Warning Letter due to unsuitable Production Equipment and insufficient Process Validation

Recommendation

6/7 June 2023

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After a tour of the production area of the Indian API manufacturer "Malladi Drugs and Pharmaceuticals Limited", the FDA inspectors quickly realised: the batches manufactured here run a high risk of being contaminated with vermin or foreign particles. The company's statement requested after the inspection had not properly addressed this risk and other observations made by the inspectors. Hence, a Warning Letter followed half a year after the inspection.

The following critical GMP deficiencies are laid down in said Warning Letter:

Vermin in the production area

Parts of the facilities in which active substances were manufactured had not been sufficiently separated from the outdoors. Inspectors observed birds and insects near the product. Open equipment is used for some of the manufacturing.

Inadequate equipment

The production equipment used does not comply with the state of the art. It is difficult to clean and carries a high risk of not removed impurities ending up in the product. The Warning Letter's next complaint shows that this has very likely already happened in the past:

Insufficient validation of the production process

Inspectors discovered OOS results after quality control for 24 batches over a period of two years due to non-specified impurities. Even though these non-compliant batches had been rejected, some of them were later reprocessed. Neither had all the main root causes for quality variations in the production process been identified nor had there been established controls throughout the production process in order to verify its robustness. This, however, is a requirement for the manufacture of validation batches in the course of a GMP compliant process validation.

Malladi Pharmaceuticals' products had already been placed on Import Alert by the FDA in December 2017.

For further details please see FDA Warning Letter to Malladi Drugs & Pharmaceuticals Ltd.