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• 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
Charles River Overview
• Research Models and Services
• Discovery Services
• Preclinical Services
• Biologics Testing Solutions
• Endotoxin and Microbial Detection
• Agrochemical and Animal Health Product Development
• Avian Vaccine Services
Building a Portfolio of Products and
Services to Meet Your Product
Development Needs
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
D J F M A M J J A S O N D J F M A4th Quarter 1st Quarter 2nd Quarter 3rd Quarter 4th Quarter 1st Quarter 2nd Quarter
• 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
1
Assay Development and Screening• Assay Development
• HT and High Content Screening
•Phenotypic Screening
• Compound Library
•Natural Products Library
•Compound Profiling
Medicinal Chemistry• Small and fragment based chemistry
• Computational Chemistry and in silico screening
In Vitro ADME
Pharmaceutical Sciences,
Preformulation Studies
& Formulation Development
In Vivo ADME/pK• Non-GLP
Process Chemistry
In Vivo ADME/ PK• GLP
GLP Toxicology• General Toxicology
• Specialty Toxicology
• Safety Pharmacology
• Carcinogenicity Studies
• DART
• Drug Dev & Regulatory Support
In vivo Pharmacology & Efficacy• Oncology
• CNS / Pain
• Metabolic / Cardiovascular
• Inflammation
• Respiratory
• Musculoskeletal
•Rare Diseases
Biomarkers / Imaging
. GLP & GCP
Bioanalysis
• GLP & GCP
Non-GLP In Vivo Toxicology
Pathology and IHC
In Vitro Toxicology
Discovery Biomarkers / Imaging
Discovery Bioanalysis• Non-GLP
Physicochemical and Analytical Development •
Disease Biology• Target Discovery and Validation
• Protein Expression
• Structural Biology & Biophysics
Respiratory
Compound
design,
synthesis &
Development
Biology &
Efficacy
Drug
Disposition
Safety
Translational
Tools
Clinical
Developmen
t
Lead-to-
Candidate
Preclinical
DevelopmentHit-to-Lead
Target
Discovery &
Validation
Hit ID
• Field Trials
• Environmental Sciences
• Veterinary Clinical Trials
• Aquatic Toxicology
• Plant Metabolism
• Livestock Feeding Studies
• Physico-Chemical Testing
• Analytical Chemistry
Chemical, Agrochemical & Animal Health
Product Development
Full program of studies to satisfy the requirements of REACH
Agrochemical Testing
Questions to Address
Efficacy
Chemistry
Enviromental
Fate
Residue
Chemistry
Tox/Ecotox
Does the development compound effectively treat the pest or disease?
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?
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
Keen to go further ?
Register to TheSource
https://www.criver.com/source/register
©Copyright, 2014 Charles River Laboratories. All rights reserved
Your Fully Integrated Discovery and
Development Partner
Our mission is to provide exactly what researchers
need to develop new therapeutics for patients as
rapidly as possible.
• 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
Charles River Profile
• 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
Building a Portfolio of Products
and Services to Meet Your Needs
• VAF/Plus® and VAF/Elite® Status
• Inbred, Outbred and Hybrid
Models
• Disease and Translational Models
• Surgically Altered Models
• Rabbits
• Nonhuman Primates
Research Models
Global leader with 22 facilities in North America, Europe and Asia
• Preconditioning Services
• Health Monitoring and
Diagnostic Services
• Contract Breeding and Aging
• Transgenic Colony Management
• Genetic Testing Services
• Consulting and Staffing
• Models In-Licensing
Research Model Services
Expert services to streamline your colonies and animal facility management
• 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
Discovery Services
Fully integrated discovery capability in all therapeutic areas, including oncology,
CNS, metabolic, cardiovascular, inflammatory and rare diseases.
• General & Specialty Toxicology
• Safety Pharmacology
• Drug Metabolism & Pharmacokinetics
• Anatomic and Clinical Pathology
• Laboratory Sciences
• Investigational New Drug Programs
• Regulatory Consulting
Safety Assessment
Over 40 years of experience designing and performing safety programs
30
• Clinical Laboratory Support
• Clinical Pathology
• Specialty Toxicology
Clinical Support
Supporting clinical trials with in vivo and in vitro nonclinical studies
• Cell Banking and Characterization
• Virus and TSE Clearance Studies
• Drug Product/Lot Release Testing
• Development/Pilot Studies
• Method Transfer/Development/Validation
• Bacterial and Viral Challenge Studies
• EP and USP Monograph Test Methods
• Protein Characterization
• Viral Vaccine Manufacture and Testing
Biologics Testing Solutions
All services compliant with international regulatory guidelines
• Endosafe®-PTS™
• Endosafe®-MCS™
• FDA-Licensed LAL Reagents
• Kinetic Instrumentation and Software
• Contract Testing
• Technical Support
Endotoxin and Microbial Detection
Breakthrough rapid technologies to streamline quality control
• Field Trials
• Environmental Sciences
• Veterinary Clinical Trials
• Aquatic Toxicology
• Plant Metabolism
• Livestock Feeding Studies
• Physico-Chemical Testing
• Analytical Chemistry
Chemical, Agrochemical and Animal
Health Product Development
Full program of studies to satisfy the requirements of REACH
• SPF Eggs
• Tissue Culture – Cell Products
• Human Virus Antigens and Antisera
• Vaccine Support Services
• Avian Antigens and Antisera
• SPF Chickens
• USDA-Licensed Plate Antigens
• Diagnostic and Regulatory Testing
Avian Vaccine Services
World’s leading commercial supplier of SPF products
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
