vendredi 28 mars 2014

Un fabricant d'API sanctionné...

La FDA a adressé une mise en demeure à un fabricant de principe actif pour des manquements répétés à "l'intégrité des données" chromatographiques :

1. Failure to maintain complete and accurate laboratory test data generated in the course of establishing compliance of your APIs to established specifications and standards.
a. There was no written explanation for deletion events observed on audit trails for your standalone HPLC units. Your standard operating procedures (SOPs) did not include instructions for the retention of electronic raw data. In response to this letter, provide your procedures describing requirements to maintain complete data.
b. Your laboratory test data did not include records of the integration parameters used for any HPLC analyses.
c. There was incomplete raw data to support the test method validation/verification activities for the test methods used for your APIs.  Your response should include new test method validation/verification data for the (b)(4) residual solvents testing that was requested during the inspection. 
d. Our investigators identified the practice of performing trial injections for HPLC analyses prior to running the release and stability tests that are then reported. There was no justification for the practice of the trial preparations and injections. 
Your response indicates that the practice has been stopped.  Provide a comprehensive retrospective review and address any trial sample injections performed. Also provide an action plan that details how you plan to implement reliable laboratory controls to prevent the misuse or misidentification of test sample injections.
e. Our investigators identified calibration and media preparation records that were not authentic in that the persons that signed each record as having performed the activity were not at work on the day the work was accomplished. 
Audit and identify the extent of this activity in your laboratory and manufacturing operations and provide an update to your investigation into this matter. 

Plus d'information sur ce lien

lundi 17 mars 2014

Encore un rappel à l'ordre de l'US FDA...

Dans la gestion des données :

2.      Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
Your firm failed to prevent raw data from being deleted from the Atomic Absorption Spectrophotometer (AAS) used for elemental analysis testing. Specifically, our investigation found laboratory analysts had access to delete and overwrite AAS raw data. This instrument did not have sufficient controls to prevent unauthorized access to, changes to, or omission of data files and folders. This is especially concerning because our inspection uncovered only 38 raw data files on the hard drive of the AAS, while analysts stated that the AAS had been used for over 400 analyses. Your firm failed to store the raw data elsewhere. Therefore, all AAS testing results for which no raw data exists are in doubt. Your firm’s improper control over the laboratory records raises concerns about the quality of the APIs your firm has released.

Et dans la gestion des "Batch records" :

4.      Failure to ensure that APIs are produced according to pre-approved instructions and that batch production records include complete information pertaining to the production of each batch.
For example:
  1. Your firm erroneously calculated and then used the incorrect amounts of starting materials on multiple occasions. The inspection found that your firm did not calculate correct proportions of starting materials that were released for the production of (b)(4) USP and (b)(4) USP. Your firm’s Master Formula Records (MFRs) specify the proportions of raw materials, but your Batch Production Records (BPRs) do not include or describe calculations to appropriately adjust the amounts of starting materials to be used for a given batch size.     
  2. Your firm released APIs using BPRs that did not include the signatures of the production operators that performed each significant step or operation
  3. Your firm released API where production records contained missing information. For example, our inspection uncovered a Cleaning Report where the rinse sample pH was entered as “nil” despite the pH being a requirement to ensure the equipment is clean. 

Plus d'information ici.

lundi 10 mars 2014

US FDA et "Data integrity"...

La liste ci-dessous résume les récentes injonctions de l'agence américaine en matière de "data integrity":

Hospira, Mar 2013, Data Integrity

Puget Sound Blood Center and Program, April 2013, Lack of I/O Verification (Data Accuracy)

RPG Life Sciences Limited, May 2013, The computer system being used for HPLC did not have adequate controls to prevent unrecorded changes to data.

Fresenius , Jul 2013, Unacceptable practices in the management of electronic data.

Agila Specialist Private Limited, September 2013, The computer system being used for HPLC did not have adequate controls to prevent unrecorded changes to data.

Wockhardt Limited, Dec 2013, The computer system being used for HPLC did not have adequate controls to prevent unrecorded changes to data.

Ranbaxy Laboratories, Inc., Jan 2014, The computer system being used for HPLC did not have adequate controls to prevent unrecorded changes to data.

USV Limited, Feb 2014, The computer system being used for quality control laboratory did not have adequate controls to prevent unrecorded changes to data.