ICH adopts Q13 guideline on continuous manufacturing
The International Council for Harmonisation (ICH) has adopted its guideline on continuous manufacturing (CM), in a nod to embracing more modern modes of manufacturing. In the final version of guidance, ICH acceded to industry’s request to clarify state of control and process dynamics.ICH in late November had announced the adoption of the Q13 guidance but the document was not yet released. (RELATED: ICH touts adoption of continuous manufacturing, safety reporting guidelines, Regulatory Focus 22 November 2022).
In the US, Food and Drug Administration (FDA) officials have been encouraging manufacturers to switch to continuous manufacturing from the more antiquated batch production process for years to improve product quality, minimize product defects and reduce shortages.
Results from a recent FDA audit showed that continuous manufacturing applicants saw quicker approvals and higher revenue than applications relying on batch manufacturing processes. (RELATED: Continuous manufacturing applicants saw quicker approvals, higher revenue than batch applications, Regulatory Focus 6 July 2022).
Despite regulators’ entreaties, adoption to this mode of manufacturing has been slow.
The scope of the 46-page guideline covers continuous manufacturing of drug substances and drug products for chemical entities and therapeutic proteins. It also applies to new drugs, generic drugs, biosimilars and the conversion of batch manufacturing to CM for existing products. The guideline “may also” apply to other biological/biotechnological products.
The guideline was released for comment on July 2021 and reached Step 4 of the ICH process in November 2022. (RELATED: ICH releases widely anticipated guidance on continuous manufacturing, Regulatory Focus, 27 July 2021)
Industry stakeholders requested changes to the draft guidance in December 2021. (RELATED: Pharmaceutical groups want more clarity on continuous manufacturing guideline, Regulatory Focus 17 December 2021)
State of control clarified
The final guidance provides more details to better illustrate what is meant by a “state of control” in continuous manufacturing. The Biotechnology Industry Organization and the International Pharmaceutical Excipients Council (IPEC) had requested this clarification.
There is additional text in Section 3.1.1 that explains how to attain a state of control. The revision states that “it is important to have mechanisms in place to evaluate the consistency of unit operations and the systems, and to identify when parameters drift or trend within the specified range. In addition, the root cause of drift or trends, such as variant of inputs, equipment fatigue, or aging of materials, should be identified.”
Revised definition of process dynamics
The final document also changes the definition of “process dynamics” for maintaining a state of control in continuous manufacturing. This change was suggested by the International Society for Pharmaceutical Engineering (ISPE) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) in their comments to the European Medicines Agency (EMA) on the draft.
These groups asserted that the draft incorrectly used the terms process dynamics and resident-time distribution (RTD) interchangeably.
The document now states that “process dynamics should be characterized to understand how output material quality is impacted by transient events. This characterization should be done by determining properties such as residence time distribution (RTD). RTD characterizes the time available for material transports and transformation, and is specific to the process composition/formulation, materials properties, equipment design and configuration.”
ICH Q13 guideline
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