On September 5th, the FDA released 89 new complete response letters (CRLs) that had been sent to pharmaceutical manufacturers in 2024 and 2025. The release of these letters, indicating that the FDA cannot approve the drug maker’s product at the present time, were part of the agency’s transparency initiative that we reported on in July. The new searchable database seems to be a very useful tool, which provides CRL results for both products that were eventually approved and those that have not yet gained FDA approval.
In a few instances, the database enabled us to update our own information regarding lingering biologic licensing applications. In one case, Celltrion’s journey to FDA approval of its aflibercept biosimilar CT-P42 was further elucidated with CRL postings in June 2024 and March 2025. The latest CRL referred to facility inspection issues (a common CRL theme) that must be resolved. The initial CRL pointed to inspection issues as well as product quality issues. Note that the latter could not be elucidated because of heavy redactions in the public CRL copy. In an Email to BR&R, Celltrion stated, “As it indicates, the CRL concerns FDA’s observations from a recent on-site inspection of external manufacturing facilities. Following receipt of those observations, Celltrion proactively took corrective actions and responded to the FDA accordingly. The FDA has since completed its review of Celltrion’s response and confirmed Celltrion’s corrective actions. Celltrion’s BLA is currently under review by the FDA, and Celltrion remains fully committed to obtaining regulatory approval.”
In another case, Lupin has been trying to get its pegfilgrastim biosimilar LUBT004 over the finish line since 2021. The new database revealed the latest CRL was issued in November 2024, which also pointed to unresolved facility inspection problems.
The database revealed that Sandoz was also a recipient of a December 2024 CRL for a trastuzumab biosimilar that it is trying to commercialize with EirGenix. This product, EG12014, was tagged for facility inspection and microbiology issues. The 351(k) application was originally filed in December 2021.
Finally, Tanvex Biopharma received its own CRL (its second) for a trastuzumab biosimilar, which was filed for approval in October 2021. TX05 was rejected in January 2025 over facility inspection issues.
One should keep in perspective, however, that a CRL is commonly issued for new drugs and biosimilars. Many biosimilar manufacturers have received CRLs and subsequently went on to receive a product approval from the FDA. It is not necessarily an indicator of poor manufacturing quality or an incomplete application submission; more frequently, it is just a delay on the road to commercialization.
In Other Biosimilar News
Celltrion, Inc. announced that it will launch Avtozma (tocilizumab-anoh) in the United States in the fourth quarter of this year, following final distribution and patient-support program preparations.
The Association for Accessible Medicines announced that Alex Keeton is the new Executive Director of its Biosimilars Council. He replaces Craig Burton, who served in that capacity from May 2022 to June 2025. Mr. Keeton was most recently Vice President of Pharmacy Care Services at UnitedHealth Group.
(Note: This post was updated September 9, 2025.)
