Celltrion Receives Warning Letter From FDA

The FDA has issued a warning letter to Celltrion, maker of the infliximab biosimilar Inflectra. The company announced today that, on January 30, the company received a letter from the agency that “raises issues related to certain manufacturing process[es]” at its Incheon, Republic of Korea facility.

Celltrion’s statement added that the company is “making progress addressing these concerns,” and is committed to working with the FDA to address the outstanding issues. Celltrion will provide a full response to the FDA’s letter within the next 15 days.

The company’s statement did not enumerate the issues of concern to the FDA, but news of the letter follows the September 2017 release of an FDA Form 483, which, while heavily redacted, indicated that, between the fourth quarter of 2015 and the time of the form’s issuance, the FDA received 140 complaints about vial stoppers, and that Celltrion had not yet implemented adequate corrective and preventive measures to address the problem.

The form noted a variety of inspection observations, including failure to review unexplained discrepancies (including issues with vial stoppers and the release of drug batches that contained particulate matter), failure to establish and follow procedures to prevent microbiological contamination, a lack of an adequate validation of the sterilization process, deficient environmental monitoring, deficient cleaning and disinfecting, inappropriate equipment design, flawed data documentation and incomplete records, failure to demonstrate that the manufacturing process can reproducibly manufacture drugs meeting quality standards, and inappropriate systems controls.

In its February 1 statement, Celltrion indicated that that the warning letter does not negatively impact the company’s ability to continue to make and supply Inflectra from the facility in question. However, it did not address whether the issues impact its rituximab biosimilar, which is authorized for marketing in the European Union as Truxima, or its trastuzumab biosimilar, which received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use in December 2017 and is awaiting final European Commission authorization.

Both the rituximab biosimilar and the trastuzumab biosimilar are currently under review by the FDA, with estimated regulatory action dates of February 2018 and March 2018, respectively. Notably, no Oncologic Drugs Advisory Committee meeting has been announced for either biosimilar.

Reuters reports that Celltrion’s shares fell by 5% on the news of the warning letter.