Warning Letter to Indian sterile Manufacturer due to Cross-Contamination and Particles

In April 2024, the FDA inspected the production facility of a manufacturer in Gujarat, India. Due to several serious GMP violations, a Warning Letter was issued by the authority. The main deficiencies identified were recurring cross-contamination and glass particles in the injectables.

Cross-contamination of products

Over a period of several months, the manufacturer repeatedly detected cross-contamination between different batches of medicinal products. This was due to inadequate cleaning of the shared production facilities. Particularly problematic was the production of a certain medicine that was considered to be particularly sticky on the contact surfaces. However, the cleaning process was not designed to completely remove this particular residue.

Despite these known deficiencies, the manufacturer continued production without conducting a comprehensive investigation to identify all affected batches and equipment. Only improved cleaning was introduced as a corrective measure, but this could not completely prevent cross-contamination. Several batches were even released, even though the manufacturer had identified a conspicuous contamination in other batches for which there was no sufficient explanation or investigation. Due to this cross-contamination, a recall was later initiated.

The manufacturer then committed to monitor products manufactured on non-dedicated equipment specifically for by-products (related substances). For the FDA, this is insufficient as this type of contamination is generally unevenly distributed and testing alone is not sufficient to determine the extent of cross-contamination and mitigate the associated risks.

Contamination with glass particles

Glass particles were found in several batches of an injection solution. Instead of conducting a thorough root cause investigation, the manufacturer limited itself to repeated visual inspections until the requirements were met without identifying the actual cause. According to the FDA, this poses a significant risk as potentially contaminated batches could be released onto the market.

In addition, the visual inspection staff were not sufficiently qualified. The glass particles found in the market goods were significantly smaller than the particles with which the staff had been trained, which according to the FDA leads to inadequate control. A recall of the injection solution followed.

Inadequate aseptic production and validation

The FDA also found aseptic working practices during production to be inadequate, particularly due to employee contact with sterile surfaces and inadequate airflow. Visualisation of the air flow (smoke studies) showed that the unidirectional air flow was not sufficient to ensure aseptic conditions during production.

The FDA requires the Indian manufacturer to take comprehensive corrective actions, including a review of cleaning, visual inspection and aseptic procedures. It was recommended to engage an external GMP consultant to avoid future violations.

The detailed Warning Letter to the Indian sterile manufacturer can be found on the FDA website.