Tackling Transparency

Transparency is the new mantra shaping drug research, regulation, and marketing. Healthcare reform legislation provides more public information on a host of health-related activities, including formulary listings, out-of-pocket costs, and comparative assessments. The new law, as well as FDA and the National Institutes of Health (NIH), seek to shed more "sunshine" on the financial relationships between industry, and scientists and physicians. Some members of Congress would like to go further and mandate broader disclosure of drug prices, as well as hospital and doctor rates, (See "Price Transparency".)

Jill Wechsler

Opening the Black Box

FDA also has launched a comprehensive Transparency Initiative to build public confidence in agency decisions by revealing more about its policies and practices. Internally, an FDA-Track program will report regularly on the performance of 100 agency offices to improve management, while also emphasizing the breadth of the agency's responsibilities and accomplishments.

New Push to Showcase Price Data

More significant for industry, FDA's Transparency Task Force proposes extensive disclosure of information on field inspections, product recalls, and the status of drug development and market applications. In announcing the program in June 2009, FDA Commissioner Margaret Hamburg stressed the need to dispel the agency's " black box" image by expanding its ability to explain its rules and processes. Under the leadership of principal deputy commissioner Joshua Sharfstein, the task force unveiled phase one of the initiative in January, which established a Web-based "FDA Basics" course on agency activities. Phase three, due this summer, will propose ways to improve how FDA communicates with regulated companies, primarily by streamlining guidance development and increasing meetings with sponsors.

Much more substantive is phase two, which was published May 21, 2010, and offers 21 proposals for disclosing regulatory documents and actions. Some are quite far-reaching and will require Congressional action to implement.

Most controversial is whether FDA should drop its long-held policy against releasing information on the status and substance of investigational products. The task force proposes that FDA disclose when a company seeks permission to launch clinical trials or to bring to market a new drug, biologic, animal drug, or medical device. FDA also wants to announce when such applications are withdrawn, rejected, or delayed. The agency also wants to release Complete Response (CR) letters explaining why it is not approving a product, as well as what the sponsor needs to do to get to market.

Pharma companies often elect to announce when they file an IND (investigational new drug application) or a license application to demonstrate that a development project is moving forward or to comply with financial reporting rules. The FDA Amendments Act, moreover, requires manufacturers to post information about ongoing clinical trials and their results on ClinicalTrials.gov, and dossiers on some products are posted as part of FDA advisory committee deliberations. But FDA itself only announces when it approves a new product.

That would change considerably under the task force proposal for FDA to disclose IND filings, including name of sponsor, date of application and anticipated indication and trade name. The agency also would indicate when an IND is placed on clinical hold or is terminated or withdrawn. Similarly, FDA would indicate 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 FDA to be able to explain that when a sponsor abandons or withdraws an application for an orphan drug due to internal business reasons, safety concerns, or regulatory issues should not deter another party from developing that needed therapy.

A significant, and controversial, proposal is for FDA to release refuse-to-file notices and CR or not-approvable letters. Sponsors often will issue a summary of a CR letter and a scenario for reaching the market in the future. But FDA wants to provide full explanations of its delay decisions, and investors and consumers want to see those statements.

However, the transparency panel decided not to seek disclosure of refusal or CR letters to generics drug manufacturers, or for manufacturing and labeling supplements; these contain considerable trade secret information that is considered less crucial to drug development.

More on Inspections

Transparency also is proposed on the compliance and safety front. The task force wants to indicate when FDA inspects a manufacturing facility or clinical research site, along with whether a site visit uncovers violations or problems requiring corrective action, or if the entity comes out clean. FDA currently makes public some inspection reports that raise important safety or regulatory issues. Otherwise, interested parties have to request this information through the agency's freedom-of-information process, which can take months, if not years. FDA believes that inspection results could help manufacturers achieve compliance, as would posting untitled letters on the FDA Web site; FDA now lists more serious warning letters, and this would expand considerably available information on company violations.

An important initiative would require regulated companies to inform FDA when they conduct a product recall. This would permit the agency to advise the public on what is being taken off the market, the number of items involved, and cause of product defect. The policy also would help FDA clarify which similar products are not being recalled, and when the recall is completed and terminated. Implementing this recall notice provision may require Congress to give FDA mandatory recall authority, a change that could be accomplished by expanding proposed food safety legislation awaiting action on Capitol Hill.

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

Guarding Secrets

An important consideration of the transparency initiative, said Sharfstein at a press briefing, is to obtain an "appropriate balance" between expanded disclosure and ensuring confidentiality of trade secret information. The task force acknowledges that protection of proprietary data is key to maintaining investment in biomedical R&D, and that a company's manufacturing methods and product formulations are trade secrets that 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 in withholding or releasing such information, as well as the often heavy cost of redacting trade secrets from to-be-disclosed material. And while FDA is not proposing here to release raw data from clinical trials—as opposed to summary information—the panel suggests that access to such information might uncover safety signals and help sponsors identify new product development opportunities.

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

Implementing many FDA transparency proposals will require legislative change. In unveiling this plan, Sharfstein explained that the task force focused on what was the "right thing" to do, policy-wise, and not on the cost or feasibility of taking such action. Now the panel 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 decisions on which proposals can be adopted internally and where it makes sense to seek Congressional action.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com