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Everything to Know About CRLs in 2025
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Key Takeaways
- A CRL signifies non-approval of a drug/application in its current form, but allows for issue resolution and potential approval.
- In 2025, the FDA began publishing CRLs to enhance transparency, addressing concerns about company honesty.
Updates to its policies have made FDA’s CRLs a key talking point.
FDA updated its CRL policy in 2025 to improve transparency.
Stock.adobe.com
What is an FDA CRL?
When a company receives a complete response letter (CRL) from FDA, this indicates that the agency has decided not to approve the drug or application in its current form. This can be for a variety of reasons. The agency may believe that the drug’s safety has not been proven, have concerns about its efficacy, or have issues with the manufacturing capabilities. CRLs are not a rejection, however, and companies have the opportunity to work with FDA to address the CRL.
Does FDA publish CRL?
In Septemeber, 2025, FDA announced that it will publish CRL’s promptly after they are received by their sponsors. Prior to 2025, FDA did not publicly publish CRLs. However, the Trump administration changed this policy in an effort to promote transparency.
What does a CRL mean?
A CRL means that FDA does not plan to approve a drug or application in its current form. It is not a rejection, however. Companies that receive a CRL have the opportunity to meet with FDA to discuss the CRL and address the issues raised within it. A drug may receive a CRL and still go on to be approved.
Has FDA issued more than 200 CRLs for transparency?
In July, 2025, FDA announced the publication of over 200 CRLs that had previously been filed in response to drug and biological products submitted to the agency between 2020 and 2024. At the time, the agency explained that the decision was made to promote transparency, as it believed that companies and sponsors were not always honest with stakeholders about the contents of a CRL. The pharma industry, however, responded with concerns that published CRLs might violate privacy and reveal trade secrets.
What companies have received CRLs?
Multiple companies have received CRLs in 2025. Most notably, FDA issued a CRL to Replimune in July for an advanced Melanoma treatment. The move surprised the company and industry experts, who believed that the drug was set for approval based on previous communications with FDA.
Is a CRL a rejection?
A CRL is not a rejection. It is a notice that FDA does not intend to approve a drug or application in its current form. Companies have the opportunity to address and fix issues presented in CRLs and obtain approval. There are also opportunities for the recipient to meet with FDA over the CRL to discuss the issues presented in the CRL and argue against the decision.
What happens if a CRL is unexpected?
Pharma companies typically communicate regularly with FDA throughout the approval process and will present plans for trial design and goals to the agency. However, there are still times that a CRL comes as a surprise. In these cases, companies may face short term issues (such as a drop in stock price) while it works with FDA to find ways to resolve the issues.
Has FDA changed its CRL policy?
In July 2025, FDA changed its policy to allow for the public publication of CRLs. Prior to this, CRLs were sent to sponsors, who then communicated the contents of the letter to shareholders. However, the new administration felt that this left room for dishonesty and wanted to promote transparency. Despite this, FDA said that it will still take time to properly redact any necessary information before publishing CRLs.
What happens after a CRL?
Companies have several options after receiving a CRL. A CRL will typically include guidance from FDA on how to address the issues presented within it. Often, companies will meet with FDA and decide upon a plan to address the CRL. If the issues are properly addressed to the agency’s satisfaction, the drug will still move to approval.
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