543 System theoretic process analysis: Identifying risks of the regulatory reliance ecosystem

Abstract

Objectives/Goals: Identify risks in the regulatory reliance ecosystem, specifically for generic reliance pathways, 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. Methods/Study Population: A systematic literature review will assess the regulatory reliance ecosystem and interactions among National Regulatory Agencies (NRAs). This will involve using a hierarchical control structure (HCS) to identify operational loop failures, decision-making, and information flow. The HCS will inform an STPA to prevent adverse outcomes like patient harm or regulatory non-compliance. With IRB approval, 10 regulatory experts will also be interviewed to gather insights on risk scenarios. Their input will be used to integrate regulatory pathways into the HCS for adaptability, and a second round of interviews will be conducted to validate the scenarios and assess the effectiveness of recommendations. Results/Anticipated Results: A preliminary literature review on regulatory reliance pathways from PubMed, WHO guidelines, and the DIA global forum, revealed potential risks in 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. The STPA framework, along with expert feedback, will uncover unknown risks like “secondary-reliance” and soft risks, leading to sustainable recommendations to improve and optimize the safety of regulatory reliance. Discussion/Significance of Impact: Safe regulatory reliance is crucial for global health equity and patient access to essential and innovative medicines. STPA will identify and address different layers of risk in the system, improving safety, efficiency, and innovation for timely patient access to therapeutics.