- Though Teva Pharmaceutical has remained confident its closely watched migraine medication fremanezumab will launch later this year, problems continue to hang over the facility responsible for producing it.
- On Tuesday, drug manufacturer Celltrion disclosed that U.S. regulators issued a Form 483 for its plant in Incheon, South Korea. Regulators observed eight manufacturing violations during a mid-July inspection, including a lack of employee training and inadequate protocols for assuring product quality and purity.
- Celltrion said it is working with the Food and Drug Administration to address the issues. The agency has been critical of the Incheon plant since late January, when it sent a warning letter detailing how — among other things — there weren't written procedures in place to prevent microbial contamination of drug products. The snafus spurred a three-month delay on the FDA's approval decision for fremanezumab.
Faced with both generic competition to its top-selling product and more than $30 billion in short- and long-term debt, Teva's under immense pressure to bring new, lucrative treatments to market. High on the company's priority list right now is fremanezumab, a monoclonal antibody that targets a protein called calcitonin gene–related peptide, or CGRP.
CGRP-focused drugs have shown promise as preventative treatments for migraines, and in May Amgen and Novartis' Aimovig (erenumab) received FDA approval for that indication. Fremanezumab was poised to be the second CGRP to market, but manufacturing problems at Celltrion have slowed its progress.
Shortly after Aimovig's thumbs up, the FDA pushed back its prescription drug user fee act (PDUFA) date for fremanezumab from June 16, 2018, to Sept. 16, 2018. The company said in an emailed statement to BioPharma that it still expects an approval decision by that September date.
"The FDA noted several observations, which is not unusual following a reinspection," Teva said in the statement, regarding the Form 483. "Teva has reviewed the observations and do not feel they will impact our approaching PDUFA date."
In their observations, regulators took particular concern with the lack of formal documentation and protocols at the Incheon plant. For example, they noted no written procedures for dealing with glass vials that break during the filling portion of the manufacturing process. They also found staff ill-equipped to take care of the problem.
"Your firm only utilizes photographs for training on this defect, however these photos are unclear and inadequate to identify glass particles in vials. Without an adequate qualification vial, your firm cannot ensure your operators can observe this defect during 100% visual inspection," the FDA wrote.
While it's unclear exactly how quickly Celltrion will remedy these issues, Teva appears to be turning its attention toward fremanezumab's launch and competing with rival CGRPs like Aimovig, Eli Lilly & Co.'s galcanezumab and Alder Biopharmaceuticals' eptinezumab.
"I don't know that it really matters whether you're second or third to market because those products will be very close," Brendan O'Grady, head of Teva's North American commercial business, said on a second quarter earnings call at the beginning of August. "Most of the payers right now are blocking Amgen's product. So it's difficult to get reimbursement as they're looking at this market to form."
O'Grady added that Teva's in talks with payers about their 2019 formularies, and guessed most of the leading CGRP migraine drugmakers will enact some form of free product sampling program "so that they can work through the insurance coverage issues."