US Pharmaceutical/Medical Device Regulatory and Product Development Overview

1. US Pharmaceutical/Medical Device Regulatory and Product Development Overview Tom Gardner

2. Product Development • Pharmaceuticals • Medical Devices • Bio-Technology • Equipment • Support Products

3. Who Am I: • 20+ years in pharmaceutical industry • Quality Analyst, Manufacturing Management, R&D Product Development, Clinical Supplies, Senior Scientist and Product and Process Development Coordinator • Involved in 7 approved FDA product/device filings and over 50 product development projects

4. Overview of Typical Pharmaceutical Product Development Product Launch Marketing Plan IP Marketing Research VALIDATION APPROVAL FILING Cost:1Preclinical to Phase II - Approximately 1-7 million Phase III - 2 - 8 million Total Costs = 10-25 million USD Validation Batches - Product Costs and Labor X 3 to 5 batches Production Start Up Costs based on Contract or Facility Total Time = 4.5 - 7.5 years FDA Approval - 13.5 months 3 Time:2,3 Preclinical to Completed Clinicals - 3-5 years Validation and Production Launch - 6-18 months 1 In 2000 Dollars - Estimates by the National Cancer Institute for all new pharmaceutical. Estimate does not consider R&D costs that are not associated with the development of the drug in question. Most drug companies use a system of cost estimates that includes the valuation of money if it had been invested andthe cost of drug development not approved by the FDA. Most studies conclude that the rate of commercialization success to be 1:5000. How Much does it cost to develop a new drug - James Love Consumer Project on Technology http://www.cptech.org April 2, 2000 2 Drug Approval Overregulation, MR Ward - CATO Regulation - http://www.cato.org/pubs/regulation/reg15n4e.htm 3 New York Times - November 8 1995 4

5. Registration Validation Clinical Trials Pre Clinical Work Commercial Production Welcome to the Jungle Filing Approval Pre Approval Inspection Stable Min. Energy Batch Phase I GO Scale Up Production Tweak Formula Re-Evaluate Stability Reset Parameters FAIL PASS Unstable Proof of Concept FAIL Launch Ad Campaign GO FAIL GO Ineffective Effective Effective GO Animal Max. Energy Batch Phase II Fill Sales & Warehouse Pipeline FAIL Reset Parameters Ineffective PASS Safe FAIL Efficacy Launch GO GO FAIL GO Effective Ineffective Inferior Toxicology FAIL Toxic Nominal Batch Phase III RESET ALL PARAMETERS Death of Product Sell Product Antimicrobial & Aseptic GO PASS FDA STUDIES Definition REFORMULATE Micro GO Phase IV FAIL FAIL GO FAIL Ineffective Effective Validation Sign Off GrowsBugs Failure is Unlikely Passes ID & Description Quarantine Product Reformulation Egg START OVER GO Clinical Report Formula Improvement Geriatric or Pediatric Chemistry FAIL Drug Interaction Validation Report Stability Testing 5 Degradants &Impurities Define LT & Side Effects

6. Is it worth the trouble?