From Indiana to Iceland, the FDA this week disclosed concerns raised during recent visits to a pair of manufacturing sites with troubled regulatory histories.
In the U.S., Novo Nordisk has been dinged for record-keeping shortfalls, lackluster control procedures over production processes and more at the Bloomington, Indiana, facility it acquired by way of Catalent when its parent, Novo Holdings, acquired the CDMO in 2024.
And further afield, biosimilar specialist Alvotech is facing new FDA reprimands over practices at its plant in Reykjavik, where the agency has flagged issues pertaining to the handling of complaints, subpar contamination-prevention procedures and poor quality and purity vetting, among other concerns.
In both cases, the agency handed down a Form 483 to the companies in charge of the offending sites following inspections earlier in 2026.
Forms 483 are doled out when the FDA identifies objectionable conditions or practices at manufacturing sites that could run afoul of the Federal Food, Drug, and Cosmetic Act. While the writeups include inspection observations, they do not represent the FDA’s final conclusions on compliance, falling short of the more serious reprimand of a warning letter.
"Since the inspection, Alvotech has submitted a comprehensive response to the FDA's observations and resubmitted the relevant Biologics License Applications," the company said in a Friday statement to Fierce Pharma Manufacturing. "We continue to work constructively with the Agency and remain confident in the quality of our ongoing manufacturing operations and regulatory review of our applications."
Novo had not yet responded to Fierce Pharma's comment request by publishing time. The fact that the companies received the Form 483 letters is not new information, with Novo’s divulged via an earlier analyst note and Alvotech announcing the outcome of its inspection in May, albeit with limited details on the FDA’s findings.
Now, inspection notes have been published to the FDA’s website.
Following an April inspection of the Catalent Indiana site, the FDA noted that “extrinsic biological particulates”—identified as mammal hair—have continued to be spotted in sterile drug products made there. Probes into the issue haven’t been timely, suggesting that Novo hasn’t figured out the root of the problem.
“Despite implementation of multiple corrective and preventative actions, you continue to observe mammalian hair in finished drug products,” the FDA pointed out in the Form 483.
The FDA also chided Novo for its investigations of roof leaks and lackluster processes around visual inspections for particulates or upon spotting “critical defects.”
“The visual inspection program is not adequately designed or implemented to ensure that in-process control procedures provide consistent detection, classification, and evaluation of product defects,” the FDA wrote, specifically pointing to the fact that the company may have failed to properly distinguish whether “light and dark fibers” identified during a visual inspection resulted from the internal manufacturing process or external contamination.
The FDA additionally flagged concerns with the adequacy of Novo’s sterility assurance programs in Bloomington, its environmental monitoring in aseptic areas, and the handling of records, controls and written procedures.
Prior to the site changeover to Novo, Catalent’s Bloomington site had already landed in the FDA’s crosshairs on several occasions. More recently, the site was hit with a warning letter last November. The FDA again harangued the company for improperly investigating more than 20 deviations linked to possible contamination of drug product from mammalian hair around the stopper region of vials. At the time, the warning letter identified the contaminants as cat and human hair.
Issues at the plant were tied to the complete response letter for Incyte’s PD-1 inhibitor Zynyz in first-line non-small cell lung cancer back in March, and both Regeneron and Scholar Rock have also been tripped up in regulatory review due to FDA concerns with the plant.
Alvotech’s Reykjavik facility is no stranger to FDA scrutiny, either, with the plant linked to the FDA’s snub of its Teva-partnered biosimilar to Johnson & Johnson’s anti-inflammatory med Simponi (golimumab) last fall. Following an inspection of the Icelandic plant that past July, the regulator said it had noted “certain deficiencies,” which needed to be resolved before the partners’ candidate could be approved.
The partners resubmitted their FDA application for the asset, coded AVT05, in June. The drug has already won regulatory nods in multiple other areas like the United Kingdom, broader Europe and Japan.
As for the observations in the recent Form 483, the FDA came down on Alvotech for its handling of complaints, pointing out that, since 2024, the Reykjavik site has received some 845 complaints related to redacted drug product batches distributed to the U.S.
The regulator also observed that procedures to prevent microbiological contamination of sterile drug products weren’t properly validated, and it further noted that Alvotech’s lab controls at the facility “do not include the establishment of scientifically sound and appropriate test procedures designed to assure drug products conform to appropriate standards of identity, strength, quality, and purity.”
The FDA also took issue with the quality of the Reykjavik team’s investigations into certain issues and the adherence of the site’s quality unit to necessary responsibilities and procedures.
Among the other Forms 483 posted this week was a citation for Zhejiang Huahai Pharmaceutical, which has also hired a former FDA staffer as its new chief quality officer in an effort to get a handle on its compliance issues. Huahai was slapped with a steep, 13-observation Form 483, some of which resurfaced deficiencies from a 2025 warning letter.
The FDA inspected Huahai’s production facility in Linhai, China, in April, the same month it paid visits to the Novo plant in Indiana and Alvotech’s Reykjavik factory.
Earlier this year, the FDA unveiled its first-ever draft guidance on best practices for responding to a Form 483, which some experts have suggested could be especially helpful for first-time responders.
That said, the depth of the responses the FDA seemed to expect in its guidance have the potential to create “tension” and exceed what smaller companies can realistically do within the regulator’s tight response window, Sonia Nath, chair of Cooley’s life sciences and healthcare regulatory practice group, said in an interview with Fierce.