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Time for FDA to Release Complete Responses Letters? Debate Reignites

Posted 23 August 2019 | By Zachary Brennan 

Time for FDA to Release Complete Responses Letters? Debate Reignites

The idea of the US Food and Drug Administration (FDA) releasing complete response letters (CRLs) resurfaced this week as Sarepta Therapeutics received a CRL but refused to make public any portion of it.

Following a question on transparency at an event Thursday, Sarepta CEO Doug Ingram said that not releasing the text of the CRL was “a service to the community” and that FDA might not want a confidential letter to be released. “The basis for the CRL is exactly as I've said it," Ingram said.

He also said the company has “to be respectful of the regulatory body…as I imagine the agency assumes it would remain confidential.”

An FDA spokesman told Focus via email: "Applicants can release the CR letter it receives from FDA (or any other correspondence it gets from us). There might be confidentiality issues with third-parties or SEC issues, but those don’t involve disclosure issues for FDA."

Peter Lurie, FDA's former associate commissioner for public health strategy and analysis, who, alongside five FDA colleagues, published an article noting the discrepancies between 61 CRLs issued by FDA between August 2008 and June 2013 and the press releases accompanying them.

"Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements," Lurie et al. wrote in 2015. "Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact."

And in response to the idea that industry pushback was stopping FDA from releasing all CRLs, former FDA Commissioner Scott Gottlieb clarified on Friday via Twitter that the “issue for us was never industry objections it was FDA resources. It would take lot of people power to redact CRLs for release. Question was: Is that best PUBLIC HEALTH use of scarce medical reviewer time. Need a strong PUBLIC HEALTH reason to allocate it, not just investor thesis.”

Gottlieb also noted that it might be better for FDA to, rather than release the letters themselves, “issue some kind of summary, but one reluctance by FDA would be around how to create a standard template and approach that consistently captures salient features lest the agency be blamed for what they decide to include or exclude.”

The European Medicines Agency uses a Q&A format to explain why a drug was denied marketing authorization.

Jim Miller, senior associate in the Department of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health, also previously explained to Focus that FDA could, without congressional action, change its regulations via a proposed rulemaking to allow for at least portions of the CRLs to be released.

And a 2017 Blueprint for FDA Transparency from Yale, Harvard and Johns Hopkins also noted: “Companies that fail once but plan to try again may consider [a CRL] release to be premature. Yet at this early stage, for innovator drugs, patent and data exclusivity protections still apply. The release of the letter serves to inform patients, doctors, investors, and others of the regulatory status of the product and to help researchers understand the potential limitations that need to be overcome in creating safe and effective alternative products.”

They also specifically call on FDA to release CRLs sent to generic manufacturers that relate to scientific issues of bioequivalence.


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Tags: CRL, FDA, Sarepta

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