Following the release of FDA's Transparency Task Force report, the agency may want to add an agenda item to its harmonization discussions with EMA.

FDA has pointed to the European Medicines Agency's disclosure rules as a justification for increased disclosure in the U.S. Andrew Emmett, the Biotechnology Industry Organization's director of science and regulatory affairs, noted that standardization of disclosure is one of many issues that BIO is examining as it evaluates FDA's proposals. [Editor's note: This story has been updated to clarify BIO's position.]

Among the ¹ 21 draft proposals the FDA Transparency Task Force released May 19 was the disclosure of when applications were : "² FDA Task Force Transparency Initiative Proposals"submitted or withdrawn and the release of redacted complete response and refuse-to-file letters (see chart).

Many of the proposed disclosure policies already are in use by the EMA (³ Also see "Can FDA Do The "Right Thing" On Transparency? Ask A Lawyer" - Pink Sheet, 19 May, 2010.). The task force said given the global nature of the pharmaceutical industry, most companies are subject to European rules already, which would mitigate potential competitive problems posed by increased FDA disclosure.

"Obviously, if a company discloses information or if it's disclosed in Europe, it's really a moot point at that point," Emmett said. "But I think there definitely is a harmonization angle here that we should probably take a closer look at."

While harmonized standards sound logical, there has not been a lot of progress to date. EMA has called for common standards among sister regulatory agencies and has alluded to the possibility of allowing worldwide approval from a single agency. The idea has not moved much, in part because of differing national health care systems and political agendas (⁴ Also see "EU Regulator Wants Closer Ties With Health Technology Assessors" - Pink Sheet, 19 February, 2010.).

Joshua Sharfstein, FDA principal deputy commissioner and task force chair, said the task force did not rely on the European rules when writing its proposals. While the recommendations are similar, the proposals are not exactly the same as the EMA disclosure policy, he said.

"I think it was helpful to our kind of assessing what is a reasonable expectation of companies as sort of the ground has shifted around transparency, but I don't think that that was the core of the policy judgment," Sharfstein said during a conference call following the proposals' release.

What Is A Trade Secret?

The task force said public availability of application and withdrawal information may reduce confusion about product development, but still would not allow a competitor to copy a product formulation.

"The potential availability of a new product on the market is not the only basis on which products compete," the task force said in the report. "For example, improved effectiveness of the product, fewer side effects, and easier use by the patient are among the factors that differentiate products on the market."

The group concluded FDA should explain publicly its reasons for not filing an application and not approving a medical product, which will improve its credibility.

"Disclosure of when and why an application is withdrawn or abandoned by the sponsor for a significant safety reason should allow researchers studying the same molecule or device ... to use that information to protect patients from the identified and potential risks," the task force said in the report.

Emmett said there are some missing details about that idea, including a clear definition of what types of information would be redacted in a public document. The task force defined trade secrets in its report, but Emmett said it is not entirely clear what FDA will call a trade secret or confidential commercial information.

"It seems that these proposals may revise FDA's processes for how they classify what is a trade secret [or] confidential commercial information and we would like to know what they envision that process looking like," he said.

Emmett also said the proposal should offer more concrete information about what levels of staff will be involved in the redaction process as well as a determination about whether sponsors will know about public disclosures prior to the release.

"I think there's also the open question of what role is the sponsor going to play both in deciding what in fact is a trade secret and confidential commercial information," he said. "And the timing of that [advance notice of public disclosure] is very important so that our companies have an opportunity to manage their relations with investors" and the media.

Investors should like the idea of releasing refuse-to-file and complete response letters in part because they would not have to rely solely on company comments to understand the problems with an application, said analysts at Robert W. Baird & Co.

"We are hard-pressed to articulate a reason not to go forward with this decision," according to a note on the transparency proposals. "Current procedures allow for significant speculation and confusion. This rule can only help make biotech more appealing to a broader shareholder base, in our view."

Raw Clinical Trial Data Release Not Endorsed

The task force did not encourage full disclosure of all agency documents. It said letters responding to chemistry, manufacturing and controls supplements, ANDAs, ANADAs, or labeling supplements did not have to be disclosed because they primarily relate to manufacturing processes and labeling negotiations, which are mostly proprietary.

The group concluded releasing those documents would "provide little insight about the rationale underlying FDA's drug review process."

Task force members did recognize the importance of public availability of clinical trial data, but would not say the raw data should be released. The group instead said FDA should make summary safety and efficacy data available from investigational applications or pending marketing applications, if it is in the interest of public health.

But the group still appeared to err on the side of releasing the data. It said a blanket policy against releasing summary safety and efficacy data does not account for the public health benefits of disclosure. And in a description of trade secrets, given earlier in the report, it hinted the value of trial data may be greater in the public domain.

"The task force believes that trade secrets have limited value for public disclosure and that the value for public disclosure of other types of data, such as clinical trial results and adverse event reports, is significantly greater," the report stated.

Harlan Krumholz, a Yale University School of Medicine professor, called for all clinical trial data to be released during a congressional hearing on the safety of GlaxoSmithKline's diabetes drug Avandia , and also said the data should be reviewed independently (⁵ Also see "Avandia Aftershocks: Will FDA Drug Safety Review Structures Crumble?" - Pink Sheet, 3 May, 2010.).

A committee of stakeholders still should talk about appropriate circumstances for the release of the raw data, the task force recommended. Sharfstein said FDA is not the only player involved in the discussion.

"I think that what this report says is we're very interested in spurring those conversations," he said. "We think that all the different ... players should be brought together and talk about whether there are basic policies that make sense."

Emmett said releasing trial data, as well as applications, could pose competitive problems, especially for small companies. But he said the group wants to talk with its members more before developing an opinion on the idea.

"I think that across all the information they're discussing to disclose it's really an enormous amount of pre-approval information that will be available for competitors with established, marketed, products," Emmett said.

Proposal Revisions Expected

The task force recommendations are the second phase of the FDA transparency initiative. Phase one included providing more information to the public about FDA operations. Phase two will include what types of information the agency can disclose and phase three will look at how FDA can be more open with industry about its processes (⁶ Also see "FDA Transparency Initiative Sees No Clear Path To Releasing Documents, Woodcock Indicates" - Pink Sheet, 26 April, 2010.).

FDA's transparency task force consists of most of the agency's top leadership (see chart: " ⁷ FDA Transparency Task Force Members "), but its report is not the last word on disclosure issues. Comments on the proposals will be accepted until July 20, and the agency will begin a legal analysis of whether the recommendations can be implemented over the summer.

Concept Capital's Washington Research Group said in a note there was a "high probability" FDA will begin disclosing complete response and refuse-to-file letters, but the proposals likely are not going to remain in their current form. "A formal policy is unlikely to take effect before the next iteration of the Prescription Drug User Fee Act reauthorization in 2012," the firm said.

- Derrick Gingery ( ⁸ d.gingery@elsevier.com )

FDA Transparency Initiative: Disclosure Rules Could Expand, Then Be Harmonized

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