mardi 24 janvier 2017

Des données incomplètes et un processus de gestion des retests incorrect...

On peut résumer ainsi les remarques présentes dans l'injonction de l'US FDA à cette société japonaise :

1.    Your firm failed to ensure that laboratory records include complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)(4)).
 
Reliance on incomplete data
Our investigator reviewed the audit trails generated by your high performance liquid chromatography (HPLC) system for impurities testing that you conducted on (b)(4) (lots (b)(4)(b)(4)(b)(4)). The audit trail showed that you performed this testing in duplicate. The audit trail indicated that you conducted a chromatography sequence analyzing impurities on samples of these lots beginning at (b)(4) on April14, 2014. The audit trail showed that a new sequence was started approximately 24 hours later, at (b)(4) on April 15, 2014, for impurities testing that again included samples for lots (b)(4)(b)(4), and (b)(4). None of the 19 chromatograms generated in the first sequence were maintained and available for review. Only the second set of chromatograms was maintained and relied upon in releasing lots (b)(4)(b)(4), and (b)(4) for use in the manufacture of products for the U.S. market. You could not provide any rationale for not maintaining the original data, and you failed to document a scientific justification for repeating the analysis.
 
Failure to appropriately maintain data
You do not maintain electronic data on your ultraviolet-visible spectrophotometer UV SP-502 which you use for content uniformity and identity testing of (b)(4) capsules, and it does not have an audit trail...
 

2.    Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).
 
Your analysts told our investigator that, until June 1, 2016, they were permitted to perform repeat testing without scientific justification or documentation. They also told our investigator that they were not required to maintain the data from the original results when performing investigations of system suitability failures, suspected errors, or out-of-trend results. Our investigator reviewed records of your investigations for a two-year period and found that you recorded only two minor deviations in the production area and no out-of-specification investigations...
 
Plus d'information sur cette injonction ici.

Plus d'information sur la gestion des OOS et la documentation des investigations ici et .

lundi 9 janvier 2017

Des enregistrements "falsifiés" pour ce fournisseur d'API...

En 2013, cette société avait déjà fait l'objet d'une injonction des autorités américaines pour des sujets similaires ; cette nouvelle injonction insiste sur la gestion des OOS, la revue des résultats, l'absence de validation de certains équipements et des défaillances dans l'enregistrement de données cGMP :

3.   Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)). While reviewing gas chromatography data on instrument QA/G07, our investigator found unreported results, including an out-of-specification (OOS) test result for raw materials. You did not investigate this OOS result or explain why you excluded the failing result from the official record. Our investigator also found that you reported only two of three chromatographic injections of sterile (b)(4) batch (b)(4) during in-process (b)(4) sample testing for residual solvent. You did not explain why you excluded the third injection. You decommissioned this instrument in July 2014 without reviewing the instrument data...

4.  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)). Our investigator found that you have not validated 12 computerized systems in your quality control laboratory. These systems are used for your stability chambers, ultraviolet (UV) and infrared (IR) spectrophotometers, and for thin layer chromatography (TLC)...

5.  Failure to record activities at the time they are performed, and destruction of original records. Data Recorded in Personal Diaries (Unofficial Notebooks)In your process development laboratory, our investigator found several unofficial notebooks recording sample preparation for OOS investigations, route-of-synthesis experiments, and scale-up data. Our investigator found discrepancies between these unofficial notebooks and the official data retained by your quality unit. Destruction of CGMP DocumentationCGMP documentation was discarded without being assessed by your quality unit. Our investigator found torn and shredded equipment maintenance documents, raw material labels, and change control work orders in your scrap yard awaiting incineration. Your staff lacked knowledge of your corporate procedure for the destruction and incineration of documents.

Plus d'information ici.

 

jeudi 5 janvier 2017

Une ligne directrice sur la gestion des documents et enregistrements

Développée en janvier 2016 par les Laboratoires Officiels de Contrôle des Médicaments (OMCL), la Directive sur la Gestion des Documents et des Enregistrements traite de la gestion des documents, enregistrements et données internes et externes relatifs aux activités des OMCL.

Cette directive, pertinente pour les laboratoires, peut être utilisée pour établir les contrôles associés à l'intégrité des données.

Cette directive peut être consultée ici.