Optimisation de votre programme de développement Cedric Lamy, PhD. Cedric.lamy@crl.com
Charles River Overview 65-year history: Founded in 1946, publicly traded (NYSE:CRL) Investment in skilled staff: ~7,500 employees Deep scientific capabilities: >500 PhDs, DVMs, MDs State-of-the-art facilities and technologies: 60 facilities in 16 countries
Building a Portfolio of Products and Services to Meet Your Product Development Needs Research Models and Services Discovery Services Preclinical Services Biologics Testing Solutions Endotoxin and Microbial Detection Agrochemical and Animal Health Product Development Avian Vaccine Services
Optimising a Test Programme
Optimising a Test Programme Collaboration; use the strengths of both parties Schedule; to support your overall product development plan ( + test item availability!) Initiate the discussion early
Optimising a Test Programme Challenge CRO s expertise : Type of test item (NCE, mab, ADC, ) Specie Dosing route and chronicity Specific tox requirement (Inhalation, Bones, Ocular, NHP Reprotox, ) Background data (to interpret findings) Data collection, delivery (MyPreclinical), interpretation, reporting.. SEND compliance.
Optimising a Test Programme Explain to CRO: Who will conduct Ph I? Attract investors, co-development partner / license-out (Large and good reputation CRO) Overall project plan / milestones (go/no-go)? We can fit our offer with your plans.
Information for Programme / Study Design
Information for Programme / Study Design NCE / Biological? Clinical objectives / plans? Therapeutic target Dose route and frequency of administration. Second therapeutic intention Existing data In-vivo pharmacology, in-vitro ADME, non-glp studies Formulation
Integrated Preclinical Programme - NCE
Integrated Preclinical Programme - mab ID Task Name Start Duration Finish 1 Test Material Receipt Mon 07/01/08 0 days Mon 07/01/08 2 Formulation Tue 08/01/08 3 mons Mon 31/03/08 3 Method Establishment/Validation (TK) Tue 08/01/08 4 mons Mon 28/04/08 4 Immunogenicity Transfer Validation Tue 08/01/08 4 mons Mon 28/04/08 5 Tissue Cross Reactivity Mon 21/01/08 4 mons Fri 09/05/08 6 Single Dose Toxicity in Rats (Intravenous) Mon 03/03/08 3 mons Fri 23/05/08 7 1 week Pilot Study in Primate Mon 07/04/08 4 mons Fri 25/07/08 8 4 week Toxicity Study in Primate (+ 4wk Recovery) Mon 26/05/08 5 mons Fri 10/10/08 9 Immunotoxicity Study Mon 26/05/08 5 mons Fri 10/10/08 10 Immune Function and Hypersensitivity Mon 26/05/08 5 mons Fri 10/10/08 11 Preparation of IMPD, CTA Mon 29/09/08 1 mon Fri 24/10/08 12 Submission to Regulatory Authority Mon 27/10/08 1.5 mons Fri 05/12/08 13 Recruitment of volunteers for Clinical Study Mon 08/12/08 1 mon Fri 02/01/09 er 1st Quarter 2nd Quarter 3rd Quarter 4th Quarter 1st Quarter D J F M A M J J A S O N D J F M This information is for guidance purposes only and timelines may change depending on individual specifications. Many test items are supplied pre-formulated and therefore the duration of the programme will change accordingly. in vitro herg is not a required assessment for all peptides. Immunotoxicity and Hypersensitivity studies would be conducted as part of the main toxicity study. Many regulators would request repeat dose toxicity studies are also conducted in a rodent species unless it is not relevant.
Safety Assessment - 1 Rodent & Non-rodent 28 Day Toxicity Studies Species selection metabolites, receptor profile, protein homology, continuity with earlier work, source of animals Dose route selection (intended clinical dose route) Duration (guideline table) Dose levels (existing data, DRF?) Target organs (pharmacology)
Safety Assessment - 2 Genetic Toxicology Impact on genes, chromosomes? In vitro and in vivo Depends if NCE / Biological Safety Pharmacology In vitro/in vivo Impact on critical physiological systems? CV, respiratory and CNS
Laboratory Sciences Support Bioanalytical Immunology Clinical Chemistry
4. Cost Drivers Your strategy (ex: FIH, orphan drug) Length of the required studies (ex: contraceptive) Dose route (ex: inhalation) Species requirement (ex : biologics) Possibility to include Safety Pharmacology in the Tox study?
Fully Integrated Discovery Portfolio Target Discovery & Validation Hit ID Hit-to-Lead Lead-to- Candidate Preclinical Development 1 Clinical Developmen t Compound design, synthesis & Development Medicinal Chemistry Small and fragment based chemistry Computational Chemistry and in silico screening Process Chemistry Pharmaceutical Sciences, Preformulation Studies & Formulation Development Physicochemical and Analytical Development Biology & Efficacy Disease Biology Target Discovery and Validation Protein Expression Structural Biology & Biophysics Assay Development and Screening Assay Development HT and High Content Screening Phenotypic Screening Compound Library Natural Products Library Compound Profiling In vivo Pharmacology & Efficacy Oncology CNS / Pain Metabolic / Cardiovascular Inflammation Respiratory Respiratory Musculoskeletal Rare Diseases Drug Disposition In Vitro ADME Discovery Bioanalysis Non-GLP In Vivo ADME/pK Non-GLP In Vivo ADME/ PK GLP Bioanalysis GLP & GCP Safety In Vitro Toxicology Non-GLP In Vivo Toxicology GLP Toxicology General Toxicology Specialty Toxicology Safety Pharmacology Carcinogenicity Studies DART Drug Dev & Regulatory Support Translational Tools Discovery Biomarkers / Imaging Pathology and IHC Biomarkers / Imaging. GLP & GCP
Chemical, Agrochemical & Animal Health Product Development Field Trials Environmental Sciences Veterinary Clinical Trials Aquatic Toxicology Plant Metabolism Livestock Feeding Studies Physico-Chemical Testing Analytical Chemistry Full program of studies to satisfy the requirements of REACH
Agrochemical Testing Questions to Address Efficacy Does the development compound effectively treat the pest or disease? Chemistry Enviromental Fate Residue Chemistry What are the physical/chemical properties? How do we formulate the compound? Do we have long term stability? Will the material migrate through the soil horizon? Will the material be metabolised in soil? Will the material break down under sunlight? Will the material metabolise/breakdown in water? Will it accumulate or dissipate in soil? What is the nature of any residue in the food chain? Is the material metabolised by plants? Is the material metabolised by food producing animals? What is the magnitude of any residue in the food chain? Tox/Ecotox What is the acceptable daily residue intake? Is the material safe for the environment?
Customer Responsibilities Share information Strategy, objectives, existing data etc Delivery of test item Suitable quantity Suitable quality (Certificate of Analysis) Draft report comments, to enable finalisation
Conclusion Optimising Collaboration It s all down to 2-way communication Sharing information enables best programme and study designs Final Benefit; saves you time and money
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Charles River Profile 67-year history: Founded in 1946, publicly traded (NYSE:CRL) Investment in skilled staff: ~7,500 employees Deep scientific capabilities: >650 PhDs, DVMs, MDs Real World Drug Discovery and Development Expertise in Key Therapeutic Areas State-of-the-art facilities and technologies: 60 facilities in 17 countries
Building a Portfolio of Products and Services to Meet Your Needs Research Models and Services Discovery Services Safety Assessment Clinical Support Biologics Testing Solutions Endotoxin and Microbial Detection Chemical, Agrochemical and Animal Health Product Development Avian Vaccine Services
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Discovery Services Integrated Drug Discovery Target Discovery / Validation Assay Development & Screening Chemistry Structural Biology & Biophysics In Vivo Pharmacology DMPK Non-GLP Toxicology Translational Tools: biomarker, imaging, discovery pathology Fully integrated discovery capability in all therapeutic areas, including oncology, CNS, metabolic, cardiovascular, inflammatory and rare diseases.
Safety Assessment General & Specialty Toxicology Safety Pharmacology Drug Metabolism & Pharmacokinetics Anatomic and Clinical Pathology Laboratory Sciences Investigational New Drug Programs Regulatory Consulting Over 40 years of experience designing and performing safety programs
Clinical Support Clinical Laboratory Support Clinical Pathology Specialty Toxicology Supporting clinical trials with in vivo and in vitro nonclinical studies 30
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Endotoxin and Microbial Detection Endosafe -PTS Endosafe -MCS FDA-Licensed LAL Reagents Kinetic Instrumentation and Software Contract Testing Technical Support Breakthrough rapid technologies to streamline quality control
Chemical, Agrochemical and Animal Health Product Development Field Trials Environmental Sciences Veterinary Clinical Trials Aquatic Toxicology Plant Metabolism Livestock Feeding Studies Physico-Chemical Testing Analytical Chemistry Full program of studies to satisfy the requirements of REACH
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Supporting the Needs of Our Clients Internal Harmonization Programs for Efficient Client Support Single Provider with Unique Portfolio Allows More Choices and Simpler Interaction Integrated Services to Reduce Timelines Investment in Innovative Technologies Expertise Across Multiple Therapeutic Areas
Why Choose Charles River as My Partner? Animal Welfare and Human Care Initiative Unique Portfolio of Products and Services Industry-Leading Scientific Support Multidisciplinary Expertise Superior Customer Service Experience Resources of a Global Company with Local Relationships