PROLOGUE
It's been about three years since I had written the three-part series of articles on Continuous Manufacturing (CM). Since then, a lot of water has flown under the bridge and there have been several developments in the field of CM. Now is probably the right time, to summarize all developments, from a technical perspective, from a regulatory perspective and in terms of the adoption of CM from the pharmaceutical industry perspective.
Continuous Manufacturing, an innovation in the advanced manufacturing field has been gaining importance over the last few years, as drug products have been getting commercially approved by regulators over the world and reaching the market. This series of three articles on this topic reviews some of the recent developments for this important topic.
The first article focuses on the recent regulatory national and international guidance and their impact on the acceptability of CM across the globe.
The second article focuses on the challenges still open to CM after the publication of ICH Q13 Guidance document and how CM could contribute to in-shoring back to US.
The third and final part article focuses on CM in China and adoption of CM for biologic products.
DEVELOPMENTS IN CM- PART 1
ABSTRACT: This paper outlines some of the global regulatory changes that have taken place for CM, their significance and what impact this has on the global acceptance of CM as an advanced manufacturing technique.
CHANGES IN GLOBAL REGULATORY LANDSCAPE
GUIDANCE FROM US-FDA
In March 2023, the FDA issued a final guidance1, titled "Q13 Continuous Manufacturing of Drug Substances and Drug Products" that describes the scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of CM. The guidance applies to CM of drug substances and drug products for chemical entities and therapeutic proteins, including biosimilars, and the conversion of batch manufacturing to CM for existing products.
The guidance proposes strategies that account for scientific and regulatory considerations that impact CM. Under the scientific considerations, development of a CM should consider process dynamics, material characterization, equipment design and system integration. Regulatory considerations include input material attributes, process monitoring and control, and drug stability to ensure quality product over time. The last section of the guidance provides examples of how to implement CM of drug substances for chemical entities and therapeutic proteins and provides additional regulatory and scientific considerations and approaches for managing disturbances.
ICH GUIDELINE Q13 ON CM OF DRUG SUBSTANCES AND DRUG PRODUCTS
After two years of analysis and comments from the first draft publication, on January 6th, 2023, the final guidance document 2, "ICH Q13 Continuous Manufacturing of Drug Substances and Drug Products", was published and became legally effective from July 10th, 2023.
This guideline describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of CM. Building on existing ICH Quality guidelines, this guideline provides clarification on CM concepts, describes scientific approaches, and presents regulatory considerations specific to CM of drug substances and drug products. This guideline applies to CM of drug substances and drug products for chemical entities and therapeutic proteins. The principles described in this guideline may also apply to other biological/biotechnological entities. It is applicable to CM for new products (e.g., new drugs, generic drugs, biosimilars) and the conversion of batch manufacturing to CM for existing products.
The European Medicines Agency (EMA) became the first regulator to adopt the International Council for Harmonization (ICH) new guideline Q13 on continuous manufacturing (CM) of drug substances and drug products, effective July 10, 2023.
Two aspects are key to this new ICH Q13 Guideline. Firstly, it has a wider scope than others, covering not only drug prod...
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