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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - PhagoPROD (GMP manufacturing & GLP diagnostic: Towards a personalised phage therapy against antimicrobial resistance)

Teaser

Summary

Phage therapy, that is the therapeutic use of bacteriophages for the treatment of pathogenic bacterial infections, is a highly promising answer to the antibiotic resistant plague (500 000 deaths a year attributable to multi-drug resistant bacteria today, 10 million forecast by 2050).
In this hopeful field, Pherecydes Pharma has been developped phages products obtained by purification and amplification of natural phages against strains such as P. aeruginosa, S. aureus and E. coli. These treatments are specific to each patient, which means that only the active phages against the strains will be administrated to the patient. In the treatment design, a diagnostic of phages activity is performed in a lab to determine which phages have to be distributed for the patient. This diagnostic is called phagogram. It was developped by Pherecydes Pharma.
Phagoprod has been defined to set-up, optimise and scale-up the GMP manufacturing and diagnostic processes currently developped at laboratory scale. In that so, the ultimate objective is to achieve large-scale commercial exploitation of Pherecydes Pharma products first at the EU then at the USA levels.
To this end, Phagoprod project has been designed with 2 major milestones :
1) a Pharmaceutical establishment status granted by the ANSM with GMP manufacturing and Quality control plant running at an industrial level
2) Medical biology laboratory status granted by the ANSM with EC markeing for diagnostic process obtained and diagnostic laboratory running at an industrial level.

This project is important for society to keep and develop Pherecydes Phama\'s expertise on phage production, on quality and on phagotherapy.

Work performed

The plan and set up of the manufacturing site have been carefully designed, followed and monitored by our own staff according to the advises of consultants. In order to support them, CERIS, an architectural firm specializing in pharmaceutical production and clean rooms have been appointed by Pherecydes Pharma. In addition, Nantes Metropole which hosts the laboratory is supported by AIA architects which is specialized in hospital and clean room installation. All these actors finalized the construction plans in April 2018. A revised version was edited early September following to the launching of the work with the selected subcontractors. Regular site construction monitoring meetings take place with Nantes metropole, AIA, CERIS and Pherecydes Pharma (Sept 3rd, Oct 10th and 26th and Dec. 14th 2018) and minor modifications/adaptations are implemented as the construction progresses.
On November 5th, 2018, Magali Vidal-Engaurran, our Pharmacist, Director of Quality control and Assurance of the future manufacturing site was appointed, more particularly to manage PhagoProd. Thus, she is currently reviewing and supervising the plan for setting up the quality control laboratories, including the choice of equipmentâ€™s and machineries in line with GMP compliance.
Another auditor, Validapro (Canada) has been appointed to review the whole process for becoming a pharmaceutical company, including the manufacturing site set up and the retro planning for obtaining the regulatory approval. A first on-site audit of the facility (January 14, 2019), being at an advanced phase of construction, revealed few points to address. A second audit, which confirm the previoius one has been done by Aktehom (June, 3, 2019)
At last, ASPE consulting (France) has been selected and appointed to support Pherecydes staff to prepare the writing of the IMPD (Investigational Medicinal Product Dossier) and IB (Investigational Brochure), in the frame of the 12 days coaching offered by the European commission in regard of a phase 2 SME grant agreement. This coaching offers an expertise in the highly regulated field of pharmaceutical drug business development, thanks to StÃ©phane Roger from the Enterprise Europe Network (EEN) team in France.
All along this year of project, Pherecydes Pharma wrote documentation required for regulatory such as detailed definition of the project, user requirement specifications for equipments, validation master plan, master standard operational procedures which explain the way Pherecydes Pharma wants to manage the site and the quality on site (deviation, change control, Preventive actions and corrective actions, training management, audit...)
From December 2018 to March 2019, Pherecydes Pharma defined its needs of equipments and choose them in regard with the developped process of production. Main of these equipments were bought and installed in the site from this date.

Final results

The biggest part of the project will be the site and equipments qualification and the process validation, essential to assure that the environnemental conditions met aseptic specifications, that the equipments work properly and are compliant with the defined user requirements and finally that the process is robust, reproducible and give products with high pharmaceutical quality.
For accomplishing these tasks, all the operational documentation must be written (such as use of each equipment, cleaning, clothing, personal and material flow, production) and people must be trained and qualified if the activities are determined to be critical (such as for example Media fill Test which is the simulation of a sterile production).