Global Standard for Managing Post-Approval Changes Moves Forward

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Regulatory authorities have published draft guidance on strategies to facilitate pharmaceutical lifecycle management.

After years of consultations and deliberations, regulatory authorities have published draft guidance negotiated by the International Council on Harmonization (ICH) on strategies to facilitate pharmaceutical lifecycle management. The 34-page ICH Q12 document aims to establish common policies and practices for data and testing required by regulators in all regions to authorize post-approval changes in facilities and production methods.

A main feature of the guidance is to establish a process for manufacturers to identify established conditions that warrant notification or prior approval by regulatory authorities, as opposed to less critical product features that need less regulatory oversight. The policy aims to reduce regulatory burdens and promote manufacturing innovation and improvements by offering a process for industry to demonstrate to regulators how increased product and process knowledge can support changes with reduced regulatory submissions. This approach aims to encourage continual improvement in products and manufacturing methods, reducing costs, and ensuring reliable supplies.

This effort to harmonize regulatory requirements for post-approval changes builds on previous ICH quality standards developed over the past 15 years that support more efficient and flexible pharmaceutical manufacturing operations that reliably produce high-quality products, with less regulatory oversight. Despite these efforts, the global spread of industry to regions with divergent regulatory requirements has greatly complicated the post-approval change process, noted Christine Moore, global head and executive director of CMC policy at Merck. She explained at the June 2018 ISPE Quality Manufacturing Conference in Arlington, VA, how variability in regulatory policies around the world adds years and costs to implementing post- approval changes, ruling out many initiatives that could make pharmaceutical production more efficient and reliable.


A main component of the Q12 guidance is to define established conditions that are critical to product safety and efficacy and should be reported to regulatory authorities when making manufacturing changes, explained Robert Iser, vice-president of Parexel Consulting, formerly with FDA. Established conditions for manufacturing operations include critical process parameters and sequences, Iser pointed out at the ISPE conference. The ICH guidance describes how manufacturers can develop a product lifecycle management strategy that presents a summary of established conditions, reporting categories, and post-approval change management protocols to address expected changes. These approaches may be most appropriate for new drugs and biologics and may be more controversial for managing change to existing products.

The hope is that ICH Q12 will provide manufacturers with more uniform reporting requirements and greater clarity on what and how to submit changes in dossiers. This approach would promote continual improvement in manufacturing and controls and enable more efficient regulatory evaluation of proposals and facilitate inspections. Although the current guidance does not establish set timelines for regulatory reviews or common requirements for regulators, the expectation is that authorities will move toward common approaches over time. FDA and other authorities are accepting comments from industry on the guidance, with the aim of finalizing the document next year. If implemented as intended, the approach outlined in Q12 could promote drug quality and consistency, encourage innovation in production processes, and help ensure a reliable global supply of needed medicines.