Case study details the right way and the wrong way to successfully develop and market a new drug Beginning with the untimely death of a young mother, A History of a cGMP Medical Event Investigation unfolds a fictitious case study that captures how unchecked human flaws during the development and launch of a new drug can lead to disastrous consequences. Moreover, it illustrates how and why Six Sigma principles and methods should be applied to fully comply with FDA regulations at every stage of drug development and commercialization. From initial transgenic mouse studies to the FDA fatality investigation, this case study introduces all the key regulations and practices that govern the development, manufacture, and marketing of a new drug, including: FDA Investigational and New Drug Application Processes FDA Code of Federal Regulations' current Good Manufacturing Practice (cGMP) ISPE Good Automated Manufacturing Practice (GAMP) Readers will also be introduced to a variety of managers and researchers whose personal agendas conflict with best practices and therefore compromise the safety and effectiveness of a new drug product. Throughout the case study, the author offers tested and proven practices and tips so that these human flaws are not translated into drug product flaws. These practices and tips are critical and typically can only be learned through years of experience working in competitive drug development environments. A History of a cGMP Medical Event Investigation is ideal for students in biotechnology, pharmacology, engineering, and business management as well as professionals in biomedical and drug development. All readers will discover what can go wrong in developing and bringing a new drug to market. Most importantly, they will also learn how to apply Six Sigma principles and methods to ensure safe and effective product design, development, and manufacturing.

Case study details the right way and the wrong way tosuccessfully develop and market a new drugBeginning with the untimely death of a young mother, AHistory of a cGMP Medical Event Investigation unfolds afictitious case study that captures how unchecked human flawsduring the development and launch of a new drug can lead todisastrous consequences. Moreover, it illustrates how and why SixSigma principles and methods should be applied to fully comply withFDA regulations at every stage of drug development andcommercialization.From initial transgenic mouse studies to the FDA fatalityinvestigation, this case study introduces all the key regulationsand practices that govern the development, manufacture, andmarketing of a new drug, including:* FDA Investigational and New Drug Application Processes* FDA Code of Federal Regulations' current Good ManufacturingPractice (cGMP)* ISPE Good Automated Manufacturing Practice (GAMP)Readers will also be introduced to a variety of managers andresearchers whose personal agendas conflict with best practices andtherefore compromise the safety and effectiveness of a new drugproduct. Throughout the case study, the author offers tested andproven practices and tips so that these human flaws are nottranslated into drug product flaws. These practices and tips arecritical and typically can only be learned through years ofexperience working in competitive drug developmentenvironments.A History of a cGMP Medical Event Investigation is idealfor students in biotechnology, pharmacology, engineering, andbusiness management as well as professionals in biomedical and drugdevelopment. All readers will discover what can go wrong indeveloping and bringing a new drug to market. Most importantlythey will also learn how to apply Six Sigma principles and methodsto ensure safe and effective product design, development, andmanufacturing.

Preface xiPart One The Event 11 Francesca 3Part Two Drug Discovery: Five Years Earlier 92 Katlin Bioscience: Transgenic Mouse Study 113 Oxy-Fox Inhaler 213.1 Kinnen Laboratories 213.2 Kinnen Laboratories: Oxy-Fox Transfer 223.3 Due-Diligence Team and Katlin Data Acceptance 23Part Three Kinnen Oxy-Fox Inhaler Market Launch Program 254 Agency IND and NDA Requirements, Six Sigma Charter, and Device Master Record 274.1 Launch Team Meeting Number 1 274.2 Meeting with Medical Affairs: Toxicity Studies 465 Meeting Minutes Guidelines 495.1 Launch Team Meeting Number 2 496 Project Timing, Marketing Plan, and Offshore Molding 556.1 Launch Team Meeting Number 3 556.2 Project Financial Review 616.3 Progress Meeting: Who Takes Credit for What? 646.4 Morning Meeting: Just-in-Time Manufacturing 657 cGMP Process Validation Requirements 697.1 Launch Team Meeting Number 4 698 Failure Mode Effects Analysis 818.1 Launch Team Meeting Number 5 819 Design for Manufacturability, Design for Six Sigma, Concurrent Design 939.1 Product Development Meeting Number 1 939.2 Update Meeting with Ed Chase and Gordon Taylor 10210 Design Fishbone Diagram 10510.1 Launch Team Meeting Number 6 10511 Product Specifications 11111.1 Product Development Meeting Number 2 11112 Design Control 11512.1 Design Team Meeting Number 7 11512.2 Product Development Staff Meeting 11812.3 Engineering One-on-One 11912.4 Program Update 12013 Design of Experiments (DOE) 12313.1 Molding Team Meeting 12314 Start-Up Issues 12914.1 Oxy-Fox Inhaler Wrap-Up and Equipment Start-Up 12914.2 The Final Management Review 135Part Four Present Day: Funeral 13915 Grief 14116 The Autopsy Results 14517 The Agency 151Part Five Agency Medical Event Letter 15518 Kinnen Notification 15718.1 Another Agency Letter 15718.2 Medical Event Review Meeting 15819 Investigation Team Management 16119.1. Morning Meeting with Gail Strom, Marcia Hines, and Dan Garvey 16120 DMAIC Investigation Process 16321 Internal Quality Review 17121.1 Meeting with Gail Strom and Marcia Hines 17121.2 Executive Management Review 17422 The Agency Audit Letter 17923 Agency Arrival 18324 The Audit 18724.1 Agency Meeting to Review Qualification Documents and the Quality Acceptance Records of First Lot to Stock 18724.2 Agency Meeting to Review the Oxy-Fox Inhaler Lot Used in the NDA Clinical Studies 18924.3 Agency Meeting to Review the Design and Program Team Meeting Minutes 19024.4 Agency Meeting to Review the Due-Diligence Report Katlin Studies, and Oxy-Fox Design History File, 19225 End-of-Day Agency Wrap-Up Meeting 19726 Kinnen Management Review 201Part Six Reckoning 20727 Blame and Responsibility 20927.1 The Investigation Is a Public Record 20927.2 Kinnen Wrap-Up 21028 Closure 213Bibliography 215Index 217