Mark J. Kontny, Ph.D.President, PDS & CSO
Partnership Opportunities in Drug Delivery ConferencePartnership Opportunities in Drug Delivery ConferenceBoston, MA
Transforming a New Drug or Technology g g gyinto a Marketed Product
Objectives
• Provide an understanding of the critical decision i t d ti i i th d l t tpoints and timing in the development process to
speed the product to market
• Emphasize the interplay between physical and h i l h t i ti f th d thchemical characteristics of the drug, the
formulation, the manufacturing process, the analytical methodology, the packaging, and clinical trial materials
• Establish criteria for selecting a vendor that can help bring a product across the finish line and into the market
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The Drug Product Development ProcessClinical & Early Development CMCClinical & Early Development CMC
Discovery PreclinicalEarly Clinical
h /Late Clinical
Registration Validation CommercialDiscovery PreclinicalPh I / II Ph II / III
Registration Validation Commercial
Early DevelopmentProduct
AlertProof of Concept
Preformulation / l l i
Formulation Development /
l i lCTM f i/ Salt Selection Analytical
DevelopmentManufacturing
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The Drug Product Development ProcessClinical and Full Development CMCClinical and Full Development CMC
Discovery PreclinicalEarly Clinical
h /Late Clinical
Registration Validation Commercialnolo
gy
Discovery PreclinicalPh I / II Ph II / III
Registration Validation Commercial
Chr
on
Decision to Register
Decision to LaunchFull Development
Final Formulation &
Process Development / CTM Registrationti
ons
Formulation & Analytical Method
Development / Scale-up &
Final Process
CTM Manufacturing
Registration Stability
Func
t
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Develop Product DevelopmentDiscovery Preclinical Clinical Review Product
Physical-Chemical Characterization
Develop the FormulationDevelop the Formulation
Develop the Process
Validate the Process
Develop the Package
Manufacture, Package, Label Clinical Supplies
Analytical Methods & Stability
Technical Reports, IND & NDA Documentation
Improve the TechnologyImprove the TechnologyPhase I Phase II Phase III
ProductIND ICH NDA Approved EOP
Proof of Decision Decision
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Product Alert Concept to Register to Launch
Key PDS Drug Product Deliverables
1. Physical chemical characterization of the drug substance (technology d l t & l t )development & regulatory)
2. Technology development (Commercial operations)– Formulation
– Manufacturing process
– Packaging
– Analytical methods
3. Clinical trial materials – CTM (Clinical)
4. Stability (Regulatory)
5. CMC sections of regulatory submissions (INDs, NDAs and BLAs)6. Intellectual Property
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Product Alert
Key CMC decision criteria to evaluate i hin humans1. Biologic properties?
– Dose
– Half-life
2. Acceptable physical & chemical properties for development?P it– Purity
– Solid form
– Chemical Stability
Solubility Assessment– Solubility Assessment
– Impurities & Degradants
3. Acceptable level and variability of bioavailability?4 F l t bl ?
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4. Formulatable?
Proof of Concept
Key CMC decision criteria to d t li i l Ph IIbproceed to clinical Phase IIb
1. API?– Purity
4. Analytical?– Robust methods
– Impurity profile
– Solid Form
– Stability (physical and chemical)
5. Package?
6. Quality?
7 QbD Ri k A e ment2. Formulation?
– Excipient compatibility
– Stability / degradants
7. QbD Risk Assessment
Stability / degradants
– Bioavailability / bioequivalence
3. Process?Reproducibility
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– Reproducibility
– Scalable
Decision to Register
Key CMC decision criteria to produce Phase III li d i iti t i t ti t bilitsupplies and initiate registration stability
1. Final API?
2. Final formulation?2. Final formulation?
3. Final process?
4. Final analytical methods?
5. Commercial manufacturing site selected?
6. Suitable registration stability protocol?
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Decision to Launch
Key CMC decision criteria to launch
1. Process validation complete?
2. Robust and characterized process?
l d3. PAI? Actions implemented?
4. Adequate commercial manufacturing volume to support market demand?
5. Stability to support desired expiration date?
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Selecting a Partner – MUST HAVES
• Technical depth and breadth – formulation, process, k i d l t l ti lpackaging development, analytical
• Quality system and track record
• Manufacturing scale – seamless scale-up from lab,Manufacturing scale seamless scale up from lab, to pilot, to intermediate, to commercial scale
• Customer service & agility
B i l f f i l i• Business plan – fee for service, royalties, terms & conditions
• Fair pricing
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Cost of Transition of Service Providers
Time• 3 - 6 months
Quality & regulatory • More audits, greater complexity of submission andMore audits, greater complexity of submission and
review
Cost • Additional technology transfer expense• Additional technology transfer expense
Knowledge loss !!
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Summary
• Delivering a drug product through the development d i t th k t l i ki tprocess and into the market place is akin to
preparing for and running a marathon
• Key drug product CMC deliverables– Clinical trial supplies
– Regulatory documentation
– Robust technology
• Development must be managed carefully to control costs, yet deliver a registered product and robust manufacturing technology
• Partnering with the right drug development partner can save time and cost throughout the process
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