French Drugmaker Gets Warning Letter for Testing Deficiencies, Process Validation

The FDA hit Biologique Recherche with a warning letter after observing multiple violations at its Paris facility, noting inadequate testing methods, quality control concerns and a lack of validation for manufacturing processes, among other issues.

The investigation revealed that the firm released an OTC drug product without properly testing its active ingredients and requested that the company provide all chemical and microbial test methods and specifications involved in analyzing OTC batches. The agency also requested a summary of test results for retain samples of relevant OTC drug products that were distributed in the U.S.

The French drug manufacturer also relied on certificates of analysis from unqualified suppliers instead of testing the attributes of incoming raw materials used in manufacturing. The company was asked to give quality control release specifications for all incoming components and the tests used for each lot. It was also requested to provide summaries of test results and procedures used to qualify COAs and contract facilities, as well as a comprehensive, independent review of its material system to ensure all ingredients and items received from suppliers are qualified.

The firm’s quality control unit also was missing numerous written procedures for various functions, such as investigating deviations, conducting annual product reviews and handling product returns. It did not have procedures to handle reconciling labels, creating batch records or approving batch records and releasing batches, and lacked procedures for investigating OOS results. The agency told the firm to provide a CAPA plan to ensure it reforms its quality unit to address the missing procedures.

The firm also failed to validate its manufacturing processes. For example, it did not conduct process performance qualification studies and had no ongoing program to monitor process control for consistent drug quality and stable manufacturing operations. The agency asked for the firm to provide its validation and qualification protocols, in addition to details on how it will monitor sources of variability in its operations to minimize batch variation and assure consistent quality.

The agency noted that the firm’s quality unit was not able to fully exercise its responsibilities due to a lack of resources and authority, and recommended that the company hire a consultant to help address its CGMP violations.