Temperature Controlled Packaging Container for Biologics and Pharmaceuticals by Melinda Phan Yufay Chow-Yee Abraham Ho Project Advisor: Peter Schuster Instructor’s Comments: Instructor’s Grade: ______________ Date: _________________________ CALIFORNIA POLYTECHNIC STATE UNIVERSITY - SAN LUIS OBISPO Temperature Controlled Packaging Container for Biologics and Pharmaceuticals Sponsor: Gerald E. Finken, Clinical Supplies Management Cal Poly Advisor: Dr. Peter Schuster December 4, 2014 FINAL PROJECT REPORT SENIOR PROJECT COMPILED AND EDITED BY Melinda Phan Abraham Ho Yufay Chow-Yee [email protected] [email protected] [email protected] 2 Statement of Disclaimer Since this project is a result of a class assignment, it has been graded and accepted as fulfillment of the course requirements. Acceptance does not imply technical accuracy or reliability. Any use of information in this report is done at the risk of the user. These risks may include catastrophic failure of the device or infringement of patent or copyright laws. California Polytechnic State University at San Luis Obispo and its staff cannot be held liable for any use or misuse of the project. 3 Table of Contents List of Tables ................................................................................................................................................. 8 List of Figures ................................................................................................................................................ 8 EXECUTIVE SUMMARY ................................................................................................................................ 11 INTRODUCTION .......................................................................................................................... 12 Sponsor Background and Need ................................................................................................... 12 Formal Problem Definition .......................................................................................................... 12 Objective/Specification Development ........................................................................................ 13 Project Management .................................................................................................................. 15 Summary of Key Events ................................................................. 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BACKGROUND ............................................................................................................................ 15 Industry Need and Relevance ..................................................................................................... 16 Additional Sponsor Background .................................................................................................. 16 Existing Products ......................................................................................................................... 17 3.3.1 Industry Leader - Credo Cube ............................................................................................. 17 3.3.2 Green Box ............................................................................................................................ 18 3.3.3 Other Competitors .............................................................................................................. 18 3.3.4 Relevant Patents ................................................................................................................. 20 Current State of the Art .............................................................................................................. 21 3.4.1 Methods of Temperature Control ....................................................................................... 24 3.4.2 Thermoelectric Cooling ....................................................................................................... 26 3.4.3 Thermal Insulation .............................................................................................................. 27 Other Relevant Technical Data ................................................................................................... 32 3.5.1 Heat Transfer Modes .......................................................................................................... 32 3.5.2 Circle Packing ...................................................................................................................... 33 3.5.3 Temperature Monitors ....................................................................................................... 34 Applicable Standards .................................................................................................................. 35 3.6.1 FDA Requirements and Other Shipping Guidelines ............................................................ 35 3.6.2 Testing Methods ................................................................................................................. 36 DESIGN DEVELOPMENT .............................................................................................................. 36 Method of Approach ................................................................................................................... 36 4 Concept Generation .................................................................................................................... 38 4.2.1 Ideation ............................................................................................................................... 38 Top Concept Selection ................................................................................................................ 42 4.3.1 Top Conceptual Designs ...................................................................................................... 46 Summary of Concepts ................................................................................................................. 55 DESCRIPTION OF FINAL DESIGN ................................................................................................. 56 Overall Description...................................................................................................................... 56 Design Description, Material Selection, and Supporting Analysis .............................................. 57 5.2.1 Macro-encapsulated PCM ................................................................................................... 57 5.2.2 Macro-Encapsulated PCM Containment ............................................................................. 61 5.2.3 VIP Containment ................................................................................................................. 62 5.2.4 Vial Fixture .......................................................................................................................... 64 Cost Analysis ............................................................................................................................... 65 Product Realization ....................................................................... Error! Bookmark not defined. Manufacturing ............................................................................................................................ 68 Assembly ..................................................................................................................................... 68 Notable Differences with Original Design ............................................................................. 74 Recommendations for Future Manufacturing....................................................................... 75 Design Verification Plan ................................................................ Error! Bookmark not defined. Specification Verification Checklist ............................................................................................. 75 Test 1: Visual Inspection of Vials ................................................................................................. 76 7.2.1 Test 1 Results ...................................................................................................................... 76 Test 2: Visual Inspection of Temperature Monitor ..................................................................... 77 7.3.1 Test 2 Results ...................................................................................................................... 77 Test 3: Time Comparison with Credo Cube Pack-Out ................................................................. 78 7.4.1 Test 3 Results ...................................................................................................................... 78 Test 4: Temperature cycles per ISTA standard ........................................................................... 79 7.5.1 Test 4 Results ...................................................................................................................... 80 Test 5: 100 Hour Test ................................................................................................................. 82 7.6.1 Test 5 Results ...................................................................................................................... 82 Test 6: Drop Test, Stresses and Loading Tests ............................................................................ 83 7.7.1 Test 6 Results ...................................................................................................................... 83 5 Test 7: Real