ICH releases widely anticipated guidance on continuous manufacturing

Regulatory NewsRegulatory News | 27 July 2021 |  By 

The International Council for Harmonisation (ICH) on Tuesday issued its Q13 guideline on continuous manufacturing, making a draft available for public comment.
The long-awaited draft was soon expected, according to an FDA official who gave an update on the status of the guideline at a 14 July CMC Strategy Forum sponsored by the California Separation Science Society (CASSS). (RELATED: Long-awaited ICH continuous manufacturing guideline coming soon, Regulatory Focus 15 July 2021)
This guideline “describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of continuous manufacturing (CM).” It also “provides clarification on CM concepts, describes scientific approaches, and presents regulatory considerations specific to CM of drug substances and drug products,” according to the draft document.
The newly released draft is now at Step 2 of the ICH process, at which a consensus draft is released by the ICH Assembly to regional regulatory authorities for internal consultation and public comment. ICH Q13 consists of a main guideline and five annexes; the guideline discusses different models of continuous manufacturing, and reviews control strategy and regulatory considerations.
Three different models of continuous manufacturing are described in the draft guideline: one includes a combination of approaches in which some unit operations operate in a batch mode while others operate in a continuous mode; the second is where all unit operations of a drug substance or drug product manufacturing processes are integrated and operate in a continuous mode; and the third is an approach in which the drug substance and drug product unit operations are integrated across the boundary between drug substance and drug product to form a single continuous manufacturing process.
The annexes discuss continuous manufacturing of drug substances, as well as continuous manufacturing of drug products, therapeutic protein drug substances, and integrated drug substances and drug products. It also includes perspectives for managing disturbances.
The guideline incorporates the ICH Q7 definition of a batch to continuous manufacturing. A batch is defined as consisting of either the quantity of the output materials, the quantity of the input materials, or the run time at a defined mass flow rate. Other “scientifically justified” approaches will also be considered for defining a batch, according to the guideline.
Plans are for the ICH Expert Working Group (EWG) to have a face-to-face meeting in November 2021 to discuss the comments received on the draft, and to sign off on the document in November 2022, advancing the guidance to ICH Step 3; adoption of the guidance will follow.
FDA has been encouraging continuous manufacturing for the past decade as a way to improve product quality, minimize product defects, and reduce drug shortages, promoting it as a more efficient process than the more antiquated batch production process. There are 10 approved continuous manufacturing applications in the US, including original applications and supplements.
The first US approval for continuous manufacturing was for Vertex’s cystic fibrosis drug Orkambi (lumacaftor/ivacaftor) in 2015; Janssen’s HIV drug Prezista (darunavir) was the first drug that FDA allowed to be switched from batch to continuous manufacturing. (RELATED: FDA Allows First Switch from Batch to Continuous Manufacturing for HIV Drug, Regulatory Focus 12 April 2016)
ICH Q13 guideline


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