Discussion forum for Pharma Quality events, Regulatory Actions
Warning letters, 483s, Recalls, Import Alerts, Audit observations
Warning letters, 483s, Recalls, Import Alerts, Audit observations
The USFDA issued a Form 483 to Strides Pharma Sciences Ltd., Bangalore facility (FEI 3004554612) following a May 2026 inspection by investigators Lisa L. Flores, Rafeeq A. Habeeb, and Constance Richard Math. The observations highlight significant lapses in:
Microbial testing procedures require a confirmatory identification test on positive samples by the Microbial identification system. But the method used for confirmatory identification of microorganisms was not validated or verified. Also, the microbial identification system was not qualified to identify all organisms routinely tested as part of Microbial Limit Testing (MLT).
The test practices were also deficient in counting / reporting the results for Total Aerobic Microbial Counts (TAMC). For a sample collected during the inspection a test result for TAMC was not considered Too Numerous to Count (TNTC) though results exceeded the alert and action limits. As per management since individual colonies can be counted the result are reported as CFU/ml and not TNTC. But upper countable colony limit for the method is not validated beyond the CFU threshold defined in the SOP. Recording the results as TNTC would have required initiating an Out-of-specification investigation. Also, there was no microbiological OOS investigations recorded in last 3 years.
In the Chromleon 7.3.2 Chromatography Data System, analysts were able to repeatedly alter integration parameters and view the numerical results and peak areas in the data processing window of the Chromatography Studio before saving the change in parameters. This allows the analysts to select favourable integration outcomes without committing changes to audit trail. Compensating controls like “Modify Processing Method – Restricted” and “Modify Processing Method – Custom” which would limit scope of editable parameters have not been activated for the Analyst roles.
Electronic audit trail records of manufacturing equipment were being permanently deleted after one year. Audit trails are reviewed only on the HMI and no print outs or electronic data are retained, resulting in electronic data not being available to review / verify for all batches in market. Audit trial review procedures do not define a limit for how many times equipment parameters can be changed during batch processing or a threshold for repeated parameter changes which will require an investigation. Due to this there is no document standard to evaluate whether a pattern of changes constitute an anomaly requiring an investigation. Also it was observed a single audit trail review procedure and checklist was applied to diverse manufacturing equipment which have different audit trail formats, alarm structures, event types.
There were multiple obsolete and unauthorised recipes in manufacturing equipment which could be selected from the HMI during commercial manufacturing to run a batch. The obsolete copies could not be deleted from the systems and there was no functional mechanism to prevent their selection during manufacturing of a batch. Recording of the recipe used in the batch manufacturing records were inconsistent and the Firm lacked dedicated procedures for recipe lifecycle management.
In the manufacturing equipment user access systems combined Quality assurance and Production personnel under same user category. This fails to enforce separation of duties when the procedures require recipe creation to be restricted to QA personnel
Deficiencies were also observed in both non serial product change over cleaning and serial batch to batch changeover cleaning. Residues were observed on the “Cleaned” status equipment in the Tablet Block after product change over cleaning; residues were also observed on top of the HEPA filter housing on the technical floor after manufacture of previous product before commencement of next product. Particulates in this zone had possibility of entering into manufacturing environment during product transition. While the cleaning procedures require cleaning to be performed with dismantling of equipment components followed by IPQA cleaning verification when equipment is in dismantled condition, it indicates these procedures are not enforced. Moreover, capsules of previous product were observed on the manufacturing line on the conveyor, chute assembly, tubing connecting line components after non-serial batch to batch changeover cleaning.
Deficiencies were also observed in ensuring testing of each shipment and each lot of high-risk components as per USFDA guidance’s. Even after procedures were revised the requirements were not implemented in time in the raw material specifications. These deficiencies were was not detected by the Firm’s Quality system, until inspection.
When advanced and sophisticated systems and solutions are implemented in cGMP operations it needs a thorough evaluation to ensure the systems are qualified covering all use cases; test procedures validated. When legacy systems having limitations in meeting current GMP requirements of computerised system controls, electronic data management are used, there should be a transition / upgradation plan to meet current requirements; in the meanwhile robust procedural controls should be established to assure equipment usage controls and integrity of data. Change control systems should be robust to ensure that when procedural changes are implemented all associated documentation, test procedures, specifications, SOPs are updated and aligned.
Leave a Comment
You must be logged in to post a comment.