Manufacturing therapies that evolve: what will it take to scale living medicines?

Living medicines, including microbiome therapeutics, phage therapies and engineered bacteria, present distinct challenges for pharmaceutical manufacturing, from maintaining product identity and potency to ensuring quality throughout the supply chain. As these therapies move towards commercialisation, developers must consider how manufacturing processes, quality control and regulatory approaches can adapt to products that are inherently more complex than traditional biologics.

In this interview, Christian Roghi discusses what it will take to manufacture living medicines consistently and deliver them to patients at scale.

What makes the manufacture of living medicines fundamentally different from traditional biologics, and where are the biggest challenges in maintaining product viability and consistency at scale?

Manufacturing is closely intertwined with product quality for all biologics. With living medicines, the additional challenge is preserving the biological activity of living cells or replicating agents throughout production, formulation, storage and transport. Their biological state can change during manufacture, so the challenge is to control that variability and ensure that the medicine reaching the patient retains its intended identity, quality and function.

Another important consideration is identity and concentration. How do you maintain both from A to B? Other key factors are viability, potency and functional stability – all of which need to be maintained. These cannot be captured through a single assay, so multiple assays are required to ensure that the product meets the necessary requirements.

One of the main challenges is the loss of biological properties during manufacturing, and there is still a lot to be done in this area.”

One of the main challenges is the loss of biological properties during manufacturing, and there is still a lot to be done in this area. For live biotherapeutic products, for example, guidance from the US Food and Drug Administration sets out expectations for the manufacturing and control information required for early clinical trials, including contamination control and stability.

As microbiome therapeutics, phage therapies and engineered bacteria move towards commercialisation, how are manufacturing quality control approaches having to evolve to accommodate these products?

Microbiome-based products could involve a single bacterium, a cocktail of bacteria, a phage or even an ecosystem, such as faecal microbiota transplantation (FMT). In each case, you need to consider strain identity, viability, potency and purity, as well as controlling microbial contamination. The measures differ by product type: for phages, infectivity and the ability to kill target bacteria are key considerations. In Europe, the pharmacopoeia has established requirements covering strain characterisation, viable organism enumeration and microbial contamination control.

For phages, there is an additional layer of complexity because they are usually produced using a host organism. Therefore, you need to control not only the phage itself but also the production organism and any associated toxins. Engineered bacterial therapeutics in development, meanwhile, require genetic stability and ensuring that the intended function is maintained throughout the production process.

Quality control is also shifting from asking, ‘Is this the right organism?’ to asking, ‘Is this the right organism in the right state, doing the right thing?’ Again, multiple assays are needed to ensure that the final product is what you expect it to be.

With specialist manufacturing capacity still limited, how should developers approach the decision between in-house manufacturing, CDMO partnerships and hybrid models as they move towards commercialisation?

It’s not as simple as making one decision; the approach will vary depending on the organisation. The first question is whether manufacturing is a strategic consideration for the organisation. If manufacturing know-how is central to your intellectual property and company value, you must decide which capabilities and knowledge to retain, and how these will be protected in any partnership. For a small company, particularly one considering a future acquisition, access to process knowledge, manufacturing data and technology transfer rights can be critical.

On the other hand, GMP infrastructure is expensive to build and requires not only substantial capital but also the right talent to run the facility.”

On the other hand, GMP infrastructure is expensive to build and requires not only substantial capital but also the right talent to run the facility. For many companies, I think a hybrid model is worth considering, as it allows them to benefit from a CDMO or related organisation for part of the process while retaining the strategic aspects in-house in one way or another.

How can manufacturers address the full supply chain and logistics requirements for these medicines while also meeting the need for cost-effective, geographically broad patient access?

A cold chain isn’t always necessary for living medicines; it really depends on the type of medicinal product. Some living medicines require cryopreservation, as well as careful management of chain of identity, timing and transport. These are fundamental to the treatment pathway: it’s not just about manufacturing but also about ensuring the medicine reaches the patient at the right temperature.

For some microbial products, lyophilisation can improve stability and may reduce cold-chain requirements. However, storage and transport conditions must be established through product-specific stability data. Where cold-chain transport is required, maintaining and measuring the temperature as the product moves from A to B can be challenging and must be built into the process. Shelf life, storage conditions, temperature and transport time must all be managed.

You must consider the entire journey, from the production line to the patient.”

Planning needs to start from the beginning. You can’t develop a medicine and then say, ‘Now we’re going to move to the next level – what do we do?’ You must consider the entire journey, from the production line to the patient. I’ve seen examples where a hospital didn’t have the right storage facilities in place, or where storage was restricted to one type of product, which then created an issue. Manufacturers must account for these considerations, to prevent delays in the delivery of medicines to patients. The delivery model also determines cost and access: storage, preparation and administration requirements influence which treatment centres can realistically use the product.

With regulatory frameworks for living medicines continuing to evolve, what needs to change across manufacturing and wider supply chains to enable these therapies to reach the market at scale?

Established regulatory frameworks already support cell therapies, including CAR-T therapies, and quality standards and guidance also exist for live biotherapeutic products. However, their scope differs across product types, and some areas are still developing. Early engagement with regulators is essential, particularly for complex microbial communities, engineered organisms and changes to product composition. Regulation is risk-based and modality-specific, so we should not try to force every product into a single pathway.

Manufacturing processes improve as products scale up, and developers need to demonstrate that these changes preserve product quality, safety and efficacy. In some cases, such as phage therapies, the composition may also need to be deliberately updated. Such changes require appropriate evidence and regulatory oversight.

Finally, we need greater alignment across the entire ecosystem. Manufacturing approval alone is not enough: GMP facilities, laboratory testing, transport, treatment centres, reimbursement systems and national regulators must all work together. The manufacturing process, regulatory pathway and delivery systems must increasingly be designed together.

Presentation: Living Medicines: Can Manufacturing Infrastructure Keep Pace with Progress? CPHI Milan 2026.