WHO finalises Paper on Continuous Manufacturing

The WHO has published the final version of its 'Points to Consider' paper on continuous manufacturing as Annex 2 to the WHO Technical Report (TRS) 1067. The draft versions of the paper had already been issued by the WHO in early 2025 with a view to providing a global framework for the implementation of continuous manufacturing processes in the pharmaceutical industry.

The document, which is now available and is intended for pharmaceutical manufacturers and regulatory authorities, contains no significant changes or surprises.
The basic structure, comprising 10 chapters, has been retained:

1. Introduction
2. Glossary
3. Benefits and challenges in continuous manufacturing
4. Good practices considerations
5. Risk management
6. Control strategy
7. Process dynamics
8. Computerized systems
9. Validation and verification
10. Stability testing

The final version contains only a few changes of emphasis, as well as some new and removed elements. Overall, the introduction has been streamlined. Chapter 3 now places greater focus on economic and environmental sustainability, listing environmental impact and water/energy consumption as factors to be assessed, among other things.
In the draft, a specific distinction was made between low-risk and high-risk changes when switching from a batch to CM (post-approval change). However, in the final version, this is phrased in much more general terms, with reference made to the need to demonstrate comparable quality and bioequivalence.

Chapter 4, 'Good Practice', focuses more strongly on material traceability and RTD (Residence time distribution). The final version more clearly explains why traceability is critical in continuous manufacturing, where multiple batches of raw materials and feedstocks can be introduced at different times, and why understanding RTD and process dynamics is essential.
The glossary has also been expanded and revised slightly. The final version contains additional definitions, as well as restructured ones, including: 'Batch size' is now a separate glossary entry; 'pharmaceutical product' is now a defined term; and 'continuous manufacturing' is now defined as two or more integrated unit operations. This numerical specification was not included previously.

You will find the paper 'WHO points to consider in continuous manufacturing of pharmaceutical products' in Annex 2 of WHO TRS 1067. The WHO is expected to make the document available as a standalone publication on its website shortly.