The European Medicines Agency (EMA) has adopted final international guidance on the continuous manufacturing of drug substances and drug products, positioning the text to come into effect in July.
 
Continuous manufacturing involves the continuous feeding of input materials into a system and removal of the output materials from the manufacturing process. The approach is distinct from the more widely used stop-start batch production technique, leading the International Council for Harmonisation (ICH) to develop the Q13 guideline on continuous manufacturing.
 
EMA’s Committee for Medicinal Products for Human Use adopted the guideline last month and released it to the public last week. The final text explains how scientific approaches such as control strategy and process verification apply to continuous manufacturing, and the regulatory expectations in areas including drug substance and drug product stability and pharmaceutical quality systems.
 
The final guidance covers the same ground as the draft version that EMA released for consultation in 2021 but features changes throughout the text. The revisions include new information about regulatory expectations for the stability data package. As in the draft, the final guideline states that the expectations “generally do not differ” between continuous and batch production but officials have added new details about chemical drug substances and drug products.
 
In two new bullet points, the guideline explains that stability batches may be produced from shorter manufacturing runs if the control strategy, mass flow rate and equipment are representative of the commercial process, and “it is demonstrated that a state of control is established and maintained when the process operates over the longer commercial run times.”
 
If manufacturers plan to increase output by means other than longer runs, for example by using larger equipment, they should justify their approach for defining primary stability batches. The ICH guideline encourages applicants “to discuss their scale-up and primary stability batches approach with regulatory authorities.”
 
In annexes to the guideline, ICH provides more specific information about continuous manufacturing of chemical entities and therapeutic proteins. ICH has made some changes to the annexes, notably to the section on therapeutic proteins. That annex now states that “the number or range of cell bank vials used to produce the specified number of drug substance batches should be defined” and that vials “should be traceable to the output drug substance batches.” [RAPS]