The World Phage Week (October 22-28) 2025 is here, celebrating the birthday of Frederick Twort, a pioneer in phage research. This year, to mark this event, The Phage and Phage Hunters Training and Research Program (PHTRP) has brought together a special webinar series starting 22, 23 & 24 October 2025, exploring the latest research in phage science, from regulatory reforms and commercialization to production scale-up.
About Dr.Frenk Smrekar
Dr.Frenk Smrekar, speaker for the third day of our webinar series, is the Vice President of PhageEU, representing the phage community and facilitating access to phage technology in the EU (European Union). Dr.Frenk is the Founder and CEO of JAFRAL BIOSOLUTIONS, founded in 2011 in Slovenia, Europe, a leading CDMO (Contract Development and Manufacturing Organization) for the production of phages. JAFRAL BIOSOLUTIONS specializes in phage-based products for human therapeutics, veterinary medicine, food safety, cosmetics, and agriculture. The company’s mission is to make phage therapy industrially scalable, affordable, and globally accessible.
With biosafety level 1 and 2 laboratories supporting both GMO (Genetically Modified Organisms) and non-GMO production, JAFRAL BIOSOLUTIONS offers end-to-end services — from phage isolation and characterization to scale-up manufacturing under Good Manufacturing Practices (GMP).
GMP, Manufacturing, and Production in Phage Development
Dr. Frenk enumerated the complete process of phage development. He explained that phage manufacturing begins with “identifying a bacterial infection, isolating the bacteria, and selecting host-specific phages”. These selected phages are then characterized for genomic suitability, stability, and manufacturing yields. Small-scale process and analytical method development follows, with results compiled in a report for scale-up.
If the report is favorable, small-scale production begins for in vitro and in vivo testing, animal trials, and initial stability testing. The final purity and formulation move for scale-up runs. Under Good Manufacturing Practice (GMP) conditions, phages are scaled up to 200 liters of production capacity.
A typical phage cocktail progresses from research to GMP-ready in 6–9 months, with current ongoing optimization at JAFRALs reducing the timeline even further.
Analytical Development and Quality Control
Dr. Frenk Smrekar explains, “Every phage produced at JAFRAL goes through thorough analytical validation and quality control. This includes tests for endotoxins, protein, and DNA, as well as plaque assays and PCR methods to identify phages. We also check morphology and sequencing to ensure purity and genetic stability.” Stability studies are carried out under a range of conditions, from accelerated temperatures (25°C and 40°C) to frozen storage (-80°C and -20°C) and standard refrigeration (2–8°C).
Most phage therapeutics are in liquid formulations, but powder, spray-dried, lyophilized, and capsule forms are under exploration for easier administration.
Over more than a decade, JAFRAL has established a robust record of excellence, with over 50+ phage and viral banks and 50+ drug substances (APIs) for clinical use. It has achieved clinical trial material manufactured under GMP conditions for studies in the US (FDA), Europe (EMEA), and Australia (TGA), which includes numerous collaborations and consultations with global regulators on phage manufacturing. The company has experience with over 1,000 different bacteriophages and a wide spectrum of bacterial species, including the ESKAPE pathogens.
GMP vs. Non-GMP Manufacturing
According to WHO, “Good Manufacturing Practices (GMP) is the aspect of quality assurance that ensures medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the product specification”. GMP regulations require a quality approach to manufacturing, enabling companies to minimize or eliminate instances of contamination and errors.
Good Manufacturing Practice (GMP) defines the strict framework for phage production for human use — from facility validation to staff training and equipment revalidation.
- In GMP Pathway: Processes are strictly defined and similar to viral vector production, including Master Cell Banks (MCB) and Master Phage Banks (MPB), which ensures long-term supply.
- Non-GMP Pathway: Provides flexibility for R&D, agriculture, and compassionate use, without full validation, however, maintaining scientific rigor.
Research Cell Banks (RCB) and Research Phage Banks (RPB) are initial research-level steps, requiring thorough characterization (e.g., sequence, PCR ID, colony/plaque shape). “Master Cell Banks (MCB) and Master Phage Banks (MPB) are produced in clean rooms under GMP conditions from RCB/RPB”. This two-tier system (MCB/MPB and Working Cell Bank/Working Phage Bank) ensures long-term stock and production capacity. This “drug substance production” follows process and analytical development, and method qualification. Engineering runs are crucial before clinical trial material production to prove process robustness, scalability, and to generate stability data under GMP conditions.
However, Non-GMP pathways can go directly from RCB to drug substance and product for non-human applications or compassionate cases, without extensive development or validation.
While GMP processes are costly due to documentation, audits, and regulatory compliance, JAFRAL advocates for smaller, continuous production facilities to help emerging countries establish local phage capacity efficiently.
Cost Implications of GMP
Extensive documentation and quality systems, labour, GMP facility certification, audits, premises and equipment validation, and raw materials of appropriate quality, additional in-house or third-party testing, periodic personnel training, all incur costs in GMP. “Maintaining a GMP facility incurs 24/7 running costs (e.g., aeration, pressure differences),” says Dr.Frenk.
Dr. Frenk’s advice for low-resource settings is “to build smaller facilities for continuous, smaller batch production rather than large, infrequent batches.” and “when applying for grants, emphasize the broader picture beyond immediate cost, such as long-term benefits of reduced resistance and fewer treatments.”
Scaling Innovation Beyond the Lab
Under Dr.Frenk, JAFRAL’s vision extends beyond manufacturing — it serves as a bridge between phage researchers and real-world applications. The company supports academic collaborations, grant applications, and small-batch production for early-stage innovators. Their expertise enables cost-effective phage development, ensuring that the therapy remains accessible and sustainable amid growing global demand.
Global Impact and Export Reach
With exports to over 40 countries, the company established itself as a trusted partner in the global phage ecosystem. Its contributions go beyond production — frequently participating in international discussions with regulators and policymakers, and sharing insights into commercial-scale phage manufacturing and quality control.
Phage Research and Development Challenges
Dr.Frenk says, “Failures are common in phage development,” owing to phages’ biological variability and unpredictability. This aspect makes Research Cell Bank and Research Phage Bank characterization a critical aspect in phage development since insufficient characterization can waste subsequent GMP efforts (e.g., uncharacterized viral vectors, prophages).
The greatest fear in the field, according to Dr. Frenk, is “the inability to make phage therapy industrially applicable and economically viable”. The main challenges in scaling up phage production under GMP conditions include ensuring process robustness and scalability, especially in bioreactor upstream and downstream processes.
Phage Manufacturing for a Healthier Future
During our discussion, Dr. Frenk highlights how biotechnology, engineering, and regulatory standards are driving the future of antimicrobial therapy, leading efforts to industrialize phage therapy, turning it from a laboratory idea into a global medical and environmental solution. JAFRAL’s GMP-certified facilities, which support its international partnerships, continue to turn bacteriophage research into practical therapeutic solutions, contributing to a healthier, antibiotic-free future.
As we celebrate World Phage Week 2025, JAFRAL BioSolutions stands as a beacon of innovation, precision, and global collaboration in the phage industry, making remarkable advances in bacteriophage therapy — a promising alternative to antibiotics in tackling resistant bacterial infections.
