FDA 483 - MSD International GmbH (Singapore Branch) - June 08, 2018

An FDA inspection conducted at MSD International GmbH (Singapore Branch) from June 4-8, 2018, revealed significant issues with the firm's manufacturing processes. The primary observation cited a lack of adequate written procedures for production and process controls, which are essential to ensure the identity, strength, quality, and purity of drug products. Specifically, the company failed to develop and validate robust controls over the process design for its drug substance, including insufficient collaboration with its manufacturing supplier to identify and characterize critical process parameters.

This deficiency led to the manufacturing process for the drug substance being insufficiently robust. Consequently, approximately 53 lots of the drug substance exhibited out-of-specification results for an unspecified impurity, identified as an oxidative degradation product, detected during incoming and recertification testing. The firm's Quality Unit initiated multiple deviation reports, prompting a temporary halt in the manufacturing of the associated tablets in February 2018. Although a cross-functional investigation identified the process as the root cause, an earlier assessment had failed to predict this impact.

As immediate action, the company implemented interim controls, including a tighter impurity specification, and resumed manufacturing in April 2018. However, the FDA’s observations, rooted in Good Manufacturing Practice (GMP) regulations, indicate that comprehensive, validated process controls and written procedures are still required to prevent recurrence and ensure consistent product quality. The firm must establish and implement these foundational controls to address the systemic vulnerabilities identified during the inspection.