The ObservationsUnderstanding the problemFDA Warning Letters Mentioning the Observation
Absence of an "adequately configured" audit trail function on data acquisition software Failure to prevent unauthorized access or changes to data, and to provide adequate controls to prevent omission of data.- This observation applies to Quality Control, Building Mangement Systems and other areas where computer generated data can impact Pharmaceutical Product Quality. Systems need to ensure that access to computer networks and servers is secure and restricted so that there is complete traceability of who performed which activity.Micro Labs, Apotex Research Private Limited, Novacyl (Thailand) Ltd, Hospira Spa Italy, Yunnan Hande BioTech Co. Ltd., VUAB Pharma, Mahendra Chemicals, Mylan Laboratories Limited, Unimark Remedies Limited, Sandoz Private Limited, Dr. Reddys Laboratories Limited, Sun Pharmaceuticals Industries Ltd., Cadila Healthcare (Zyfine), Zhejiang Hisun Pharmaceutical Co. Ltd.
Analysts with the power to delete/change test results Failure to maintain complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards Lab testing data saved into computers can be deleted by analysts. In addition the possibility exists where back-up files can be overwritten. The ability to delete results coupled with inadeqaute retention of complete raw data is not an acceptable GMP practice. The Information Technology (IT) department should be in placeMicro Labs, Novacyl (Thailand) Ltd , Hospira Spa, Italy, Yunnan Hande BioTech Co. Ltd. , VUAB Pharma, Mahendra Chemicals, Unimark Remedies Limited , Dr. Reddys Laboratories Limited, Cadila Healthcare (Zyfine), Zhejiang Hisun Pharmaceutical Co., Ltd.
Use of "Trial" or "Test" injections to confirm results before actual injections A culture of parallel testing is created where failing results are not recorded, investigated or stored per GMP guidelines. The "parallel" testing information is moved to random locations on the hard drive for storage. In many cases they may be in the “wastebasket” or in a “test” folder. While conducting test injections of actual samples is problematic, the management of the resulting data (either passing or failing) creates the actual deficiency in conforming to regulations.Micro Labs, Apotex Research Private Limited, Hospira Spa
GMP Documents found in the garbage Failure to maintain all quality-related documents appropriately. All GMP documentation records need to be stored for a duration longer than the expiry date of the product. 'Parallel' documentation cultures have investigators finding information, which can affect product quality, in unauthorized areas.Sandoz Private Limited, Dr. Reddys Laboratories Limited
Existence of a separate laboratory to conduct non-GMP activities The problem here is that the laboratory was not reported in the filing to the FDA, and rather than conducting non-GMP activities the data generated was used in GMP decision making. Development laboratories routinely assist in investigations upon which GMP decisions are made. Thus, their instrumentation and associated computer systems and written records should be compliant with the GMP requirements.Dr. Reddys Laboratories Limited
GMP Documentation was not completed at the time the activity was performed or had erroneous statements. Failure to record activities at the time they are performed. GMP stands for do-what-you-say, say-what-you-do and this needs to be done in real-time not after the activity has been performed.Transox Inc., Mahendra Chemicals, Unimark Remedies Limited, Sandoz Private Limited, Dr. Reddys Laboratories Limited, Cadila Healthcare (Zyfine)
Employee interviews made inspectors discover problems with GMP compliance. Poor training, poor understanding, overly complicated procedures, or employees simply following common unwritten practices supported by some level of management all create non-compliance problems during inspections.Mahendra Chemicals, Sandoz Private Limited
Selective Testing & Record Keeping Failure of your quality unit to ensure that materials are appropriately tested and the results are reported. Batch release decisions made by an incomplete review and evaluation of lab records is simply not acceptable. Failure to perform all the necessary tests, as required by the quality control release is also a non-compliance. The observations apply to various areas of Quality Control like HPLC, GC, IR, Karl-Fischer, Microbiological test plates, Water analysis etc.Micro Labs, Apotex Research Private Limited , Novacyl (Thailand) Ltd , Yunnan Hande BioTech Co. Ltd. , Transox Inc. , Pan Drugs Limited , Unimark Remedies Limited , Dr. Reddys Laboratories Limited , Zhejiang Hisun Pharmaceutical Co., Ltd.
Repeat testing of out-of-specification (OOS) or customer complaint results without an investigation or repeated failures of manufacturing process without an assignable cause Failure to thoroughly investigate any unexplained discrepancy or failure of a batch Failing product is a problem and a much bigger one if the product has already been released to the market. Companies need to investigate the exact cause of the problem and not keep testing failing material until they find a result or convenient rationale that is acceptable to them.Apotex Research Private Limited, Novacyl (Thailand) Ltd, Hospira Spa Italy, VUAB Pharma, Mylan Laboratories Limited, Sandoz Private Limited, Dr. Reddys Laboratories Limited, Sun Pharmaceuticals Industries Ltd. , Cadila Healthcare, Zhejiang Hisun Pharmaceutical Co. Ltd.
Disparity in Information Provided During the Site Inspection versus FDA records Pan Drugs Limited