A Practical Approach to Post-Approval Change Processes to Mitigate Shortage Risks to Global Supplies

Pharmaceutical industries operate under highly regulated environments where quality and compliance are of the utmost importance. Post-approval changes to drug products are inevitable due to technological advancement, regulatory requirements changing quickly, and continual improvement efforts. Unfortunately, global approval processes for these changes often lead to significant delays which impede innovation, disrupt supply chains, heighten risks of drug shortages affecting patient safety directly and decrease supply chain efficiency resulting in patient harm. A robust risk-based approach based on International Council for Harmonization guidelines may provide an effective transformative solution.?

Complex global regulatory approval processes often result in significant delays, which impede innovation, disrupt supply chains and increase risks of drug shortages - directly impacting patient safety. To meet these challenges, taking an ICH guidelines-inspired risk-based approach to product authorization changes offers a transformative solution.?

Post-Approval Changes and Their Challenges?

Post-approval changes include any modifications to manufacturing processes, facilities, control strategies or product formulations after an authority has approved. Often these modifications aim to increase efficiency, maintain compliance with current good manufacturing practices (cGMP) or address new scientific research; however, their regulatory framework often remains disparate with differing requirements across regions that create barriers to timely implementation, leaving manufacturers vulnerable to compliance risks and supply interruptions.?

The 2020 report from the One-Voice-of-Quality (1VQ) initiative emphasizes industrywide efforts to simplify post-approval change management through an enhanced Pharmaceutical Quality System (PQS). By integrating quality risk management (QRM) and knowledge management (KM), companies can streamline post-approval change processes while protecting product quality and patient well-being.?

Risk-Based Approach for Post-Approval Change Management?

An approach outlined by ICH Q10 and Q12 that prioritizes changes based on their potential effects on product quality, safety and efficacy can reduce regulatory burden and strengthen supply chain resilience. A risk-based approach prioritizes changes based on their potential effects on these elements of quality management, safety and efficacy and is classified accordingly - prioritizing high-risk changes that need prior approval by regulatory bodies with low to moderate-risk changes that can be managed within PQS or with notifications as manageable risks within its PQS system or through notifications). Benefits of such a framework include faster implementation of PACs while reduced regulatory burden as well as enhanced supply chain resilience in this framework.?

Key elements of the risk-based approach include:?

1. Quality Risk Management (QRM): Proactive identification and assessment of risks associated with PACs, ensuring no unacceptable risks are introduced to product quality or patient safety.?

1. Knowledge Management (KM): Systematic acquisition and dissemination of product and process knowledge to inform PAC decisions and ensure continuous improvement.?

1. Enhanced PQS Elements: Effective management of PACs relies on robust PQS components, including Process Performance and Product Quality Monitoring Systems (PPPQMS), Corrective and Preventive Actions (CAPA), and Change Management Systems.?

Steps for Implementing a Risk-Based PAC Strategy?

Step 1: Strengthen PQS Foundations??

Establish a robust Pharmaceutical Quality System (PQS), complete with CAPA procedures and management reviews to effectively handle PACs.?

Step Two: Integrate QRM and KM?

Introduce risk and knowledge management practices throughout the product lifecycle by employing data-driven insights to proactively identify and address risks as soon as they emerge.?

Step 3: Accelerate Approval Processes?

To speed the approval of changes quickly and easily, Post-Approval Change Management Protocols (PACMPs) provide a framework to engage regulatory authorities early and streamline classification and approval procedures.?

Step 4: Push for Global Regulatory Convergence?

To reduce duplicative efforts and speed change implementation, push for global harmonization of PAC requirements to harmonize them globally and avoid duplication in change implementation efforts.?

Benefits of Adopting a Science-Based Approach?

Adopting this risk-based framework yields concrete advantages:?

• Mitigate drug shortages to ensure timely changes are implemented to maintain uninterrupted supply chains.??

• Simplified regulatory processes will reduce administrative burdens by prioritizing high-risk changes.??

• Foster innovations to promote cutting-edge technologies and process improvements more rapidly.?

• Enhance product quality and safety to provide greater control, while aligning with patient-centric goals.?

Conclusion?

Reducing post-approval change complexity necessitates an industry-wide shift towards an aligned, science-driven strategy. Pharmaceutical manufacturers can utilize risk management strategies and PQS elements to mitigate supply risks, improve innovation, and remain compliant.?

DDReg can assist pharmaceutical companies in navigating these changes, ensuring both compliance and innovation. Contact us today to discover how we can assist you in leveraging these transformative technologies. Read more from DDReg here: Insight into How Real-World Data Is Transforming Pharmacovigilance?

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