Issue link: https://www.e-digitaleditions.com/i/1462155
54 Pharmaceutical Technology QUALITY AND REGULATORY SOURCEBOOK EBOOK MARCH 2022 P h a r mTe c h . c o m Standards bioreactors have been successfully implemented for cell growth/production in biologic processes, the transition from upstream to downstream pro- cessing has proven to be more challenging. A truly continuous process requires inline or at-line ana- lytical capabilities for in-process analysis. These types of analyses represent a paradigm shift in analytical methodology over what is currently used for conventional process analysis. Manag- ing and analyzing all the data generated by a BCM process are also challenging and require the addi- tion of new types of technical specialties, such as data management, into the process design space. To develop truly continuous vial-to-vial processes will be highly challenging when it comes to includ- ing the final fill/finish operations into the process. For manufacturers contemplating use of BCM, other important considerations are evolving regulations, the cost of training new specialists, and the chal- lenges associated with changing an established pro- cess post-approval. There can be hesitancy in chang- ing an established process—even if it would benefit from BCM—because of perceived risks associated with the change. This is true for biosimilars that need to demonstrate comparability to a reference product and batch processes for existing products where the perceived risk and regulatory uncertainty of making substantial changes to the manufacturing process are considerable. As with any new technol- ogy, wider acceptance will need regulatory support to facilitate the adoption of the technology. Moving forward with CM PharmTech: What types of regulatory guidance would be helpful in expanding use of CM? Kokai-Kun (USP): The draft International Council for Harmonisation (ICH) guideline Q13 Continu- ous Manufacturing of Drug Substances and Drug Products (1) published last summer is certainly a good start , but additional guidance and regulatory strategies are needed to facilitate adoption of BCM. ICH Q12 currently provides a framework to fa- cilitate the management of post-approval changes more predictably and efficiently across the product lifecycle (2). Streamlined regulatory pathways to allow adaptation of approved batch processes into BCM processes resulting in a comparable product would also facilitate adoption of this technology for existing products. PharmTech: What do you anticipate for the next steps at USP? Kokai-Kun (USP): Developing physical or perfor- mance standards for these technologies will require time; however, USP is actively working on guid- ance and documentary standards to assist industry, and several General Chapters are already avail- able in the United States Pharmacopeia-National Formulary. For example, USP recently published for comment proposed chapter <1220> Analyti- cal Procedure Life Cycle (3). The chapter demon- strates the suitability of an analytical method over a product's entire lifecycle, including development, validation, and continuous verification and may be useful for adoption of new technologies. Besides standards, there is also a need for educational ma- terial for stakeholders to understand the benefits of these technologies and how to best implement and review their performance. References 1. ICH, Continuous Manufacturing of Drug Substances and Drug Products Q13, Draft Version, Step 2 (July 27, 2021). 2. ICH, Technical and Regulatory Considerations for Pharmaceuti- cal Product Lifecycle Management Q12 (Nov. 20, 2019). 3. USP, Proposed Chapter <1220>, "Analy tical Procedure Life Cycle," Pharmacopeial Forum 46 (5). PT