The US Food and Drug Administration (FDA) last month sent a warning letter to Celltrion Inc following an inspection at its biomanufacturing site in Incheon, Korea.
The facility makes a number of biologics for Celltrion and its partners, and while the Korean firm has stated supplies of approved products – including Pfizer’s Remicade (infliximab) biosimilar, Inflectra – will not be affected, the letter may be problematic for candidates currently under review.
This includes Teva’s fremanezumab, an anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibody for the preventive treatment of migraine, accepted for US regulatory review in December last year.
According to Teva’s CEO Kåre Schultz, the active pharmaceutical ingredient (API) for the candidate is made at the same site, albeit not the part under direct regulatory scrutiny.
“It's a huge facility, but the part of the facility that was inspected was the finish-fill and pack manufacturing side, not the API part,” he said during a Q4 conference call last week. “But from a regulatory point of view it's the same facility site number, so to speak.”
The FDA has set a PDUFA date of mid-June, but Schultz admitted the warning could push this back.
“The key issue here is that our manufacturing of API is happening in a completely separate part of the facility, which was not inspected by the FDA. So we will, of course, be in a dialogue with FDA where we can hopefully conclude that it's a good idea to inspect that part in a PAI [Pre-Approval Inspection] and then based on the result of that, see whether we can get the approval on time.
“But that all remains to be seen and we'll be in a dialogue with the FDA about it.”
Fremanezumab – formerly known as LBR-101 – was added to Teva’s pipeline through the acquisition of Labrys Biologics in 2014 in a deal worth up to $825m.
Biosimilar problem
In October 2016, Teva inked a $160m deal with Celltrion for the potential commercialisation of two biosimilars in the US and Canada. The Incheon facility manufactures versions of Roche’s Herceptin (trastuzumab) and Rituxan (rituximab), both of which have been submitted by Teva for US regulatory review.
“It is possible that the remediation by Celltrion of the issues contained in the Warning Letter may impact the timeline of FDA review and approval of biosimilar rituximab (CT-P10) or biosimilar trastuzumab (CT-P6),” Teva spokesperson Kaelan Hollon told this publication.
“Celltrion is making progress addressing the concerns contained in the Warning Letter, and is committed to working with the agency to fully resolve all outstanding issues.”
Hollon was unable to comment further but said Teva remains committed to the commercialisation of these products in the US and Canada.