Ce fabricant chinois a reçu une injonction sévère des autorités américaines dont certaines sont liées à l'intégrité des données :
3.Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.
For example, our investigator reviewed the audit trail from your assay testing for (b)(4) lot (b)(4), and found that you tested the same sample set three times over several days without documentation or investigation. You reported only the result of the third and final test for purposes of completing your certificate of analysis and releasing this batch of API.
4.Failure to prepare adequate batch production records and record the activities at the time they are performed.
For example, our investigator found that your operator used process parameter values from previous batches of (b)(4) to complete new batch records when she was too tired to immediately record the data and had forgotten the values.
L'agence américaine mentionne l'incapacité de cette société indienne à fournir des enregistrements électroniques à des fins d'inspection :
3.Failure to provide records required to be readily available for authorized inspection (21 CFR 211.180(c)).
During the inspection on October 18, 2016, your firm did not provide batch records to our investigator. At the conclusion of the inspection, you stated that you would provide these records electronically within a matter of days. To date, FDA has not received any batch records.
Pour ce fabricant d'API chinois, les certificats d'analyse émis sont incomplets :
1.Failure to transfer all quality or regulatory information received from the API manufacturer to your customers.
You omitted the name and address of the original API manufacturers on the certificates of analysis (COA) you issued to your customers, and did not include copies of the original batch certificate.
For multiple API, you generated COA by copying and pasting analytical results from the original API manufacturers, replacing the manufacturers’ information with your letterhead, then issuing these COA to your customers. You omitted critical information, including the original manufacturers’ names and addresses and the names, addresses, and telephone numbers of laboratories that performed the testing.
Customers and regulators rely on COA for information about the quality and sourcing of drugs and their components. Omitting information from COA compromises supply-chain accountability and traceability, and may put consumers at risk.
Cette mise en demeure met l'accent sur la copie des enregistrements à destination des inspecteurs :
3.Limiting access to or copying of records
Your firm limited access to or copying of records that our investigators were entitled to inspect. For example, our investigators requested records of your audit trail data from all chromatographic systems used to test drugs for the U.S. market at your facility. The files you ultimately provided (in the form of Excel spreadsheets rather than direct exports from your chromatographic software) were not the original records or true copies, and showed signs of manipulation. The records you did provide contained highlighting, used inconsistent date formats, and lacked timestamp data; these features are inconsistent with original data directly exported from chromatographic testing software.
Our investigators and their supervisor explained at least twice that the data you provided was not representative of actual audit trail data from the chromatographic systems, and requested that you provide the original, unmodified records. Your firm stated, without reasonable explanation, that you could not provide the requested audit trail records. When our investigators explained that your failure to provide the requested records would be documented as a refusal, you acknowledged the refusal.
Our investigators documented other instances in which your firm limited the inspection by providing some, but not all, of the records requested by the FDA investigator that FDA had authority to inspect. At multiple times during the inspection, FDA requested records of CGMP activities performed in your R&D laboratories at the behest of your quality unit. However, you limited the inspection by providing only a subset of the requested records, and our investigators also found at least one of the requested records shredded in the trash. Finally, our investigators requested chromatograms to substantiate your claim that you had identified and quantitated the impurities in (b)(4), but you never provided the records that our investigators asked for to support your claim.
2.Failure to prevent unauthorized access or changes to data and failure to provide adequate controls to prevent manipulation and omission of data.
During the inspection, our investigators discovered a lack of basic laboratory controls to prevent changes to and deletions from your firm’s electronically-stored data in laboratories where you conduct CGMP activities. Specifically, audit trail functionality for some systems you used to conduct CGMP operations was enabled only the day before the inspection, and there were no quality unit procedures in place to review and evaluate the audit trail data. For example, you used standalone HPLC (2-RD HP/SM/32) to conduct analyses for Drug Master File (DMF) submissions and investigations, such as characterization of a starting material for your (b)(4) DMF. You also used uncontrolled systems to conduct out-of-specification (OOS) investigations for in-process materials used to manufacture (b)(4) API.