FDA 483 - GlaxoSmithKline Biologicals - March 12, 2024

GlaxoSmithKline Biologicals received an FDA Form 483 following an inspection at its Saint-Amand-Les-Eaux, France manufacturing facility from March 4-12, 2024. The inspection revealed several significant observations indicating deficiencies in manufacturing controls and regulatory reporting, representing non-compliance with Good Manufacturing Practices. Key issues included a failure to thoroughly investigate unexplained discrepancies, specifically a 46-day delay in addressing atypical cracks in glass vials used for Shingrix vaccine, despite supplier reports confirming a weakness. This issue affected millions of Shingrix vials released to the U.S. market and was corroborated by customer complaints about broken vials. Further observations noted inadequate procedures for equipment cleaning and maintenance, evidenced by splinter-like cracks on equipment in the aseptic filling area. The company also failed to perform annual visual inspections of Shingrix vaccine reserve samples for deterioration. Critically, 84 serious and unexpected adverse drug experiences for Shingrix were reported to the FDA significantly past the required 15-day deadline, with delays extending up to 357 days. The firm also lacked timely corrective and preventative actions to prevent future reporting delays. These observations require GlaxoSmithKline Biologicals to implement comprehensive corrective actions to address the identified manufacturing, quality control, and regulatory reporting deficiencies to ensure product quality and patient safety.