- Poor aseptic practices and a failure to adequately investigate scores of complaints spurred the Food and Drug Administration to issue a warning letter to Celltrion Inc.'s manufacturing plant in Incheon, South Korea, according to the recently released document.
- Celltrion, which is best known for its expertise in biosimilars, disclosed receipt of the warning letter on Feb. 1, but the actual document itself hadn't been available online until the FDA posted it earlier this week.
- While Celltrion has said it doesn't expect the letter to disrupt its ability to supply Pfizer Inc. with Inflectra finished drug product, Teva Pharmaceutical Industries Ltd. may been in more of a bind. The Israeli drugmaker said the letter would likely result in delayed approval of biosimilars partnered with Celltrion.
The FDA's warning letter to Celltrion details several notable violations of current good manufacturing practices (CGMP), observed by the regulator in inspections from late May into June.
Perhaps most notably, the FDA noted Celltrion had received roughly 140 complaints over a nearly two-year period regarding the lack of an unspecified "something" in vials. While the key words are redacted in the letter, a "substantial number" of these complaints concerned U.S. batches.
Whatever was missing, the FDA warned that "this defect can significantly affect multiple quality attributes of your product over its shelf life."
Celltrion told the FDA it made changes, but the FDA was displeased with the conduct of the drugmaker's investigation.
Additionally, inspectors from the agency cited poor aseptic practices during the set-up and filling of vials. Celltrion revised its procedures, but the FDA noted the company failed to perform a retrospective investigation of the offending practice's potential impact.
In the letter, the FDA asked Celltrion to develop a corrective action and preventive action (CAPA) plan to address the potential contamination hazard. The agency also recommended Celltrion retain a CGMP consultant to help it remedy the deficiencies.
All of that may be too late to help Teva, which noted in its fourth quarter earnings that the warning letter had the potential to disrupt the timing of approval for both its biosimilar pipeline and key experimental drug fremanezumab.
Celltrion is the sole-source provider of active pharmaceutical ingredient for fremanezumab as well as two biosimilar candidates Teva and Celltrion are developing together.
Teva said it would work with the FDA in an effort to maintain the current priority review of fremanezumab, a CGRP inhibitor for the prevention of migraine.