Risk-Based Quality and Safety Management in Clinical Trials with Wound Care Combination Products in Changing Global Regulatory Environment

Background: The emergence of novel combination products in wound care field has triggered new regulatory, strategic, and technological challenges. While progress has been made at clarifying the issues that arise most frequently, regulatory authorities and product developers continue to struggle with complex regulatory and technical issues encompassing the development programs for combination products for regenerative medicine. A risk - based approach requires not only a strategy but also tools to define key indicators to measure specific risks. Key risk indicators (KRIs) and risk-based quality management (RBQM) systems should focus on safety of research subjects and data integrity.

Methods: We analyzed current regulatory guidelines throughout lifecycle of combination wound care products, and compared old and new approaches to risk-based quality and compliance management for current good manufacturing practices; and during pre-clinical and clinical phases of combination products development. Cause-effect analysis for major risk categories in clinical trials with combination wounds care products was performed.

Results: The results of our analysis are based on observations from 15 clinical trials, which were conducted with combination products in wound care field. Based on our findings, we proposed practical recommendations for development of KRIs to improve conduct and ensure safety of research subjects in trials with combination products by utilizing risk-based quality management approach.

Conclusion: Combination products, due to their specific nature, can increase risks while being tested in clinical trials. Metrics critical to risks and quality management should be linked to particular processes within development program for wound care products. Ongoing collaboration between regulators, industry, and other stakeholders is essential to streamlining of the global combination entities development and approval process in a way that will produce safe and effective products for consumers.