The US Food and Drug Administration (FDA) recently announced the availability of the first-ever centralized database of Complete Response Letters (CRLs) on openFDA, one of several steps taken under the agency’s initiatives to increase transparency.
The published records were FDA letters originally issued following reviews of new drug applications (NDAs) and biologics license applications (BLAs) that were subsequently approved between 2020 and 2024.
FDA provides CRLs to product sponsors when the agency determines that it cannot approve a product application following a review cycle. Because CRLs typically detail deficiencies in the application and often contain trade secrets or highly sensitive proprietary information, historically, FDA did not proactively publicize the letters or make them widely available to the public.
Previously, the substance of these letters would reach the public under narrow circumstances, such as: in response to a Freedom of Information Act (FOIA) request with relevant redactions of protected information; when an applicant voluntarily shared the details in a press release or through selective disclosure in securities filings; or as a part of the final publicly available approval package once the drug is approved.
This new repository of CRLs is intended to streamline public access in “real time” to FDA’s reasoning in denying marketing applications. The contemplated policy could mean publicizing the CRL at the same time or before the sponsor is notified, raising a number of policy and strategic issues for FDA and industry.
What does a CRL mean for a drug sponsor?
When FDA issues a CRL, this means that the NDA, Abbreviated New Drug Application (ANDA), or BLA was not approved in its submitted form. However, FDA’s position is that a CRL is an advisory communication and not a final agency action that can be challenged in court.
FDA may issue a CRL for various reasons, such as manufacturing method deficiencies, lack of evidence of a drug’s intended effect, or other concerns related to the safety and effectiveness of the product. A CRL may sometimes include recommendations for addressing identified deficiencies.
In response to a CRL, sponsors have the option to address the identified deficiencies and resubmit the application, withdraw the application, request a hearing on the CRL, or submit a request for reconsideration.
What has been uploaded to the CRL database to date?
On July 10, 2025, FDA released an initial batch of more than 200 redacted CRLs issued from 2020 to 2024. One estimate provides that almost 60 percent of the uploaded CRLs were for products submitted through the 505(b)(2) pathway for follow-on drugs.[1] However, about 89 percent of these CRLs were already publicly available as part of approval packages published on the Drugs@FDA database.[2]
Why is FDA publishing CRLs?
Under Section 916 of the Food and Drug Administration Amendments Act of 2007 (codified at 21 U.S.C. § 355(l)(2)), FDA must post online action packages for approved original NDAs and BLAs within 30 calendar days of approval or within 30 days of the third FOIA request for that package. These packages contain, among other things, documents generated by FDA related to review of the application – and in practice, the agency has included CRLs.
Prior to posting, these packages must be redacted to protect trade secrets and confidential commercial information under 21 U.S.C. § 355(l)(2)(E) and Exemption 4 of FOIA.[3] However, the policy of proactively publishing CRLs in “real time” is not expressly addressed in the statute or regulations. While FDA has the statutory authority to publicize its findings and decisions if doing so does not disclose trade secrets or other confidential commercial information, the long-term policy and practical implications of this choice remain to be seen.
Although CRLs could be accessed through other means, FDA’s decision to centrally publish these letters appears to be rooted in several motivations. First, the agency aims to enhance public health through “radical transparency” by providing clinicians, researchers, payors, and patients with a better understanding of the scientific and regulatory shortcomings that prevent approval.
This initiative aligns with Commissioner Marty Makary’s assertion that “FDA does not belong to the industry; it belongs to the American people.”[4] In that same vein, FDA intends to share its reasoning for refusing to approve an application in order to counteract inefficiencies. This information may help other drug developers avoid costly delays in their product development process.
In addition, the policy purports to address the potential for applicants to obscure meaningful safety or efficacy concerns through their own characterizations or descriptions of the CRL. Specifically, because FDA historically does not publish CRLs for pending or unapproved applications, company stakeholders and the public rely on sponsors’ explanations regarding the rationale behind FDA’s decisions pertaining to their NDA or BLA.
According to FDA, the agency previously found that sponsors publicly announcing that their application was not approved did not mention 85 percent of FDA’s safety and efficacy concerns.[5] Further, the agency found that when FDA requests a new clinical trial for safety or efficacy in a CRL, sponsors failed to disclose that fact approximately 40 percent of the time.[6] Because disclosing this sort of information often has a direct impact on investments, funding of company research and development, or other rights and obligations, companies are necessarily thoughtful about how they communicate FDA’s findings and how they plan to address the agency’s concerns.
What are the potential implications for drug sponsors?
Although the majority of the CRLs published in July had previously been made publicly available through other methods, FDA has said that it is in the process of publishing additional CRLs from its archives and is continuously exploring ways of providing the public with greater transparency into its decision-making process.
Notably, Commissioner Makary has stated that the agency plans to release CRLs in real time,[7] even before it makes approval decisions – which would not only provide insight to drug developers on how the FDA thinks, but would also provide company shareholders greater visibility into exactly what the FDA has said about a drug in development. These letters would provide insight into FDA’s reasoning for denying a product application – information that could significantly help other applicants in their pursuit of market approval, especially if developing similar products.
At the same time, publishing CRLs related to pending applications may give competitors real-time insight into an applicant’s business and commercial strategy, despite the redaction of confidential and trade secret information addressed in a letter. The prospect of real-time publication also limits sponsors’ ability to assess or challenge FDA’s bases for the CRL or to correct potential inaccuracies in the CRL before the document is publicly available.
However, health regulators in other jurisdictions, such as the European Medicines Agency (EMA), publish similar assessment reports detailing reasons for authorization refusal opinions. While FDA- and EMA-specific requirements and processes for applications for marketing authorization can differ in certain ways, companies seeking to commercialize products in different countries have had to manage the impact of health authorities publishing similar product candidate evaluations for years. Some have suggested the benefit of gaining earlier access to FDA feedback on similar or competitor applications may outweigh the risks of competitors learning select details related to a company’s commercial plans through CRLs with a well-structured regulatory strategy.
Furthermore, sponsors with currently unpublished CRLs are encouraged to consider the potential legal ramifications if FDA ultimately releases those CRLs that had previously been private, as stakeholders may attempt to use information in a newly public CRL as the basis for various types of litigation ranging from product liability to securities fraud.
Incidentally, people holding an interest in a drug company may soon have access to CRLs issued for product candidates that were not ultimately approved and may determine that the company previously made material misrepresentations about FDA’s reasoning in those letters, potentially opening the door to securities claims against sponsors for misleading shareholders.
Similarly, companies are encouraged to evaluate the commercial impact real-time publication of CRLs may have on the business. Since issues raised in CRLs are generally resolved for approved products, letters made available prior to approval could affect public opinion of a product candidate or the sponsor generally, possibly impacting the trajectory of that company’s pipeline or commercial products. For example, any FDA findings of deficiencies with respect to manufacturing may negatively impact perception of the company as a whole, extending beyond the subject molecule to commercially available drugs that may be manufactured in the same facility. As such, sponsors can consider their legal and advocacy options to address these pre-approval CRL publications and how to best mitigate any material effects on the business.
What can we expect with future batches of CRLs?
As FDA has indicated, the agency is in the process of redacting thousands of letters[8] despite potential operational hurdles to publication, such as (1) lack of agency resources for redaction following the reductions in force and (2) providing the final materials in an interface that is more streamlined than a zip file that must be manually downloaded to access the letters.
FDA also faces potential legal hurdles to expanded publication. If the agency begins to release CRLs for products pending approval – which may be considered confidential commercial documents – this could open the door to legal challenges by sponsors seeking to maintain confidentiality of their development approaches and strategies.
However, the agency’s current position is that while commercial, financial, and trade secret information contained in CRLs always belongs to the applicant, “the deliberations of agency scientists are not the property of the drug’s sponsor.”[9] This position favoring greater transparency of agency deliberations may open the door to future challenges for FDA, as the agency has historically sought to protect certain aspects of its early deliberations pursuant to FOIA disclosure exemptions for agency “deliberative process privilege.”
FDA’s authority to publish CRLs in real time has not been challenged in a public proceeding yet. There may be arguments that “real-time” publication of CRLs prior to approval are not consistent with FOIA regulations and longstanding agency practices – including, for example, the practice provided in the regulations for FDA to (1) provide advanced notice to the holder of information that is subject to a request for disclosure and (2) make a determination whether to withhold or release information.
Looking ahead
In sum, FDA’s decision to centrally publish the CRLs reflects a marked shift toward regulatory transparency, driven by the principle that timely, balanced disclosure of the scientific basis for non-approval ultimately advances patient welfare, scientific rigor, and public trust.
Although the scope of the initial publication batch is confined to letters pertaining to subsequently approved drug and biologics applications, FDA signals a clear intent to continue publishing more materials.
In anticipation of FDA’s continued “radical transparency” initiatives, DLA Piper is monitoring the development of this complete response letter publication policy and possible expansion into pending applications and other areas, such as Not-Substantially-Equivalent (NSE) letters or major deficiency letters issued for medical device applications.
[1] https://home.agencyiq.com/article/00000197-faa0-d8be-adff-feb38f3c0000.
[2] Id.
[3] 5 U.S.C. § 552(b)(4).
[4] https://www.washingtonpost.com/opinions/2025/07/11/fda-transparency-new-drugs/.
[5] https://www.fda.gov/news-events/press-announcements/fda-embraces-radical-transparency-publishing-complete-response-letters.
[6] Id.
[7] https://www.cnbc.com/2025/07/11/fda-to-consider-drug-affordability-when-speeding-up-approvals-makary.html.
[8] https://www.cnbc.com/2025/07/11/fda-to-consider-drug-affordability-when-speeding-up-approvals-makary.html.
[9] https://www.washingtonpost.com/opinions/2025/07/11/fda-transparency-new-drugs/.
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