The world of Live Biotherapeutic Products (LBPs) represents a paradigm shift in medicine, harnessing the power of live microorganisms to treat and prevent diseases. As these complex, living drugs move from discovery to clinical reality, their Formulation Development and Quality Establishment become the most critical-and challenging-steps. Unlike small molecules or traditional biologics, LBPs require specialized expertise to ensure the viability, stability, potency, and regulatory compliance of the final drug product.
Our Contract Research Organization (CRO) specializes in this complex landscape. Creative Biolabs provides a comprehensive, end-to-end solution for LBP Formulation Development and Quality Establishment, designed to de-risk your program, accelerate your path to Investigational New Drug (IND) filing, and ensure a manufacturable, high-quality therapeutic. We transform your promising microbial strain into a stable, potent, and compliant drug product.
Service Background & Necessity
The efficacy of an LBP is directly linked to the number of live organisms (Colony Forming Units or CFUs) that reach the target site. Developers face three primary enemies:
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Oxygen Exposure: Many next-generation candidates (e.g., Akkermansia, Faecalibacterium) are strict anaerobes that perish rapidly in air.
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Gastric Acidity: Without protection, low stomach pH can destroy up to 99% of uncoated bacteria.
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Shelf-Life Instability: Moisture and temperature fluctuations during storage can degrade membrane integrity, leading to potency loss over time.
Our service treats your strain not just as a culture, but as a pharmaceutical dosage form, applying Quality by Design (QbD) principles to solve these challenges early in development.
Service Content and Methodology
This service is a fully integrated CMC (Chemistry, Manufacturing, and Controls) solution focusing on the pre-clinical and early-clinical stages of LBP development. Our goal is to define the optimal drug product composition and process (Formulation Development) and establish the necessary analytical methods and quality controls to prove its identity, strength, quality, and purity (Quality Establishment).
Samples
Deliverables
Turnaround Time
Formulation Development
Formulation is paramount for LBPs, directly impacting the organism's viability, stability, and therapeutic efficacy upon administration. We focus on developing a stable dosage form that maximizes organism survival through manufacturing, storage, and passage through the harsh gastrointestinal (GI) tract.
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Pre-Formulation Characterization
a) Strain Stability Profiling: Assessing the inherent stability and stress tolerance of the LBP strain (e.g., thermal, moisture, oxygen, pH tolerance).
b) Cryoprotectant and Lyoprotectant Screening: Identifying optimal excipient cocktails (sugars, polymers, salts) to maintain cell viability during lyophilization (freeze-drying) and subsequent storage.
c) Excipient Compatibility Studies: Testing the LBP strain's compatibility with a wide range of Generally Recognized as Safe (GRAS) excipients to prevent cell death or genomic instability.
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Dosage Form Development & Optimization
a) Lyophilized Powder (Drug Substance): Optimizing the lyophilization cycle parameters (freezing rate, primary/secondary drying time, vacuum pressure) for maximal yield and residual moisture control.
b) Drug Product Formulation (e.g., Capsules, Tablets): Developing the final dosage form to ensure targeted release and protection from the gastric environment (e.g., enteric coating formulation).
c) Process Robustness Testing: Defining Critical Process Parameters (CPP) and Critical Quality Attributes (CQA) through Design of Experiments to ensure batch-to-batch consistency and scalability.
Quality Establishment & CMC Analytical Services
A robust Quality Control (QC) strategy, underpinned by validated analytical methods, is essential for regulatory approval. We establish and qualify the critical assays that will be used for product release and stability testing.
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Potency Assay Development & Validation
a) Viable Cell Count: Developing accurate methods (e.g., CFU plating, flow cytometry) to quantify live organisms.
b) Strain-Specific Potency: Developing functional assays to measure the LBP's mechanism of action (e.g., metabolite production, enzyme activity, immunomodulatory effect) as a true measure of strength.
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Identity and Purity Testing
a) Identity: Establishing methods for unambiguous strain identification (e.g., 16S rRNA sequencing, whole-genome sequencing (WGS), or strain-specific qPCR).
b) Purity/Contamination: Developing and validating assays to test for microbial contaminants, adventitious viruses, and endotoxins (e.g., Bioburden, Sterility Testing).
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Stability Studies:
a) ICH-Compliant Studies: Designing and executing stability programs under various storage conditions (long-term, accelerated, stress) to determine shelf-life.
b) Critical Quality Attributes (CQA) Monitoring: Tracking key parameters like viability, moisture content, dissolution/release rate, and potency over time.
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Method Qualification/Validation
Performing rigorous qualification or full validation of all critical analytical methods (e.g., linearity, accuracy, precision, limit of detection, limit of quantitation).
Sample Submission & Requirements
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LBP Master Cell Bank (MCB) and Working Cell Bank (WCB): Well-characterized, qualified, and purity-tested microbial cultures.
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Initial Growth Media and Downstream Processing (DSP) Buffers/Materials: Information on existing manufacturing processes, if any.
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Target Product Profile: Desired dosage form, dose strength, route of administration, and target shelf-life.
Deliverables
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Comprehensive Formulation Report: Detailed data on excipient screening, stabilization method (e.g., optimized lyophilization cycle), and final product composition.
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Finalized Formulation Prototype (Lab-Scale): Stable LBP product manufactured under the optimized process.
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Qualified Analytical Method Reports: Detailed Standard Operating Procedures for all established QC assays (Identity, Potency, Purity).
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Stability Study Protocol & Data: Real-time and/or accelerated stability data.
Turnaround Time
Timelines are estimates for single-strain LBP programs. Complex multi-strain consortia or novel delivery systems may require extended timelines.
Ready to start your formulation project? Click here to request a quote and consultation!
Our Competitive Advantages
Partnering with us means leveraging specialized expertise and infrastructure specifically designed for the unique challenges of LBPs:
LBP-Specific Infrastructure
Access to facilities with specialized anaerobic and humidity-controlled cleanrooms is necessary for handling sensitive microbial strains.
Deep Microbiome Expertise
Our team of microbiologists, pharmaceutical scientists, and regulatory experts has a proven track record in microbial stability, strain-specific potency assay development, and LBP CMC requirements.
Phase-Appropriate Strategy
We utilize a risk-based, phase-appropriate approach to quality establishment, ensuring you only invest in the necessary level of method validation for your current clinical stage.
Regulatory Foresight
We provide proactive regulatory guidance, translating complex, evolving LBP guidelines into a clear, actionable CMC strategy, thereby minimizing the risk of CMC-related clinical holds.
Applications
Our comprehensive LBP Formulation and Quality services are applicable across the entire spectrum of live biotherapeutic development:
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Single-Strain LBPs: Targeted development for a single, therapeutically active organism.
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Defined Microbial Consortia: Complex development for products containing multiple, co-fermented, or blended strains, optimizing viability and compatibility of all components.
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Engineered Probiotics (NGPs): Formulating genetically modified organisms, requiring specialized containment and more rigorous strain stability and shedding assays.
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Early-Stage Drug Product Selection: Choosing the most stable and patient-compliant dosage form (capsule, oral suspension, enema, etc.).
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IND-Enabling CMC: Generating the critical data required for regulatory submission to the global health authorities.
The development of Live Biotherapeutic Products is one of the most exciting and complex frontiers in medicine. The successful transition from discovery to a stable, compliant drug product hinges on sophisticated Formulation Development and rigorous Quality Establishment. By partnering with our specialized CRO, you gain more than just data; you secure a strategic partner with the expertise, infrastructure, and regulatory intelligence to navigate the unique CMC challenges of LBPs. We reduce your technical risk, streamline your development timeline, and build the quality foundation necessary for regulatory success. Let us accelerate your living medicine to the patients who need it most.
Would you like to schedule an initial consultation with our LBP formulation experts to discuss your specific microbial strain and target product profile?
Frequently Asked Questions (FAQs)
What is the biggest challenge in LBP formulation?
The primary challenge is maximizing organism viability and stability throughout the manufacturing process and shelf life. Lyophilization is a common method, but optimizing the cryoprotectant formulation and the drying cycle is strain-specific and must be robust enough to maintain >109 viable cells per dose for years.
How is the LBP potency assay different from standard microbial testing?
Standard testing measures total organism count (CFU/mL). An LBP potency assay is a functional assay that measures the organism's therapeutic activity—its ability to produce a key metabolite, modulate an immune pathway, or inhibit a pathogen. It's the true measure of a drug's Strength and is required for regulatory filing.
Do you offer GMP manufacturing for formulated LBPs?
While our core service is R&D-stage Formulation and Quality Establishment, we work closely with a network of trusted LBP-focused CDMOs and can facilitate a seamless, data-rich tech transfer of your optimized formulation and validated methods for GMP clinical or commercial supply.
