INFORMATION TECHNOLOGY
As per the FDA Warning Letter of 2018, the regulations most frequently cited are: 21 CFR reference
Title of CFR Section
211.194
Laboratory Records, Review of All Data
211.188
Batch Production and Control Record
211.192
Production Record Review, Deviations and Investigations
211.68
Automatic, Mechanical and electronic Equipment
211.165(a and b)
Testing and Release for Distribution
Data integrity enforcement action
Poor data integrity practices in the manufacturing and testing of pharmaceuticals products have resulted in a steady rise in the number of enforcement actions, such as warning letters, import alerts and consent decrees. Criticality of data integrity is substantiated by a global report that states that roughly 50 per cent of all Center for Drug Evaluation and Research (CDER) inspection observations (form 483) issued between 2014 and 2018 cite data integrity violations. These violations are even more prevalent in warning letters, with 79 per cent of global drug warning letters during this period citing data integrity issues. Further, the underlying similarity in the recent warning letters issued by the FDA is to engage a consultant to audit a company’s operations and assist in meeting FDA requirements for the data integrity remediation activity. Examples from warning letters include:
“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 comprehensive investigation into the extent of the inaccuracies in data records and reporting.”
“We acknowledge that you are using a consultant to audit your operation and assist in meeting FDA requirements. We strongly recommend that you retain a qualified consultant to assist in your remediation…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 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. ” Conclusion
With the increase in the issuance of warning letters and forms 483 over the years, pharmaceutical companies have become increasingly cognisant of the importance of data integrity to ensure the safety, efficacy and quality of their products. Under the pressures of the
AUTHOR BIO
may include procedural controls, organizational controls and functional controls.” (WHO)
COVID-19 pandemic in particular, company leadership should focus on taking proactive measures to manage data integrity risk and ensure compliance with the CGMP regulations before the next FDA inspection happens. These efforts may include review and assessment of procedures as per the guidance of CGMP for responding to COVID-19 infection in employees, to prevent or mitigate potential adverse effects on the safety and quality of drugs from an infected or potentially infected employee engaged in drug manufacturing. Companies should also utilise advanced digital tools and technologies that can proactively identify data integrity lapses in electronic data of certain equipment (e.g. Chromatography Data Systems (CDS), NON-CDS, LIMS, etc.) and highlight on a real-time basis, so management can enable the company to take necessary actions. Companies that have already received a form 483 and warning letter should consider implementing a remediation plan for the violations identified. This would involve a comprehensive investigation that includes identification of the causes of the lapse, ongoing monitoring and preventive steps for potential recurrence. Since data integrity is a critical component of the basis for maintaining quality and the confidence of regulators, pharmaceutical companies should seek the expertise of a third-party expert to audit company operations and assist in meeting FDA requirements. References are available at www.pharmafocusasia.com
Ankush Lamba is a Managing Director in FTI Consulting’s Technology segment in Mumbai. He brings more than 12 years of experience in fraud data analytics and digital forensics. He has worked on high profile data integrity investigations for pharma companies involving regulators including the USFDA.
www.pharmafocusasia.com
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