USFDA 483 to Eugia Polepally unit cites deficient aseptic practices

USFDA had inspected Aurobindo’s Eugia SEZ Pvt Ltd facility at Polepally, Telengana in India in Feb 2024. This was the third Eugia facility (FEI 3011905047) to be inspected by FDA in a span of 3 months after the Eugia US facility (December 2023) and Eugia Pharma Specialities (January 2024). USFDA investigators Ashar P Parikh and Marcellinus D Dordunoo inspected the facility and issued USFDA483 with seven observations. The USFDA 483 cites

1. Procedures to prevent microbial contamination of sterile products are not followed
   • All critical interventions into Grade A area are not covered by process simulation studies – operator leaning over to remove stoppers and vials with arm, fabric of cleanroom gown over vials. Personnel monitoring is not performed on operators after performing critical interventions into the Grade A area like removing vials, stoppers, touching multiple surfaces within the Grade A area.
   • A personal monitoring plate was observed to have one colony while both analyst and reviewer reported NIL colony.
2. Inadequate investigation and documentation
   • Failure of a product for Bacterial endotoxins was attributed to API used, API manufacturer investigation did not identify any definitive root causes and the probable causes identified were not specific only to API batches tested positive for endotoxins. Eugia tested all API batches and containers in stock (from the supplier) for endotoxins and released all batches which tested negative for endotoxins, though the API batches were manufactured before the API manufacturer taking any corrective action.
3. The NVPC (Non Viable Particle Counter) was not in the place it was intended to be inside the Grade A Area, due to which there is no data to represent the conditions during operations and interventions in the Grade A area.
4. Control procedures for the manufacturing processes are inadequate – Inspection Machine was not validated to detect particulates at the lower end of the visual range; inspection process cannot detect particulates from stopper material.
5. Inadequate backup of data. NVPC counters lack the functionality to save / back up electronic data, lack audit trail functionality for configuration of user accounts, passwords, date and time. There records are managed through manual logs and the electronic data cannot be verified.
6. Cleaning and disinfection in aseptic area are deficient to produce aseptic conditions
   • No disinfectant efficacy study on the tubing used to transfer the drug product; exterior of the tubing is not sterilised prior to installation in the filling assembly in Grade A area. No routine monitoring performed for various surfaces like step ladders, laminar airflow cabinets in Grade B, Gade A areas; a plate sample from step ladder was observed to have microbial growth.
7. Training for Visual inspection for inspectors are deficient to assess ability of inspectors to identify integrity defects.

USFDA 483 to Eugia SEZ Private Limited, Polepally, Telengana (Feb 2024)