Live Biotherapeutic Products: The Future of Microbiome-Based Medicine

The pharmaceutical industry is entering a new phase where medicines are no longer limited to chemically synthesised molecules or biologically engineered proteins. A growing area of innovation is live biotherapeutic products (LBPs), therapies that contain living microorganisms designed to prevent, treat, or cure disease. As our understanding of the human microbiome expands, LBPs are emerging as a powerful and precise way to influence health at a biological ecosystem level rather than targeting a single pathway.

Unlike traditional drugs that act through chemical interactions, live biotherapeutic products work by restoring, modifying, or supporting the natural microbial balance of the human body. This shift represents a fundamental change in how diseases, especially those linked to gut health, immunity, and metabolism, are treated.

What Are Live Biotherapeutic Products?

Live biotherapeutic products are biological medicinal products that contain live microorganisms, such as bacteria, intended for therapeutic use in humans. These products are regulated as drugs, not as foods or supplements, and must meet strict pharmaceutical standards for safety, quality, and efficacy.

LBPs are often confused with probiotics, but the two are not the same. Probiotics are typically sold as dietary supplements or functional foods and are not required to demonstrate clinical efficacy for specific diseases. Live biotherapeutic products, on the other hand, are developed through controlled clinical trials and are intended to treat or prevent defined medical conditions.

Regulatory agencies such as the US FDA define LBPs as biological products that:

• Contain live organisms
• They are used to prevent, treat, or cure a disease
• Are not vaccines

This definition places LBPs firmly within the pharmaceutical development and regulatory framework.

The Science Behind Live Biotherapeutic Products

The human body hosts trillions of microorganisms, collectively known as the microbiome, with the gut microbiome being the most studied. These microbes play a key role in digestion, immune regulation, vitamin synthesis, and protection against harmful pathogens.

Disruptions to the microbiome, often caused by antibiotics, poor diet, illness, or stress, have been linked to conditions such as inflammatory bowel disease, recurrent infections, metabolic disorders, and even neurological conditions.

Live biotherapeutic products are designed to address these disruptions by:

• Replacing missing or depleted beneficial bacteria
• Suppressing the growth of harmful microorganisms
• Modulating immune responses
• Producing beneficial metabolites directly in the body

Unlike traditional therapies, LBPs often act locally in the gut and interact dynamically with the host’s biology, making them both promising and complex.

Therapeutic Applications of Live Biotherapeutic Products

LBPs are being explored across multiple therapeutic areas, with gastrointestinal diseases currently leading development efforts.

One of the most advanced applications is the treatment of recurrent Clostridioides difficile infection (CDI). In this condition, repeated antibiotic use disrupts gut microbiota, allowing C. difficile to thrive. Live biotherapeutic products help restore microbial diversity, reducing recurrence rates more effectively than antibiotics alone.

Beyond CDI, LBPs are being studied for:

• Inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease
• Irritable bowel syndrome
• Metabolic disorders, including obesity and type 2 diabetes
• Liver diseases such as hepatic encephalopathy
• Immune-mediated and allergic conditions
• Oncology, where microbiome modulation may improve immunotherapy response

Research is also expanding into neurological and psychiatric conditions, reflecting growing interest in the gut–brain axis.

Development and Manufacturing Challenges

Developing live biotherapeutic products is far more complex than producing conventional pharmaceuticals. Since the active ingredient is a living organism, maintaining its identity, purity, potency, and stability presents unique challenges.

One major challenge is strain selection and characterisation. Each microbial strain must be fully identified at the genetic level, and its mechanism of action must be understood. Even closely related strains can behave very differently in the human body.

Manufacturing LBPs requires specialised processes, including:

• Controlled fermentation under sterile conditions
• Strict anaerobic handling for oxygen-sensitive organisms
• Precise control of temperature, pH, and nutrients
• Lyophilisation or other stabilisation techniques

Unlike chemical drugs, LBPs are highly sensitive to environmental conditions. Minor manufacturing variations can affect viability and clinical performance, making robust process validation essential.

Quality Control and Stability Considerations

Quality control for live biotherapeutic products goes beyond traditional pharmaceutical testing. In addition to standard microbiological safety tests, manufacturers must ensure:

• Correct strain identity throughout shelf life
• Consistent viable cell count (potency)
• Absence of contaminants, including bacteriophages
• Genetic stability over multiple production cycles

Stability testing is particularly challenging because live organisms can lose viability over time. Storage conditions, packaging materials, and transportation all play a critical role in maintaining product quality. Cold-chain logistics are often required, adding complexity and cost to commercialisation.

Regulatory Landscape for Live Biotherapeutic Products

Regulatory agencies globally recognise LBPs as a distinct class of therapeutics, but regulatory frameworks are still evolving.

In the United States, LBPs are regulated by the FDA’s Center for Biologics Evaluation and Research (CBER). Developers must submit Investigational New Drug (IND) applications and conduct phased clinical trials, similar to other biologics.

Key regulatory considerations include:

• Comprehensive strain characterisation
• Clear definition of the mechanism of action
• Justification of dosing based on viable organisms
• Long-term safety monitoring due to the live nature of the product

In Europe, the EMA classifies LBPs as biological medicinal products and requires compliance with Good Manufacturing Practice (GMP) requirements specific to biologics.

The lack of harmonised global guidelines can make international development challenging, but regulatory clarity is improving as more products enter late-stage development.

Clinical Development and Safety Considerations

Clinical trials for live biotherapeutic products must account for the complexity of host–microbe interactions. Unlike conventional drugs, LBPs may behave differently depending on the patient’s existing microbiome, diet, and immune status.

Safety assessments focus not only on adverse events but also on:

• Risk of systemic infection
• Horizontal gene transfer, including antibiotic resistance genes
• Long-term effects on microbiome composition

To date, most LBPs have shown favourable safety profiles, especially when administered orally and designed to act locally in the gut. However, careful patient selection and post-marketing surveillance remain critical.

Commercial Potential and Market Outlook

The global interest in microbiome-based therapies has driven significant investment in the development of live biotherapeutic products. Pharmaceutical companies, biotech startups, and academic institutions are actively collaborating to accelerate innovation in this space.

As the first LBPs receive regulatory approval, the market is expected to expand rapidly, particularly in areas with high unmet medical needs and limited treatment options.

Commercial success will depend not only on clinical efficacy but also on scalable manufacturing, a strong supply chain, and physician education. Since LBPs represent a new treatment paradigm, clear communication of their benefits and limitations will be essential for adoption.

The Future of Live Biotherapeutic Products

Live biotherapeutic products represent a shift from treating symptoms to restoring biological balance. As microbiome science advances, future LBPs may be personalised, targeting specific microbial profiles or genetic markers.

Advances in synthetic biology, genomics, and bioinformatics are expected to improve strain design, predict patient response, and optimise therapeutic outcomes. Over time, LBPs may become a standard part of treatment strategies across multiple disease areas.

While challenges remain, the progress seen so far suggests that live biotherapeutic products will play a central role in the next generation of pharmaceutical innovation.

FAQ

1. What are live biotherapeutic products used for?

Live biotherapeutic products are used to prevent or treat diseases by restoring or modifying the body’s microbiome.

2. How are live biotherapeutic products different from probiotics?

LBPs are regulated drugs with proven clinical efficacy, while probiotics are dietary supplements without disease claims.

3. Are live biotherapeutic products safe?

Yes, when properly developed and regulated, LBPs have shown strong safety profiles in clinical trials.

4. Which diseases can live biotherapeutic products treat?

They are mainly used for gut-related conditions but are also being studied in metabolic, immune, and cancer therapies.

5. Are live biotherapeutic products approved by regulators?

Several LBPs have reached late-stage development, and regulatory approvals are increasing as guidelines mature.