PDA Letter Article

Facilitating Continual Improvement, Innovation, and Reducing Drug Shortages through Enhanced Science and Risk-based PACs

by Marilyn Foster, PDA

Regulators, legislators, pharmacies, healthcare providers, and industry each play a part in ensuring patients have access to “every dose of their medicine on time, every time,” said Emma Ramnarine, Genentech/Roche.

Achieving the “unifying goal of an uninterrupted supply of safe, efficacious medicine” depends on a complex dynamic of global, national and local stakeholders, said the Genentech Sr. Director of Global Head of External Development Collaborations. Ramnarine made these remarks during her presentation at the 2020 PDA Virtual Annual Meeting.

Ramnarine stressed the importance of product quality systems and post-approval changes in realizing the goal.

She summarized steps that have been taken to ensure product quality and address the issue of drug shortages—PDA Technical Report No. 68: Risk-Based Approach for Prevention and Management of Drug Shortages, U.S. FDA’s Journey to 21st Century Manufacturing and ICH guidelines Q8-Q11. Over almost two decades, she said, the FDA/ICH vision has only been partly achieved, to some extent, due to the lack of clarity in dealing with regulatory issues.

Getting products to patients is a complex process involving multiple sites for manufacturing, packaging and distribution through wholesalers, pharmacies and hospitals. During the commercial life of a product—which can be 20-35 years—each of those entities is affected by advances in knowledge, improvements in technology and changes in regulations. And each of those effects, Ramnarine said, triggers the need for post-approval changes. An interruption anywhere along the line can affect the entire supply chain, possibly resulting in a drug shortage.

Ramnarine demonstrated the complexity of drug shortages, relating the 10 characteristics of a “Wicked Problem”—defined as an issue or concern that is difficult to explain and inherently impossible to solve—to the interconnected factors involved in a medicine supply chain. She described how industry is aligning globally to develop solutions to the PAC problem through the One-Voice-of-Quality approach. This stresses the need for companies to put effective PQS in place, so regulators learn to trust company assessments of risk change, enabling them to reduce PAC reporting categories.

With the crisis of the COVID-19 pandemic, EMA put into place an “Exceptional Change Management Process” that details what is expected to qualify and provides a timeline for the process. Ramnarine questioned why it is only in crisis mode with the possibility of shortages imminent that regulators can find a way to balance risk assessment with patient safety. She suggested this process apply not only in a time of crisis, but perhaps become “the new, better normal,” always keeping patient safety in mind.