Data Integrity Remediation


In a recently posted warning letter, the FDA identified significant data integrity issues associated with electronic data logs for production equipment and laboratory records.

This citation was based on:

  • The firms electronic data logs not retaining alarm messages indicating when certain manufacturing parameters exceed their limits during production operations.  Additionally, FDA identified a lack of evidence that these excursions were investigated for impact to product quality.
  • The firms laboratory audit trails identified multiple occasions of additional testing for various patches that were not reported, and non-unique (non-traceable) sample names which prevent traceability of cGMP activity.

The FDA included a three part response request for Data Integrity Remedation (reproduced below):

Data Integrity Remediation
 
Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. We strongly recommend that you retain a qualified consultant to assist in your remediation. In response to this letter, provide the following.
A.    A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:
  • A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.
  • Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.
  • An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.
  • A comprehensive retrospective evaluation of the nature of the testing and manufacturing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.
B.     A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations.
C.    A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:
  • A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all of the data you generate, including analytical data, manufacturing records, and all data submitted to FDA.
  • A comprehensive description of the root causes of your data integrity lapses, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.
  • Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.
  • Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.
  • A status report for any of the above activities already underway or completed.

FDA has stressed data integrity as a component of cGMP inspections and issued specific guidance (draft) to clarify agency expectations.  Several warning letters have been issued to domestic and international pharmaceutical manufacturers.  This warning letter provides a good example of the potential ramifications when a firm falls short of FDA expectations for managing their GMP data.