Comprehensive List of Testing for Dupont™ Tyvek® MPTP

Comprehensive List of Testing for DuPont™ Tyvek® MPTP

The DuPont™ Tyvek® Medical Packaging Transition Project (MPTP) includes a systematic method for generating data to prove that Transition Protocol material is functionally equivalent in performance to current Tyvek®, in an effort to help mitigate requalification.

This document provides a comprehensive listing of all testing that will be conducted for each of the three MPTP study components: • U.S. FDA Transition Protocol • Phantom Protocol • Biocompatibility, Food Contact and Pharmacopeia Testing It is designed to help you with your risk assessment and change control management procedures by providing an overview of all MPTP testing in one document.

To date, we have posted extensive Transition Protocol material data, some Phantom Protocol data and Biocompatibility, Food Contact and Pharmacopeia Testing data on our website (www.Transition.Tyvek.com). We will continue to share data in future webcasts and will post industry publications of MPTP test results on our website, including: 1A—Pre- and post-sterilization (t=0), initial results 1B—Pre- and post-sterilization (t=0), final results 2—Accelerated aging (1, 3 and 5 years) and real-time aging (1 year) 3—Real-time aging (3 years) and accelerated aging (7 and 10 years)* 4—Real-time aging (5 years) 5—Real-time aging (10 years)*

* Eleven cells designated for extended accelerated aging (7 and 10 years) and real-time aging (10 years). DuPont™ Tyvek® MPTP Package Testing January 31, 2014

Real-Time Accelerated No. Package Sterilization Pre- Post- Aging Protocol Test Methods Tests - Description Aging Conditions of Cells Format† Method* Sterilization Sterilization Conditions (Years) (Years) Visual, Seal Strength, Coated 1073B ASTM F1886M, F88‡, FDA 6 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, ASTM F1886M, F88‡, FDA 6 Coated 1073B FFS EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 F1929, F2638 • • Microbial Barrier Visual, Seal Strength, 1, 3, 5; Coated 1073B ASTM F1886M, F88‡, 1, 3, 5; FDA 9 EO** Package Integrity (Dye), one cell Lids/Rigid Trays F1929, F2638 • • one cell 7 & 10 also Microbial Barrier 10 also Visual, Seal Strength, 1, 3, 5; Uncoated 1073B ASTM F1886M, F88‡, 1, 3, 5; FDA 6 EO** Package Integrity (Dye), one cell Pouches/Bags F1929, F2638 • • one cell 7 & 10 also Microbial Barrier 10 also Visual, Seal Strength, 1, 3, 5; Coated 1073B ASTM F1886M, F88‡, 1, 3, 5; FDA 3 Gamma Package Integrity (Dye), two cells Pouches/Bags F1929, F2638 • • two cells 7 & 10 also Microbial Barrier 10 also Visual, Seal Strength, 1, 3, 5; ASTM F1886M, F88‡, 1, 3, 5; FDA 3 Coated 1073B FFS Gamma Package Integrity (Dye), one cell F1929, F2638 • • one cell 7 & 10 also Microbial Barrier 10 also Visual, Seal Strength, 1, 3, 5; Coated 1073B ASTM F1886M, F88‡, 1, 3, 5; FDA 6 Gamma Package Integrity (Dye), five cells Lids/Rigid Trays F1929, F2638 • • five cells 7 & 10 also Microbial Barrier 10 also Visual, Seal Strength, Uncoated 1073B ASTM F1886M, F88‡, FDA 3 Gamma Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, ASTM F1886M, F88‡, FDA 3 Coated 1073B FFS Electron-beam Package Integrity (Dye), 1, 3, 5 1, 3, 5 F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Uncoated 1073B ASTM F1886M, F88‡, FDA 3 Electron-beam Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, ASTM F1886M, F88‡, FDA 3 Coated 1059B FFS EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Uncoated 1059B ASTM F1886M, F88‡, FDA 6 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Uncoated ASTM F1886M, F88‡, FDA 3 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 1059B FFS F1929, F2638 • • Microbial Barrier

Visual, Seal Strength, Coated 1073B ASTM F1886M, F88‡, Phantom 1 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, ASTM F1886M, F88‡, Phantom 1 Coated 1073B FFS EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Coated 1073B ASTM F1886M, F88‡, Phantom 2 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 Lids/Rigid Trays F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Uncoated 1073B ASTM F1886M, F88‡, Phantom 1 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Coated 1073B ASTM F1886M, F88‡, Phantom 2 Gamma Package Integrity (Dye), 1, 3, 5 1, 3, 5 Lids/Rigid Trays F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Uncoated 1059B ASTM F1886M, F88‡, Phantom 1 EO** Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Coated 1073B ASTM F1886M, F88‡, Phantom 3 Steam Package Integrity (Dye), 1, 3, 5 1, 3, 5 Lids/Rigid Trays F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Uncoated 1073B ASTM F1886M, F88‡, Phantom 2 Steam Package Integrity (Dye), 1, 3, 5 1, 3, 5 Pouches/Bags F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Coated 1073B ASTM F1886M, F88‡, Phantom 1 Dry Heat Package Integrity (Dye), 1, 3, 5 1, 3, 5 Lids/Rigid Trays F1929, F2638 • • Microbial Barrier Visual, Seal Strength, Coated 1073B Low Temp. ASTM F1886M, F88‡, Phantom 1 Package Integrity (Dye), 1, 3, 5, 7, 10 1, 3, 5, 10 Pouches/Bags H O F1929, F2638 • • 2 2 Microbial Barrier Visual, Seal Strength, Coated 1073B Low Temp. ASTM F1886M, F88‡, Phantom 1 Package Integrity (Dye), 1, 3, 5 1, 3, 5 Lids/Rigid Trays C H O F1929, F2638 • • 2 4 3 Microbial Barrier Visual, Seal Strength, ASTM F1886M, F88‡, Phantom 1 Coated 1059B FFS Gamma Package Integrity (Dye), 1, 3, 5 1, 3, 5 F1929, F2638 • • Microbial Barrier Visual, Seal Strength, ASTM F1886M, F88‡, Phantom 1 Coated 1059B FFS Electron-beam Package Integrity (Dye), 1, 3, 5 1, 3, 5 F1929, F2638 • • Microbial Barrier Coated & Uncoated eleven cells eleven cells Total 78 ALL ALL 1073B & 1059Bt 7 & 10 also 10 also

NOTES: † Packages made at upper, lower and nominal sealing conditions for three lots of Transition Protocol material and three lots of current Tyvek®. * Sterilization cycles are described in cell descriptors which can be found using the MPTP Cell Descriptor Selector Tool at www.Transition.Tyvek.com. ** EO residuals are measured and compared between Transition Protocol material and current Tyvek®. ‡ ASTM F88 technique per cell per medical device manufacturer’s (MDM’s) standard practice. t Specific material combinations are described in cell descriptors which can be found using the MPTP Cell Descriptor Selector Tool at www.Transition.Tyvek.com. Phantom Protocol Testing January 31, 2014

Accelerated Real-Time Test Sterilization Pre- Post- Property Aging Conditions Aging Conditions Status Method(s) Method/Details Sterilization Sterilization (Years) (Years) EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy Testing Testing MD Tensile Strength Aging work ASTM D5034 electron-beam; steam; completed; completed; 1, 3, 5, 7, 10 1, 3, 5, 7, 10 & Elongation ® in progress STERRAD 100S; report pending report pending vapor hydrogen peroxide EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy Testing Testing CD Tensile Strength Aging work ASTM D5034 electron-beam; steam; completed; completed; 1, 3, 5, 7, 10 1, 3, 5, 7, 10 & Elongation ® in progress STERRAD 100S; report pending report pending vapor hydrogen peroxide EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy Testing Testing Aging work Puncture Strength ASTM F1342 electron-beam; steam; completed; completed; 1, 3, 5, 7, 10 1, 3, 5, 7, 10 ® in progress STERRAD 100S; report pending report pending vapor hydrogen peroxide EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy Work in Microbial Barrier ASTM F1608 electron-beam; steam; • • 5, 10 x ® progress STERRAD 100S; vapor hydrogen peroxide EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy Testing Testing Aging work Microbial Barrier ASTM F2638 electron-beam; steam; completed; completed; 1, 3, 5, 7, 10 1, 3, 5, 7, 10 ® in progress STERRAD 100S; report pending report pending vapor hydrogen peroxide Differential Scanning Completed Calorimetry (DSC) • x x x

Attenuated Total Reflectance - Fourier Transform Infrared • x x x Completed Spectroscopy (ATR-FTIR)

Area Shrinkage (%) steam: 121°C, 123°C, Completed after Steam Sterilization 125°C, 127°C, 129°C, 131°C x • x x Testing Gurley Hill Porosity (GHP) "Modified GHP" steam: 121°C, 123°C, completed; after Steam Sterilization ISO 5636-5 125°C, 127°C, 129°C, 131°C x • x x report pending

Hydrostatic Head (HH) ® Testing AATCC TM 127 STERRAD 100S; after Low-Temperature completed; EN 20811 vapor hydrogen peroxide x • x x Oxidative Sterilization report pending

MD/CD Steam Sterilize - Dimensional Tensile Strength, Freeze (-80°C) - Work in Stability Puncture Resistance, Thaw - Freeze (-80°C ) - x • x x progress Study Microbial Barrier Thaw - Test ASTM F2638

Testing "Modified Gelbo" Particle Generation completed; ISO 9073-10 • x x x report pending

Flexography Work in Printability Thermal Transfer • x x x progress

Testing Parker Surface completed; Smoothness • x x x report pending

Contact Angle Work in Surface Energy Dyne Pen • x x x progress

MD/CD Tensile e.g.: Isopropanol, Iodine, Work in Chemical Resistance Strength Hydrogen Peroxide, etc. • x x x progress

Dynamic Work in Coefficient of Friction Static • x x x progress EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy L,a,b Color electron-beam; steam; • • 1, 5, 10† 1, 5, 10† Not started Measurements ® STERRAD 100S; vapor hydrogen peroxide EO; 25, 50 & 100 kGy gamma; 25, 50 & 100 kGy Low-intensity Visual electron-beam; steam; • • x x Not started UV Stability Assessment ® STERRAD 100S; vapor hydrogen peroxide

Notes: • = Will be tested X = Will not be tested † = Only those sterilization methods shown in red will be tested under these aging conditions. Biocompatibility, Food Contact and Pharmacopeia Testing January 31, 2014

5 and 10 year PASS (pre-sterilization, EO, 100 kGy gamma, 100 kGy Cytotoxicity (ISO 10993-5) accelerated aging electron-beam, STERRAD® 100S, vapor hydrogen peroxide, steam) in progress

Endotoxins (USP <85>) PASS (pre-sterilization) Completed

Skin irritation and sensitization PASS (pre-sterilization) Completed (ISO 10993-10)

Bioburden (ISO 11737-1) Similar performance to current Tyvek® (pre-sterilization) Completed

Extractables and leachables Additional (ISO 10993-18; Infrared OK (pre-sterilization, 100 kGy gamma, 100 kGy electron-beam) sterilization data spectroscopy; ICP-MS; in progress GC-MS; UPLC-MS)

U.S. Food Contact

PASS (pre-sterilization, EO, 100 kGy gamma, 100 kGy 21 CFR 177.1520 ® Completed electron-beam, STERRAD 100S, vapor hydrogen peroxide, steam)

U.S. Pharmacopeia

USP <88> Class VI PASS (pre-sterilization) Completed

PASS (pre-sterilization, EO, 100 kGy gamma, 100 kGy USP <661> ® Completed electron-beam, STERRAD 100S, vapor hydrogen peroxide, steam)

European Food Contact

PASS (pre-sterilization, EO, 100 kGy gamma, EC Reg. 10/2011 Completed 100 kGy electron-beam, steam)

European Pharmacopeia

Meets the compositional and extractable requirements EP 3.1.5 and EP 3.1.3 Completed (pre-sterilization) EP 3.1.5 Selected Testing: (1) Identification A: PASS (EO, 100 kGy gamma, 100 kGy electron-beam, ® Completed IR Spectrometry STERRAD 100S, vapor hydrogen peroxide, steam) (2) Hexane Solubility