mercredi 27 juillet 2016

Des nouvelles défaillances de "Data Integrity"...

Des nouvelles injonctions de l'agence américaine mettent à jour des pratiques frauduleuses liées à la "data integrity" :

Pour cette société allemande :

4.     Failure to exercise sufficient controls over computerized systems to prevent unauthorized access or changes to data, and to provide adequate controls to prevent omission of data.

Our investigator found that your (b)(4) system used for (b)(4) and (b)(4) testing lacked access controls and audit trail capabilities. For example, all employees had administrator privileges and shared one user name, so actions could not be attributed or traced to specific individuals. This exposed your electronic data to manipulation and/or deletion without traceability.

Our investigator also noted that your firm copied raw data to a CD (b)(4), and then deleted the data from the (b)(4) system to free space on the hard drive. Files copied to the CD were selected manually; the selection process was not supervised. Without audit trail capabilities or supervised file selection, there was no assurance that all raw data files were copied to the CD before they were permanently deleted from the system.

Pour cette société chinoise :

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

During the inspection, an FDA investigator discovered a lack of basic laboratory controls to prevent changes to your firm’s electronically stored data and paper records. Your firm relied on incomplete records to evaluate the quality of your drugs and to determine whether your drugs conformed with established specifications and standards.

Our investigator found that your firm routinely re-tested samples without justification, and deleted analytical data. We observed systemic data manipulation across your facility, including actions taken by multiple analysts and on multiple pieces of testing equipment.

Specifically, your Quality Control (QC) analysts used administrator privileges and passwords to manipulate your high performance liquid chromatography (HPLC) computer clock to alter the recorded chronology of laboratory testing events.

3.     Failure to record activities at the time they are performed, and destruction of raw data.

Your employees did not complete batch production and control records immediately after activities were performed. Your operators used “mock” sheets (copies of the uncontrolled copy of the master production records) to capture critical manufacturing data. Your employees then completed and backdated batch production records days after operations ended.

Our investigator noted discrepancies between the “mock” sheets and the complete batch production record that your firm represented as the official record for that lot. Because of your uncontrolled documentation practices, you could not produce evidence that your batch production records were accurate.

Batch production records must be generated contemporaneously and include complete and accurate information on the production and control of each batch. The practice of using unbound, uncontrolled loose paper, in conjunction with backdating records, raises additional concerns about the integrity, authenticity, and reliability of all your data, and the quality of your API.
Enfin deux agences européennes ont relevés des manquements dans la gestion des données et des documents pour deux sociétés indiennes

Plus d'information ici et .

mardi 26 juillet 2016

Appel à commentaire de la MHRA sur la révision de son guide sur la "data integrity"

L'agence britannique publie une révision de son guide sur la "data integrity" 18 mois après sa publication initiale.

Ce guide est soumis à commentaires jusqu'au 31 octobre 2016.

Plus d'information ici

lundi 11 juillet 2016

Un point de vue de la MHRA sur le reporting électronique des événements d'essais cliniques

Cet article fait le point sur les systèmes de collecte de données cliniques au format électronique et les défaillances observées notamment au niveau de la gestion du changement des données, des manques de tests de recette (UAT), de la sécurité d'accès...

Cet article doit être lu au regard du point de vue de l'EMA publié précédemment.

Plus d'information ici

La FDA publie un guide de spécifications pour les "Quality Metrics"

La FDA a publié un document de 10 pages de spécifications techniques sur la présentation des données à l'appui des "Quality metrics" dans le cadre du cycle de vie de la validation du procédé et de l'évaluation du système de qualité pharmaceutique. Le guide sert de référence technique pour la mise en œuvre du projet de directives FDA «Quality metrics" qui a été publié en Juillet 2015 et peut être considéré comme un supplément.

Plus d'information ici.

lundi 4 juillet 2016

Des nouvelles injonctions de l'US FDA pour des sites chinois

L'agence américaine vient de publier deux mises en demeure adressées à des sites chinois ; certains des écarts portent sur les règles ALCOA de "Data Integrity" : 

1.   Failure to prevent unauthorized access or changes to data and failure to provide adequate controls to prevent manipulation and omission of data... a.    Our investigator’s review of the audit trail for the residual solvent stability testing indicated that an analyst manipulated your computerized gas chromatography (GC) system to falsify residual solvent stability results for multiple batches of (b)(4) API distributed to the U.S. For example, on March 4, 2016, your analyst set the GC personal computer (PC) clock back to make it appear as if testing had been done seven months earlier – on August 3, 2015. The analyst then performed five different injections to produce falsified results for long term stability 25C/65% RH 12 month time-point residual solvent testing for finished API lot (b)(4). The analyst deleted the first four backdated results and reported only the results of the fifth and final injection as passing in the quality control data package. Your quality unit relied on this incomplete data package to evaluate the quality of this lot of API and determine whether it was within specification. Our investigator observed that long-term stability results for at least five other lots of (b)(4) API were falsified using this technique of setting back the clock on the GC personal computer and then performing multiple injections until favorable results were obtained. Your firm failed to prevent analysts’ access to manipulate and delete laboratory data. In addition, your laboratory equipment lacked software controls to assure data integrity. b.    Our investigator’s review of the audit trails for the high performance liquid chromatography (HPLC) system indicated that, just prior to the completion of certain stability analyses for (b)(4) API, analysts routinely aborted the ongoing tests to prevent your HPLC system from recording some assay and impurities test data. Your HPLC system, controlled by Chemstation software, was configured to automatically delete the results if a test was aborted prior to completion. Our investigator’s review of the system’s limited audit trails indicated that when an analyst aborted assay and impurities tests, the partial results from the aborted tests were automatically deleted from your computerized HPLC system’s records.
 Et encore :

1.    Failure to have laboratory control records that include complete data derived from all tests conducted to ensure compliance with established specifications and standards. Your laboratory personnel conducted “unofficial” testing without appropriate documentation, justification, and investigation. The original, unofficial analyses were stored in a separate “Test” folder and were not part of the official quality control records. Our inspection found that your firm performed circa 8,400 of these unofficial chromatographic analyses between 2012 and 2014. According to your SOP-B-QC-022-01, Instrument Use Standard Operating Procedure, analysis of samples must be documented. The volume of data in these auxiliary “Test Folders” suggests that performing unofficial analyses is a common practice at your facility.

Plus d'information ici et .