WHO outlines best practices for continuous manufacturing
The World Health Organization has issued a draft document to guide the adoption of continuous manufacturing (CM). The document applies to finished products, as well as excipients and active pharmaceutical ingredients (APIs) produced on a CM line.The “points to consider” document mainly focuses on solid oral dosage forms, but its principles also apply to biologics and vaccines. The initial working document was published in June 2024 and was finalized by an informal drafting group in November 2024. WHO plans to review comments and issue a working document for possible adoption by its Expert Committee on Specifications for Pharmaceutical Preparations (ECSPP) in June 2025.
The WHO document includes sections on risk management, control strategies, process dynamics, validation of computerized systems, and verification and stability testing. Additionally, the document discusses both the benefits and challenges associated with continuous manufacturing.
Some of the benefits of CM include “increasing output of product in a shorter timeframe than traditional batch processing. It may also provide safety benefits due to lower exposure risk to operators.”
Some challenges in industry adoption include a lack of process knowledge, logistical concerns related to new equipment, and the use of advanced control strategies that involve complex analytical instruments.
There is concern that CM may not be accepted in countries outside the frameworks of the US Food and Drug Administration (FDA) and the International Council for Harmonisation (ICH), which have their own established guidelines for CM.
The WHO document addresses a series of good practices covering CM. It states that this mode of manufacturing “may require manufacturers to acquire new equipment; implement new ways of managing existing equipment; acquire new instruments and computerized systems as well as software; and establish new modes of operation.”
It also notes that since CM may pose additional risks compared to traditional batch processing, risk management and risk assessment “should be integral parts of the PQS [pharmaceutical quality system] where CM is employed.”
In their risk management plans, manufacturers should evaluate the impact of parameter settings such as time, temperature, rotation per minute, amperage, speed, and pressure during sifting, milling, blending, granulation, and drying on the final product.
The control strategy should define and describe all steps to ensure that the manufacturing process is operating in a state of control. The strategy should address input materials, process monitoring, material diversion, real-time release testing (RTRT), specification, and process equipment.
Stability studies for products manufactured by CM must follow the same principles outlined in the WHO's guidelines on stability testing. Manufacturers should be able to justify their selection of batches for stability testing, as well as the number of batches that are tested.
WHO is accepting comments on the document through an online platform. The deadline for submitting feedback is 7 March.
WHO
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