FDA releases denial letters for unapproved drugs, a step toward transparency

Yesterday, the Food and Drug Administration announced the release of 89 marketing denial letters, called Complete Response Letters (CRLs), for unapproved drugs, and announced its intent to release future CRLs at the time they are issued. This action follows through on a longstanding recommendation put forth by both those inside and outside the agency. This is a crucial step forward, and we urge FDA to remain committed to this policy.

The release of CRLs is far more than a technical, bureaucratic victory. In a 2015 study led by Center for Science in the Public Interest President Dr. Peter G. Lurie when he was an Associate Commissioner at FDA, and previously cited by FDA Commissioner Makary, most CRLs (87 percent) issued between 2008 and 2013 cited important clinical deficiencies in safety, efficacy, or both. Companies sometimes issued press releases about these letters, but the study found that only 15 percent of the safety information and 16 percent of the effectiveness information in the CRLs were mentioned in those public statements. In a subsequent FDA analysis of more than 100 CRLs for biological agents, manufacturing facility deficiencies were the most commonly cited issue for non-approval.

The information included in CRLs is critical to researchers who wish to design future research based on the most up-to-date science. It is critical to pharmaceutical companies and investors who do not wish to sink resources into scientific areas likely to prove unsuccessful. And ultimately it is critical to patients and their doctors who need safe and effective treatments developed as efficiently as possible, not hampered by a lack of agency transparency.

Disclosure of CRLs has long been supported by a variety of stakeholders including the public, investors, and the agency itself. In a 2022 survey of over 1,000 Americans, 86 percent supported disclosure of the reasons that drugs are not approved. Investors in drug product development have also supported the clarity provided by CRLs. In January, then Director of FDA's Center for Drug Evaluation and Research Patrizia Cavazzoni endorsed disclosure of CRLs, saying at a conference that it is "the right thing to do for the patients, for the public, but also for shared learning across development programs." FDA is under constant pressure to speed up innovation, but disclosing CRLs reinforces FDA's critical role in protecting the public from drugs that are unsafe, ineffective, or poorly manufactured, and holds the pharmaceutical industry to account.

The real test of this initiative, however, will be FDA's resolve to continue publishing these letters in the face of inevitable industry pressure. FDA must hold its ground to ensure this policy delivers on its promise of true transparency, according to CSPI. It will also be critical for FDA to ensure that key information, such as safety and efficacy concerns, continues to be disclosed and is not redacted.

CSPI is currently working on a comprehensive FDA transparency report, funded by Arnold Ventures and due to be completed in the fall. One of its recommendations was to be the public release of CRLs.

"The release of these documents, while long overdue, is an important step forward in the efficient search for treatments that can truly benefit patients," said Lurie. "The veil of secrecy around these critical documents has finally been lifted."

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• Food and Drug Administration
• Medications

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• Government Accountability

Contact Info: Lisa Flores, 202-777-8368 or Jeff Cronin, 202-777-8370