P318: System Theoretic Process Analysis: Identifying Risks of the Regulatory Reliance Ecosystem
Poster Presenter
Apurva Uniyal
Regulatory Innovation Research Scientist
The DK Kim International Center, Department of Regulatory and Quality Sciences, United States
Objectives
Identify risks in the regulatory reliance ecosystem, using System Theoretic Process Analysis (STPA), a proactive hazard analysis method, and create sustainable solutions to ensure global accessibility to the highest attainable standard of health, for scientific and noncommercial purposes.
Method
STPA is a multi-step hazard analysis. The findings from a systematic review assessed the reliance landscape and were used to map a Hierarchical Control Structure (HCS) which is the foundational diagram for STPA. With IRB approval, 10 regulatory experts were interviewed on the HCS to provide input. A second round of interviews will assess improvements.
Results
A preliminary literature review on regulatory reliance pathways from PubMed, WHO guidelines and the DIA global forum, revealed potential risks in National Regulatory
Agencies (NRA) interactions, such as overly redacted reports obscuring critical details and discrepancies in product versions or incomplete reviews affecting evaluations. Diverging guidelines and failure to adapt to country-specific needs are potential risks that also impact patient access to essential medicines.
Those potential risks were presented through abridged and verification draft flowcharts and a HCS to subject matter experts (SMEs). The first round of interviews with the regulatory SMEs of different professional backgrounds, and STPA framework uncovered unknown risks like ‘secondary-reliance’ and soft risks. The feedback obtained on the HCS and flowcharts led to the development of over 400 risk scenarios and tailored recommendations with varied approaches. The recommendations were created through four channels- the process behavior, feedback path, control path and controller behavior.
The risk scenarios and subsequent recommendations were narrowed down to 10 by assessing their severity and impact which will be presented to the SMEs for further feedback. The second round of interviews will optimize the recommendations generated and assess their real-life implications and sustainability in the reliance ecosystem to improve safety and efficacy of medicine for patients around the world.
Conclusion
As regulations become increasingly complex and globally interconnected, the concept of Regulatory Reliance has emerged as a WHO best practice to address this need. This approach allows a regulatory authority to use the work done by a trusted regulatory authority to inform its decisions. While Regulatory Reliance helps reduce redundant efforts, promotes cross-border collaboration, and shortens authorization times, its potential risks have not been fully explored.
Safe regulatory reliance is crucial for global health equity and patient access to essential and innovative medicines. STPA identifies and addresses different layers of risk in the system, improving safety, efficiency, and innovation for timely patient access to therapeutics. The STPA framework allows for risk identification to go beyond two entities but examines the system as a whole and uncovers gaps, communication failures and other challenges that may otherwise remain hidden.
The goal is to provide practical and system-level recommendations to make reliance more reliable, ultimately helping to ensure people worldwide get the medicines they need while enabling the relying agency to remain independent in their decision making. Ultimately, this work strives to enhance trust, transparency and safety in reliance-based decision making. A digital tool will be created to visualize the steps in abridged and verifi cation review pathways with the potential risks and corresponding recommendations at each stage. The interactive format will allow users to explore specifi c process steps, view associated hazards and understand targeted mitigation strategies, supporting more informed and resilient regulatory implementation.
