483 Observation Library

"Batch production records reviewed by the Quality Unit did not include documentation of the investigation into an atypical viscosity result observed during coating operations. No written record exists demonstrating that the released batch met all specifications and that investigation of the atypical result was satisfactory prior to distribution."

"Your firm's Quality Unit approved batch records without reviewing all required laboratory testing. The QP signature on the batch record was obtained prior to completion of stability testing required under your written procedures. No record documents the basis for the authorization decision or identifies what evidence was available to the QP at the time of release."

"Written batch production and control records do not contain complete information relating to the production and control of each batch. Records for batches containing out-of-trend dissolution results do not document the basis for the Quality Unit's decision to release product, what standards were applied to evaluate the trend, or the identity of the individual who authorized the release determination."

"The Quality Unit's review and approval of batch records does not include documentation sufficient to reconstruct the basis for release decisions. Reviewer signatures on batch records do not indicate what specific documentation was reviewed, what regulatory standards were applied, what alternative conclusions were considered, or what evidence supported the final release determination."

"Your written procedures do not include requirements for documenting the authorization decision when batch records contain deviations or out-of-trend results. Review of batch records containing flagged exceptions found that none contained a separate authorization document capturing the evidence reviewed, the standards applied, or the rationale for the release determination."

"CAPA records were closed without documented effectiveness verification. Your CAPA procedure requires effectiveness checks at 30 and 90 days post-implementation. No records exist demonstrating these checks were performed or that a qualified individual reviewed the effectiveness data and formally authorized the closure determination."

"The root cause identified in the current CAPA represents a recurrence of a deviation type addressed in a prior CAPA closed eighteen months prior. No record exists demonstrating that the effectiveness determination for the prior CAPA was reviewed as part of the current investigation, or that the prior authorization of effectiveness was evaluated in light of the recurrence."

"CAPA effectiveness was determined by the originating department without Quality Unit review or approval. Your CAPA procedure requires Quality Unit authorization of effectiveness determinations prior to closure. No records document Quality Unit involvement in the closure of multiple CAPAs reviewed during this inspection."

"CAPA closure records contain conclusions that corrective actions were effective without referencing specific data, metrics, or observations reviewed to support that determination. No record identifies what evidence was evaluated, over what time period, or what threshold was used to determine effectiveness had been demonstrated."

"The effectiveness check timeframe specified in CAPA records was extended beyond the required period without documented authorization. No record exists of who approved the extension, what data was available at the required check date, or what justified delaying the effectiveness determination."

"Laboratory investigation of an out-of-specification result failed to include documented authorization of the invalidity conclusion. Your investigation concluded the OOS result was attributable to analyst error. No record identifies the specific evidence reviewed, the evidentiary standard applied to support the invalidity determination, or the individual authorized to make the invalidity conclusion."

"Out-of-specification results were invalidated without completing a full Phase II investigation. Investigation records document a Phase I conclusion that assignable cause was identified, but no record exists of who authorized the decision to terminate investigation at Phase I, what standard was applied to determine assignable cause was sufficiently established, or the basis for proceeding directly to product disposition."

"Your firm's written procedure for OOS investigation does not require documentation of who authorized the final disposition decision — whether to reject, retest, or release — or what evidence was reviewed in making that determination. Review of OOS investigation records found that none contained a disposition authorization document separate from the investigation summary."

"Retesting of out-of-specification samples was initiated without documented authorization. No record exists of who authorized the retest, what basis supported the decision to retest rather than reject, or what protocol governed the number of retests to be performed and the interpretation of retest results."

"OOS investigation records were closed with the notation that root cause was not identified. No record exists of who authorized the inconclusive closure, what investigation activities were completed prior to closure, what additional activities were considered and rejected, or the basis for concluding that further investigation would not yield an assignable cause."

"A production deviation from written procedures was documented and a risk assessment completed. No record exists of the authorization decision to continue manufacturing — specifically, who authorized continuation, what evidence was reviewed at the time of the authorization, and under what risk framework the decision to proceed was made."

"Your deviation management procedure does not require documentation of the authorization decision for deviations classified as minor. Review of minor deviation records found that none contained documentation of who made the classification decision, what criteria were applied, or what evidence supported the determination that the deviation did not require investigation."

"Deviation records were closed without documented root cause determination. Closure records contain the notation that root cause was not identified but provide no record of who authorized this conclusion, what investigation activities were performed, what evidence was reviewed, or what supported the determination that investigation was complete."

"Your firm experienced a recurring deviation from the same written procedure that was the subject of a deviation closed in the prior period. No record demonstrates that the prior deviation investigation was reviewed as part of the current event, or that the prior authorization of closure was evaluated in light of recurrence."

"Immediate corrective actions taken in response to a production deviation were implemented without documented authorization of the product impact assessment. No record identifies who authorized the conclusion that the deviation did not adversely affect product quality, what evidence supported that determination, or what regulatory standard was applied."

"A change to your validated cleaning process was approved without documented risk assessment authorization. Your change control procedure requires a validation impact assessment for changes to validated processes. No record identifies who performed this assessment, what criteria were evaluated, or who authorized the conclusion that revalidation was not required."

"Your firm implemented process changes with Quality Unit approval signatures on change control records that do not document what the QU reviewed, what risk the change posed to product quality, or the basis for concluding the change did not require additional validation activities. The QU signature demonstrates approval was obtained; it does not demonstrate that the authorization decision was made on the basis of a complete risk evaluation."

"A software update to a system used in GMP operations was implemented without documented authorization of the qualification impact assessment. No record identifies who determined that the update did not require IQ/OQ/PQ activities, what testing was performed to confirm the update did not alter system functionality, or who authorized the conclusion that the existing validation remained valid."

"A change in raw material supplier was implemented following approval of the change control record. No documentation exists of the authorization decision regarding whether re-qualification of the affected process was required, what comparative analytical testing was performed, or who authorized the conclusion that existing process validation remained applicable to the new material source."

"Review of change control records identified instances where changes were implemented prior to formal approval of the change control record. No record documents who authorized early implementation, what risk assessment supported the decision to proceed before formal approval, or what retrospective review was performed to confirm the pre-approved implementation did not adversely affect product quality."

"Audit trail review identified instances of data deletion in GMP systems. No record exists of who authorized the deletion activities, what data was deleted, whether Quality Unit review occurred prior to the activity, or what regulatory basis supported the conclusion that deletion was appropriate."

"Your firm's procedure for audit trail review does not require documentation of who reviewed the audit trail, what anomalies were identified, what investigation was performed for identified anomalies, or who authorized the conclusion that anomalies did not represent GMP data integrity violations."

"Your firm used shared login credentials for GMP data entry systems, preventing attribution of individual data entries to specific operators. No record demonstrates who entered specific data values, who authorized specific data entries, or who is accountable for specific decisions reflected in the system record."

"Laboratory records contain manually transcribed data from instrument printouts. No written procedure requires documentation of who authorized the transcription, verification that the transcribed values match the original source data, or second-person review of transcription accuracy. Multiple instances were identified where the transcribed value differed from the instrument record."

"Your firm uses electronic signatures on GMP records without written procedures defining the meaning of each signature, the standards that must be met before a signature is applied, or the authorization granted by specific signature types. Electronic signature application procedures reviewed during the inspection did not specify what each signatory was certifying."