FDA Seeks Transparency in Data and Decisions

Transparency is the new mantra shaping biomedical research, production, regulation, and marketing. The US Food and Drug Administration and the National Institutes of Health (NIH) are requiring more disclosure of financial relationships between the industry and scientists and physicians. A new FDA-track program will issue regular reports on the work and performance of 100 agency offices. Health reform legislation authorizes public access to more extensive information on health-related activities, including formulary listings, out-of-pocket costs, and payments from pharmaceutical companies to health professionals. Some members of Congress would like to go further and require public disclosure of prices charged for pharmaceuticals, as well as for hospital care and doctor visits.

Jill Wechsler

OPENING THE BLACK BOX

Most significant for pharmaceutical and biotech companies is the FDA initiative to provide the public with more information on field inspections, product recalls, and the status of drug development and market applications. The agency's Transparency Task Force suggests that broader disclosure about FDA activities will build public confidence in its decisions. In announcing the program in June 2009, Commissioner Margaret Hamburg emphasized the need to dispel the FDA's "black box" image by expanding its ability to explain agency rules and processes.

Under the leadership of Principal Deputy Commissioner Joshua Sharfstein, the task force released Phase 1 of the initiative in January, which established an Internet-based "FDA basics" course to promote public understanding of FDA processes and policies. Phase 2 was unveiled May 21, 2010, offering 21 proposals for disclosing regulatory documents and actions. Some are quite far-reaching and will require Congressional action to implement. Phase 3, which should be released this summer, will propose ways for the FDA to improve communications with regulated companies, namely by streamlining guidance development and increasing meetings with sponsors.

To better explain its enforcement activities, the FDA proposes to make public when it inspects a manufacturing facility or clinical research site. The task force wants such listings to indicate whether a site visit uncovers violations or problems requiring corrective action, or if the entity comes out clean. Manufacturer compliance status also could be clarified by posting untitled letters on the FDA web site, expanding what the agency now does with warning letters and with untitled letters related to biologics and drug marketing.

An important initiative would require manufacturers to inform the FDA when they conduct a product recall so that the agency can advise the public on the number of items involved and the cause of the product defect. At the same time, the FDA wants to be able to clarify which similar products are not being recalled and when the recall is completed and terminated. Implementing this recall notice provision may require that Congress give the FDA mandatory recall authority, as proposed in food safety legislation awaiting action on Capitol.

Another proposal would expand public access to adverse event reports through more user-friendly information system. The FDA also seeks to publish weekly listings of enforcement issues that are so important that the US Department of Justice is taking the issue to court.

SUBMISSIONS AND DENIALS

Even more significant are proposals to disclose when manufacturers seek FDA approval to launch clinical trials or to bring to market a new drug, biologic, animal drug, or medical device. The FDA also wants to announce when such applications are withdrawn, rejected, or delayed, and to release complete response (CR) letters that spell out why the agency is not approving a submission and what the sponsor needs to do to get to market.

Sponsors often elect to announce when they file an investigational new drug application (IND) or a license application to demonstrate that a development project is moving forward, and the FDA Amendments Act of 2007 requires manufacturers to post information about ongoing clinical trials and their results on the ClinicalTrials.gov web site. But FDA regulations currently prohibit the release of most information on the status or substance of investigational products.

The task force proposes that the FDA disclose IND filings, including sponsor name, date of application, and anticipated indication and trade name. The agency also could indicate when an IND is placed on clinical hold, or is terminated or withdrawn.

The FDA would provide similar information on the status of market applications for new drugs, biologics, and medical products under this plan. The agency now announces only when it approves a medical product for market, but not when a manufacturer files such an application. Interested parties may glean such information from company financial reports and FDA advisory committee review materials.

The agency now seeks the authority to disclose when a company files a market application or efficacy supplement, as well as when such applications are withdrawn or abandoned. Related to this, the task force wants the FDA to be able to explain that when a sponsor abandons or withdraws an application for an orphan drug for business reasons, as opposed to safety concerns, that should not deter another party from continuing development of a needed therapy for a rare disease.

An important, and controversial, proposal is for the FDA to release refuse-to-file notices and CR or not-approvable letters. Sponsors often issue a summary of a CR letter to acknowledge a delay in approval and outline a scenario for reaching the market in the future. But the FDA wants to fully explain its non-approval decisions, and investors and consumers support access to the agency's full statements.

However, the transparency panel decided not to seek disclosure of refusal or CR letters to generic drug manufacturers or for manufacturing and labeling supplements. The hundreds of manufacturing supplements filed each year contain a great deal of trade secret information that would be difficult to redact, and, the task force notes, "would provide little insight about the rationale underlying the FDA's drug review process."

GUARDING SECRETS

An important consideration of the transparency initiative, said Sharfstein in a press briefing, is to obtain an "appropriate balance" between expanded disclosure and ensuring the confidentiality of trade secret information, which the task force acknowledges is key to maintaining investment in biomedical R&D. The panel says that a company's manufacturing methods and processes and its product formulations generally meet the trade secret definition and should remain private. But other data, such as clinical trial results and adverse event reports, may be more appropriate for disclosure. The task force wants to consider the public benefit withholding or releasing such information, as well as the often heavy cost of redacting trade secrets from to-be-disclosed material. Although the FDA is not proposing to release raw data from clinical trials, as opposed to summary information, the panel suggests that access to such information might be useful in some situations.

One factor guiding some FDA transparency proposals is the desire to harmonize US policies with those adopted by the European Medicines Agency (EMA). The Europeans already disclose when a company files a marketing application or withdraws one, as well as the agency's evaluation of the product. The EMA also posts its reasons for denying approval of a new product or additional indication, similar to the FDA's proposal for releasing CR letters.

Implementing many of the FDA transparency proposals will require legislative action, as well as new rulemaking. In unveiling these proposals, Sharfstein explained that the task force focused on what was the "right thing" to do, policy-wise, and did not evaluate the cost or feasibility of taking such action. Now the task force will review public comments on these proposals, which can be submitted through July 20, and conduct a legal and resource analysis for each item. Commissioner Hamburg will make the final decision on which proposals can be adopted internally and where it makes sense to seek Congressional action to permit more transparency in FDA decisions and documents.

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, jwechsler@advanstar.com