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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