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Warning letters, 483s, Recalls, Import Alerts, Audit observations
Warning letters, 483s, Recalls, Import Alerts, Audit observations
USFDA Inspected UCB Farchim site at Bulle, Switzerland (FEI 3005023799) in June / July 2023. The site was inspected by USFDA investigator Arsen Karapetyan. The site was issued Form 483 with four observations. Some observations cite fundamental cGMP deficiencies like gaps in Data Integrity programme, lack of electronic data review, interrupting/ aborting of chromatographic runs, QA /QC personnel are able to delete data from desktops. Other observations include gaps in method verification / validation programs and inadequate procedures for material receipt and handling.
Observation 3
Deficiencies in Method validations, method transfers
 Firm has not performed analytical method transfers for (specific) active pharmaceutical Ingredients. Standard and sample solution stability has not been established as part of theHPLC method validation reports
Observation 4
Written procedures for Warehouse facility operations lack sufficient details for material receipt activities.
The regulatory requirements for method transfers, method validations are well defined and established. The USFDA require that accuracy, sensitivity, specificity, and reproducibility of test methods employed … shall be established and documented. The suitability of all testing methods used shall be verified under actual conditions of use (Guidelines: USFDA CFR 211.165, 211.194). Similar requirements are echoed in ICH Q7A (Section 12.8). ICH Q2 (R1) – Validation Of Analytical Procedure guideline recommends that If measurements are susceptible to variations in analytical conditions – example stability of analytical solutions – the analytical conditions should be suitably controlled or a precautionary statement should be included in the procedure (8. Robustness). USP 1224 – Transfer of Analytical procedures defines method transfer as an activity that qualifies a laboratory to use a method originated in another laboratory.
In line with the same it is imperative that analytical methods are either fully validated by a laboratory, or methods are verified (if it’s a compendial method) or transferred from the originating laboratory to the receiving laboratory to comply to the requirement that the method is verified under actual conditions of use. If a drug product manufacturer adopts a method for raw material (API) from the supplier and its fully validated at the supplier end, still a method transfer (can be achieved by a revalidation or partial validation) shall be performed and documented. This shall be defined in the Firm’s Validation Policy and Method Validation procedures. The robustness studies conducted as part of method validation shall verify the stability of the solution (to ascertain susceptibility of the method to variations in analytical conditions – like time delay for injection of standard / sample solutions) and based on the studies define the solution stability time in the analytical procedure.
Material receipt procedures in Warehouse shall be described procedure and ensured through appropriate checklists covering visual examination, labelling, name of material, supplier name & details (and is it an approved supplier), container damage, tampering of seals, contamination. (Guidelines: USFDA CFR 211.80, 211.82, ICH Q7A:Section 7.2)
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