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PDA Program to Address Post-Approval Hurdles

A Call to Action

The seamless delivery of high quality, effective and safe medicines to patients is the primary responsibility of every pharmaceutical company. Doing so, however, is by no means effortless. Just look at any of the lists of drug shortages on the websites of global regulators. The lists are too long and include too many critical therapies.

The availability of medicines is challenged by a variety of factors, one of which is global supply chain segmentation due to global regulatory hurdles imposed on product-related post-approval changes (PACs).

Manufacturing changes are performed for several reasons. New and updated regulatory requirements must be implemented in order for companies to remain compliant. During the commercial lifecycle of a product, companies naturally gain more knowledge which can be used to improve the manufacturing process and/or analytical methods. In addition, changes in suppliers, evolution of technologies, innovation, ongoing risk management, and continual improvement can also result in PACs.

Today, most companies operate globally; therefore, PACs are intended to apply globally. Many require approval, however, by the national regulatory authority of each country before the company can deliver a product manufactured using improved processes. In practice, this can result in submitting change filings for assessment to more than a hundred individual regulatory bodies. Across the globe, regulatory PAC processes can be characterized as complex and inconsistent due to varying classifications, different submission requirements, and lengthy implementation timelines (it is not uncommon for a simple change to take more than five years to receive approval). All of these complexities create a disincentive—albeit unintentional—for manufacturers to integrate growing product and process knowledge, continually improve, or innovate technologies. The current PAC environment also represents a challenge for standardizing the implementation of a regulatory change across multiple countries. This forces companies to segment their inventory for different markets, leading to increased costs for inventory, manufacturing, and testing, and reduces the company’s ability to respond to sudden demand changes in a timely and predictable manner.

[Editor's Note: Learn more about the "wicked problem" of drug shortages from Anders Vinther.]

Companies actually want to innovate and improve on top of maintaining compliance with current regulations. But in order to avoid the burden of implementing changes in such a complex process, many find it easier to postpone improvements to facilities, processes, and analytics, or simply refrain from planning advancements at all.

Segmentation of inventory and disincentives for continual improvement results in the unintended consequence of drug shortages.

PDA Task Force Seeks Comprehensive PAC Reform

If the current state of country-specific requirements continues, innovation will stop, drug shortages will increase, and the patients who depend on these drugs will be the ones who lose. It is time for both industry and regulators to transform the current paradigm for PACs.

This is a call to action to:

  • Accelerate awareness of the current challenges of PACs and activate a dialog at a broader industry and regulatory scale to drive significant change
  • Apply science and risk-based approaches to change management in order to expedite PACs and reduce the global regulatory filing burden
  • Demonstrate streamlined PAC processes to enable international regulatory convergence and mutual reliance for improved availability of medicines to patients

The industry must do its part to contribute to this broad and sweeping reform for PAC. PDA’s Post Approval Change: Innovation for Availability of Medicines (PAC iAMsm) Program will identify, assess, and address current barriers to implementation of PACs. Specifically, PDA is working on the following deliverables:

  • Publication of science- and risk-based approaches to lifecycle management
  • Templates for standardized global post-approval change management protocols (PACMPs) for specific changes to manufacturing processes and analytical technologies
  • A library of real world examples of best practices for PACs using a science- and risk-based approach
  • Forums to encourage collaboration and open dialog among stakeholders in healthcare

PDA appreciates and supports ongoing activities that streamline PAC approval, including the efforts on ICH Q12: Technical and Regulatory Considerations for Pharmaceutical Lifecycle Management, and the World Health Assembly resolution on strengthening the regulatory system for medical products (1).

PDA would like to see timelines for the implementation of global PACs reduced from years to months. This should incentivize innovation and continual improvement within the industry and enable uninterrupted supply of medicines to patients.

PDA is currently looking for volunteers to develop a PDA technical report on PACs and product lifecycle management (LCM), and to catalogue examples of practical application of global Post Approval Change Management Protocols (PACMPs).

PDA seeks individuals with experience in PAC from a development, manufacturing, analytical, change control, manufacturing science and technology, or regulatory CMC perspective in all aspects of manufacturing (small molecules, generics, biologics, etc.). If you are interested in participating on the team developing the technical report or want to help identify specific global PACMPs, please email PDA's Science and Regulatory Affairs department.

Reference

  1. WHA 67.20 – Regulatory System Strengthening for Medical Products. WHA Resolution; sixty seventh World Health Assembly, World Health Organization, May 24, 2014

Post Approval Change: Innovation for Availability of Medicines (PAC iAM) Task Force members

  • Anders Vinther, PhD, Sanofi-Pasteur (chair)
  • Emma Ramnarine, Genentech (co-chair)
  • Ursula Busse, PhD, Novartis
  • Franck Chassant, Sanofi-Pasteur
  • Marcello Colao, GSK Biologicals
  • Julia Edwards, Biogen
  • Maik Jornitz, G-Con LLC
  • Marina Kozak, Friends of Cancer Research
  • Morten Munk, NNE Pharmaplan
  • Melissa Seymour, Biogen
  • Mihaela Simianu, Consultant
  • Lisa Skeens, PhD, Hospira
  • Denyse Baker, PDA