lundi 30 novembre 2015

Encore un cas significatif de manquement aux "Good Documentation Practices"...

Ce laboratoire allemand qui dispose de deux sites en Inde a été mis en demeure par l'agence américaine notamment sur les écarts suivants :

1.    Your firm failed to prepare batch production and control records for each batch of drug product that include documentation of the accomplishment of each significant step in the manufacture, processing, packing, or holding of the batch (21 CFR 211.188(b)).
On August 28, 2014, FDA investigators identified instances of non-contemporaneous documentation of batch production activities. Two uncontrolled Excel spreadsheets were used to record discrepancies and certain in-process drug quality data. This data was initially missing in the batch manufacturing record. Your firm later entered this data into batch records and backdated them.
2.    Your firm failed to maintain adequate written records of major equipment maintenance (21 CFR 211.182).
On August 25, 2014, FDA investigators found original preventive maintenance work orders in trash bags.  A partially-completed document retrieved from the waste receptacle included handwritten notes about the condition of equipment observed during preventive maintenance. However, the corresponding official record did not include the same information. Your response did not sufficiently identify the scope of these practices at your facility. 

3.    Your firm failed to ensure that each person engaged in the manufacture, processing, packing, or holding of a drug product has the education, training, and experience, or any combination thereof, to enable that person to perform his or her assigned functions, and that training in current good manufacturing practice is conducted by qualified individuals (21 CFR 211.25(a)).
During interviews with our investigators, your contract employee who trains other contract employees on good documentation practices was unable to explain the material he was required to present during training. In addition, while a significant number of your contract employees do not speak English, you only provided English training materials to these employees.  
We also found an employee’s failing equipment qualification training assessment form in the trash, yet that employee’s official file showed passing results.  According to your company policies, personnel with failing scores must be retrained, but your firm was unable to provide evidence of retraining in the employee’s official record.
 5.    Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)). 
On August 25, 2014, we found there were no access restrictions to laboratory data generated by the (b)(4) instrument used to test and release raw materials and in-process drug products.  Your laboratory computer systems lack necessary controls to prevent data tampering and to detect data that may have been compromised. 
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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.

Plus d'information ici.