Vaccine Production Methods PDF

Methods for vaccine production Development of Drugs and Heath Products Master TU08 Biotechnology [email protected] October 2024 Vaccines are biopharmaceutical products unlike any others Vac...

Methods for vaccine production Development of Drugs and Heath Products Master TU08 Biotechnology [email protected] October 2024 Vaccines are biopharmaceutical products unlike any others Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio- molecular derivatives, administrated for the prevention, amelioration, or treatment of infectious and other diseases (WHO) amelioration means an improvement or enhancement of something Goal: Safe reproduction of the immune response elicited by a pathogen èInduction of a memory immune response that is activated upon contact with the virulent wild-type pathogen Biodrug: Drug substance produced by or extratcted from a biological source Well characterized & described manufacturing and purification process Characterization and quality assessment need a combination of physical, chemical and biological assays EU definition of Biologic (Directive 2001/83/EC as amended, Annex 1 Active substance 3.2.1.1.b) 2 Ø Long development Long clinical experimentation Complex manufacturing process Highly regulated quality and control environments for maximum safety Ø Preventive approach Healthy individuals (including paediatric population)èBenefit/risk ratio Perception of benefit is not visible (not immediate) Large treated populations + paediatric populations Side effects not accepted 3 General vaccine mechanism of action Goal: to induce specific and adaptive immune responses to protect from a micro-organism infection: bacteria (extra- cell) or virus (intra-cell) = Active immunization Adaptive immunity Humoral response Adaptive immunity  Different vaccine strategies Live attenuated Inactivated Non- (killed) replicating vector Purified antigen, Replicating Vaccines Sub-unit recombinant antigen, vector polysaccharidic, conjugated virus-like Multivalent vaccines = targeting ADN particles (VLP) several strains of the same pathogen (e.g. 23-valent vaccine prevents ARNm pneumococcal infection) Combined vaccines = targeting several pathogens (e.g. DT-Polio prevents against 3 diseases: Not all strategies are commercially available diphtheria, tetanus and polio) 5 Commercialized vaccines Sub unit vaccines Recombinant: Live attenuated vaccines B Hepatitis Papillomavirus Killed Smallpox Pertussis (acellular) vaccines(inactivated, BCG Purified: inert) Rage Polysaccharidic: Yellow Fever Meningococcus Typhoid Polio (oral Sabin) Pneumococcus Cholera Measles Typhoid Plague Mumps Conjuguated: Pertussis Rubeole Hib InfluenzaPolio Adenovirus Meningococcus (injectable) Chickenpox Pneumococcus Japanese encephalitis Rotavirus Anatoxin: A Hepatitis Japanese encephalitis Tetanus (inactivated) Diphteria ARNm Non-replicable vector COVID-19 6  General Generalscheme for scheme for a vaccine a vaccine development development Average development time : 12 years Average development time : 12 years Average of global investment: >0.5 Billions € Average of global investment: >0.5 Billions € 70%70%time lineline time is for Quality is for control Quality control R&D Experimental Preclinical Phase I Phase II Phase III Regulatory follow-up phase phase 9-14 years Industrial operations Development Development of the Operational Germ Product launch First of the feasibility Biomass Harverst Purification Inactivation Valence Formulation Registration Lyophilization Conditioning Dirtribution Batch Batch manufacturing industrial assembly release registration process production process 6 to 22 months Commercial operations Product target profile: Evaluation Target population of needs Vaccine candidate? Batch commercialization Quality control, Quality insurance Pharmacovigilance 7 General scheme for vaccine production (industrial operations) USP Germ Biomass Production No inactivation step for live DSP Clarification/Concentration: attenuated vaccines Filtration Chromatography Purification Chromatography Précipitation Harvest purification inactivation Filtration Centrifugation Solvent/detergent: Filtration Hydrogen peroxide Keep supernatant OR cells Formaldehyde, Glutaraldehyde Pepsin pH4 Damp heat 6 8  efficacy of MF59-adjuvanted subunit vaccine in young children, 40 nm diame healthy adults, and elderly individuals [74–77]. Additionally, influenza spl MF59 has similar immunostimulatory effects in combination with in individuals prepandemic vaccine formulations. Overall, MF59 has thus far. Further proven to be a very effective adjuvant for the stimulation of influenza-spe humoral responses againstFormulation both seasonal and prepandemic influ- of saponin ba enza vaccines. clinical study Similar Purposeto: MF59, AS03 is also an oil-in-water emulsion based on vaccine. # Maintenance squalene droplets. of However, the structure unlike and stability of theAS03 is currently only MF59, dose sparing active substance used# inVaccine pandemic influenza increased vaccines. and sustained stability AS03 adjuvanted influenza responses. M vaccines were significantly # Increasing more the potency of the immunogenic vaccine with added than their unadju- H7N9 VLP va vanted counterparts both in primed and unprimed individuals adjuvant Minimising adverse effects vanted VLP v [79,80]. Furthermore, AS03-adjuvanted influenza vaccines were rates after va Stabilisers: lactose, sorbitol also able to confer seroprotection in immunocompromised. Adjuvants: The European Pharmacopoeia recommends a maximum amount of 1.25 mg of aluminium Table 2 (Al3+) per dose (between 0.125 and 0.82 mg for children