This guideline 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 and describes scientific approaches and 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. 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 this guideline may also apply to other biological/biotechnological entities.
CM involves the continuous feeding of input materials into, the transformation of in-process materials within, and the concomitant removal of output materials from a manufacturing process.
While this description may apply to an individual unit operation (e.g., process chromatography, tableting, perfusion cell culture), this guideline focuses on the integrated aspects of a CM system in which two or more unit operations are directly connected. In this context, any changes made in a unit operation of a CM system may have impact on downstream and upstream unit operations (e.g., back pressure resulting in forward mixing) and output material quality.
Fundamental aspects of CM that are generally not specific to technology, dosage form, or molecule type are described within the main body of this guideline. Annexes are provided to augment the main guideline by providing illustrative examples and considerations specific to certain modalities (e.g., chemical entities, therapeutic proteins), technologies, and production methods (e.g., integration of drug substance and drug product manufacturing). The examples and approaches described in these annexes are illustrative, and alternative approaches can be used. Topics that are broadly applicable to both CM and batch manufacturing are not in the scope of this guideline, and other existing ICH guidelines should be used as appropriate