CDER has issued the final guidance, ICH Q13 Continuous Manufacturing of Drug Substances and Drug Products, which provides for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM), applying to both drug substances and drug products for chemical entities, therapeutic proteins for new products, and conversion of existing products. A copy of the guidance can be found here.
The guidance is written in a general context for CM, not focusing on any specific technology but addressing the integrated aspects of a CM system in which two or more-unit operations are directly connected.
A key component of the guidance is related to the CM Control Strategy, which considers the principles within Q7, Q8, Q9, and Q10 and includes: process for evaluating the performance of CM operations; understanding/characterization of process dynamics; material characterization and control, including those incoming material critical attributes and their impact on the CM operations; equipment design and system integration, including an understanding of the characteristics of the integrated and individual equipment and impact on CM process performance; process monitoring and control, which includes the use of process analytical technology (PAT) as a means of automated process adjustment along with real‑time release testing; material traceability and diversion, which addresses the risk of process disturbances and the ability to divert potential non‑conforming product; and the role of process models when developing the CM operation.
There is also discussion and guidance addressing various approaches to changing CM production output and consideration of the impact on the control strategy. It is clear from the guidance that PAT tools are integral to CM, which is somewhat intuitive as real‑time process monitoring is essential to ensuring the state of control and allows the generation of development data at the same scale of commercial manufacture supporting early execution of process validation and the adoption of continuous process verification.
There is a significant section dedicated to Regulatory Considerations that provides guidance for the CM process dossier per ICH M4 as well as Annexes.
If you have any questions relating to continuous manufacturing, Lachman Consultants can help you! Please contact Paul Mason at p.mason@lachmanconsultants.com for support with this critical undertaking.
