Jérôme LE HIR

Leading the R&D Biology department (>40 FTEs) dedicated to CMC strategy (Section II) and industrial transfer. Acting as a technical authority for the group's global biopharmaceutical network. Key Achievements: Global Network Strategy: Directing process & analytical alignment across international R&D and manufacturing centers. M&A & Expansion: Led technical Due Diligence processes supporting the group's external growth strategy in key Asian markets. Strategic Investment: Managed a multi-million euro CAPEX project (>€25M) for the revamping of R&D laboratories and the creation of a Pilot Plant to support industrialization. Portfolio Management: Overseeing development for a wide range of modalities including attenuated, inactivated, subunit, RNA vaccines and mAbs.

Managed the development and scale-up of upstream (USP) and downstream (DSP) bioprocesses across multiple platforms. Key Achievements: Multi-Platform Expertise: Developed processes using various expression systems (Microbial, Mammalian, and Insect cells). Compliance: Ensured strict GMP and HSE compliance while managing laboratory operations and equipment investments. Team Leadership: Structured the process development team to meet increasing portfolio demands and regulatory standards.

Developpment / Industrialization / USP/DSP Technological Process Transfert

- Developpment of a new industrial manufacturing process for BCG production (Upstream & Downstream). - Improvement of production rate and product purification. - Management of industrialization (scale-up and transfer to CMO). - Work in accordance with Quality by Design, GMP, ICH. - Technical skills: Fermentation, development and optimization of a chemically defined culture medium, HPLC (Amino Acid, Sugar, Organic Acid), purification (Ultrafiltration), single used technologies. - Management of two FTE (Engineering degree level).

Thesis in collaboration with Sanofi Pasteur. Title: “Understanding the cellular metabolism and the synthesis of the capsular polysaccharide from Haemophilus influenzae type b.” ♣ Application of my thesis: Optimization of the Hib vaccine production process (SANOFI PASTEUR) Patented (first inventor). Security, robustness of the process and increase of production rates. ♣ Technical skills: - Fermentation (2, 5 and 1000L: work on process scale-up in respect to performance, robustness and quality) - Biochemistry: Development and optimization of a chemically defined culture medium, HPLC purification, protein assays, enzymatic activities, NMR... - Molecular biology: Genetic characterization of strains via qPCR and PFGE (pulsed-field gel electrophoresis), fusion proteins, PCR and RT-PCR... - Bioinformatics: Sequencing, annotation, genome comparison... - Transcriptomics: Comparative analysis of gene expression during cell growth: kinetics and different culture conditions. Determinations of key genes required for a given product’s synthesis. - Fluxomics: Metabolic flux analysis (NMR) for the in vivo characterization of biosynthetic pathways of metabolites or interesting products. - Development of techniques / protocols (Innovation) - Work in a safety level BL2 and BL3 environments

Supervision of Practical Work of microbiology and enzymology (teaching load: 20 to 30 hours / year)

Study of the influence of culture parameters on the production of an antigen with Haemophilus influenzae type b (Studies in flasks and fermenters, HPLC analyzes). - Demonstration of the metabolic flexibility of the strain - Identification of key factors of productivity

Expression and purification of fusion proteins required for the development of new biochips (medical miniaturized laboratory analysis). - Study on SAW device, SPR BIAcore, purification, cloning and crosslinking.

Creating fusion protein “GFP-bax” to study its interaction with mitochondrial membranes. - Bibliographic research of apoptosis - Bax gene amplification by PCR (primers…) - Insertion of BAX into a GFP plasmid (restriction enzymes, ligation, QuickChange PCR…), transformation and expression in E. coli and protein purification (purification by NI ball/Tag Hist, western immunoblot, SDS PAGE, spectroscopy, dialysis…) - Extraction and purification of mitochondria (S.cerevisiae) In the beginning of my internship I was helped by a laboratory technician but was independent after a two weeks period.

“Understanding the cellular metabolism and the synthesis of the capsular polysaccharide from Haemophilus influenzae type b.”

Studied subjects: Metabolic biochemistry, bacterial genetics, regulation, genetic engineering, enzymatic engineering, biochemical engineering, Bioprocess engineering, material transfer, microbial physiology, cell culturing, bioinformatics, thermo transfer and laboratory work: cloning, purification, expression, microbiology, hydraulic engineering, numerical analysis, regulation, molecular biology, enzymology, organic chemistry, structural chemistry, Bio separation, statistics and probability.

Studied subjects: Thermodynamics, physics, mathematics, molecular biology, microbiology, enzymology and biochemistry.