GMP-Grade Phage Production Services
BackgroundService ProcedureOur AdvantagesCase StudyFAQs
Background
GMP (Good Manufacturing Practice)-grade phage production is a critical process designed to ensure the safety, efficacy, and consistency of phage-based medicinal products. As phage therapy gains traction as a potential solution for antibiotic-resistant infections, the need for GMP-compliant phage production has become increasingly important. GMP standards are essential for the development of phage therapies, particularly for clinical trials and market authorization.
Key Components of GMP-Grade Phage Production
Figure 1. General schema of GMP phage manufacturing. (Regulski et al., 2021)
Starting Materials
- Bacterial Strains: Must be well-defined with confirmed identity, purity, and no toxins or resistance genes. Master and working cell banks ensure production consistency.
- Phage Banks: Master and working phage banks are maintained with detailed records. NGS is commonly used for identity and purity verification.
Materials and Consumables
Reagents must be animal-free and validated. Suppliers are audited, and each batch undergoes quality control
Primary Containers
Containers in contact with the product must be sterile, endotoxin-free, and phage-compatible to avoid contamination.
Cleaning and Decontamination
Validated cleaning procedures tailored for phage production prevent cross-contamination.
Process Development
- Upstream Processing: Optimizes phage growth via control of bacterial density, MOI, and media to boost yield and reduce impurities.
- Downstream Processing: Purifies phages by removing debris, endotoxins, and DNA using filtration and chromatography.
Quality Control
QC ensures phage identity, purity, and potency throughout production. Bacterial and phage banks are tested for viability and contaminants. NGS aids characterization but GMP validation remains complex.
At Creative BioMart Microbe, we are committed to delivering high-quality, GMP-compliant phage production services to support your clinical and commercial development needs. With advanced facilities, strict quality control, and deep expertise in phage biotechnology, we ensure reliable, scalable, and regulatory-ready solutions. Contact us today to discuss how our GMP-grade phage production capabilities can accelerate your program from research to application.
Service Procedure
Service Details
- Custom Phage Manufacturing: From early-stage development to full-scale GMP production, we support phage candidates tailored for clinical, veterinary, or industrial applications.
- Process Development and Optimization: Scalable upstream and downstream process development, including phage propagation, purification, and formulation, designed for high yield and product consistency.
- Analytical Testing & Quality Control: Comprehensive QC testing at each production stage, including phage identity, potency, sterility, endotoxin levels, and genomic integrity.
- Master & Working Phage Bank Creation: Establishment and long-term storage of validated phage banks with full traceability and genetic characterization.
- Fill & Finish Services: Aseptic filling of final phage preparations into validated primary containers (vials, syringes, etc.).
Comparison: Research-Grade vs. GMP-Grade Phage Production
| Feature |
Research-Grade |
GMP-Grade |
| Intended Use |
Laboratory & preclinical research |
Clinical trials & commercial applications |
| Facility Requirements |
BSL-2 lab or clean area |
ISO-classified cleanrooms |
| Documentation |
Technical report, CoA (optional) |
Full GMP documentation & batch records |
| Regulatory Compliance |
Not regulated |
FDA/EMA GMP compliant |
| Quality Control |
Basic QC (titer, sterility, etc.) |
Full QC suite (ICH/Ph. Eur./USP standards) |
| Scalability |
Limited scalability |
Scalable to clinical/commercial volumes |
| Release Requirements |
Internal QC acceptance |
QP or QA release required |
| Timeline |
4–8 weeks |
3–6 months |
Platforms & Instruments
Upstream Bioprocessing Platforms
- Controlled bioreactors (1L to 100L scale) for optimized phage amplification
- Automated cell culture and infection systems
- Online monitoring for growth parameters and phage kinetics
Downstream Processing Equipment
- High-throughput filtration units (TFF and sterile filtration)
- Chromatography systems for precise purification
- Endotoxin and host cell DNA removal technologies
Analytical & Quality Control Instruments
- qPCR and droplet digital PCR for phage quantification and identity
- Next-Generation Sequencing (NGS) for genomic analysis
- Limulus Amebocyte Lysate (LAL) assays for endotoxin detection
- HPLC, SDS-PAGE, and ELISA platforms for purity and stability testing
Our Advantages
- GMP-Certified Facilities: Production performed in ISO-classified cleanrooms under validated processes and equipment.
- End-to-End Regulatory Support: From pre-IND to product registration, we provide documentation and guidance at every stage.
- Customizable Manufacturing Protocols: Flexible scale, formulation, and container options to meet clinical and commercial demands.
- Strict Quality Control: Each step adheres to ICH, USP, and Ph. Eur. standards with full traceability.
- Experienced GMP Team: Decades of expertise in phage biology, viral manufacturing, and clinical-grade bioproduction.
- Seamless Tech Transfer: We support scale-up and tech transfer to CDMOs or internal GMP facilities when needed.
Case Study
Case Study 1: High throughput manufacturing of bacteriophages continuous stirred tank bioreactors connected in series.
To meet future industrial demands for large-scale phage production, this study developed a scalable, cGMP-compliant continuous production system for E. coli T3 bacteriophages. The system used a three-reactor setup: two continuous stirred tank bioreactors (CSTRs) in series for steady-state bacterial and phage propagation, and a third semi-batch reactor for completing the phage infection cycle.
The key innovation of this study is the decoupling of bacterial growth and phage amplification. This reduced phage-resistant mutants and stabilized production. Researchers manipulated bacterial physiological states by adjusting the dilution rate (0.1–0.6 hr-1) in the first reactor to optimize intracellular phage productivity.
Figure 2. (a) Filled circles (●) represent the concentration of host bacterial cells in R1, and filled squares (■) represent the host bacterial cell productivity in reactor 1 (R1), which are plotted as a function of different dilution rates in R1. (b) Host growth rate data fitted with Monod kinetics (3) linearized as a Lineweaver–Burk plot. (c) Glucose conversion as a function of dilution rates in R1. The black filled circles (●) represent the percentage of glucose (compared with the inlet substrate concentration to R1) consumed by E. coli to produce new cells. The residence time in R1 was controlled using the dilution rate D1. (Mancuso et al., 2018)
Case Study 2: GMP production of phages for Staphylococcus aureus therapy.
Phage therapy is a promising strategy to combat antibiotic-resistant Staphylococcus aureus, including both methicillin-susceptible and -resistant strains. To ensure clinical applicability, the development of therapeutic phages must comply with Good Manufacturing Practice (GMP) standards. In this study, three novel Silviavirus phages demonstrated broad activity against 82% of a global collection of S. aureus strains. A quality-by-design approach was employed to optimize phage amplification, focusing on maximizing yields (up to 1011 PFU/mL in 4 hours) and minimizing contaminants from the bacterial host.
Key factors influencing production included host strain selection, media composition, and multiplicity of infection (MOI). Selective media enabled the highest and fastest titres, while higher MOIs accelerated phage amplification. However, phage stability decreased significantly after prolonged incubation, underlining the need for timely harvesting. This work contributes a GMP-aligned production framework emphasizing phage purity and concentration as critical quality attributes, and supports the advancement of phage therapy toward regulatory and clinical acceptance.
Figure 3. Impact of the multiplicity of infection (MOI) on phage production yields and kinetics in TSB medium. (A) Bar charts represent the means of three replicates with standard deviation. Symbols ∆ indicate time points at which maximal phage titres were reached. (B) Time necessary to reach maximum yields and maximal titres obtained in the different tested conditions are indicated. (Kolenda et al., 2022)
FAQs
Q: Can you help us transition from research-grade to GMP-grade production?
A: Yes, we offer tech transfer, process optimization, and pre-GMP pilot batches to streamline this transition.
Q: Do you support multi-phage cocktails?
A: Absolutely. We can produce, purify, and validate complex phage mixtures under GMP guidelines.
Q: How do you ensure phage purity and minimize host-related contaminants?
A: We use rigorously selected production strains, implement high-precision purification protocols, and conduct thorough QC testing to eliminate endotoxins, residual DNA, host proteins, and temperate phages.
Q: What scale of GMP phage production do you offer?
A: We support flexible batch sizes—from small-scale pilot lots for early-phase clinical trials to larger GMP-grade production for late-stage development—tailored to your specific needs.
Q: Do you offer phage characterization and stability testing as part of your service?
A: Yes, our service includes in-depth phage characterization (EOP, host range, genome analysis) and stability studies under various storage conditions to ensure product consistency and shelf-life.
Q: How long does a GMP production project typically take?
A: From initiation to batch release, it takes 3 to 6 months, depending on scope and regulatory requirements.
References:
- Jones JD, Trippett C, Suleman M, Clokie MRJ, Clark JR. The future of clinical phage therapy in the United Kingdom. Viruses. 2023;15(3):721. doi:10.3390/v15030721
- Kolenda C, Medina M, Bonhomme M, et al. Phage therapy against Staphylococcus aureus: selection and optimization of production protocols of novel broad-spectrum Silviavirus phages. Pharmaceutics. 2022;14(9):1885. doi:10.3390/pharmaceutics14091885
- Mancuso F, Shi J, Malik DJ. High throughput manufacturing of bacteriophages using continuous stirred tank bioreactors connected in series to ensure optimum host bacteria physiology for phage production. Viruses. 2018;10(10):537. doi:10.3390/v10100537
- Regulski K, Champion-Arnaud P, Gabard J. Bacteriophage manufacturing: from early twentieth-century processes to current GMP. In: Harper DR, Abedon ST, Burrowes BH, McConville ML, eds. Bacteriophages. Springer International Publishing; 2021:699-729. doi:10.1007/978-3-319-41986-2_25
