R&D (bio) médicaments

Ce mémento propose une vision synthétique du développement du (bio)médicament de la phase de conception jusqu’à la phase clinique, aussi bien pour la nouvelle entité chimique que pour un biomédicament.

Pour chacune de ces étapes, les fiches associées proposent :

  • Une courte description des attendus indispensables pour aborder l’étape suivante
  • les questions à instruire, les points à prendre en considération ou les critères de sélection
  • une liste non exhaustive des ressources possibles (experts, publications, laboratoires ou sociétés prestataires*, sources de financement potentielles) susceptibles d’apporter une aide à l’étape considérée.

Ce site s’adresse à tous chercheurs confrontés à un projet de développement de médicament.

* Les sociétés prestataires indiquées sont répertoriées sur la base de leur offre et n’engagent en rien Aviesan. Par ailleurs, le management du projet par le chercheur est essentiel même en cas de recours à une société prestataire afin de permettre un développement harmonieux.


R&D Biomédicaments
Cliquez sur l'image pour accéder aux documents

Le dépôt de brevet, qui constitue un moment clé lors de ce parcours de développement, doit être abordé avec les structures de valorisation ad hoc. Néanmoins, afin de qualifier le stade de développement des projets notamment pour la recherche de fonds et/ou de partenariats, une échelle de niveau de maturité technologique (échelle TRL, Technology Readiness Level) adaptée aux (bio)médicaments est proposée. Les niveaux de développement correspondants sont par ailleurs indiqués dans les différentes fiches.


1 2 3 4 5 6 7 8 9

TRL 1 Review of Scientific Knowledge Base

Active monitoring of scientific knowledge base. Scientific findings are reviewed and assessed as a foundation for characterizing new technologies.

Source : FDA

TRL 2 Development of Hypotheses and Experimental Designs

Scientific "paper studies" to generate research ideas, hypotheses, and experimental designs for addressing the related scientific issues. Focus on practical applications based on basic principles observed. Use of computer simulation or other virtual platforms to test hypotheses.

Source : FDA

TRL 3 Target/Candidate Identification and Characterization of Preliminary Candidate(s)

Begin research, data collection, and analysis in order to test hypothesis. Explore alternative concepts, identify and evaluate critical technologies and components, and begin characterization of candidate(s). Preliminary efficacy demonstrated in vivo.

  • 3A Identify target and/or candidate.
  • 3B Demonstrate in vitro activity of candidate(s) to counteract the effects of the threat agent.
  • 3C Generate preliminary in vivo proof-of-concept efficacy data (non-GLP (Good Laboratory Practice)).

Source : FDA

TRL 4 Candidate Optimization and Non-GLP In Vivo Demonstration of Activity and Efficacy

Integration of critical technologies for candidate development. Initiation of animal model development. Non-GLP in vivo toxicity and efficacy demonstration in accordance with the product's intended use. Initiation of experiments to identify markers, correlates of protection, assays, and endpoints for further non-clinical and clinical studies.

  • Animal Models: Initiate development of appropriate and relevant animal model(s) for the desired indications.
  • Assays: Initiate development of appropriate and relevant assays and associated reagents for the desired indications.
  • Manufacturing: Manufacture laboratory-scale (i.e. non-GMP (Good Manufacturing Practice)) quantities of bulk product and proposed formulated product.
  • 4A Demonstrate non-GLP in vivo activity and potential for efficacy consistent with the product's intended use (i.e. dose, schedule, duration, route of administration, and route of threat agent challenge).
  • 4B Conduct initial non-GLP toxicity studies and determine pharmacodynamics and pharmacokinetics and/or immune response in appropriate animal models (as applicable).
  • 4C Initiate experiments to determine assays, parameters, surrogate markers, correlates of protection, and endpoints to be used during non-clinical and clinical studies to further evaluate and characterize candidate(s).

Source : FDA

TRL 5 Advanced Characterization of Candidate and Initiation of GMP Process Development

Continue non-GLP in vivo studies, and animal model and assay development. Establish draft Target Product Profiles. Develop a scalable and reproducible manufacturing process amenable to GMP.

  • Animal Models: Continue development of animal models for efficacy and dose-ranging studies.
  • Assays: Initiate development of in-process assays and analytical methods for product characterization and release, including assessments of potency, purity, identity, strength, sterility, and quality as appropriate.
  • Manufacturing: Initiate process development for small-scale manufacturing amenable to GMP.
  • Target Product Profile: Draft preliminary Target Product Profile. Questions of shelf life, storage conditions, and packaging should be considered to ensure that anticipated use of the product is consistent with the intended use for which approval will be sought from FDA.
  • 5A Demonstrate acceptable Absorption, Distribution, Metabolism and Elimination characteristics and/or immune responses in non-GLP animal studies as necessary for IND filing.
  • 5B Continue establishing correlates of protection, endpoints, and/or surrogate markers for efficacy for use in future GLP studies in animal models. Identify minimally effective dose to facilitate determination of "humanized" dose once clinical data are obtained.

Source : FDA

TRL 6 GMP Pilot Lot Production, IND Submission, and Phase 1 Clinical Trial(s)

Manufacture GMP-compliant pilot lots. Prepare and submit Investigational New Drug (IND) package to FDA and conduct Phase 1 clinical trial(s) to determine the safety and pharmacokinetics of the clinical test article.

  • Animal Models: Continue animal model development via toxicology, pharmacology, and immunogenicity studies.
  • Assays: Qualify assays for manufacturing quality control and immunogenicity, if applicable.
  • Manufacturing: Manufacture, release and conduct stability testing of GMP-compliant bulk and formulated product in support of the IND and clinical trial(s).
  • Target Product Profile: Update Target Product Profile as appropriate.
  • 6A Conduct GLP non-clinical studies for toxicology, pharmacology, and immunogenicity as appropriate.
  • 6B Prepare and submit full IND package to FDA to support initial clinical trial(s).
  • 6C Complete Phase 1 clinical trial(s) that establish an initial safety, pharmacokinetics and immunogenicity assessment as appropriate.

Source : FDA

TRL 7 Scale-up, Initiation of GMP Process Validation, and Phase 2 Clinical Trial(s)

Scale-up and initiate validation of GMP manufacturing process. Conduct animal efficacy studies as appropriate. Conduct Phase 2 clinical trial(s).

  • Animal Models: Refine animal model development in preparation for pivotal GLP animal efficacy studies.
  • Assays: Validate assays for manufacturing quality control and immunogenicity if applicable.
  • Manufacturing: Scale-up and validate GMP manufacturing process at a scale compatible with USG requirements. Begin stability studies of the GMP product in a formulation, dosage form, and container consistent with Target Product Profile. Initiate manufacturing process validation and consistency lot production.
  • Target Product Profile: Update Target Product Profile as appropriate.
  • 7A Conduct GLP animal efficacy studies as appropriate for the product at this stage.
  • 7B Complete expanded clinical safety trials as appropriate for the product (e.g., Phase 2).

Source : FDA

TRL 8 Completion of GMP Validation and Consistency Lot Manufacturing, Pivotal Animal Efficacy Studies or Clinical Trials 3, and FDA Approval or Licensure

Finalize GMP manufacturing process. Complete pivotal animal efficacy studies or clinical trials (e.g., Phase 3), and/or expanded clinical safety trials as appropriate. Prepare and submit NDA/BLA.

  • Manufacturing: Complete validation and manufacturing of consistency lots at a scale compatible with USG requirements. Complete stability studies in support of label expiry dating.
  • Target Product Profile: Finalize Target Product Profile in preparation for FDA approval.
  • 8A Complete pivotal GLP animal efficacy studies or pivotal clinical trials (e.g., Phase 3), and any additional expanded clinical safety trials as appropriate for the product.3
  • 8B Prepare and submit New Drug Application (NDA) or Biologics Licensing Application (BLA) to the FDA.
  • 8C Obtain FDA approval or licensure.

Source : FDA

TRL 9 Post-Licensure and Post-Approval Activities

  • 9A Commence post-licensure/post-approval and Phase 4 studies (post-marketing commitments), such as safety surveillance, studies to support use in special populations, and clinical trials to confirm safety and efficacy as feasible and appropriate.
  • 9B Maintain manufacturing capability as appropriate.

Source : FDA

View Edit Create here