Warning Letter due to falsified Data and poor Maintenance

Recommendation

22/23 February 2024
Munich, Germany

API Regulatory Starting Materials
Definition, Manufacture, Assessment and handling post-approval Changes

Unhygienic conditions in a production facility, in which laboratory data was falsified, as well - each in its own right a show-stopper for passing an FDA inspection. Inspectors of the US supervisory authority found both offences at the facilities of Indian API manufacturer Alchymars ICM SM Private Limited. The resulting Warning Letter describes the findings as follows:

Quality control

The points-of-use for water in the production facility had been checked routinely for germ count by counting the colony forming units (CFU) on plates. When checking the plates, the inspector found CFU values that were significantly higher than in the quality control records. He also found microbial growth on plates with selective medium for which the record had declared "no growth". The inspector therefore concluded that the lab data was systematically falsified.

Maintenance of production equipment

The applicable production area SOP on handling the gaskets for equipment and piping in direct contact with the product had not been followed. The regular changing of gaskets as required by the SOP could not be retraced since there were no records of it.

Investigation into quality complaints

Despite the fact that earlier complaints could clearly be led back to worn gaskets, the quality assurance unit failed to conduct a root cause analysis for recent quality complaints. The complaint about "black spots" in the product was classified as "minor and unjustified", even though it must have been clear that the gasket wear is most likely to be blamed.

Hygiene deficiencies

The inspectors found the equipment washroom in a filthy condition (standing water on the floor, damaged tiles, dirty and sometimes malfunctioning hand washing facilities). The hand washing stations neither had hot water nor soap or hand drying equipment; furthermore, they were only accessible for personnel who had already put on their gloves and gowns for class-100,000 rooms.

Overall, the FDA inspectors classified the GMP deficiencies as major because there are APIs for parenteral dosage forms being produced in rooms with appropriate clean room classification at this site. The FDA therefore reserves the right not to process authorisation applications in which the company is named as the API supplier until such time as the deficiencies are fixed and the agency can confirm the company's compliance once again.

Please see the FDA Warning Letter to Alchymars ICM SM Private Limited for the details.