Confidential 10 TH ANNUAL BIOMARKER CONFERENCE Vincent Drouillon, PharmD., Clin.Bio Sr. Director, Translational Biomarker Solutions and Hematology Covance Central Laboratory Services Indianapolis and Greenfield, IN, USA Biomarkers in Discovery and Drug Development: Choosing the right CRO partner
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Biomarkers in Discovery and Drug Development: Choosing the right CRO partner
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Confidential
10TH ANNUAL BIOMARKER CONFERENCE
Vincent Drouillon, PharmD., Clin.BioSr. Director, Translational BiomarkerSolutions and Hematology
Covance Central Laboratory ServicesIndianapolis and Greenfield, IN, USA
Biomarkers in Discovery and Drug Development:Choosing the right CRO partner
Confidential
Agenda
• Importance of Biomarkers in discovery and drug development
• Choosing the right CRO partner for biomarkers:• Pre-analytical considerations• Analytical and regulatory challenges• ‘Smart’ Biobanking• Project management and Scientific support
• From Biomarker to Companion Diagnostics: lessons learnt
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Importance of Biomarkers in Drug Development
ADDRESSING THE HIGH ATTRITION RATE
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Innovation in the Biopharmaceutical Pipeline – Jan 2013 – G. Long & J. Works
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Importance of Biomarkers in Drug Development
IMPROVING APPROVAL RATE
4 Approved drugs | 2013. Report. U.S Food and Drug Administration
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Importance of Biomarkers in Drug Development
• ‘Safer drug, in greater numbers, approved more quickly’1
• Use of biomarkers highly featured in FDA Critical Path Opportunities list
• The 5 ‘R’ approach2: the right Target, Patient, Tissue, Safety, Commercial potential = reduced failure rate
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1 The AAPS Journal, 2007 9 (1), Article 10, “Biomarker qualification pilot process at the FDA”, F. Goodsais et al.2 “Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework”, Nature Reviews Drug discovery, D. Cook and al., Vol.13, June 2014, p.419-431
DO IT SMARTER, FASTER AND CHEAPER WITH BIOMARKERS
Reduced attrition in development = reduced cost of development = more affordable healthcare
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Analytical and regulatorychallenges
The right validation level at the right stage
Pre-Analytical considerations
Avoiding the ‘pre-analytical’ biomarker
‘Smart’ bio-banking
Project Management and Scientific Support
Choosing the right CRO partner for Biomarkers
Maximizing sample utilization
Driving biomarker studies through the challenges
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In-Transit Temperature Monitoring Transportation time vs. established stability Onsite Shipping Support Monitor, Intercept, & Re-ice as needed Pre-configured Shipping Materials
TRANSPORTATION
1,250,000 Shipments/Year 95 + Countries 99% On-Time Delivery
Pre-analytical considerationsAVOIDING THE ‘PRE-ANALYTICAL BIOMARKER’
SAMPLE COLLECTION
Non invasive whenever possible
Minimum volume of blood(to balance with potential retest and sample storage)
Sample type definition (collection tube/device)
Validation driven decisions
Standardized biomarker specific collection and shipping instructions in investigator manual and
planned logistics to minimize variability and maximize data yield
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Pre-analytical considerationsAVOIDING THE ‘PRE-ANALYTICAL BIOMARKER’
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Analytical and Regulatory ChallengesTHE RIGHT LEVEL OF VALIDATION
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• Sample Type, Collection and Handling• Linearity/Analytical Measurement Range (AMR) • Precision (intra- and inter-assay)• Accuracy/Recovery • Sensitivity/Limits of Quantitation • Analytical Specificity (Interference) • Dilution verification • Verification/Definition of Reference Interval • Stability (short- and long-term) • Specimen Carryover • Period of Analyte Stability (length of run)
FeasibilityExploratoryAdvanced
Validation types:
How will I know my test work? FIT-FOR-PURPOSE VALIDATION
Pre-ClinicalClinical
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Analytical and Regulatory ChallengesTHE RIGHT LEVEL OF VALIDATION
Plate nAnalyte stability day nPrecision (continued)
• Feasibility validation: go/no-go decision…• Exploratory validation: candidate selection, proof of concept in pre-clinical setting...• Advanced validation: first in human – full CLIA validation as needed.
If in doubt, talk to regulatory agency (FDA,EMA…)
Fit-for-purpose validation approach at Covance TBS – Immuno-assays
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Analytical and Regulatory ChallengesTHE RIGHT LEVEL OF VALIDATION
Concept Lead ID
LaunchCandidateSelection
Quality principles
Target ID In-vitroScreening
EfficacyScreening
LeadOptimizationToxicology
DefinitiveToxicology
ClinicalDevelopment
Post-LaunchActivities
GCP CAP/CLIAGLP GMP
Critical choice for ability to submit dataand time/cost optimization
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• Choosing the right technologysensitivity, quantitative vs. qualitative…
• Planning for data combinabilityinitial verification: inter-instrument/lab correlationmonitoring: use of existing external survey, ‘split testing’, internal QC program…
• Testing days and Turn Around Timeinclusion criteria, dosing…
• Timelines for assay development and or validationregulatory environment, LDT vs. IVD test, need of disease state samples for validation…
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Analytical and Regulatory ChallengesOTHER CONSIDERATIONS
Cost and Readiness directly driven by all these factors
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Retrospective study Prospective study Bridging study
TESTING IS NOT THE LAST STEP WHAT MAKES SAMPLES VALUABLE
Lab testing and clinical information Appropriate consent (think ahead!)
Smart BiobankingMAXIMIZING SAMPLE UTILIZATION
Volume Location
KEEPING TRACK OF SAMPLES
Stability Thaws
Physical protection Temperature control
KEEP YOUR SAMPLES SAFE
Backup storage Limit sample movements
Leverage IT solutions to consolidate information
>10,000,000 samples in biorepository13
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Project Management and Scientific SupportDRIVING BIOMARKER STUDIES THROUGH THE CHALLENGES
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Request
Feasibility assessment
Covance/Client
discussion
Final proposal
Work executionTroubleshooting
as needed
Reporting
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Pan-Covance Services
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Discovery, Lead Optimization, Research Models
Toxicology and Safety Pharmacology
Bioanalytical and DMPK
Translational Biomarkers Solutions (TBS)
Clinical Pharmacology
Clinical Development
Market Access
CAP/CLIA Central Laboratories
Research Preclinical Phase l Phase ll Phase lll Phase lV
DEVELOPMENT COMMERCIALIZATIONDISCOVERY
IND NDA
Covance generates more drug development data for the regulatory evaluation of efficacy and safety than any other company in the world
FROM DISCOVERY TO COMMERCIALIZATION
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Covance Central Laboratory ServicesTRANSLATIONAL BIOMARKER SOLUTIONS (TBS)
Research environment(«Quality principles»)
providing Flexibility and Agility
Discovery DevelopmentTarget discovery Lead
discoveryLead
optimization Pre-clinical Phase I Phase II Phase III
Translational Biomarker Solutions
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Informatics
Molecule Characterization
Cell Based AnalysisPathology core lab and Immuno-assays
Biomarker Strategy and Consulting
Covance Central Laboratory ServicesTRANSLATIONAL BIOMARKER SOLUTIONS (TBS)