1. Overview of Pharmaceutical Product Development

1. 1. Overview of Pharmaceutical Product Development Anthony Taylor

2. Overview of Pharmaceutical Product Development Objective; • To achieve a predictable therapeutic response to a drug included in a formulation which is capable of large scale manufacture with reproducible product quality.

3. Overview of Pharmaceutical Product Development • Development of the Drug Product • Development of a Manufacturing Process • Development of Product Controls • Specifications • Test methodology • Stability testing • Support to the Development process • Preclinical/clinical pharmacology • Manufacture and Supply of Investigational Medicinal Products (IMPs)

4. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Phase IIb/ Phase III studies Post-marketing studies Safety/ tolerability/ PoC in humans Lead Series Identified Candidate Selected Concept Proven Approval for FTIH Product Launched

5. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Safety/ tolerability/ PoC in humans Phase IIb/ Phase III studies Post-marketing studies Lead Series Identified Candidate Selected Approval for FTIH Concept Proven Product Launched Preformulation & developability assessment

6. Preformulation and Developability Assessment • Purpose • Determination of fundamental physical and chemical properties of the drug molecule • Identifies potential dosage forms • Identifies potential issues in the development of dosage forms • Assessment of likelihood of being able to turn drug into a Medicinal Product

7. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Safety/ tolerability/ PoC in humans Phase IIb/ Phase III studies Post-marketing studies Product Candidate Approval Concept Lead Series Launched Identified Selected for FTIM Proven Preformulation & developability assessment Formulation development for Safety assessment and Clinical Pharmacology/Clinical Studies

8. Formulation Development and Testing for Safety Assessment • Purpose • Facilitate dosing in safety assessment studies • Ensure quality of test material • Issues • High exposures • Limited drug supply • Consistency with clinical products

9. Formulation Development for Clinical Pharmacology & Clinical Studies • Purpose • Facilitate unequivocal testing in humans • Ensure quality of test material • Issues • Simple, flexible dosage form required early on • Limited drug supply • Consistency with final product

10. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Safety/ tolerability/ PoC in humans Phase IIb/ Phase III studies Post-marketing studies Product Candidate Approval Lead Series Concept Launched Identified Selected for FTIM Proven Preformulation & developability assessment Formulation development for Safety assessment and Clinical Pharmacology/Clinical Studies Formulation development for market

11. Formulation Development for Market • Purpose • Design of optimal dosage form • Assurance of safety & quality • Demonstration of consistency of performance • Issues • Dose may be unknown • Feedback from Clin Pharm studies required • Drug substance may change • Timing of introduction (Phase IIb, Phase III, Launch?)

12. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Safety/ tolerability/ PoC in humans Phase IIb/ Phase III studies Post-marketing studies Product Candidate Approval Lead Series Concept Launched Identified Selected for FTIM Proven Preformulation & developability assessment Formulation development for Safety assessment and Clinical Pharmacology/Clinical Studies Formulation development for market Manufacturing Process Development

13. Manufacturing Process Development • Purpose • Develop and validate commercial manufacturing process • Issues • Product must be equivalent to Phase III product • Manufacturing site • Product volumes • Drug substance may change

14. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Safety/ tolerability/ PoC in humans Phase IIb/ Phase III studies Post-marketing studies Product Candidate Approval Lead Series Concept Launched Identified Selected for FTIM Proven Preformulation & developability assessment Formulation development for Safety assessment and Clinical Pharmacology/Clinical Studies Formulation development for market Manufacturing Process Development Product Line extensions

15. Product Line Extension Development • Purpose • Improve therapy (efficacy and/or safety) • Support additional indications • Patient convenience

16. Overview of Pharmaceutical Product Development Lead Optimisation Preclinical Evaluation Safety/ tolerability/ PoC in humans Phase IIb/ Phase III studies Post-marketing studies Product Candidate Approval Lead Series Concept Launched Identified Selected for FTIM Proven Preformulation & developability assessment Formulation development for Safety assessment and Clinical Pharmacology/Clinical Studies Formulation development for market Manufacturing Process Development Product Line extensions Product Control - Specifications, Method development, Testing

17. Overview of Pharmaceutical Product Development • Product Control - Specifications, Method Development and Testing • Purpose • Define standards for safety, efficacy and quality of product • Assurance of product quality for preclinical, clinical and marketed product, i.e. at all stages of development

18. Overview of Pharmaceutical Product Development • Summary; • To turn a drugsubstance into a viable medicinal product which delivers the drug to the right place at the right time in the right quantity to exert the desired effect by….

19. Overview of Pharmaceutical Product Development • Ensuring that the drug product is sufficiently stable that it reproducibly and reliably affects the desired pharmacological response • no loss of activity • no loss of performance • no increase in side effects

20. Overview of Pharmaceutical Product Development • Ensuring that the manufacturing process is robust, reliable and able to meet the predicted sales volumes for the product

21. Overview of Pharmaceutical Product Development • Developing analytical test methods to provide assurance of the quality of the medicinal product

22. Overview of Pharmaceutical Product Development • Commercial pressures; • How can we turn this drug into a medicine? Vs • Can we turn this compound into the medicine we want? • Primarily a question of drug substance control • Pharmacist has many approaches for formulating “difficult” compounds • How difficult is development likely to be?

23. Product Development Design Case Study

24. Case StudyProduct Line extension • Your company markets an oral product for migraine – you are the PLE department and the commercial team have asked you to design a faster acting product. • The product development team is asked to ‘brainstorm’ options for this development • You have 20 minutes to discuss before feeding back your best concept to the Product Development Board What do you need to know about the patient population? What do you need to know about the disease? What do you need to know about the properties of the drug? What formulation technology will you use?