Plant on the Road to Remediation as Celltrion Resubmits Biosimilars

Celltrion has completed the resubmission of versions of Herceptin and Rituxan to the US FDA after receiving complete response letters for the two biosimilars in April.

Earlier this year, the US Food and Drug Administration (FDA) issued complete response letters (CRLs) to South Korean drugmaker Celltrion for its rituximab and trastuzumab biosimilars. The letters cited a warning letter​ sent to the firm in January highlighting “multiple poor aseptic practices” at its production site in Songdo, Incheon.

The firm resubmitted CT-P10, a proposed biosimilar to Rituxan (rituximab) late last month, and this week the resubmission of CT-P6, a proposed biosimilar to Roche’s Herceptin (trastuzumab), has been completed.

“We expect the approval of CT-P6 and CT-P10 within this calendar year,” a spokesperson told this publication.

The resubmissions bring confidence that the GMP issues at the Incheon site are close to being resolved.

“FDA has notified us of its re-inspection schedule, and separately from this procedure, it has confirmed the resumption of the review procedure for the two proposed biosimilars upon the resubmission of the aBLAs [abbreviated Biologic License Applications].”

Teva

If approved, the two biosimilars will be commercialized in North America by Israel’s Teva Pharmaceutical Industries. The firm forged a partnership in 2016 worth US$160 million.

Teva has also contracted Celltrion to make the active pharmaceutical ingredient (API) for its proposed monoclonal antibody migraine treatment fremanezumab.

The warning letter pushed back the FDA’s Prescription Drug User Fee Act (PDUFA) action date for the candidate from mid-June to September.

The FDA directed its criticisms to the fill & finish plant, and not the production suite from where fremanezumab API is made. But the Federal Food, Drug, and Cosmetic (FD&C) Acts – Section 501(a)(2)(B) – states there is no distinction between API and finished pharmaceuticals when defining whether a facility is in CGMP compliance.

Both Teva and independent analysts are confident fremanezumab Celltrion’s issues will be fixed and the product will be approved.