16-18 November 2021
Due to deficiencies in the investigation of the scope and root causes of reported complaints, the U.S. Food and Drug Administration (FDA) has issued a warning letter to an Indian drug manufacturer. The FDA inspection already took place in December of 2016. Because of the non-satisfactory reply in regards to the inspection findings by the manufacturer, the FDA issued the warning letter in August 2017.
The FDA inspectors noticed that investigations into process deviations and out-of-specification (OOS) laboratory results were insufficient, and did not include scientifically-supported conclusions. According to FDA the manufacturer´s response to this observation was inadequate because, amongst others, it failed to fully investigate the scope and root causes of a reported complaint. The FDA now expects the manufacturer to retrospectively review all complaint, manufacturing, and laboratory investigations associated with each product that is produced for the U.S. market. Furthermore, a plan to ensure that all future investigations are thorough, scientifically sound, and result in appropriate and effective CAPA (corrective actions and preventive actions) should be provided.
Another major deficiency was that the firm failed to follow the company´s own written procedures regarding the recall of failing products (for example: after receiving a complaint sample the defect has been confirmed, but a product recall as directed by company´s own procedures regarding recalls of defective products has not been initiated in time). Therefore, the FDA demands to provide a list and summary explanation for all other instances in which product(s) distributed within the last five years failed to meet established specifications, but for which actions prescribed in the firm´s Quality System Manual and recall procedure have not been taken. Additionally, the planned CAPA for each such instance should be provided including an explanation of CAPAs for ensuring to follow own procedures regarding product quality and recalls.
In addition the FDA observed deficiencies in cleaning operations. The authority demands sampling procedures and analytical methods used to test residues found during the inspection, including validation protocols and validation reports. Furthermore, a plan is required to ensure that personnel responsible for cleaning, verifying equipment cleanliness, and maintaining equipment are appropriately trained and capable of performing their assigned duties. An overall assessment of the adequacy of your cleaning program for all equipment, with special emphasis on difficult-to-clean parts should be provided.
Another deficiency was found regarding Process Controls. The FDA observed that the firm "does not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality". FDA’s guidance document, Process Validation: General Principles and Practices, for general principles and approaches that FDA considers appropriate elements of process validation, should be followed.
Find the details in the original FDA Warning Letter to Hetero Labs Limited.