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What ICH Q13 covers and what it does not
ICH Q13 deals with continuous manufacturing of drug substances and drug products, for both chemical entities and therapeutic proteins. Section 1.2 says it applies to new products, including generics and biosimilars, and to converting existing products from batch to continuous. It adds that its principles may also apply to other biological products.
The guideline focuses on systems where two or more unit operations are directly connected. As examples of a single unit operation it mentions process chromatography and perfusion cell culture. The FDA published it as guidance for industry in March 2023, and the EMA lists it as a scientific guideline with an effective date of 10 July 2023.
What Annex III says about therapeutic proteins
Annex III sketches an example continuous process for proteins. It has a bioreactor compatible with perfusion culture, continuous capture chromatography, virus inactivation, polishing chromatography, virus filtration and a TFF step for buffer exchange and concentration. The guideline itself says the example is illustrative and that other approaches can be used.
For equipment makers, the annex gives very concrete pointers. It asks for the integrity of single-use components to be ensured during use, since connections may run for long periods or be changed often. It covers changing filters and integrity testing them without interrupting the process, surge tanks and in-line sensors. It also notes that continuous bioreactors may run far longer than batch ones.
Is ICH Q13 mandatory for equipment manufacturers?
It is a harmonised guideline written for the company that makes the medicine and files the dossier. It looks at equipment from that company's point of view and sets no obligations for equipment manufacturers. The FDA published it as guidance for industry and the EMA as a scientific guideline. On your website, say what data your equipment provides for the customer's control strategy.
How to talk about the guideline without selling it as a rule
ICH Q13 is written for the company that makes the medicine and files the dossier. The customer decides how a batch is defined. Section 2.2 says the size of a continuous batch can be set by the quantity of output material, the quantity of input material or the run time at a defined mass flow rate. Your equipment does not make that call.
That is why claims that use the guideline like a seal of approval backfire. A quality lead knows no piece of equipment complies with ICH Q13 on its own. The table lists common claims and a more accurate way to put them.
| Risky claim | Why it is a problem | More accurate alternative |
|---|---|---|
| ICH Q13 compliant equipment | The guideline is for drug manufacturers and does not certify equipment | Equipment designed for continuous processes, with data for the customer's control strategy |
| Continuous manufacturing ready | It does not say in which mode or for how long it was tested | Tested in perfusion culture, with the duration and test conditions next to it |
| Validated continuous batch | Per sections 4.3 and 4.7, batch size and validation are described in the drug dossier | Long run performance data to support the customer's validation |
| Guaranteed real-time release | Section 4.2 says real-time release testing is not a regulatory requirement for continuous manufacturing | In-line sensors that can be part of the customer's monitoring strategy |
Can I say my equipment is ICH Q13 compliant?
Better not. The guideline does not certify equipment and has no list of approved systems. Describe what the equipment does in a continuous process instead, for example how long it was tested without stopping, which in-line sensors it carries, how it connects to the rest of the line and what documentation you supply for qualification.
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Review my datasheetsWhat to put on the datasheet of continuous process equipment
The datasheet should say how the equipment behaves inside a continuous process. Section 3.1.4 lists design considerations such as components that hold up for the maximum run time, the physical connections and digital control interfaces between equipment, and where the sampling and material diversion points sit.
The same goes for “perfusion ready”. Say which cell retention device it was tested with, for how many consecutive days and what data you have. A CDMO can do the same on its website with the operating modes it runs and the campaigns it has already completed.
- Which modes the equipment supports, standalone, integrated with other unit operations or with a surge tank.
- How long it has been tested without stopping, and under which conditions.
- Which connections and communication protocols it uses to talk to the rest of the line.
- Which in-line sensors it carries or accepts, such as pH or UV protein concentration.
- The service life of resins, membranes and single-use components over long runs.
If I make batch equipment, does continuous manufacturing leave me out?
Not necessarily. Section 2.1 of the guideline describes processes where some unit operations run in batch mode and others continuously, as well as surge tanks to keep material flowing. If your equipment can work in a hybrid process, show it with a diagram and the conditions under which it was tested.
Which evidence convinces a process development team
The strongest evidence answers the risks the guideline itself lists. Section 3.2 says issues not seen in short runs may appear as run time increases. It names process drift, rising equipment temperatures, material build-up, exceeding resin cycle limits, membrane or sensor fouling and microbial contamination.
A test report with the real run time or an application note showing how drift is detected is worth more than any adjective. Section 3.1.5 says process analytical technology, PAT, is well suited to continuous manufacturing, and gives in-line UV flow cells for protein concentration as an example.
What should a CDMO explain about continuous manufacturing?
Which modes it runs, from single unit operations to integrated lines, which campaigns it has completed and how long they lasted, which in-line sensors it has and how it handles disturbances. Section 4.8 of the guideline describes a plan for managing disturbances and diverting material within the quality system. Explaining yours builds trust.
A shared glossary and sales answers for web and sales teams
Continuous manufacturing brings new vocabulary, and your website, brochures and sales team should all use it the same way. Section 5 of the guideline defines, among others, residence time distribution, disturbances, diversion and soft sensors. You can turn them into a glossary page that links to each product.
Sales answers can be prepared too. Customers will ask how long the equipment runs without stopping, how it flags drift, how it connects to their automation and what happens if a filter fails. For disturbances, Annex V of the guideline gives examples of how to manage them.
David Monje, founder of crida studio, led marketing at TECNIC Bioprocess Solutions for four and a half years and acted as the bridge between engineering, product and sales. At crida studio we build the glossary and the answers with your technical team and then carry them into the website, the datasheets and your emails.
