FDA 483 - ADMA Biologics, Inc - December 11, 2024

An FDA inspection of ADMA Biologics, Inc., a licensed biological drug manufacturer in Boca Raton, FL, conducted from December 3-11, 2024, identified significant compliance deficiencies. The firm received an FDA Form 483 detailing multiple observations primarily related to quality system failures and inadequate aseptic processing controls for its Bivigam product.

Key issues included a failure to thoroughly investigate unexplained discrepancies. Inspectors noted instances of Bivigam bulk material undergoing unapproved temperature cycling and reprocessing during halted filling operations, without proper impact assessment or approved procedures. Crucially, the company inadequately assessed risk and failed to submit required deviation reports after five HIV NAT positive plasma units were inadvertently used in two Bivigam lots subsequently released to market. Additionally, a hypothesized root cause for low flow rate during processing was not fully investigated or addressed.

Environmental monitoring in aseptic processing areas was also deficient. Particulate levels in the Grade A filling area were poorly controlled, with numerous deviations exceeding action limits and improper particle counter placement. Furthermore, there was an absence of air monitoring for microorganisms during aseptic filling, and routine environmental monitoring for the Grade A area only met less stringent Grade C standards. Finally, the firm lacked established procedures for handling and responding to environmental excursions (e.g., temperature, humidity, particulates) during critical sterile filling operations. These observations highlight significant deviations from regulatory expectations, requiring ADMA Biologics to implement comprehensive corrective actions to ensure product quality and patient safety.