Large Number of Deficiencies at Indian Manufacturer leads to Warning Letter

In January 2024, the FDA conducted an inspection at the Indian company Eugia Pharma Specialities Limited in Hyderabad. The FDA found a number of deficiencies, which it addressed in a Warning Letter dated 20 August 2024 after the company's responses to the previous 483 form were deemed inadequate. In summary, the list of deficiencies is as follows.

1. Incomplete laboratory documentation and data integrity

The above company failed to ensure that all required test data was fully and accurately documented in the laboratory records and process simulations, resulting in significant data integrity deficiencies. There were failures in the testing and monitoring of processes, which increased the risk of product contamination. In addition, environmental monitoring data was manipulated, e.g. the monitoring protocols of the ISO 5 and ISO 7 areas, which revealed systematic problems in production and quality assurance. Regarding the response to the 483 letter, the FDA stated:

"It appears from your response that you are denying affected employees access to the aseptic area while you conduct your investigation. However, your response did not adequately address how you plan to ensure that the individuals responsible for the data integrity violations are removed from positions where they can influence CGMP-related data at your facility. You also have not provided sufficient information to ensure the integrity of the data in your production and process simulations. Document control and data management are critical for CGMP to ensure the completeness, consistency and accuracy of data. Data should be assignable, legible, contemporaneously recorded, original or copy, and accurate (ALCOA) to ensure that complete and accurate records are analysed by the quality unit (QU) to support batch release."

2. Deficiencies in the documentation of production and control during cleaning and disinfection

Records of cleaning, disinfection and sterilisation of devices were incomplete and inaccurate. Employees documented cleaning activities without actually performing them, leading to potential contamination risks. Again, the FDA deemed the company's response inadequate. It wrote:

"In your response, you state that production and cleaning activities are performed under supervision and that video surveillance is also provided. However, your response is inadequate because it does not address how the video retention time will be sufficient for quality assurance to review the video footage as part of the batch release under 21 CFR 211.180(a). In addition, you have not adequately explained how you will ensure that your device records are checked for accuracy and completeness."

3. Failures in aseptic procedures - inadequate establishment of procedures for interventions, lack of validations and more

Serious deficiencies were found in the establishment of written procedures to prevent microbiological contamination. Where procedures existed, it was not ensured that they were followed. Employees were not following the prescribed aseptic behaviours, which increased the risk of product contamination, e.g. a high number of manual interventions. Again, the company's responses did not provide sufficient measures to reduce manual intervention and ensure compliance with aseptic procedures and behaviours.

4. Insufficient investigation of deviations

Eugia Pharma was also unable to demonstrate thorough investigations of deviations and effective corrective actions in production, particularly in the case of vial breakages or deviations during process simulations. The root cause analysis was inadequate, as was the establishment of CAPAs, which favoured the recurrence of problems.

FDA requirements

The FDA requires a comprehensive review and improvement of the CAPA programme, assurance of data integrity and regular audits. The authority expects the company to take measures to ensure data reliability and prevent potential violations. A management strategy and long-term measures are required to ensure the quality and safety of your products.

You can find more detailed information on this directly in the FDA Warning Letter.