Written from the deficiency categories regulators publish, not from named reports. Each entry shows the observation in the inspector's style, why it was cited, and the practice that would have prevented it.
Product quality review: no evaluation of trends in finished product or in-process results
The Product Quality Review for Product X (PQR-25-011) presented finished product and critical in-process results for 40 batches in tabular form with a conformance column. No control charts, control limits, capability assessment or comparison with the previous review period were included for any parameter. The review concluded that 'the process remains in a validated state of control'. On review of the tabulated data, dissolution at 30 minutes had declined from a mean of 91 per cent in the first quarter to 84 per cent in the fourth quarter against a limit of not less than 80 per cent. This trend was not identified in the review.
Product quality review: not conducted in a timely manner; no documented extension
Site procedure QA-SOP-042 requires the approved Product Quality Review to be issued within six months of the end of the review period. At the time of inspection, the reviews for four of the site's eleven products for the period ending 31 December of the previous year had not been approved, the latest being nine months beyond the procedural deadline. No deviation, extension or risk assessment had been raised for any of the four. The QP responsible for certification of these products was not aware that the reviews were outstanding.
Product quality review: results not evaluated; no assessment of need for CAPA or revalidation
The Product Quality Review for Product Y (PQR-25-004) recorded twelve deviations during the period, of which eight related to tablet weight variation at compression on line C, a stability study in which the principal degradant had reached 0.42 per cent at 18 months against a shelf-life limit of 0.5 per cent, and two complaints of chipped tablets. The conclusion stated that 'the process is considered to be in a state of control, the specifications remain appropriate and no corrective or preventive actions are required'. The conclusion was identical in wording to that of the previous year's review. No assessment of whether CAPA or revalidation was required had been documented.
Outsourced activities: contract giver failed to evaluate the product quality review; technical agreement inadequate
The marketing authorisation holder's product file for Product Z contained the contract manufacturer's Product Quality Reviews for the last three periods. None bore any evidence of review, assessment or approval by the MAH. The most recent review recorded 'no marketing authorisation variations submitted' whereas the MAH had submitted and been granted two variations affecting the finished product specification in the period; the MAH had not supplied this information to the manufacturer. The quality agreement stated only that 'the Contract Acceptor shall perform Product Quality Reviews in accordance with EU GMP' and did not define the parties' responsibilities in producing the review or the MAH's role in evaluating it.
Product quality review: adequacy of previous corrective actions not reviewed
Section 9 of the Product Quality Review for Product W, 'Review of adequacy of previous corrective actions', stated 'Not applicable' for both the current and the previous review period. The review two periods earlier had raised three actions: replacement of the coating pan exhaust filter, revision of the in-process limit for coating weight gain, and requalification of the purified water loop. The status of these actions was not recorded in either subsequent review. On enquiry, the water loop requalification had not been performed.
