On November 16th of 2022, the ICH Q13 Guideline on Continuous Manufacturing of Drug Substances and Drug Products (Step 4) was finally adopted during the General Assembly of the International Council for Harmonisation (ICH). With the adoption within the ICH organization, the guidelines are considered harmonized and thus represent the current state of science and technology. A concept paper for the Guideline was first submitted in November 2018.
The guideline applies to continuous manufacturing *CM (of drug substances and drug products for chemical entities and therapeutic proteins. 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 principles described in the guideline may also apply to other biological/biotechnological entities.
The document describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM). Building on existing ICH Quality guidelines, this guideline provides clarification on CM concepts, describes scientific approaches and regulatory considerations specific to CM of drug substances and drug products, focuses on the integrated aspects of a CM system in which two or more-unit operations are directly connected and includes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of CM.
The introductory Part I of the guideline addresses CM concepts, the scientific approach, and regulatory considerations, such as manufacturing processes, control strategies, batch sizes, product stability, process validation, or the pharmaceutical quality system. Included are sensible recommendations regarding regulatory expectations that provide manufacturers with a flexible approach.
Part II includes five annexes that offer concise explanations and practical examples. These include flowcharts with manufacturing processes and also various examples of how to handle process disturbances:
- Annex 1: Considerations for CM of drug substances.
- Annex 2: Considerations for CM of drug products
- Annex 3: Considerations for CM of drug substances (therapeutic proteins)
- Annex 4: Considerations for integrated drug substances and drug products CM
- Annex 5: Perspectives of managing disturbances