The FDA has issued the ICH final guidance, Q13 Continuous Manufacturing of Drug Substances and Drug Products. The guidance, which was prepared under the support of the International Council for Harmonization (ICH), describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM). It also provides clarification on CM concepts and describes scientific approaches and regulatory considerations specific to the CM of drug substances and drug products.
The guidance applies to the 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 guidance may also apply to other biological/biotechnological entities.
The guidance 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 guidance. Annexes are provided to augment the main body of the guidance 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 guidance, and other existing ICH guidances should be used as appropriate.
To download the Q13 Continuous Manufacturing of Drug Substances and Drug Products final guidance, click here.