Un nouvel exemple de manquement à la "Data Integrity"...

Ce laboratoire indien connu a reçu une mise en demeure sévère de la US FDA dont voici les écarts les plus significatifs en terme de "Data Integrity" :

1.    Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.

 

Your laboratory records did not contain all raw data generated during each test for API batches manufactured at your firm. The investigator found that batch samples were routinely re-tested following failing or atypical results until acceptable results were obtained, and that failing or atypical results were not investigated or included in the official laboratory control records. 

 

During the inspection, the presence of an uncontrolled “Custom QC laboratory” (CQC) was discovered by our inspection team. The existence of this laboratory was previously unknown to FDA. Your QC Associate Director acknowledged that the CQC laboratory was involved in CGMP analysis of APIs intended for export to the United States through 2012. This discovery was made one day before the end of the inspection...

 2.    Failure to prevent unauthorized access or changes to data, and to provide adequate controls to prevent omission of data.

During the inspection we found the following examples of uncontrolled access to electronic systems used to generate data in your Product Development Laboratory (PD Lab).

 

a.    Your HPLC systems are configured so that no passwords are required to log in. Credentials are unverified.  Anyone who accesses the system can use software administrator privileges, which means that there is no electronic or procedural control to prevent manipulation of data.

 

b.    Your HPLC system had no access controls to prevent alteration or deletion of data. Furthermore, your HPLC software lacked an audit trail feature to document all activities related to the chromatographic analysis.  Because of this failure, neither your quality unit nor your laboratory staff could demonstrate that HPLC records included complete and unaltered data. They were also unable to verify that there had been no alterations or deletions.

 

c.    One of your analysts stated that another, unknown individual had logged into the system using the analyst’s credentials.  This unknown individual performed injections and deletions without the analyst’s knowledge.

 3.    Failure to record activities at the time they are performed.

Your employees did not complete batch production and control records immediately after activities were performed. When QA reviewers noticed missing entries in the batch records, they made a list of all the missing items on separate, uncontrolled pieces of paper that were provided to the production manager. Data were later entered into CGMP documents after operations had already ended as though they had been entered at the time of the operation.  

 

For example, on November 17, 2014, we saw eight production records for (b)(4) and (b)(4) that had blank entries for weights of material used for production, checked-by signatures, accessories used, in-house batch numbers, quantity added, and product labeling for material dried specimens. The yield report sheet and batch summary sheet were also incomplete.

 

Missing information was recorded on uncontrolled sheets of paper instead of in your official records.  Your staff told us that they write on sheets of paper to make management aware of missing data in the batch record.  Your December 15, 2014 response to this finding stated, “[w]e acknowledge and regret that some of the data such as weights, checked by signature etc…were not entered” (sic). You claim this practice was only observed in records related to the manufacture of (b)(4) active ingredients, and that the missing entries for weights were due to manufacturing equipment inadequacies.

 4.    Failure to control the issuance, revision, superseding and withdrawal of all documents with maintenance of revision histories.

a.    Your SOP 01-017/02 “Documentation Practices” requires that all controlled documents are completed and archived. However, on November 17, 2014, our investigator observed copies of issued, partially-used and unused batch records, analytical raw data, analytical results, training records, and cleaning validation protocols in the waste area.  These controlled documents had not been completed or archived in accordance with your SOP on documentation practices.

Enfin sur la libération des lots :

 3.    Failure to prevent unauthorized access or changes to data.

During the inspection, we found that QC laboratory analysts were authorized to release finished product in your firm’s computerized SAP inventory management system. Release or rejection of finished product is a non-delegable responsibility of the quality unit, and cannot be shared with laboratory analysts or other personnel. However, your SAP system permitted QC laboratory analysts to release intermediates from one process to the next process, as well as to release finished product into the market without requiring quality unit oversight.

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