FDA warns contract testing laboratory for CGMP deviations
The US Food and Drug Administration (FDA) last month issued a warning letter to New Jersey-based contract testing laboratory International Trading Pharmaceutical Laboratories (ITPL) over significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).During a two-week inspection in October 2019, FDA found that ITPL’s Quality Unit had not acted on findings of an out-of-specification (OOS) investigation; chromatographic injections of samples were not included in the investigation or reviewed. Also, the client was not informed of OOS findings.
Data from several samples tested with chromatographic injections were either omitted from the analyst’s notebook, or not included in the OOS investigation, and samples were used for test runs.
FDA issued the warning letter after determining ITPL’s response to its inspection report did not provide enough detail and evidence of corrective actions. The response was deemed inadequate because the firm had not reviewed its electronic chromatographic data. Further, the updated procedure proposed by ITPL’s response to the inspection report failed to make clear that sample materials cannot be used for test, preparation, or equilibration runs.
Corrective actions required of ITPL include updating procedures for chromatography analysis that explicitly addresses trial run materials and providing a comprehensive assessment and remediation plan for the firm’s quality unit.
The warning letter noted a second finding that an investigation into critical deviations and failures of API batches to meet specifications had been closed without adequate scientific justification. Testing of four samples in October 2017 showed that an unknown peak was co-eluting with the sample peak. The client was unwilling to conduct sample stability studies to determine whether the age of the sample – 15 days at testing – was responsible for the co-eluting peak, but the FDA deemed this response inadequate, noting in the warning letter that “Contract analytical testing laboratories are responsible for operating in compliance with CGMP for the operations they conduct, regardless of discussions they may have with clients. Such labs must employ adequate controls to ensure that data, equipment, and test results are reliable and maintained in accordance with CGMP requirements.”
The FDA required an independent review looking back at 3 years of OOS results for drug product and API testing, as well as a comprehensive review and remediation plan for ITPL’s OOS result investigation systems.
Third, ITPL was found to have failed to ensure the suitability of analytic methods for drug samples. In its inspection, the FDA found that multiple API samples had been subject to assays and identity testing without verifying suitability of the tests under actual conditions of use.
ITPL is to remedy this failure by providing results of a comprehensive independent assessment of its drug test methods to determine suitability, with a plan for any needed verification or validation. Procedures and training records reflecting updates and changes should also be provided.
A final finding of insufficient computer and data controls addressed a lack of data integrity for high performance liquid chromatography (HPLC) and gas chromatography (GC) testing. Both HPLC and GC systems were run on stand-alone computers, making it possible to alter date and time stamps and delete data files. The lack of an audit trail prevented the detection of such data manipulation.
The FDA said that ITPL’s proposed remediation were inadequate because the lack of an audit trail wasn’t properly addressed, and the proposed generation of a paper trail of chromatogram printouts does not sufficiently capture the dynamic nature of electronic records.
The FDA strongly recommended that ITPL retain a consultant for data remediation efforts. The firm is to provide results of a comprehensive investigation of data records and reporting inaccuracies. Additionally, ITPL is to conduct a risk assessment of the failures observed by the FDA on test results, including risks to patients. Finally, the FDA called for a management strategy that includes a corrective action plan, a root cause analysis of the data integrity problems, and interim and long-term remediation measures, as well as a status report.
FDA