PDA TR 91 PDF

The complexity of global post-approval change/variation (PAC) processes and the time required to receive their approval presents a challenge for industry when it is working to implement needed changes and operating with a focus on continual improvement. Industry benchmarking shows that receiving approval for a PAC requiring global approval can take between two and five years, and the time it takes from original submission can vary from six months to several years depending on the jurisdiction and review pathway (1). For new products, where the amount of commercial process or product data at the time of the initial submission is limited, this timing can significantly impact the ability to implement necessary process improvements identified as more data becomes available. In specific cases, when a change is needed to ensure the product remains safe, efficacious, and of high quality or provides additional capacity based on high product demand, the global approval timing can result in drug product shortages.

The current regulatory pathway to implement change is highly complex. For each jurisdiction in which a product is licensed, the respective regulatory agency typically requires a notification, based on its risk reporting category, or it must preapprove certain PACs for certain products. Differences in country- and region-specific requirements for PAC filings, filing procedures, and associated timelines can often make simultaneous implementation of changes problematic, necessitating a product be tested or produced using different processes based on where it will be distributed. Companies must consider this factor when deciding to implement a change.

These challenges were highlighted during the COVID-19 pandemic, as companies continued to manufacture lifesaving products despite the extreme strain on supply chains for raw materials, components, and manufacturing supplies. As alternative sources of supply or alternative materials were identified, the complexity of the global regulatory PAC process presented a significant challenge to product supply, highlighting the need for a harmonized approach to PAC implementation.