The story of how an FDA write-up at one of Catalent's European plants contributed to supply difficulties for Novo Nordisk's obesity med Wegovy has been slow to develop, but more details are now coming to light.
Investigators dinged Catalent’s syringe filling facility in Brussels, Belgium for failing to thoroughly investigate batch failures or discrepancies, according to an FDA citation published Tuesday by BioProcess International. The CDMO also struggled with issues related to high-efficiency particulate absorbing (HEPA) filter failures, problems establishing written procedures for production and process control, plus subpar equipment maintenance, among other glitches highlighted in the seven-observation Form 483.
The regulator inspected Catalent’s Brussels, Belgium, plant from Oct. 18 through Oct. 26, 2021, according to the document.
On Tuesday, a Catalent spokesperson confirmed that the company "received Form 483 observations after a recent FDA inspection of its Brussels, Belgium, sterile filling facility."
“Catalent takes all FDA observations seriously and has made a proactive decision to implement engineering and quality upgrades for the air filtration system," he added.
Problems at the plant have “allegedly” fueled recent supply woes on Novo Nordisk’s obesity blockbuster-in-waiting Wegovy, BioProcess International first reported in early January. For its part, Novo last month said that a contract manufacturer doing syringe filling on the GLP-1 med had temporarily halted deliveries following a good manufacturing practices glitch. Then, this month, a Novo Nordisk spokesperson confirmed to Fierce Pharma that “the contract manufacturer referred to in the Dec 17 Company Announcement is Catalent.”
In the FDA citation, inspectors said Catalent didn’t “thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether the batch has already been distributed.”
The report homed in on a HEPA filter failure on a certain fill line. Catalent’s own investigation “failed to provide a comprehensive and detailed impact assessment for all products produced and distributed to the United States for the time period the Grade A environment was compromised and to prevent a recurrence of the failure,” the FDA said in its write-up.
Despite the issue, the regulator said four batches had subsequently been shipped to the U.S.
Meanwhile, the FDA also flagged other manufacturing areas with “a similar elevated level of HEPA filter failures."
Inspectors also dinged Catalent for failing to create written procedures for production and process control, which are meant to ensure that drug products come out with the proper identity, strength, quality and purity. The heavily redacted report flagged one drug product for which Catalent had not demonstrated that its filling process was “under control to ensure the prevention of contamination," the document says.
Microbial contamination also proved a sticking point. The FDA said that Catalent didn’t work out thorough validations to prevent microbial contamination of drug product that’s meant to be sterile. The manufacturer hadn’t drawn up adequate written procedures to prevent product contamination during aseptic processing, either, the FDA said.
Observation 5 concerned subpar equipment and facility maintenance, the FDA said. Alongside a piece of damaged equipment, the FDA flagged “two black lines” on a mechanical piston system, whose source Catalent couldn’t determine, according to the document.
Meanwhile, the manufacturer’s “laboratory analytical method for endotoxin has not been adequately validated,” and standard operating procedures aren’t followed “or are deficient,” the regulator’s write-up concludes. As for that last citation, the operating procedures for visual inspection of a certain media fill doesn’t include instructions for mixing samples prior to inspection, the FDA said. The FDA also noted several incomplete logbooks.
Catalent has worked up “a comprehensive plan to address all the observations,” the company's spokesperson said over email. “This plan is now in the process of being implemented and reviewed with customers and regulatory authorities.”
In its December communiqué, Novo Nordisk said that because of the manufacturing hiccup, which it left vague, it didn't expect to be able to meet Wegovy demand in the U.S. during the first half of 2022. At the time, the Danish drugmaker added that “few new patients are expected to be able to initiate treatment.”