FDA 483 - Valneva Scotland Ltd. - April 24, 2018

During an inspection from April 16 to 24, 2018, the FDA issued a Form 483 to Valneva Scotland Limited, a vaccine sterile bulk manufacturer. The document detailed significant observations indicating non-compliance with regulatory requirements for Good Manufacturing Practices (GMP).

Key violations included a systemic failure to thoroughly investigate unexplained discrepancies and out-of-specification (OOS) results. Many OOS investigations were inadequate, lacking robust root cause analysis, such as attributing temperature issues to external weather without supporting internal data, or failing to assess the impact of changes at external laboratories. The firm also did not track critical system stoppages or generate required problem notifications. Further deficiencies were noted in quality management, including a lack of written records for investigations, such as for failed HVAC recertification and the use of unapproved sample containers. This led to drug product batches being released without proper conformance to final specifications, including one batch sent to the U.S. market before the alternative containers' suitability was confirmed.

Environmental controls were also problematic, with HVAC units failing to maintain appropriate temperature and humidity, resulting in OOS conditions and mold excursions. Pressure differential controls were inadequate due to defective door seals and insufficient monitoring. Environmental monitoring probes were improperly positioned. Lastly, procedures for documenting critical system restarts were based on an unsubstantiated study, leading to restarts not being formally investigated. Valneva Scotland Limited is required to address these observations by implementing comprehensive corrective actions.