Celltrion has received a US FDA Form 483 at its troubled biomanufacturing plant in Korea with eight observations not raised in a previous warning letter.
In January, the US Food and Drug Administration (FDA) sent Korean drugmaker Celltrion a warning letter highlighting “multiple poor aseptic practices” at its production site in Songdo, Incheon. An FDA reinspection last month has now resulted in a Form 483 with eight observations.
The 483 itself, uploaded by the Agency, cites issues with Celltrion’s drug product and drug substance facility including a lack of training among processing staff, failures in having written procedures for production and process controls, deficient procedures describing the calibration of instruments and apparatus. In a heavily redacted section of the Form, the Agency also found issues during the transfer of product from the harvest tank and said Celltrion has “no procedures in place to address downstream spills.”
Celltrion said the eight observations at the facility in Songdo, Incheon are “manageable and correctible” in a statement sent to BioProcess Insider.
“Celltrion provided comprehensive response ahead of schedule to the agency to address the observations. Celltrion awaits the outcome of the recent re-inspection and expects outstanding observations will be lifted very soon.”
Spokesperson Daniel Yoo added all eight observations are “separate from the issues raised in the previous warning letter. The previous observations in the warning letter are not mentioned at all in the latest Form 483.”
‘No impact’ on Teva’s fremanezumab
The January warning letter was cited in complete response letters (CRLs) sent to Celltrion in April concerning two biosimilar products: CT-P10, a proposed biosimilar to Rituxan (rituximab), and CT-P6, a proposed biosimilar to Roche’s Herceptin (trastuzumab).
Both were resubmitted by Celltrion and despite the 483 the firm told us it “is committed to working with the agency to gain approval of CT-P10 and CT-P6 by the end of this year.”
Similarly, Celltrion’s troubles had a knock-on effect for its client Teva Pharmaceutical Industries, pushing back the FDA’s Prescription Drug User Fee Act (PDUFA) action date for proposed monoclonal antibody migraine treatment fremanezumab from mid-June to September.
Teva spokesperson Yonatan Beker told us the firm is pleased the FDA has completed its reinspection of Celltrion’s facility, as well as the Pre-Approval Inspection (PAI) for fremanezumab.
“We remain on track for the Prescription Drug User Fee Act (PDUFA) action date of September 16, 2018. The FDA noted several observations, which is not unusual following a reinspection. Teva has reviewed the observations and do not feel they will impact our approaching PDUFA date.”