First, it allows the public to scrutinize FDA's decisions concerning human testing of investigational drugs to ensure that the decisions are not based on faulty data or analyses. As FDA explained when it adopted its disclosure regulations in 1974, the policy of open disclosure "has, of course, properly encouraged closer public scrutiny of Food and Drug Administration actions, and thus has fostered greater public accountability of the agency." 39 Fed. Reg. 44602, 44602 (1974). Second, disclosure of the safety and effectiveness data decreases the likelihood that other drug companies will replicate potentially hazardous human testing. See Thomas O. McGarity & Sidney A. Shapiro, The Trade Secret Status of Health and Safety Testing Information: Reforming Agency Disclosure Policies, 93 Harv. L. Rev. 837, 840-48 (1980).
B. HMR's Experimental Drug
HMR's IND at issue in this case involves an antibiotic drug used primarily to treat serious infections, typically in hospitalized patients. See Waller Dec. ¶ 20. The drug has been approved for marketing in "numerous" countries around the world, Waller Dec. ¶ 22, but has not been approved in the United States because health and safety concerns stalled clinical testing. HMR filed the IND for the drug in mid-1987 so that HMR could begin clinical studies in the United States. Id. ¶ 20. While testing on humans began at various times in 1987, 1990, and 1991, FDA placed holds on the studies in response to concerns raised by results of foreign and domestic studies of the drug. Id. In 1992, FDA approved the initiation of four clinical studies to evaluate the pharmacokinetics/pharmacodynamics of the drug, but those studies never began. Id. ¶¶ 20-21. In June 1994, HMR requested that the IND be placed on inactive status. Id. ¶ 21. Since that time, the IND has remained on inactive status, but HMR claims that it is "actively considering whether and how to undertake reactivation of the IND and resumption of clinical studies with appropriate indications and dosing regimens." Id. ¶ 22.
C. The Decision Below
Public Citizen's FOIA request was made as part of its ongoing efforts to protect consumer health and safety. Declaration of Dr. Sidney M. Wolfe ("Wolfe Dec."), filed March 11, 1994, ¶ 4; Supp. Wolfe Dec. ¶¶ 3,6. Specifically, Public Citizen requested access to safety and effectiveness studies for all prescription drugs for which the clinical trials were discontinued because of a death or serious injury of patients or because of safety concerns arising from pre-clinical studies within a two year time frame. Access to the data will allow Public Citizen to review whether the FDA is adequately analyzing the data submitted in INDs before allowing human testing to begin and whether safety problems uncovered in clinical trials result in prompt cessation of those trials. Supp. Wolfe Dec. ¶ 8. FDA regulations, as expressly codified by Congress, require that such safety and effectiveness data be made public when no work is going to be undertaken to have the drug approved and no extraordinary circumstances exist. 21 C.F.R. § 314.430(f)(1); 21 U.S.C. § 355(l)(1).
To escape the strong disclosure mandate -- which exists independent of FOIA -- defendants argued below that the "extraordinary circumstances" standard is superfluous. Rather than point to any "extraordinary" circumstances that differentiate the competitive value of the data at issue in this case from the data concerning any other abandoned drug, FDA and Schering (but not HMR) argued that a showing of competitive commercial harm is sufficient to satisfy the "extraordinary circumstances" standard. The district court recognized that the case thus presented a question of first impression: Is the showing that must be made by the FDA and an intervenor-sponsor in order to avoid release of safety and effectiveness data more stringent in cases in which the IND has been abandoned? Put another way, does a showing under FOIA's Exemption 4 of substantial competitive harm to the drug's sponsor from release of an IND itself qualify as a showing of extraordinary circumstances? See Public Citizen, slip op. at 23-24.
The district court rejected defendants' argument, and found that "extraordinary circumstances" means just what it says -- out of the ordinary. Recognizing that "Congress has directly spoken to the precise question at issue," the district court found that the "FOIA exemption 4 standard of 'a likelihood of substantial competitive harm,' in order to preclude disclosure, without more, is not an extraordinary circumstance, as that term is understood under 21 U.S.C. § 355(l)." Id. at 34.
Because Schering conceded that it had abandoned the development of its three drugs but did not demonstrate that the situation it faces is somehow "extraordinary, uncommon or otherwise atypical of the situation faced by many (if not the majority) of sponsors of INDs when no work is being done or will be done to have that sponsor's application approved," the district court ordered release of the Schering INDs. Id. at 35. FDA and Schering have appealed that decision and, thus, the meaning of "extraordinary circumstances" will be fully briefed and argued before this Court.
For its part, HMR asserted below that it had not abandoned the pursuit of FDA approval for its drug, even though the IND had been on inactive status for three years and HMR had taken no steps with the FDA to resume the approval process. In response, Public Citizen argued that HMR's mere declaration in an affidavit that an IND has not been abandoned is insufficient and that the Court should require evidence in the form of concrete action taken by a sponsor to demonstrate that an IND has not been abandoned. The district court, however, relied on HMR's bare-bones declaration of non-abandonment, and found that the disclosure requirement in 21 U.S.C. § 355(l) was not triggered. Id. at 40. Thus, this cross-appeal raises the question of what showing FDA and drug sponsors must make to demonstrate that "no work is being taken or will be undertaken to have the application approved" before the statutory "extraordinary circumstances" exception kicks in -- a question that is appropriately considered at the same time that this Court hears argument and briefing on the meaning of "extraordinary circumstances."
Moreover, even if the disclosure statute does not apply to the HMR records, this cross-appeal raises another important question deserving of full briefing and argument: When testing of a drug in the United States has been stopped because of safety concerns, but is being marketed in numerous countries abroad, does FOIA Exemption 4 allow FDA to refuse to release even the name of the drug to the public? As demonstrated below, Public Citizen has strong arguments that the district court was wrong in deciding to withhold even the name of HMR's drug, and thus, this appeal should not be resolved in a summary way.
The motion for partial summary affirmance should be denied because the issues presented in this cross-appeal are relevant to consideration of an issue of first impression and are intertwined with interpretive questions involving the same provision of a law that will be presented to a full merits panel. This Court has admonished that "parties should avoid requesting summary disposition of issues of first impression for the Court." Handbook of Practice and Internal Procedures, United States Court of Appeals for the District of Columbia Circuit, at 75. Moreover, a party seeking summary disposition "bears the heavy burden of establishing that the merits of his case are so clear that expedited action is justified." Taxpayers Watchdog, Inc. v. Stanley, 819 F.2d 294, 297 (D.C. Cir. 1987). To affirm an order of the district court summarily, this Court must conclude that "plenary briefing, oral argument, and the traditional collegiality of the decisional process would not affect [the court's] decision.'" Cascade Broadcasting Group. Lt. v. FCC, 822 F.2d 1172, 1174 (D.C. Cir. 1987)(citation omitted). Defendants' motion falls well short of these requirements.
I. SUMMARY AFFIRMANCE SHOULD BE DENIED BECAUSE THE ISSUES ARE DIRECTLY RELATED TO A QUESTION OF FIRST IMPRESSION, AND RAISE INTERPRETIVE QUESTIONS INVOLVING THE SAME PROVISION OF A LAW THAT WILL BE CONSIDERED BY A FULL MERITS PANEL.
FDA and HMR attempt to separate the issues raised by the district court's order regarding the HMR records from those raised regarding the Schering records. Yet, both sets of records were responsive to Public Citizen's request for safety and effectiveness information about experimental drugs where the clinical testing was stopped because of risks to the patients. Congress and FDA require the release of such information, unless extraordinary circumstances are shown. This Court will be hearing Schering and FDA's appeal of the district court's decision on the meaning of "extraordinary circumstances." If this statutory disclosure policy is to have any effect, the courts must, in addition to following the district court's common-sense interpretation of "extraordinary circumstances," put the burden on FDA and drug sponsors to show concrete action that an experimental drug has not been abandoned.
The district court's uncritical acceptance of HMR's claims of non-abandonment provides a blueprint to drug companies on how to bury information about drug testing that has gone awry and endangered patients. The opinion allows companies to sustain claims of substantial competitive harm by making highly generalized and entirely self-serving claims about potential exploitation of drugs, even where the clinical trials were terminated because of the risks to patients and where the INDs have been inactive for years. As the district court recognized, the decision "has created a situation in which sponsors of INDs will often endeavor not to terminate their applications solely out of fear that such terminations will trigger the mandatory disclosure of safety and effectiveness data." Public Citizen, slip op. at 35. Moreover, under the district court's decision, a claim of non-abandonment shifts the burden from the company to the requester, who must then prove a negative -- that is, that a company is not, in fact, wasting its money by trying to develop a drug that poses risks to patients who take it. This burden is intolerably high.(1)
In its opening submission, HMR's only support for its claim of non-abandonment was a statement that HMR is "actively considering whether and how to undertake reactivation of the IND." Waller Dec. ¶ 22 (emphasis added). To bolster its original meager declaration, HMR added with its reply that it "is considering the potential out-licensing of the drug for the U.S. market." Supp. Waller Dec. ¶ 3 (emphasis added). HMR did not point to any concrete steps it has taken toward reactivation or toward out-licensing the drug, nor did it claim to have even identified or begun discussions with potential licensees.
HMR did not substantiate its claims of future intentions for its IND at issue in this case. The last human trials on the drug appear to have been conducted in 1990, and at the time Public Citizen's motion for summary judgment was filed, the IND had been on formal inactive status -- at HMR's request -- for three years. Id. ¶¶ 20-21. By placing the IND on inactive status, HMR was relieved of the obligation of filing annual reports. 21 C.F.R. § 312.45(c); Waller Dec. ¶ 21. To reactivate the IND, HMR would need to (1) submit the proposed general investigational plan for the coming year and appropriate protocols to the FDA, and (2) wait 30 days before resuming clinical trials unless the FDA placed a clinical hold on the IND. 21 C.F.R. § 312.45(d). Yet HMR did not point to any concrete action it had taken to reactivate the IND, only that it was discussing reactivation. Waller Dec. ¶ 22. HMR was informed of this litigation well before September 20, 1996, see Supp. Hooton Dec. ¶¶ 36-38, but has taken no formal steps to reactivate the IND since then.
To ensure that the statutory disclosure mandate truly results in the disclosure of abandoned INDs in the majority of circumstances as Congress intended, drug sponsors must be required to substantiate claims of non-abandonment with objective evidence to show that work on an IND -- despite its formal inactive status -- will proceed. In light of the significant period of inactivity on the HMR IND and the lack of any concrete steps taken by the company to reactivate it, the district court's decision that HMR had made a sufficient showing of non-abandonment should be subject to full briefing and argument along with FDA's and Schering's appeal in Nos. 98-5161 and 98-5162 on the meaning of "extraordinary circumstances."
II. SUMMARY AFFIRMANCE SHOULD BE DENIED BECAUSE PLAINTIFF HAS STRONG ARGUMENTS THAT THE DISTRICT COURT ERRED IN DECIDING THAT FOIA EXEMPTION 4 PROTECTS INFORMATION INVOLVING DRUGS THAT POSE HEALTH OR SAFETY CONCERNS.
A. Even setting aside Public Citizen's arguments on the statutory and regulatory disclosure mandate for abandoned INDs, Public Citizen has strong arguments that the district court erred when it found that release of any information in HMR's IND -- including even the name of the drug -- would cause the company substantial competitive harm when the drug is already on the market abroad. HMR's IND involves a drug that is already on the market in "numerous" countries around the world. Waller Dec. ¶ 22. As the FDA recognizes, "[t]he marketing of a drug abroad or the publication of information about the drug constitutes public notice of the existence of the drug entity and the probability that the company will be considering marketing it," and in such circumstances existence of an IND will not be regarded as confidential. 39 Fed. Reg. at 44,633. Because defendants have not even released the name of the drug involved in HMR's IND, Public Citizen was unable to provide the district court with evidence of the extent of information in the public domain about the particular antibiotic drug involved here. Despite this lack of information, Public Citizen did provide the Court with evidence, as examples, of the comprehensive information available about two HMR antibiotic drugs marketed abroad but not marketed in the United States -- roxithromycin and rolitetracycline -- one of which may even be the subject of the IND at issue here. See Supp. Wolfe Dec. ¶ 17 & Exh. 3-5.
In light of the extensive information available about drugs marketed abroad, Public Citizen argued below that HMR's claim that it will suffer competitive injury from the release of any IND information related to a drug marketed elsewhere in the world is not credible. Information that has been publicly disseminated or is available from other sources cannot be withheld under exemption 4. See Anderson v. HHS, 907 F.2d 936, 952 (10th Cir. 1990); CNA Financial Corp. v. Donovan, 830 F.2d 1132, 1154 (D.C. Cir. 1987). Although the district court recognized that data and studies relating to HMR's drug are publicly available as a result of the drug being on the market abroad, the court found that it is the disclosure of the IND information in the context of an FDA clinical hold that constitutes valuable commercial information because disclosure would reveal that the particular drug had been the subject of an FDA clinical hold due to safety concerns. See Public Citizen, slip op. at 22.
Competitive harm refers to "harm flowing from the affirmative use of proprietary information by competitors," CNA Financial Corp., 830 F.2d at 1154, and not to adverse public reaction. Id. (no competitive harm in disclosure of affirmative action data, despite showing of customer and employee disgruntlement). Yet, HMR's sole concern appears to be that the public -- and its overseas market -- would learn that FDA has determined that its drug posed such significant health risks that testing of the drug had to be terminated. Release of the name of the drug does not provide competitors with any data not already available to them in the public domain, so FDA's statement that the release "would unfairly give competitors the ability to submit or use valuable data gathered at HMR expense in support of their own INDs and subsequent NDAs, prior to approval of HMR's drug," is patently incorrect. FDA's Opposition Brief at 14. Competitors already have the data at their disposal; release of the identity of the drug would more likely cause competitors to decide against submitting the data in support of their own drug applications.
The district court's decision is particularly disturbing in light of the fact that the drug is being marketed abroad. The notion that U.S. law forbids FDA from releasing information on its clinical holds and therefore that doctors prescribing the drug abroad and the patients taking it are not entitled to the information should not be endorsed. Exemption 4 was not intended to risk patients' health to protect corporate profits. See Public Citizen Health Research Group v. FDA, 704 F.2d 1280, 1291 n. 30 (D.C. Cir. 1983).
B. Finally, this appeal also challenges the district court's denial of Public Citizen's discovery requests. Public Citizen is entitled to discovery to demonstrate that HMR's claims of non-abandonment and of competitive injury are baseless. Discovery is necessary in FOIA cases, like this one, where competitive harm is alleged in order to determine whether the information withheld is maintained in secrecy, how commercially valuable it is, and whether it is truly the end product of either innovation or substantial effort. See Sears, Roebuck & Co. v. GSA, 553 F.2d 1378, 1382-83 (D.C. Cir. 1977) (discovery by interrogatories, oral depositions, and requests for admissions appropriate to determine existence and nature of adverse consequences to commercial interests); Silverberg v. HHS, No. 89-2743, slip op. at 2-3 (D.D.C. June 26, 1990) (permitting discovery, in Exemption 4 case, of responses by private drug-testing laboratories to agency's inquiry concerning whether their "performance test results" are customarily released to public).
As demonstrated in the Supplemental Declaration of Dr. Wolfe, limited discovery would allow Public Citizen to further support the illegitimacy of defendants' claims of substantial competitive harm. Supp. Wolfe Dec. ¶¶ 16, 18-21. For example, Public Citizen sought access to the name of the drug involved in HMR's IND, which would allow Public Citizen to demonstrate specifically the extent of safety and effectiveness information already publicly available about the drug. Public Citizen also sought access to information on the status of HMR's deliberations to reactivate its IND in order to determine whether HMR's claim that it has not abandoned its IND is substantiated by any concrete action. Finally, Public Citizen sought access to information from HMR to identify the particular IND studies that caused the testing on humans to be discontinued. This information is discoverable so that those studies that do reveal health and safety concerns may be released. See Teich v. FDA, 751 F. Supp. at 253 ("[t]he benefit of releasing this type of [health and safety] information far outstrips the negligible competitive harm that defendants allege.")
For the foregoing reasons, cross-appellee's motion for partial summary affirmance should be denied.
Lucinda A. Sikes
Public Citizen Litigation Group
Counsel for Public Citizen
Health Research Group
July 20, 1998