FDA Flags Sterility, Cleaning and Quality at Alvotech Facility

FDA has cited Alvotech’s Reykjavik, Iceland, manufacturing site for widespread sterility assurance, environmental monitoring, and quality-system failures following a June–July inspection, according to a 13-page Form 483. Investigators from CDER’s Office of Pharmaceutical Quality identified fundamental lapses in aseptic processing controls, cleaning programs, water-system oversight, and deviation management — problems that could compromise the sterility of both drug substance and drug product manufactured at the site, according to the inspection form.

For example, investigators found that room pressurization between classified spaces was not properly established or maintained, creating potential pathways for contamination. The firm’s environmental qualification studies also failed to challenge operations under true worst-case conditions, including inadequate simulation of maximum personnel occupancy in critical rooms.

Routine environmental monitoring was deemed insufficient, with too few sampling locations and no established alert limits for contamination recovery rates in some Grade C areas. Inspectors also observed operators removing shoe covers and exposing gown components when transitioning between Grade D and Grade C rooms — direct violations of aseptic gowning requirements.

During the inspection, FDA found that Alvotech lacked a validated, facility-wide cleaning and sanitization program. Disinfectant efficacy studies were incomplete, did not include testing at end-of-use dating, and often relied on mechanical wiping rather than evaluating the disinfectants themselves, the inspection form said.

During the facility walkthrough, inspectors saw sticky floors, standing water, debris, and an errant cleanroom wipe on the floor of a Grade C filling room just before drug-product operations, according to the agency. Crowded rooms and low-profile benches made it impossible to effectively clean certain areas, raising concerns about persistent contamination risk.

Inspectors also directly observed aseptic operators disrupting first air during setup and filling operations, handling unprotected sterile parts, and touching critical components with gloved hands that had contacted non-sterile surfaces. The company’s visual-inspection program also failed to classify vials with internal foreign matter as critical defects, despite their potential to compromise container integrity, FDA said.

Additionally, FDA’s inspection found systemic failures in how Alvotech documented, investigated, and trended deviations and out-of-specification (OOS) results. A 2024 update to the company’s quality-management system allowed laboratory OOS events to bypass deviation records entirely, limiting visibility into manufacturing issues.

The agency also cited widespread cancellation of deviations without proper investigation — including contamination events and equipment installation errors — as well as repeated data-integrity and document-control incidents that were closed without full follow-up.

FDA said multiple quality incidents involving missed logbook reviews, temperature excursions, and late data entries were treated as minor, despite representing GMP failures. The agency noted that required recurrence checks were incomplete and often failed to capture similar past events.