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

Product Development  Pharmaceuticals  Medical Devices  Bio-Technology  Equipment  Support Products  Pharmaceuticals  Medical Devices  Bio-Technology  Equipment  Support Products

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  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

Overview of Typical Pharmaceutical Product Development 4 PreClinical Work Clinical Studies Registration Validation Commercial Production FILINGFILING APPROVALAPPROVAL VALIDATIONVALIDATION IP Marketing Research Marketing Plan 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 April 2, 2000http:// 2 Drug Approval Overregulation, MR Ward - CATO Regulation New York Times - November Cost: 1 Preclinical to Phase II - Approximately 1-7 million Phase III million Time: 2,3 Validation Batches - Product Costs and Labor X 3 to 5 batches Production Start Up Costs based on Contract or Facility Total Costs = million USD Preclinical to Completed Clinicals years FDA Approval months 3 Validation and Production Launch months Total Time = years Product Launch

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

Is it worth the trouble?