Overview
Newly released FDA complete response letters offer healthcare entrepreneurs insight into why drug applications fail and how to avoid the same mistakes.
Agency Releases Two Decades of Rejection Letters in Transparency Push
Companies developing new medicines can finally learn lessons from the failures of prior applications to the FDA, now that the regulatory agency has published more than 200 complete response letters (CRLs), detailing why certain drugs and biologics were rejected.
The letters, released via the “openFDA” portal, describe the agency’s objections to New Drug Applications (NDAs) and Biologics License Applications (BLAs) that were later approved after revision.
In many cases, the documents explain why a product failed to meet regulatory standards for approval, citing gaps in clinical data, manufacturing problems, or safety and efficacy concerns.
“For far too long, drug developers have been playing a guessing game when navigating the FDA,” said FDA Commissioner Marty Makary in a July 10 news release. “Drug developers and capital markets alike want predictability. So today we’re one step closer to delivering it to them.”
The FDA said the letters were redacted to remove trade secrets and confidential commercial information. All documents pertain to products that ultimately won approval, and the agency said that it is in the process of publishing additional CRLs from its archives.
The transparency initiative follows a 2015 internal study by FDA staff that found sponsors often omitted critical details when announcing that an application was not approved. According to the FDA press release, companies avoided mentioning 85 percent of the FDA’s safety and efficacy concerns. In 40 percent of cases where the agency requested new clinical trials, that detail went undisclosed.
Learning Opportunity and a Legal Risk for Future FDA Submissions
Law firms and consultants have urged companies to treat the newly available documents as both a learning opportunity and a legal risk. One firm, Akin Gump, suggested organizations will need to carefully consider what information they include in their applications, in case it is ever publicized by the FDA in a CRL.
“It is possible that this will lead to more application withdrawals and may even hinder innovation in these areas,” Akin Gump said in a blog post. “In turn, product developers, investors and others will potentially have greater insights into FDA’s expectations for particular types of drugs and biologics.”
According to Hogan Lovells, some redacted letters may still reveal information about internal decision-making, intellectual property strategy or development challenges, including whether a company struggled to enroll patients in their clinical trial, failed to meet a particular clinical endpoint in patient subgroups, or had difficulty in determining the right dose to test.
“There is considerable risk that third parties could use these breadcrumbs to advance their own interests, from companies developing competing products to shareholders or product liability plaintiffs seeking to bolster litigation claims against the sponsor,” the firm wrote in a post.
‘Real-World Case Studes’
Still, several firms noted the information is a critical resource for companies developing new therapies, especially startups and resource-strapped biopharma companies that don’t have the resources to hire teams of regulatory advisors.
“FDA’s decision to publish these letters does potentially provide drug developers with an opportunity to more clearly understand the Agency’s thinking and expectations across a range of precedents,” the firm Sidley Austin wrote in a blog post. “This information can and should be incorporated into new and existing drug development strategies in an effort to reduce the time it takes to bring new drugs to market and to bring additional predictability to outcomes.”
Contract research organizations and manufacturers are also studying the archive. In a ProPharma Group blog post, James Meckstroth, the company’s vice president of compliance and quality assurance, called the public CRLs “real-world case studies” that may help reduce rework and submission delays by clarifying common regulatory pitfalls.
For drug developers, “this means less time guessing and more time executing,” Meckstroth wrote. “For patients, it means faster access to safe, effective treatments. It's a win built on clarity, accountability, and smarter collaboration for everyone.”