Risk assessment of GMP inspection of overseas pharmaceutical manufacturers based on pic/s desktop inspection

Abstract

Good manufacturing practice (GMP) inspection of overseas manufacturers is regulated under desktop inspection by Thailand Food and Drug Administration (Thai FDA). The desktop inspection system is verified mainly by document without on-site inspection like for local manufacturers. The inspection results may thus cause certain gaps in terms of quality and reliability. In addition, none has reported the risk assessment of desktop inspection system in Thailand and the limited research articles investigated these gaps. This work utilized the quality risk management (QRM) of International Council for Harmonization Q9 (ICH Q9) guideline with Failure Mode and Effects Analysis (FMEA) tool to study risk assessment and risk control of GMP desktop inspection system of overseas pharmaceutical manufacturers in Thailand. The study design consisted of 5 steps. First, pre-assessment step was to set up a risk assessment team and data analysis of desktop inspection and drug quality defect situation over three years in 2016 – 2018. Next, risk identification step was performed by analysis of regulation gap and routine workflow. The regulation gap was analyzed by comparing Thai regulations against five globally-selected countries/organizations, namely; Singapore, Malaysia, Australia, World Health Organization (WHO) and The Pharmaceutical Inspection Co-operation Scheme (PIC/S). Followed by risk analysis and risk evaluation step, brainstorming based on team discussion, along with using FMEA tool and risk priority number (RPN) were conducted. Finally, risk reduction step described all the risk mitigation approaches, verified by implementation and re-assessment. The results showed that the most potential negative effects on the quality and reliability of the desktop inspection system with highest RPN values were desktop inspection pathway for non-PIC/S or non-WHO prequalification certified manufacturers (RPN = 100) and lack of stepwise approach in document review (RPN = 80) that were analyzed as the high-risk level based on the regulation gap and workflow analysis, respectively. Such overseas manufacturers tended to have various GMP standards based on their own quality system criteria and be inspected by different levels of the authorized inspectorate. Meanwhiles, lack of this stepwise can lead to missing critical points and difference in inspection results. Nevertheless, after implementation, stepwise procedures justified the quality of inspection results and reduced RPN value and risk level to acceptable level. This work can be very useful for the Thai FDA to manage and minimize all potential risks for continual quality improvement of the desktop inspection system for overseas pharmaceutical manufacturers in Thailand.