1. Mark J. Kontny, Ph.D.
President, PDS & CSO
Partnership Opportunities in Drug Delivery Conference
Boston, MA
Transforming a New Drug or Technology
g g gy
into a Marketed Product

2. Objectives
• Provide an understanding of the critical decision
points and timing in the development process to
i t d ti i i th d l t t
speed the product to market
• Emphasize the interplay between physical and
chemical characteristics of the drug, the
h i l h t i ti f th d th
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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3. The Drug Product Development Process
Clinical & Early Development CMC
Early Clinical Late Clinical
Discovery Preclinical Registration Validation Commercial
Ph I / II
h Ph II / III
Product Proof of
Alert Early Development Concept
Formulation
Preformulation Development / CTM
/ Salt Selection
l l i Analytical
l i l Manufacturing
f i
Development
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4. The Drug Product Development Process
Clinical and Full Development CMC
nology
Early Clinical Late Clinical
Discovery Preclinical Registration Validation Commercial
Chron
Ph I / II
h Ph II / III
Decision Decision
to Register Full Development to Launch
tions
Final Process
Formulation & Development / CTM Registration
Funct
Analytical Scale-up & Manufacturing Stability
Method Final Process
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5. Develop Product Development
Discovery Preclinical Clinical Review Product
Physical-Chemical Characterization
Develop 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 Technology
Phase I Phase II Phase III
IND ICH NDA Approved EOP
Product Proof of Decision Decision
Alert Concept to Register to Launch
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6. Key PDS Drug Product Deliverables
1. Physical chemical characterization of the drug substance (technology
development & regulatory)
d l t l t )
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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7. Product Alert
Key CMC decision criteria to evaluate
in h
i humans
1. Biologic properties?
– Dose
– Half-life
2. Acceptable physical & chemical properties
for development?
– P it
Purity
– Solid form
– Chemical Stability
– Solubility Assessment
– Impurities & Degradants
3. Acceptable level and variability of bioavailability?
4. Formulatable?
4 F l t bl ?
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8. Proof of Concept
Key CMC decision criteria to
proceed t clinical Phase IIb
d to li i l Ph
1. API? 4. Analytical?
– Purity – Robust methods
– Impurity profile 5. Package?
– Solid Form
6. Quality?
– Stability (physical and chemical)
7.
7 QbD Ri k Assessment
Risk A e ment
2. Formulation?
– Excipient compatibility
– Stability / degradants
– Bioavailability / bioequivalence
3. Process?
– Reproducibility
– Scalable
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9. Decision to Register
Key CMC decision criteria to produce Phase III
supplies and i iti t registration stability
li d initiate i t ti t bilit
1. Final API?
2. Final formulation?
3. Final process?
4. Final analytical methods?
5. Commercial manufacturing site selected?
6. Suitable registration stability protocol?
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10. Decision to Launch
Key CMC decision criteria to launch
1. Process validation complete?
2. Robust and characterized process?
3. PAI? Actions implemented?
l d
4. Adequate commercial manufacturing volume
to support market demand?
5. Stability to support desired expiration date?
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11. Selecting a Partner – MUST HAVES
• Technical depth and breadth – formulation, process,
packaging development, analytical
k i d l t l ti l
• Quality system and track record
• Manufacturing scale – seamless scale-up from lab,
scale up
to pilot, to intermediate, to commercial scale
• Customer service & agility
• B i
Business plan – f f service, royalties, terms
l fee for i li
& conditions
• Fair pricing
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12. Cost of Transition of Service Providers
Time
• 3 - 6 months
Quality & regulatory
• More audits, greater complexity of submission and
review
Cost
• Additional technology transfer expense
Knowledge loss !!
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13. Summary
• Delivering a drug product through the development
process and into the market place is akin to
d i t th k t l i ki t
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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