Scaling live biotherapeutics: Key challenges and opportunities

However, the path to scale remains challenging. Traditional bioprocessing infrastructure is not designed for strict anaerobes, viability‑dependent products, or multi‑strain consortia. The sector faces capability gaps in anaerobic upstream processing, integrated high‑throughput analytics, predictable freeze‑drying performance, and GMP‑ready manufacturing capacity in the UK and Europe. These are bottlenecks that have kept many promising LBP candidates in early development far longer than intended. 

At the same time, new opportunities are emerging. Digital twins, automated anaerobic workflows, and rapid molecular characterisation tools such as ddPCR are redefining what’s possible in both discovery and development. Together, these advances point towards a future where model‑informed co‑culture design, real‑time viability monitoring, and data‑driven formulation strategies enable faster, more reliable translation to clinic. 

Ultimately, the promise of LBPs lies in their ability to deliver meaningful patient impact – reducing relapse rates, preventing hospitalisations, restoring microbial balance after antibiotic treatment, and offering new options where conventional therapeutics fall short. Realising this potential requires a cohesive ecosystem that can bridge science, engineering, and regulation. 

This is precisely where CPI comes in. We provide the bioprocessing capability, analytical platforms, translational experience, and collaborative environment needed to de‑risk development and accelerate the journey from promising concept to real‑world patient benefit. 

A market ready to scale 

The LBPs market is entering a period of expansion, fuelled by deeper microbiome insight and a growing recognition that targeted microbial interventions can transform how we prevent and treat disease. Organisations across the UK, Europe, and the globe, are now developing novel microbial consortia, precision‑engineered strains, and next‑generation manufacturing solutions aimed at addressing major healthcare challenges; from recurrent infections and inflammatory disorders to metabolic and immune‑related conditions. As investment accelerates and innovative companies push boundaries in strain design, analytics, formulation, and scalable bioprocessing, the LBP sector is shifting from scientific curiosity to a credible, high‑growth therapeutic modality with the potential to reshape healthcare.

LBPs are now moving firmly into the commercial arena, with the first FDA‑approved products demonstrating that living microbes can be deployed safely and effectively as medicines. Rebyota, a donor‑derived whole‑community product, became the first approved LBP for recurrent C. difficile infection, validating ecosystem‑restoration approaches. This was followed by Vowst (SER‑109), a defined spore‑based consortium that showed how purified, rationally selected strains can achieve reproducible clinical outcomes and scalable manufacturing. With these early successes, the LBP pipeline is rapidly expanding across single-strain products, defined consortia, and engineered microbes, each offering distinct therapeutic and manufacturing advantages. 

Smarter production through co-culture 

Multi-strain LBPs can provide enhanced functionality but introduce significant manufacturing complexity, as each additional strain requires dedicated cultivation, banking, characterisation, and control strategies, increasing development time, cost, and operational burden. 

One promising approach is co‑culturing, where compatible strains are grown together to reduce processing burden and better reflect natural microbial interactions. 

Co‑culture is not without challenges. Manufacturers must navigate lactic acid and other inhibitory by‑product accumulation, inter‑strain competition, differing nutrient and environmental requirements, and the inherent difficulty of optimising media for multiple species simultaneously. These factors make achieving stable, balanced growth a sophisticated process that requires careful design and real‑time oversight. 

Despite this, evidence suggests that continuous co‑culture systems can maintain a more stable population structure and offer a more sustainable alternative to running multiple discrete fermentations. When supported by robust analytics and well‑engineered bioprocess controls, co‑culture provides a credible pathway to scalable, commercially viable multi‑strain LBP production. 

Purifying LBPs without compromising viability 

While many downstream processing methods, such as filtration, centrifugation, and clarification, are broadly transferable from traditional microbial bioprocessing, LBPs introduce a unique layer of complexity. Achieving the high‑density concentrations required for dose delivery must be balanced against maintaining cell viability throughout every step, from harvest to final formulation. LBPs also exhibit limited tolerance for hold times between upstream, purification, and analytical activities, meaning that even short delays can impact product quality. 

Processes often need to operate under strict anaerobic conditions, and sterility requirements are uncompromising given the live nature of the product. These constraints demand seamless coordination between upstream, downstream, formulation, and analytical teams to ensure that cells remain viable, stable, and clinically relevant throughout purification. When executed well, purification becomes a critical enabler of consistent, high‑quality LBP manufacture. 

Strain-level characterisation 

Robust analytical characterisation is central to LBP development, with regulators placing significant emphasis on both process‑driven attributes and strain‑specific features such as genetic identity, stability, and the potential for virulence or antibiotic‑resistance gene transfer. Demonstrating control at the strain level requires fast, reliable, and high‑throughput tools capable of tracking composition and viability throughout development. Core methods include CFU plate screens for viability, 16S sequencing for profiling, qPCR for targeted detection, and flow cytometry for rapid, single‑cell analysis. 

At CPI, droplet digital PCR (ddPCR) has shown particular promise, enabling sensitive and precise quantification of strains within mixed or co‑culture systems - an essential capability as multi‑strain LBPs become more prevalent. Together, these analytical approaches form the backbone of evidence needed to progress LBPs confidently toward clinical evaluation. 

Lyophilisation: Protecting viability for the long-term 

Final formulation and lyophilisation are critical steps in converting an LBP into a stable, patient-ready product. Freeze-drying can enable long-term storage, simplified distribution, and improved product stability, but it is also one of the most sensitive stages of the manufacturing process. Suboptimal lyophilisation conditions may reduce cell viability, alter functionality, shorten shelf life, and ultimately impact product performance. 

As a result, formulation development should be considered early in process design rather than as a final downstream activity. Formulation components, including cryoprotectants and excipients, interact closely with upstream cultivation and downstream processing conditions, requiring an integrated development approach. By combining formulation science with process engineering, manufacturers can maximise strain survival, preserve functional activity, and ensure the final product remains stable and effective throughout its intended shelf life. 

Laying the groundwork: Choosing the right strains

Selecting the right strains is one of the most critical determinants of LBP success. Given the complexity and diversity of the gut microbiome, focusing on the most therapeutically relevant organisms helps ensure clinical impact while avoiding unnecessary development and manufacturing burden. Close collaboration between upstream scientists and analytical teams is essential to refine cultivation methods, validate strain identity, and build robust characterisation assays that can reliably track each strain through development.

Attention is often placed on taxa known to decline sharply following antibiotic treatment - including Lactococcus, Bifidobacterium, Lactobacilli, Lachnospiraceae, and Eubacteria - as restoring these groups can offer clear clinical benefit. Understanding which strains suffer the steepest depletion allows developers to prioritise the organisms most likely to drive therapeutic effect, forming a strong scientific basis for LBP formulation strategies. Emerging multi‑omics approaches - integrating genomics, transcriptomics, proteomics, and metabolomics - are increasingly being used to understand strain function at a systems level and to design precision‑engineered microbial solutions with enhanced therapeutic potential. 

Regulatory landscape: A work in progress 

Regulation remains one of the most rapidly evolving aspects of the Live Biotherapeutic Product (LBP) field. Recognising the unique nature of microbiome-derived medicines, the UK Medicines and Healthcare products Regulatory Agency (MHRA) has published its position on the regulation of microbiome-based medicinal products, acknowledging that these therapies present distinct challenges compared with conventional pharmaceuticals and biologics. The guidance highlights the importance of demonstrating product quality, consistency, safety, potency, and robust characterisation throughout development, while recognising that living microbial products often require novel approaches to manufacturing and control.

For developers, this creates several challenges. LBPs are inherently complex, with product performance linked not only to manufacturing consistency but also to microbial viability, strain identity, genetic stability, and, in the case of consortia, the interaction between multiple organisms. Establishing appropriate potency assays, demonstrating comparability following process changes, controlling anaerobic manufacturing environments, and defining acceptable specifications remain areas where industry best practice is still emerging. These uncertainties can increase development timelines and contribute to investment risk, particularly for early-stage companies seeking to translate promising science into clinical products.  

However, these challenges also represent a substantial opportunity for growth and innovation. As regulatory expectations become clearer, there is increasing demand for advanced analytical methods, scalable anaerobic manufacturing platforms, digital approaches to process monitoring, and integrated development strategies that can provide regulators with greater confidence in product quality and control. Organisations that can establish robust manufacturing processes, generate high-quality characterisation data, and engage proactively with regulators will be well positioned to accelerate product development and become leaders in this rapidly expanding sector. The continued dialogue between industry, MHRA, NIBSC, and international regulators is helping to shape a regulatory framework that supports both innovation and patient safety.  

This evolving landscape presents a significant opportunity for the UK to establish itself as a global hub for microbiome innovation, combining scientific excellence, regulatory engagement, and advanced biomanufacturing capability to accelerate the development and commercialisation of next-generation microbiome medicines. 

Building the path to market 

Bringing LBPs successfully to market demands far more than excellence in any single step; it requires a fully defined, end‑to‑end development pathway that links strain selection, co‑culture optimisation, purification, formulation, and lyophilisation into a coherent, controlled process. As the sector matures, regulators, clinicians, and commercial partners will expect LBPs to be developed with the same rigour and reproducibility as other advanced biotherapeutics - supported by robust analytics, scalable manufacturing, and clear regulatory evidence. The organisations that succeed will be those able to integrate biology, engineering, and quality from the outset, ensuring that every stage upstream and downstream protects viability, consistency, and safety. 
 
Through the Microbiome: Accelerating Innovation & Development (MAID) programme, CPI and the University of Liverpool are helping to strengthen the microbiome ecosystem across the Liverpool City Region and the wider UK, connecting innovators with the expertise, capabilities, and networks needed to accelerate development. By bringing together world-leading microbiome research with industrial scale-up and manufacturing expertise, MAID is helping companies overcome barriers to commercialisation and unlock the growth potential of this emerging sector. CPI combines expertise in microbial bioprocessing, advanced characterisation, anaerobic processing, and translational scale-up to help address the key manufacturing challenges facing live biotherapeutics. By integrating robust process development and product characterisation from an early stage, we can accelerate the translation of promising microbiome therapies into clinically and commercially viable products.