Elise Biopharma’s Bacterial Fermentation Services harness the unrivaled speed, yield, and adaptability of bacterial hosts to move your biologic or enzyme from first construct to industrial-scale supply—without the scale-up drama. We integrate AI-assisted strain design, codon and secretion pathway tuning, and DoE-driven upstream development with a PAT-instrumented bioreactor fleet to deliver data-tight, regulator-ready processes. From there, our downstream playbook—high-pressure homogenization, clarified harvest, capture/polish chromatography, and UF/DF—locks in purity while protecting activity and recovery. Whether you’re de-risking a milligram-scale proof-of-concept protein, securing kilogram-class clinical supply, or standing up multi-metric-ton enzyme campaigns for global markets, our QbD framework and GMP-compliant execution give you reproducible titers, clean release packages, and a tech-transfer kit that travels. We don’t just run fermentors—we build control strategies that keep CPPs where they belong and CQAs behaving across sites, scales, and seasons.
Why Bacteria?
Rapid Growth Kinetics
Minutes, not days. Doubling times as fast as ~20 minutes collapse design–build–test cycles, enabling dense DoE campaigns and quick iteration on promoters, signal peptides, and chaperone co-expression. Faster biomass ramps shorten time-to-first-batch and let you explore more of the design space before critical program gates.
High Productivity
Real titers, real timelines. Well-tuned Escherichia coli lines routinely exceed 5 g/L for intracellular or periplasmic proteins, while Bacillus platforms push ≥10 g/L for secreted enzymes—often with simplified capture. With soft-sensor-guided feeding and oxygen-transfer control, we convert productivity into soluble expression and downstreamable pools, not inclusion bodies.
Cost Efficiency
Lean inputs, smart control. Media simplicity, compact footprints, and shorter campaigns reduce fixed and variable costs. Closed-loop control trims overfeeding, antifoam, and utility burn; downstream designs emphasize right-first-time capture to minimize resin load and buffer volumes—driving competitive $ / g from pilot through commercial.
Regulatory Familiarity
A well-trodden path. Decades of marketed, bacteria-derived products mean clear expectations for endotoxin, HCP, and residual DNA control, plus mature comparability frameworks. Our QbD dossiers map CPP→CQA with audit-ready data trails, smoothing IND/IMPD filings and accelerating review cycles.
Precision Strain Engineering
AI‑Powered Chassis Design
- Genome‑Scale Models predict metabolic flux toward product formation and identify gene targets for knockout or overexpression.
- Host Tailoring implements codon usage, tRNA enhancements, and chaperone co‑expression for optimal folding.
Construct & Vector Optimization
- Promoter Selection: T7, pLac, pBAD, or tunable synthetic systems for tight expression control.
- Signal Peptides: Direct proteins to periplasm or medium to simplify purification.
- Codon Harmonization minimizes ribosomal pausing and inclusion‑body formation.
Developability Screening
- In Silico Tools flag aggregation hotspots, high‑risk motifs, and solubility issues.
- Pilot Expression in deep‑well plates or 2 L bioreactors to confirm yield, solubility, and activity.
Upstream Process Development
Design of Experiments (DoE) & QbD
- Critical Process Parameters (CPPs): pH, temperature, dissolved oxygen, feed schedule.
- Risk Assessment via FMEA to identify high‑impact variables and establish control strategies.
Smart Bioreactor Integration
- Real‑Time PAT: Inline Raman for metabolite profiling; off‑gas MS for respiratory quotient.
- Automated Controls: PLC/SCADA systems adjust feed/airflow based on live data, ensuring consistent performance.
Scale‑Up & Scale‑Down Models
- Laboratory Scale: 1–5 L benchtop systems replicating large‑scale mixing and oxygen transfer.
- Pilot & Production: Single‑use or stainless steel reactors from 50 L to 2 000 L validated for comparable yield and quality.
Downstream Processing
Cell Harvest & Lysis
- Harvest Technologies: Centrifugation or crossflow microfiltration optimized by host and product.
- Lysis Options: High‑pressure homogenization, enzymatic/chemical methods, or sonication selected for maximum recovery.
Clarification & Capture
- Depth Filtration removes debris rapidly at pilot or commercial scale.
- Affinity Capture: His‑tag IMAC, Protein A/G for Fc‑fusions, or custom resins for native targets.
Polishing & Concentration
- Ion‑Exchange & HIC remove host‑cell proteins and contaminants.
- Tangential Flow Filtration (TFF) for buffer exchange and final concentration.
Sterile Fill‑Finish
- 0.2 µm Filtration in Grade A/B suites
- Automated Filling into vials, syringes, or bulk containers with weight and visual checks.
Host Systems & Applications
| Bacterial Host | Typical Products |
|---|---|
| E. coli | Recombinant enzymes, therapeutic proteins, plasmid DNA |
| Bacillus subtilis / megaterium | GRAS enzymes, spore probiotics, industrial biocatalysts |
| Corynebacterium | Vitamins, amino acids, specialty metabolites |
| Streptomyces | Antibiotics, polyketides, secondary metabolites |
| Facultative Anaerobes | Live biotherapeutics, gut‑targeted therapies |
Analytical & Quality Control
- Metabolic Profiling: GC‑MS and HPLC monitor substrate consumption and byproduct formation.
- Purity & Integrity: SDS‑PAGE, SEC‑HPLC, and mass spectrometry confirm product identity and homogeneity.
- Residuals Testing: Endotoxin (<0.1 EU/mg), host‑cell protein ELISA, and DNA quantification.
- Stability Studies: ICH Q1A real‑time and accelerated protocols to establish shelf life.
Tech Transfer & Regulatory Support
- Process Documentation: Detailed batch records, control plans, and SOPs.
- Scale‑Down Correlation: Ensures pilot and commercial batches are comparable for regulatory filings.
- Validation Packages: IQ/OQ/PQ protocols for equipment and processes.
- Filing Support: IND/ANDA/MAA dossiers for FDA, EMA, and other global agencies.
Case Study: Metric‑Ton‑Scale Enzyme Production
- Challenge: Manufacture 1 000 kg/year of cellulase for biofuel applications.
- Solution:
- Engineered Bacillus strain with enhanced secretion pathway.
- DoE‑optimized fed‑batch in 2 000 L reactors achieving 15 g/L titer.
- Continuous downstream train delivering >95 % purity.
- Outcome:
- On‑time supply for global bio‑refinery launch.
- COGS reduced by 25 % versus incumbent process.
Why Elise Biopharma?
- Deep Bacterial CDMO Expertise
Proven track record with E. coli, Bacillus, and specialty hosts as your dedicated bacterial CDMO partner. - QbD & PAT‑Driven Fermentation Services
Robust design space, Design of Experiments, and real‑time PAT controls ensure consistent, high‑yield bacterial fermentation services. - Flexible Scale from R&D to Commercial
Seamlessly transition from mg‑scale discovery fermentations to multi‑ton commercial batches under one roof. - Integrated End‑to‑End Services
Strain engineering, upstream/downstream process development, and GMP fill/finish—all in a single bacterial CDMO platform. - Regulatory Confidence
Multiple bacterial‑derived biologics successfully filed worldwide—your fermentation services backed by proven compliance.
Next Steps
Ready to unlock the potential of bacterial fermentation for your molecule?
Email: info@elisebiopharma.com
Learn more about about our: Microbial CDMO Services <——Here!