FDA Transparency: Agency’s Hands Tied by its own Regulations

Ask a US Food and Drug Administration (FDA) official how many biosimilar applications are actually under review, or the details of a recent Complete Response Letter (CRL), and he or she will explain how the agency cannot offer any more details than what is already publicly known, even if what has been made public is not aligned with reality.

And in some areas, like with CRLs, which are letters sent by FDA when medical product applications cannot be approved, research from 2015 from FDA associate commissioner Peter Lurie and colleagues shows that press releases are not the best indicators of what FDA actually told the company.

"Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements," Lurie’s research found.

When Focus asked FDA how many biosimilar applications are currently under review, the response from a spokesperson was: "Under federal law, FDA cannot discuss the number or nature of pending applications. However, as of February, 2017, there are nine companies that have publicly announced they have submitted a total of 13 applications (351(k) BLAs) to the FDA for proposed biosimilar products."

But the actual number of 351(k) applications submitted may be higher. Janet Woodcock, director of FDA’s Center for Drug Evaluation and Research, also said earlier this month that the agency is working on 64 biosimilar development programs that will provide competition for 23 biologics.

But for both CRLs and biosimilar application numbers, the lack of FDA transparency is not an issue with federal statute set by Congress, but by FDA regulations that the agency proposes and imposes on itself.

Jim Miller, JD, MPH, senior associate in the Department of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health, explained to Focus that FDA could, without congressional action, change its regulations via a proposed rulemaking to allow for at least portions of CRLs to be released by FDA and for the agency to disclose biosimilar application numbers and more if it decided to.

Granted, such a rulemaking process would be lengthy and time-consuming and would have to be an initiative that FDA leadership wanted to undertake, but with President Donald Trump’s new "two out, one in," executive order, there may be regulations that could be cut out to free FDA up to be more transparent.

As far as the argument that CRLs and biosimilar and other applications contain companies’ trade secrets or confidential information that would legally bar FDA from releasing such information, Miller said the Federal, Food, Drug and Cosmetic Act governing FDA actually has a "narrow definition" of what constitutes trade secrets.

"It would be an unusual CRL that contains trade secret information," Miller said. And though manufacturing details in biosimilar applications would likely be designated as trade secrets, he noted that releasing the number of applications and applicants would not run counter to federal statute if FDA changed its regulations.

Blueprint for Transparency

Miller was also part of a group of Johns Hopkins, Yale and Harvard medical and law professors who compiled a new report with five areas FDA should focus on to improve transparency.

The report, released Monday and accepted for publication later this year in the Journal of Law, Medicine & Ethics, calls on FDA to disclose more information about key milestones in the application process; disclose more of its own analysis and decision-making; disclose more about the application and review process for generic drugs and biosimilars; correct misleading information in the market; and further disclose data from scientific studies.

Joseph Ross, an associate professor of medicine at Yale University who worked on the report, told Focus, "We carefully considered areas that we believe FDA has regulatory authority to pursue now – no new Congressional actions would need to be taken in order to follow any of our recommendations."

In addition to the biosimilar application and CRL disclosures, the report’s 18 specific recommendations, building off 2010 recommendations from the FDA’s Transparency Task Force, include:

• Disclosing in investigational notices and marketing applications the class of medication and mechanism of action, if known.
• Including in disclosures of investigational notices and new applications the ClinicalTrials.gov numbers for all trials conducted or relied upon as pivotal for marketing approval.
• Releasing a summary of the reasons for a clinical hold related to safety or efficacy within 10 days.
• Disclosing whether a marketing application has been designated for an expedited development or review program and, if so, provide the scientific basis for that designation.
• Disclosing written requests for pediatric studies at the time such requests are made, as well as other documents indicating agreement on changes to the initial request.
• Making public FDA’s clinical and statistical reviews of products not approved or for which the marketing applications are abandoned or withdrawn.
• Making FDA’s pooled data sets, masked and de-identified as appropriate, and FDA’s analyses of these data sets, available to the medical and research community through clinical data repositories.
• Releasing the final reports that fulfill Postmarketing Requirements and Postmarketing Commitment at the time FDA considers the sponsor’s obligation to conduct a study to be fulfilled.
• And when FDA enters into a Special Protocol Assessment, the agency should release the text relevant to safety and efficacy after the study is completed.

"The Agency might consider adopting a standard based on whether the information has the potential to cause significant confusion in the medical community and among patients about the safety or efficacy of a medical product for approved or unapproved uses," the report notes. "Even with such a standard, FDA should retain the authority to release information under other circumstances vital to public health."

With respect to correcting misinformation, the report makes clear that FDA "cannot possibly police all statements by sponsors and others" so correcting some information "creates the risk that silence by the Agency will be publicly understood as agreement with whatever is being said. It will be important for FDA to dispel this notion. We do not believe the risk of this misunderstanding outweighs the benefit of clearing up substantial confusion about the safety and efficacy of medical products."

BLUEPRINT FOR TRANSPARENCY AT THE U.S. FOOD AND DRUG ADMINISTRATION

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