When Celltrion received an FDA Form 483 last fall for the plant where it produces Pfizer’s biosimilars, the South Korean company shrugged it off by saying it was routine. But that routine citation has now been elevated by the FDA to a warning letter.
Celltrion today said the warning letter was issued Jan. 30 for one of its plants in Incheon and “raises issues related to certain manufacturing process at the facility.”
The drugmaker said it is making progress in resolving the problems and that the action does not affect its production of Inflectra, the Remicade biosimilar it produces with Pfizer. It said it currently does not anticipate any supply issues stemming from the action.
Pfizer didn't comment beyond saying it does not expect any supply issues for Inflectra, which had worldwide sales of $420 million last year, $118 million of which was in the U.S. where it has struggled to get traction against Johnson & Johnson's Remicade.
The agency action tracks back to an inspection it did at the Incheon plant in May and June. The 10-page, 12-observation Form 483 issued at the time focused (PDF) to a large degree on Celltrion’s slow response to investigating 140 customer complaints of issues tied to vial stoppers. Those were complaints over vials of the Remicade biosimilar that Pfizer has sold for several years in Europe as Remsima and launched last year in the U.S. as Inflectra.
The FDA also faulted Celltrion’s methods for preventing contamination of the sterile products and for not promptly investigating reports of particulate in some vials.
At the time the Form 483 was made public, Celltrion pointed out that the 140 complaints noted in the Form 483 were over vials of Inflectra in Europe, not "for Inflectra being marketed in the US.” It said the European Medicines Agency has reviewed and approved the fixes it has put in place to address the vial stopper concerns. Apparently, the FDA was less impressed.
The agency has been active of late with plant inspections in South Korea where a large part of the biologics capacity is now located. That has created issues for other U.S. companies. Last week, Irvine, California-based Evolus told investors that an FDA pre-approval inspection of the Daewoong Pharmaceutical plant in South Korea that will make its Botox biosimilar had received a Form 483 with 10 observations.
Daewoong assured Evolus that it has the situation in hand and expects “no significant further actions” from the FDA but the biotech acknowledged there are no guarantees. If the FDA makes Daewoong take additional corrective actions and go through a reinspection, its biosimilar candidate could be delayed, the company observed.