|UNITED STATES DISTRICT COURT
FOR THE DISTRICT OF COLUMBIA
PUBLIC CITIZEN HEALTH
FOOD AND DRUG ADMINISTRATION,
HOECHST MARION ROUSSEL, INC., and
Civil Action No. 94-0018
MEMORANDUM OF POINTS AND AUTHORITIES IN SUPPORT OF
PLAINTIFF'S CROSS-MOTION FOR SUMMARY JUDGMENT
AND IN OPPOSITION TO DEFENDANT'S AND DEFENDANT-INTERVENORS'
MOTION FOR SUMMARY JUDGMENT
In this action, Public Citizen Health Research Group ("HRG") seeks access under the Freedom of Information Act ("FOIA"), 5 U.S.C. § 552, to Food and Drug Administration ("FDA") records concerning four experimental drugs. These four drugs were being tested on humans as part of the FDA's Investigational New Drug Application ("IND") process, but the testing of each drug was stopped because of health or safety concerns. In circumstances such as those presented here, FDA regulations, as expressly codified by Congress, require that safety and effectiveness data be released to the 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).
Based on the FDA's disclosure policy, HRG requested the data from the testing of the four experimental drugs in order to review how well the IND process safeguards patient health. Before testing a new drug on human subjects, a drug's sponsor must submit an INDto the FDA. An IND contains the results of laboratory and animal tests (pre-clinical testing) as well as the plans for and results from the testing in human subjects (clinical testing). See 21 U.S.C. § 355(i); 21 C.F.R. Part 312.
Defendant-intervenor Schering Corporation ("Schering") is the sponsor of three of the drugs, while defendant-intervenor Hoechst Marion Roussel ("HMR") is the sponsor of the other drug at issue in this case. Both companies claim that release of the requested records will cause them substantial competitive harm, notwithstanding the fact that human testing of the drugs was discontinued because the drugs posed unreasonable risks to the patients.
Schering concedes that it has abandoned the development of its three drugs. And Schering does not point to any "extraordinary" circumstances that differentiate the competitive value of the data at issue here from the data concerning any other abandoned drug. Because FDA regulations require the release of the requested data in such circumstances, plaintiff's motion for summary judgment as to the Schering data should be granted.
For its part, HMR asserts that it has not abandoned the pursuit of FDA approval for its drug, even though the IND has been on inactive status for three years. A company may not shoulder its burden of showing substantial competitive harm by making highlygeneralized and entirely self-serving claims about potential exploitation of drugs. Moreover, HMR's IND involves an antibiotic drug that is currently being marketed abroad. Yet HMR asserts that no information -- including even the drug's name -- may be released, even though once a drug is on the market in other countries, competitors have access to substantial therapeutic and toxicological data on the drug in the published literature. In light of the information that is already publicly available, release of the IND data could not possibly cause competitive harm to HMR. For that reason, plaintiff's motion for summary judgment as to the HMR data should be granted as well.
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 grant approval of 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. 21 U.S.C. 355(d). Before the drug may be administered to humans, the sponsor must first submit an IND to the FDA. 21 U.S.C. § 355(i).
The IND must include information about pharmacological and toxicological studies of the drug involving 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. 21 C.F.R. § 312.23(a)(8). However, the FDA permits human testing tobegin well before animal studies are concluded and evaluated to determine whether the drug poses long-term health problems. 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, as this case makes clear, 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. 21 C.F.R. § 314.340(f); Supplemental Declaration of Carolann W. Hooton ("Supp. Hooton Dec."), filed April 21, 1997, ¶ 16. The regulation is designed in recognition that under such circumstances, full safety and effectiveness reports will no longer be of competitive value to the drug's sponsor. Id. As defendant-intervenor HMR's declarant aptly describes, "[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 ofthe Waxman-Hatch Amendments to the Federal Food, Drug, and Cosmetic Act ("FD&C Act"). 21 U.S.C. § 355(l); Supp. Hooton Dec. ¶ 16.
The FDA's disclosure policy on abandoned INDs serves the public interest in two important ways. Supp. Wolfe Dec. ¶ 11. 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. Id. As FDA explained when it adopted its disclosure regulations in 1974, the new 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. Supp. Wolfe Dec. ¶ 11.
HRG's FOIA Request
Plaintiff's FOIA request was made as part of HRG's 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. Since its founding 25 years ago, HRG has actively monitored the activities of the FDA and has been particularly concerned about the safety of drugs, both on the market and in clinical testing. Indeed, in May 1973, HRG filed a petition with the FDA for new regulations on human drug experiments, urging FDA to require the completion of chronic animal tests before human tests are initiated and to require adequatefollow-up of patients that underwent testing. Supp. Wolfe Dec. ¶ 6 & Exh. 1. The petition was denied.
HRG again became alarmed with the FDA's monitoring of pre- clinical and clinical studies after the tragedy involving the drug fialuridine ("FIAU"). The clinical trials relating to FIAU were discontinued in June 1993 because of irreversible liver damage to the participants in one such trial, resulting in the deaths of five patients. HRG's review of the tragic experience with FIAU found clear, substantial, and early evidence of both animal and human hepatotoxicity with FIAU, and a cover-up of data on liver toxicity by Eli Lilly, Inc., the licensee of the drug. HRG submitted a FOIA request for the records concerning pre-clinical and clinical studies involving FIAU, and at the same time submitted the FOIA request at issue in this case in order to review whether the IND process is safeguarding patient health with respect to other investigational drugs. Specifically, HRG 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. The request was limited to drugs whose clinical trials were stopped between January 1, 1990 and the date of the request, July 12, 1993. Def. Exh. A. Access to the data will allow HRG to conduct a review of 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.
In response to plaintiff's FOIA request, FDA identified 230 INDs that were discontinued during the designated time frame, and with respect to which safety concerns had been raised during their clinical trials. Although the FDA claimed that HRG had failed to reasonably describe the records sought and moved to dismiss this action on that basis, this Court denied the government's motion and ordered the parties to reach an agreement on the search to be conducted. Order, February 9, 1996. In accordance with an agreed- upon process and timetable, the FDA identified 14 of the 230 IND files as responsive to HRG's FOIA request. Supp. Hooton Dec. ¶ 35. However, according to the FDA, none of the documents in the 14 INDs could be released to HRG. Supp. Hooton Dec. ¶ 38 & Exh. 1. Despite FDA regulations specifically requiring the disclosure of safety and efficacy data in most situations -- like the ones involved here -- when the sponsors of drug applications have stopped their efforts to have the application approved, the FDA claimed that all information in all 14 INDs had to be withheld because release would cause competitive harm to the IND sponsors. Id.
As the date for the filing of defendants' dispositive motions approached, three of the six IND sponsors -- Abbott Laboratories, Astra U.S.A., and Wyeth-Ayerst -- withdrew their objections to disclosure of the responsive records in their INDs. Supp. Hooton Dec. ¶ 39. Therefore, FDA released those three INDs in their entirety, representing 13,626 pages of information on theinvestigational drugs' pre-clinical and clinical testing.
Moreover, plaintiff entered into settlement discussions with R.W. Johnson Pharmaceutical Research Institute, another of the IND sponsors, and as a result, obtained the vast majority of responsive records in that company's INDs. HRG no longer seeks access to R.W. Johnson's INDs.
Two IND sponsors, Schering and HMR, continue to object to the release of their INDs. Therefore, FDA will not disclose these records. Relying on FOIA Exemption 4, defendants claim that disclosure of the responsive records in the six INDs will cause substantial competitive harm to the drugs' sponsors.
Schering is the sponsor of three different investigational drugs involving five INDs. Schering has abandoned all five applications and concedes that it will not seek FDA approval of the drugs. However, Schering claims that because it continues to develop other drugs for similar purposes, release of information about the testing of the abandoned drugs will cause it substantial competitive harm.
1. INDs 35757, 34465, and 31911
Three related INDs involve an antifungal agent used to treat a particular type of fungus. Declaration of George H. Miller ("Miller Dec.") ¶ 10. Schering has withdrawn all three INDs, presumably because of health or safety concerns raised during the testing of the drugs. Although Schering is no longer developing the particular drug at issue in these three INDs, the company is currently testing a new compound that it developed based upon its experiences with the INDs. Id. ¶ 9.
2. IND 18113
IND 18113 involves a substance that is one of four isomers making up Labetalol, a prescription medication currently marketed by Schering and indicated for use in controlling blood pressure in cases of severe hypertension. Declaration of Ronald J. Garutti ("Garutti Dec.") ¶ 20. Schering has withdrawn the application, but objects to the release of any information in the IND, claiming that it would be of substantial assistance to any company developing other drugs -- alpha- or beta-blocking products -- or attempting to commercialize one or more of the three unmarketed isomers ofLabetalol. Schering's Brief at 3. Schering does not assert that the company itself plans to develop any of the other three isomers of Labetalol.
3. IND 30647
IND 30647 involves an asthma and allergy drug. Declaration of Francis Cuss ("Cuss Dec.") ¶ 10. Schering has withdrawn the application, but is developing related compounds. Schering originally believed that the anti-inflammatory action of the drug was due to its activity as a leukotrine inhibitor. Id. However, Schering is now developing compounds based on the theory that the drug in IND 30647 employed a different mechanism of action. Id. ¶ 19. The pre-clinical pharmacology studies and the protocols of clinical studies for this drug were released to HRG on May 30, 1997, but Schering claims that release of any other information in the IND will cause it competitive injury. From the released documents, it appears that testing of this drug on humans was stopped because of carcinogenicity concerns. Supp. Wolfe Dec. ¶ 15. Indeed, the FDA asked Schering to ensure that annual mammograms were conducted on those patients who had taken the drug. Id. ¶ 15 & Exh. 2. Yet because the safety and effectiveness data for this experimental drug is being withheld, HRG cannot determine whether the FDA adequately protected human subjects in these clinical trials. Id.
HMR's IND involves an antibiotic drug used primarily to treat serious infections, typically in hospitalized patients. Declaration of Elaine S. Waller ("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. The IND remains 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.
HMR's IND has been on inactive status for three years, and it appears that the last clinical trials on the drug were conducted in 1990. Id. ¶¶ 20-21. Nevertheless, HMR argues that the IND has not been abandoned and that disclosure of the IND will cause it substantial competitive harm. Id. ¶ 22. Specifically, HMR argues that disclosure would (1) allow competitors to develop their ownproducts earlier than otherwise possible, and (2) would divulge HMR drug research and development practices and commercial plans. HMR provides no explanation for why significant information about the drug is not already available to its competitors in light of the fact that the drug is already on the market abroad.
The FOIA was enacted to provide citizens the right to scrutinize the operations of their government. H.R. Rep. No. 1497, 89th Cong., 2d Sess. 6 (1966), reprinted in 1966 U.S. Code Cong. & Ad. News, 2418, 2423; Department of the Air Force v. Rose, 425 U.S. 352, 361 (1976). It requires an agency possessing the requested records to disclose them unless they are exempt under one of the Act's nine narrow exemptions. See 5 U.S.C. § 552(a). Department of Justice v. Tax Analysts, 492 U.S. 136, 150-51 (1989). Here, FDA, Schering, and HMR rely on exemption 4 as grounds for withholding the IND data. "Like all FOIA exemptions, exemption 4 is to be read narrowly in light of the dominant disclosure motif expressed in the statute." Washington Post v. HHS, 865 F.2d 320, 324 (D.C. Cir. 1989) (citations omitted). The burden of proof lies with the agency seeking to avoid disclosure to show that an exemption applies, National Parks and Conservation Ass'n v. Kleppe, 547 F.2d 673, 679 (D.C. Cir. 1976), and the reviewing court must make a de novo determination that the agency has correctly applied any claimed exemptions. See 5 U.S.C. § 552(a)(4)(B).
Under Rule 56(c) of the Federal Rules of Civil Procedure, summary judgment shall be granted in FOIA cases when it can beshown "that there is no genuine issue as to any material fact and that the moving party is entitled to a judgment as a matter of law." See Washington Post v. HHS, 865 F.2d 320, 325 (D.C. Cir. 1989); National Ass'n of Government Employees v. Campbell, 593 F.2d 1023, 1027 (D.C. Cir. 1978). The party opposing summary judgment cannot rest on conclusory allegations included in its pleadings, but rather must come forward with evidence "sufficient to establish the existence of an element essential to the party's case, and on which that party will bear the burden of proof at trial." Celotex Corp. v. Catrett, 477 U.S. 317, 322 (1986). Where the non-movant fails to provide any "significantly probative" evidence supporting any one of these elements, summary judgment is required. See Anderson v. Liberty Lobby, Inc., 477 U.S. 242, 249-50 (1986).
Here, as demonstrated below, the evidentiary record does not support either the FDA's or defendant-intervenors Schering's or HMR's contentions of non-disclosability of the INDs at issue in this case. Because defendants have failed to provide any "significantly probative" evidence, or any specific evidence at all, supporting their exemption claims, defendants' motions for summary judgment should be denied and plaintiff's motion for summary judgment should be granted.
DEFENDANTS HAVE FAILED TO SUSTAIN THEIR CLAIM THAT THE INVESTIGATIVE DRUG RECORDS ARE EXEMPT FROM DISCLOSURE UNDER EXEMPTION 4.
Exemption 4 of the FOIA exempts from disclosure only those documents which contain "trade secrets and commercial or financial information obtained from a person and privileged or confidential." 5 U.S.C. § 552(b)(4). Plaintiff does not dispute that the records at issue are "commercial" or that they were "obtained from a person," nor do the defendants claim that they are "privileged." Thus, the only issue for resolution by this Court is whether defendants have shown that the IND records related to the pre- clinical and clinical trials of the four investigative drugs at issue in this case are "confidential" within the meaning of the exemption.
As demonstrated below, defendants have not sustained their burden of showing that the INDs are entitled to exemption 4 protection. First, FDA's own regulations dictate the release of safety and effectiveness data when, as here, the sponsors of an IND have abandoned work on a particular application. Second, defendants have not sustained their burden of showing substantial competitive injury from release of the data in light of the particular circumstances surrounding the INDs at issue in this case.
A. FDA Regulations, As Later Codified By Congress, Require Release Of The INDs.
FDA regulations mandate disclosure of IND data when the sponsors of an IND have stopped work on a particular application. 21 C.F.R. § 314.430(f)(1) (1993). Generally, at that point, the sponsor retains no commercial interest in the compound andtherefore could not be harmed by a competitor's use of information in the application. Hooton Dec. ¶ 16; Waller Dec. ¶ 19.
Section 314.430(f) provides, in relevant part, that:
All safety and effectiveness data and information which have been submitted in an [new drug] application and which have not previously been disclosed to the public are available to the public, upon request, at the time any one of the following events occurs unless extraordinary circumstances are shown:
(1) No work is being or will be undertaken to have the application approved. . . .
Although this provision refers to a New Drug Application ("NDA"), the regulations make clear that information in IND files must be treated in precisely the same fashion as information in NDA files. 21 C.F.R. § 312.130(b) (availability for public disclosure of all data and information in an IND will be handled in accordance with provisions established for NDAs in § 314.430). Thus, FDA's own regulations recognize that when work on a particular IND has ceased, the safety and effectiveness data submitted in support of that application must, in the absence of "extraordinary circumstances," be disclosed to the public.
FDA's disclosure policy was codified by Congress in section 505(l) of the FD&C Act, 21 U.S.C. § 355(l), in 1984. Tracking closely FDA's disclosure regulation, the FD&C Act provides:
Safety and effectiveness data and information which have been submitted in an application under subsection (b) [i.e., an NDA] for a drug and which have not previously been disclosed to the public shall be made available to the public, upon request, unless extraordinary circumstances are shown--
(1) if no work is being or will be undertaken to have the application approved, . . . .
21 U.S.C. § 355(l).
The legislative history makes clear that Congress intended this provision to codify FDA's disclosure policy, and, therefore, as defendants acknowledge (FDA's Brief at 6-7; HMR's brief at 9 n.2), it should be applied equally to NDA and IND files, just as FDA has always done. See, e.g., H.R. Rep. No. 857, pt. 1, 98th Cong., 2d Sess. 35, reprinted in 1984 U.S. Code Cong. & Ad. News 2647, 2668 (section 505(l) is "merely a restatement of the current regulation," and "all terms" should be given "the same meaning that they have in the regulation"); id. at 36 (Congress did not intend to change other regulations regarding the "confidentiality of IND, NDA and master file safety and effectiveness information and data"); 130 Cong. Rec. 24425 (Sept. 6, 1984) (remarks of Rep. Waxman) (provision "statutorily codifies the current FDA regulation" and "adopts [the] same approach" as explained in the 1974 Federal Register preamble). Thus, under section 505(l), safety and effectiveness information in an IND is generally available to the public once the application has been abandoned.
1. Because Schering Has Abandoned Work on Its INDs, the Schering INDs Must Be Disclosed.
There is no dispute that Schering has stopped working on the five INDs at issue here, since all five have been withdrawn. Thus, under FDA regulations and the statutory provision, the safety and effectiveness data in the INDs must be released unless defendants can show that extraordinary circumstances exist.
Defendants have not shouldered this burden. Instead, they argue that (1) a successor drug to INDs 35757, 34465, and 31911 is being developed; (2) although Schering itself has no plans to develop them, a competitor may develop three different isomers of IND 18113; and (3) related compounds to IND 30647 are being developed. None of these circumstances are at all "extraordinary." It is quite normal for manufacturers to learn from work conducted on INDs that are abandoned and then to follow up on research with related drug development projects. Supp. Wolfe Dec. ¶ 12-13. Indeed, one benefit of the disclosure rule is to avoid forcing other researchers to travel down the same blind alleys that an abandoned IND sponsor discovered might endanger patients. Id. ¶ 11; see also 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).
Defendants' claim that the safety and efficacy data in theSchering INDs have significant applicability to other companies' development of competing products is no different from the claim that any other IND or NDA sponsor could make after abandoning a drug application. The defendants' argument, then, relies on anything but extraordinary circumstances; their argument can be made in every situation in which an IND is abandoned and, if adopted here, would swallow the FDA's rule in its entirety.
Indeed, similar arguments were made in 1974 in objecting to FDA's proposal to disclose IND safety and effectiveness data once an IND has been abandoned. 39 Fed. Reg. at 44637. The drug industry argued that abandonment was "irrelevant" to the issue of whether or not release of information would cause competitive harm. Id. Claims were made that "simply knowing a process does or does not work is worth hundreds of thousands of dollars and years of research to a competitor," that "drugs subject to termination may be found to have congeners which are safer and more effective, and that initial investigations may indicate a metabolite of the drug under study is the more active form and investigational efforts may be diverted to studies of the metabolite," and that "data in an investigational file may later become essential when related drugs are being investigated." Id. Despite these comments urging the agency not to adopt a disclosure presumption for abandoned INDs, FDA promulgated the rule, limiting confidentiality of abandoned INDs to genuinely "extraordinary circumstances." To accept defendants' argument here, would be tantamount to adopting the very position rejected by the agency in 1974.
Defendants must be able to demonstrate "extraordinary," or unusual, circumstances in order to prevent disclosure. As the FDA explained when it promulgated its disclosure policy, the party opposing disclosure bears a heavy burden of demonstrating unusual circumstances based on the particular facts of the case that overcome the presumption of disclosure:
[T]his type of provision creates a strong presumption of disclosure and requires any person who believes that a specific record falling within the rule should not be disclosed bears the burden of overcoming that presumption by showing unusual circumstances that justify nondisclosure. Because it is impossible to predict what facts would be sufficient to satisfy this burden, . . . this type of provision will be administered on the basis of the facts shown in each case.
39 Fed. Reg. 44,602, 44,603 (1974) (promulgation of FDA's FOIA regulations).
Accordingly, unless FDA and Schering demonstrate that extraordinary circumstances exist, the safety and effectiveness data from the Schering INDs must be publicly disclosed.
2. HMR Has Not Sustained Its Burden Of Demonstrating That Its IND Has Not Been Abandoned.
Recognizing that an abandoned IND is subject to publicdisclosure, see HMR's Brief at 9, HMR claims that it has not abandoned its inactive IND, but is "actively considering whether and how to undertake reactivation of the IND." Waller Dec. ¶ 22. And because the agency has "no reason to challenge the validity of the HMR's assertion of its intentions," FDA accepts HMR's claims and has withheld disclosure of HMR's IND on that ground. Supp. Hooton Dec. ¶ 46.
The FDA's uncritical acceptance of HMR's claim clearly violates FDA's own policy that "[w]here the issue [of future intentions] is in doubt, the Food and Drug Administration will require submission of further information from the person who submitted the IND. Any statement relating to the future intentions of that person with respect to the IND would be subject to the False Reports to the Government Act, 18 U.S.C. 1001." 39 Fed. Reg. at 44634; see also 37 Fed. Reg. 9128, 9130 (1972) ("Disclosure or nondisclosure of such [safety and effectiveness] data must depend upon the legal status of the product or ingredient as determined by FDA and not as determined by a manufacturer or a competitor, since FDA is not bound by anyone else's determination of that legal status.") The FDA's policy of requiring substantiation for claims of future development intentions, though disregarded here, is a sensible one. Otherwise, a drug sponsor can always claim that an application has not been abandoned, because to admit abandonment would mean disclosure of safety and effectiveness data -- information that, while not commercially valuable, may show, for example, that a sponsor did not adequately follow up on indicationsof adverse reactions, or may simply be embarrassing. Unless sponsors are required to substantiate their claims that an application has not been abandoned -- and to do so in a formal way -- FDA's regulations requiring disclosure in such circumstances would be meaningless. 21 C.F.R. § 314.430(f), § 312.130(b). Thus, to ensure that FDA's disclosure policy truly results in the disclosure of abandoned INDs in the majority of circumstances, drug sponsors must be required to substantiate claims of nonabandonment with objective evidence to show that work on an inactive IND -- despite its formal status -- will proceed.
HMR has not substantiated 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 the IND has 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 has not pointed to any concrete action it has taken to reactivate the IND, only that it is discussing reactivation. Id. ¶ 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 in the more than eight months since then. In light of thesignificant period of inactivity on the HMR IND and the lack of any concrete steps taken by the company to reactivate it, HMR's claim that the IND has not been abandoned is not credible. Accordingly, the safety and effectiveness data from the HMR IND should be publicly disclosed pursuant to FDA regulations as codified by Congress, unless HMR demonstrates that extraordinary circumstances exist.
B. Defendants Have Not Sustained Their Burden of Showing How Release Of Information In INDs Involving Drugs That Pose Health Or Safety Concerns Will Cause Schering or HMR Substantial Competitive Injury.
As demonstrated above, the INDs at issue in this case must be released based on the disclosure provisions of the FD&C Act and FDA regulations. See 21 U.S.C. § 355(l)(1); 21 C.F.R. § 314.430(f)(1). Congress and the FDA have already made the determination that abandoned INDs do not deserve exemption 4 protection except in extraordinary circumstances -- circumstances not presented here. Moreover, even apart from the statutory disclosure mandate, defendants have not sustained their burden of showing that the records are "confidential" within the meaning of exemption 4.
To be considered "confidential" under exemption 4, the agency must show that disclosure of information "is likely to cause substantial harm to the competitive position of the person from whom the information was obtained." National Parks and Conservation Ass'n v. Morton, 498 F.2d 765, 770 (D.C. Cir. 1974); see also Critical Mass Energy Project v. NRC, 975 F.2d 871, 880 (D.C. Cir. 1992) (en banc). In order to demonstrate the likelihood of substantial competitive harm, the agency must (1) show that thesubmitter faces actual competition and (2) demonstrate with specific and direct evidence the likely consequences of disclosure. Gulf & Western Industries v. U.S., 615 F.2d 527, 530 (D.C. Cir. 1979); National Parks, 547 F.2d at 679. While the agency "need not conduct a sophisticated economic analysis of the likely effects of disclosure," it cannot rest on "conclusory and generalized allegations of substantial competitive harm." Public Citizen I, 704 F.2d at 1291; see also Hercules, Inc. v. Marsh, 839 F.2d 1027, 1030 (4th Cir. 1988) (contractor's claims regarding competitive injury rejected on grounds they were "entirely conclusive or speculative"). The requirement for specific and direct evidence ensures that the agency has satisfied its burden of showing that nondisclosure is proper:
Conclusory and generalized allegations are indeed unacceptable as a means of sustaining the burden of nondisclosure under the FOIA, since such allegations necessarily elude the beneficial scrutiny of adversary proceedings . . . and generally frustrate the fair assertion of rights under the Act.
National Parks, 547 F.2d at 680.
As demonstrated below, the defendants have not sustained their claim of substantial competitive injury with specific and direct evidence.
1. Schering Has Not Sustained Its Burden Of Showing How Release Of Information In Abandoned INDs Will Cause It Substantial Competitive Injury.
The Schering IND data should be released because Schering and the FDA have failed to sustain their burden of showing how release of information about investigational drugs that have been abandoned for health or safety concerns will result in substantialcompetitive injury to Schering.
Defendants' principal argument is that, if any of the withheld data is released, competitors will gain advantage in their efforts to develop competing products because they will be able to use the data to focus and direct their own research into other drugs without any of the associated development costs. FDA's Brief at 15-18; Schering's Brief at 11-18. To the extent that this claim is valid, it would also be valid for any drug application sponsor who abandons a drug application or whose drug is eligible for generic competition. Yet Congress has determined that, in these circumstances, safety and effectiveness data lack continuing commercial value and should be publicly disclosed except in extraordinary circumstances. 21 U.S.C. § 355(l). Schering has made no showing that its IND data are somehow more commercially valuable than the safety and effectiveness data produced by any other company, and the facts here -- that all INDs were abandoned for health or safety reasons -- strongly suggest that just the opposite is true.
Each of Schering's INDs were withdrawn because of health or safety concerns raised during the clinical or pre-clinical studies. Defendants' argument that the studies in these INDs, which demonstrate the drugs' toxicity, should be kept confidential in order to prevent competitors from gaining an unfair advantage is particularly disturbing because nondisclosure may well lead other manufacturers to put additional patients at risk. Indeed, defendants' claim here is indistinguishable from Dow Corning'sclaim that data submitted to the FDA concerning silicone breast implants should be withheld under exemption 4. In rejecting that claim, this Court held that:
[D]isclosure of the positive tests, which demonstrate that a product poses a danger when used in a certain manner, is unquestionably in the public interest. To argue that this type of information is confidential suggests that, in order to protect whatever marginal commercial benefit Dow Corning may get from having independently discovered certain risks, other manufacturers be permitted to blindly put out potentially damaging products. Certainly Dow Corning, as a good citizen, would not risk the public health in this manner. The benefit of releasing this type of information far outstrips the negligible competitive harm that defendants allege.
Teich v. FDA, 751 F. Supp. 243, 253 (D.D.C. 1990). Similarly, information in the Schering INDs should be released.
Defendants rely on Public Citizen Health Research Group v. FDA, No. 94-0017 (D.D.C. April 26, 1995) (Public Citizen II) (copy attached to FDA's brief) to support their arguments that Schering will suffer competitive injury if the IND data is released. However, in Public Citizen II, the sponsor of the IND there had not abandoned work on the IND. Slip op. at 11. Thus, the Court relied on the sponsor's declaration that it had not abandoned its IND to find that (1) FDA regulations requiring release of safety and effectiveness data when an IND has been abandoned did not apply; and (2) release of the information would cause the drug's sponsor substantial competitive harm because the company intended to develop the drug for treatment of the same or other diseases. Slip op. at 12. In contrast here, Schering has abandoned its INDs, and any related development efforts are limited to other compounds, not the compounds studied in the IND. FDA's Brief at 16-17; Schering'sBrief at 2-3, 12-14, 15-16; Miller Dec. ¶¶ 14, 21, 23, 27; Cuss Dec. ¶¶ 11, 19, 21.
Because Schering renounced any commercial interest in the three investigational drugs here, Schering's claims of a continued commercial interest in data related to the drugs' safety and effectiveness are not credible. Schering has not shown with the specificity required under FOIA how the withheld data -- most of which relates specifically to the safety and efficacy of the abandoned drug -- could substantially harm its efforts to develop other drugs. See Gulf & Western Industries, 615 F.2d at 530; National Parks, 547 F.2d at 679. In particular, defendants' arguments fail to address how material in an abandoned IND is more commercially valuable than material that is routinely released when a drug is approved.
Certain categories of information from an IND are routinely disclosed by the FDA once an NDA is approved to allow the public to scrutinize the basis for FDA decisions. See 21 C.F.R. § 314.430(e)(2). For example, the FDA releases extensive summaries of the safety and effectiveness data once an NDA is approved. Id. According to the FDA, summaries are appropriate for public disclosure because "such information is commonly published in thescientific literature and distributed to the scientific community" and therefore, "cannot be said to be customarily held in strict confidence." 39 Fed. Reg. at 44637. Moreover, summaries "will not ease the burden on a subsequent new drug applicant in this country since such an applicant would nonetheless be responsible for running the required tests." 39 Fed. Reg. at 44636. It appears that many of the Schering documents being withheld simply summarize the results of pre-clinical and clinical testing. See, e.g., annual and supplemental reports discussed in Cuss Dec. ¶ 22 & n. 4, Miller Dec. ¶ 28 & n. 7, & Garutti Dec. ¶ 36 & n. 7. Defendants have not explained why these documents have more commercial value now than they would have if they concerned a drug on the market, i.e., a drug with an approved NDA. Competitors are much more likely to be interested in utilizing data concerning an approved drug than they would be in data concerning a drug whose clinical testing was halted due to health or safety concerns. In sum, defendants' claim that disclosure of documents which simply summarize the results of testing of an abandoned investigational drug should be withheld when the same type of information would be released for an approved drug, which would be of much more interest to competitors, is implausible and cannot support their motions for summary judgment.
Defendants have also withheld other information that is routinely released by the FDA after an NDA is approved: protocols, "adverse reaction reports, product experience reports, consumer complaints, and other similar data and information," and "allcorrespondence and written summaries of oral discussions between FDA and the applicant relating to the application." 21 C.F.R. § 314.430 (e)(3),(4) & (7). For instance, defendants have withheld several documents that appear to provide the FDA with information about individual patient reactions. See, e.g. Vaughn Index for IND 18113, docs. 114, 116, 193, 206, 220, 226, 233. Again, defendants have not explained why these documents have more -- rather than less -- commercial value now than they would if they concerned a drug on the market.
A brief description of one of these withheld documents illustrates the weakness of defendants' claim of substantial competitive harm. Document 204 from the Vaughn index for IND 18113 is described as a "Letter from Schering to FDA re: patient death." Defendants claim that "[d]isclosure would reveal proprietary and commercially-valuable information regarding the safety and effectiveness in man of related chemical compounds and other compounds used in the treatment of hypertension and angina, which would guide Schering's competitors in the development and testing of new products indicated for use in the treatment of hypertension and angina, and cardiovascular diseases generally." It is difficult to imagine how reports on individual patient reactions could possibly be used to suggest additional lines of research. More likely, observation reports like this one may provide HRG and the public with important information about patient reactions to these abandoned drugs, whether the companies fully complied with the FDA reporting regulations, and whether FDA responded adequatelyto these reports.
2. Defendants FDA and HMR Have Not Sustained Their Burden Of Showing How Release Of Any Information About A Drug That Is Already On The Market Abroad Would Cause Competitive Injury.
As discussed above, HMR's unsubstantiated claim that it has abandoned its IND cannot support its motion for summary judgment. Independently, HMR has not met its burden of showing how release of any information about a drug that is already on the market abroad would cause substantial competitive injury.
HMR's IND involves a drug that is already on the market in "numerous" countries around the world. Waller Dec. ¶ 22. Yet defendants' submissions fail to address how release of the IND will cause competitive injury when competitors already have access to a great deal of information about any drug that is marketed abroad. Supp. Wolfe Dec. ¶ 16. Defendants have not even released the name of the drug involved in HMR's IND, so it is impossible to provide evidence of the extent of information in the public domain about the particular antibiotic drug involved here. However, for example, take 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.
Roxithromycin is an antibiotic marketed in France andSwitzerland beginning in 1987. It is used to treat several types of infections including streptococcal pharyngitis, skin and soft tissue infections, upper and lower respiratory tract infections, isosporiasis, Lyme disease, and otitis media. Supp. Wolfe Dec. ¶ 17 & Exh. 4. At least 119 published studies provide details about the pre-clinical and clinical testing of the drug, with titles such as "Pharmacokinetics of a new macrolide, roxithromycin, in infants and children," "The in vitro activity of roxithromycin compared with that of three other macrolides against Legionella," "Roxithromycin: pharmacokinetic and metabolism study in humans," and "Roxithromycin as a possible agent for prophylaxis of endocarditis: a study in normal volunteers." Exh. 4. And, to the extent that HMR is working to have roxithromycin approved in the United States, competitors would not be surprised because Drugs Available Abroad, a pharmacological compendium readily available in medical libraries, informs them under the heading "U.S. Status" that "Hoechst-Roussel is in Phase III clinical trials of roxithromycin." Supp. Wolfe Dec. ¶ 17, Exh. 3.
Similarly, competitors have access to significant information about another HMR antibiotic marketed abroad but not in the United States, rolitetracycline. Rolitetracycline is marketed by HMR under the brand name Reverin in Australia, Belgium, Germany, Italy, Netherlands, South Africa and Switzerland for treating infections. Exh. 3. The drug can potentially cause liver damage when given in high intravenous doses. Id. The MICROMEDEX drug evaluation monograph for rolitetracycline -- available on CD Rom inpharmacies, drug information services, and medical libraries -- refers to 31 publications, including "Intramuscular rolitetracycline nitrate in non-specific urethritis," and "Rolitetracycline by injection and tetracycline phosphate complex by mouth given in a single session in the treatment of gonorrhea in males." Exh. 5.
In light of the extensive information available about drugs marketed abroad, 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. 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). Because defendants have failed to explain how HMR's competitors would benefit from release of IND information given the information already publicly available on any drug marketed abroad, defendants' motions for summary judgment should be denied.
3. Plaintiff Is Entitled To Discovery To Demonstrate That Defendants' Claims Of Substantial Competitive Injury Are Baseless.
On the current record, defendants' claims cannot suffice as a basis for withholding the information in the Schering or HMR INDs under exemption 4, and thus, defendants' motions for summary judgment should be denied. However, in the event the Court is not inclined to grant summary judgment to plaintiff at this time, HRG is entitled to discovery in order to demonstrate that Schering's and HMR's claims of competitive injury are baseless.
This Circuit has routinely allowed discovery in FOIA cases in order to preserve the adversarial nature of the litigation process. Londrigan v. FBI, 670 F.2d 1164 (D.C. Cir. 1981) (FOIA plaintiff allowed to depose FBI agents who prepared reports subject to FOIA claim); Schaffer v. Kissinger, 505 F.2d 389 (D.C. Cir. 1974) (case remanded to district court with instructions to permit discovery); see also Renegotiation Bd. v. Grumman Aircraft Engineering Corp., 421 U.S. 168, 181 (1975) (Court noted that FOIA plaintiff allowed to conduct depositions). Discovery is particularly relevant in exemption 4 cases. The existence of adverse consequences to a submitter's competitive position from the disclosure of commercial information is a factual question. Worthington Compressors, Inc. v. Costle, 662 F.2d 45, 54 (D.C. Cir. 1981), request for modification denied sub nom. Worthington Compressors, Inc. v. Gorsuch, 668 F.2d 1371 (D.C. Cir. 1981); Sears, Roebuck & Co. v. GSA, 553 F.2d 1378, 1382 (D.C. Cir. 1977); National Ass'n of Government Employees v. Campbell, 593 F.2d 1023, 1028 (D.C. Cir. 1978). Discovery is necessary in cases, like this one, where competitive harm is alleged in order to determine whether theinformation withheld is maintained in secrecy, how commercially valuable it is, or whether it is truly the end product of either innovation or substantial effort. 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).
As demonstrated pursuant to Federal Rule of Civil Procedure 56(f) in the Supplemental Declaration of Dr. Wolfe, limited discovery will allow plaintiff to further support the illegitimacy of defendants' claims of substantial competitive harm. Supp. Wolfe Dec. ¶¶ 16, 18-21. For example, plaintiff seeks access to the name of the drug involved in HMR's IND, which would allow plaintiff to demonstrate specifically the extent of safety and effectiveness information already publicly available about the drug. Plaintiff also seeks 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. In addition, because Schering's claim of competitive harm relies on its development of compounds other than the ones involved in the INDs at issue, plaintiff seeks information about the patent status of those compounds in order to show that Schering's claims are implausible in light of any existing patents. Based on the responses to the discovery requests, plaintiff may be able to show that existing patents offer sufficient protection to Schering's efforts to develop other drugs. Finally, plaintiffseeks access to information from both Schering and HMR on which of the IND studies revealed the health and safety concerns that caused the testing on humans to be discontinued. At a minimum, these particular studies, which demonstrate the toxicity of an experimental drug, should be released as "[t]he benefit of releasing this type of information far outstrips the negligible competitive harm that defendants allege." Teich v. FDA, 751 F. Supp. at 253.
For the foregoing reasons, the motions for summary judgment of the FDA, HMR, and Schering should be denied, and plaintiff's motion for summary judgment should be granted. In the event the Court denies both motions, plaintiff should be allowed to conduct limited discovery to develop the record further.
Lucinda A. Sikes
D.C. Bar No. 431949
D.C. Bar No. 427491
Public Citizen Litigation Group
1600 20th Street, N.W.
Washington, D.C. 20009
Attorneys for Plaintiff
June 10, 1997
In the event the Court is not inclined to grant summary judgment to HRG at this time, HRG needs limited discovery, as discussed below, in order to show that Schering's claims of competitive harm are unfounded.
Limited redactions were made to protect personal privacy information. Supp. Hooton Dec. ¶ 39.
FDA is also withholding ten documents from the HMR IND on the basis of FOIA Exemption 5. HMR claims that it may reactivate its IND. The ten documents being withheld on exemption 5 grounds were prepared by FDA employees and have not been disclosed to HMR because they will, FDA argues, become essential to FDA's internal deliberations concerning HMR's application if the IND is reactivated. Hooton Dec. ¶¶ 46-49. Plaintiff disputes the adequacy of HMR's showing that the IND has not been abandoned but does not challenge FDA's exemption 5 determination.
A different IND must be submitted for each dosage form of a drug. Thus, IND 31911 and IND 34465 involve the same therapeutic entity, a mixture of two enantiomers (compounds that have the same chemical composition but whose molecular structures are mirror images of one another); IND 34465 is for an oral suspension and IND 31911 is for an oral capsule. IND 35757 contained only the pharmaceutically-active enantiomer of the entity that was the subject of the other two INDs. Miller Dec. ¶ 10.
Isomers are compounds that have the same chemical composition, but one or more of whose atoms are differently placed, resulting in different physical or chemical properties.
A leukotrine inhibitor blocks the effect of a chemical -- leukotrine -- that may have a role in the processes that cause bronchial restriction and difficulty in breathing.
Plaintiff is not interested in obtaining information about the manufacturing process for these drugs. Therefore, plaintiff has no objection to the redaction of trade secret information, as narrowly defined in Public Citizen Health Research Group v. FDA, 704 F.2d 1280, 1288 (D.C. Cir. 1983) (Public Citizen I), from any of the requested studies.
Ignoring the plain pro-disclosure tenor of the statute, HMR tries to characterize this statute as a nondisclosure statute and asserts that the provision qualifies as an exemption 3 statute under the FOIA. See 5 U.S.C. § 552(b)(3) (exempting from disclosure records that are "specifically exempted from disclosure by statute . . .") HMR's Brief at 9, fn. 2. Even a cursory reading of the statute refutes this claim, since the whole point of its enactment is to compel release of documents. Moreover, the courts have held that the statutory authority to disclose particular types of information does not imply the converse authority to keep other types of information secret. For instance, in Public Citizen I, 704 F.2d at 1284-5, this Circuit held that a statute which compels the FDA to divulge summaries of safety and effectiveness data does not reflect a congressional authorization for the FDA to withhold raw data. Similarly, the statute at issue in this case -- section 505(l) ofthe FD&C Act -- which compels FDA
to release safety and effectiveness data in certain circumstances, does not reflect a congressional authorization for FDA to withhold that data in all other circumstances.
As noted above, the FDA refused to remove termination of an application as a trigger for disclosure in response to comments that termination is irrelevant to whether or not information should be disclosed. 39 Fed. Reg. at 44,637. To be sure, the FDA stated that "a situation in which one IND or NDA directly affects another might be viewed as an extraordinary circumstance." Id. at 44638 (emphasis added). This statement suggests that if another IND or NDA were pending for the same use of the same drug as an abandoned drug application, extraordinary circumstances might exist. That is not the case here, where there is no pending or contemplated IND or NDA application for the same drugs involved in the withdrawn applications but only for other compounds.
Notably, Schering does not even claim to be developing one of the three other isomers of Labetalol. It claims only that it "markets a number of products indicated for various cardiovascular problems and continues actively to conduct research and development efforts in this area." Garutti Dec. ¶ 21. Schering asserts it has a competitive interest in preventing competitors from developing those three unmarketed isomers, id. ¶¶ 28, 31, even though the company itself is not developing them.
At a bare minimum, FDA must reveal the name of the drug that HMR's IND involves. 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.
HMR argues that like the drug sponsor in Public Citizen II, it has not abandoned its IND, and therefore, that all HMR's IND data is protected by exemption 4. HMR asserts that its entire IND must be withheld, despite the fact that competitors already have access to a great deal of information about the drug since it is marketed in other countries. In Public Citizen II, however, HRG received considerable information about FIAU and its pre-clinical and clinical trials; only information that had not already been released to the public was withheld. Slip op. at 2. Here again, HMR has objected to even the release of the drug's name.