Committee F02 on Flexible Barrier Packaging Microbial Barrier Testing of Porous Sterile Barrier Materials: ASTM F2638 An evolution of testing

Transcription

1 Committee F02 on Flexible Barrier Packaging Microbial Barrier Testing of Porous Sterile Barrier Materials: ASTM F2638 An evolution of testing ASTM F02 Meeting Belfast September 2014 Jane Severin, PhD Director, Regulatory Affairs North America DuPont Medical & Pharmaceutical Protection

2 Porous Sterile a paradox Allow the sterilization gases to enter and exit the package Allow the package to adapt to changing pressures and temperatures as well as volume changes But also, Must prevent the ingress of microorganisms in order to maintain sterility 9/23/14 Microbial Barrier Properties of Porous Sterile 2

3 Two Fundamental Questions Why is Microbial Barrier Important? The key factor in selecting packaging materials for medical devices is the ability of the package to maintain sterility from the point of sterilization until it is opened for use Why is Microbial Barrier Testing Important? Need to understand how the packaging material will perform as a microbial barrier during handling, distribution and storage; post sterilization 9/23/14 Microbial Barrier Properties of Porous Sterile 3

4 Package Validation - ISO : : Porous materials shall provide an adequate microbial barrier to microorganisms in order to provide integrity of the sterile barrier system and product safety. 6.3 Packaging-system performance testing Integrity of the sterile barrier system shall be demonstrated after sterilization and subsequent performance testing Physical tests, along with microbial barrier testing of porous packaging materials, can be used to establish the capability of the sterile barrier system to maintain sterility In the absence of applicable validated tests (for the complete package), microbial barrier performance requirements can be established by testing: The microbial barrier properties of materials The integrity of seals and closures 9/23/14 Microbial Barrier Properties of Porous Sterile 4

5 Microbial Barrier Testing An Evolution Filtration Theory ASTM F1608 Standard Test Method for Microbial Ranking of Porous Packaging Materials (Exposure Chamber Method) ASTM F2638 Standard Test Method for Using Aerosol Filtration for Measuring the Performance of Porous Packaging Materials as a Surrogate Microbial Barrier 9/23/14 Microbial Barrier Properties of Porous Sterile 5

6 A Review of Filtration Theory Slime mold stack and spore cap E. coli Borrelia burgdorferi Streptococcus Fungal spores Pseudomonas Amoebae Bacillus anthracis Flu Virus The size of the particle challenge varies: from microns diameter for viruses to 100 microns diameter for spores attached to dust particles. (largest diameter particle that can remain suspended in the air for a significant length of time.) Paramecium Pictures from ASM.org

7 Filtration Theory Size Exclusion: Membrane with holes of a defined maximum diameter that capture particles based upon the size of the hole and the size of the particle Depth Filtration: Filter that retains particles through well defined mechanisms and is dependent upon the depth of the filter (basis weight), the packing density (bonding), and the fiber diameter 9/23/14 Microbial Barrier Properties of Porous Sterile 7

8 Inertial Impaction Circle = fiber Dashed line = air stream Capture of particle when air stream is split by filter fiber Particle s path coincides with centerline of fiber and hits fiber without changing direction Effectiveness is directly related to particle mass and speed of air stream resulting in high inertia Predominate above 0.4 μm; highly efficient for particles larger than 10 micrometers; progressively less effective as the size decreases. Impaction is not efficient for particles less than 0.3 μm due to their low inertia. 8

9 Interception Circle = fiber Dashed line = air stream Capture of a particle that is diverted from the air stream as it flows around fiber Occurs in various degrees at all particle sizes and flow rates Probability of capture is directly proportional to the number of fibers encountered (fiber diameter, packing density and depth of the filter) 9

10 Diffusion Circle = fiber Interception by fiber due to Brownian motion and, for some materials, electrostatic attraction Most effective on particles <0.1µm diameter Effectiveness inversely related to particle mass and speed of air stream 10

11 Overall Filtration Mechanism All three filtration mechanisms operate at all flow rates and for all particle sizes. Inertial impaction dominates at higher flow rates and larger particles. Interception is constant at all flow rates and particle sizes Diffusion dominates at lower flow rates and smaller particles 11

12 HOW BEST TO TEST? 12

13 ASTM F Background Initiated in the mid 1990s by U.S. FDA representatives sitting on ASTM committee F02.06 Significant improvement over whole package aerosol challenge testing Industry accepted ASTM F1608 as a replacement for whole package aerosol challenge testing 9/23/14 Microbial Barrier Properties of Porous Sterile 13

14 ASTM F Shortcomings Uses an aerosol of microbial spores that must be incubated and enumerated by traditional methods Operates at a defined flow rate well into the range where impaction is the dominant filtration mechanism Some porous materials appear to provide a much better barrier than they actually do when tested with real-world conditions (handling, distribution, typical package environment) 9/23/14 Microbial Barrier Properties of Porous Sterile 14

15 How close is F1608 to the real world? Method or Exposure Face Velocity cm/min Air Transport 0.10 Handling 1.00 ASTM F /23/14 Microbial Barrier Properties of Porous Sterile 15

16 Criteria for Better Microbial Barrier Package Testing Create a universally recognized standard Reduced test cost Faster time to result Elimination of the use of live spores Ability to conduct testing without use of a microbiology laboratory Use of flow rates that simulate real-world package life conditions 9/23/14 Microbial Barrier Properties of Porous Sterile 16

17 Barrier Test Consortium (BTC) Project Objective Develop a rapid, accurate and affordable test method for measuring the ability of microorganisms to penetrate porous barrier materials Requirements Based upon established, scientifically sound filtration principles Applicable to the range and variety of commercial medical packaging materials (including papers, latex-based papers, nonwovens and cellulose/synthetic mixed papers) Fully definable and describable Recognized by an accredited organization (ISO, CEN, U.S. FDA, ASTM) as an acceptable method for testing the microbial barrier properties of medical packaging materials 9/23/14 Microbial Barrier Properties of Porous Sterile 17

18 Members of the BTC Amcor Flexibles (formerly Rexam Medical Packaging) Billerud (formerly Henry Cooke) DuPont Kimberly-Clark Oliver Medical (formerly Oliver Products) Perfecseal, a division of Bemis Corp. Westfield Medical Packaging 9/23/14 Microbial Barrier Properties of Porous Sterile 18

19 BTC Call for Research Awarded to Air Dispersions, Ltd., Manchester, UK, a research organization led by Alan Tallentire, Professor Emeritus, and Dr. Colin Sinclair Results published and peer reviewed 9/23/14 Microbial Barrier Properties of Porous Sterile 19

20 Particle Filtration Theory Air Dispersions, Ltd. proved that Flow rate is an important factor Microorganisms behave like particles and follow the filtration theory 9/23/14 Microbial Barrier Properties of Porous Sterile 20

21 Particulate Barrier Test Air Dispersions, Ltd. also proved that particle filtration testing correlates with the bacterial test* *Sinclair, C.S. and A. Tallentire, Definition of a correlation between microbiological and physical particulate barrier performances for porous medical packaging materials. PDA J Pharm Sci Technol, (1): p /23/14 Microbial Barrier Properties of Porous Sterile 21

22 ASTM F grew out of the results of this work Standard Test Method for Using Aerosol Filtration for Measuring the Performance of Porous Packaging Materials as a Surrogate Microbial Barrier Utilizes an aerosol of 1.0 micron diameter polystyrene spheres to measure filtration efficiency of porous materials Provides almost instantaneous test results Generates data over a range of flow rates that are considered to be more representative of the environment encountered by sealed packages during normal handling and distribution cycles 9/23/14 Microbial Barrier Properties of Porous Sterile 22

23 ASTM F2638 Particulate Barrier Test Equipment Components: Aerosol generator Particle dryer Sample holder Particle counter Manometer 9/23/14 Microbial Barrier Properties of Porous Sterile 23

24 Interlaboratory Study Protocol Two laboratories analyzed four different porous packaging materials on a total of six test units One laboratory housed one test unit and the remaining five test units were located at the other laboratory A total of five operators, each with varying levels of experience conducting the test method, participated in the study Precision statement was determined through statistical examination of 72 results, submitted by two laboratories, on four different materials 9/23/14 Microbial Barrier Properties of Porous Sterile 24

25 Materials Tested Sample A : Medical-grade Coated Paper Sample B: Synthetic Fiber Reinforced Coated Paper Sample C: 55# Medical-grade Coated Paper Sample D: Flashspun High-Density Polyethylene 9/23/14 Microbial Barrier Properties of Porous Sterile 25

26 % Penetration Curves with ASTM F1608 Flow Reference Point ASTM F2638 Filtration Efficiency Curves Face Velocity, cm/min 9/23/14 Microbial Barrier Properties of Porous Sterile 26

27 % Penetration Breathable Materials ASTM F2638 Filtration Efficiency Curves Face Velocity, cm/min - Air Transportation 0.1 cm/min - Handling 1.0 cm/min 9/23/14 Microbial Barrier Properties of Porous Sterile 27

28 % Penetration Tyvek for Medical and Pharmaceutical Packaging ASTM F2638 Filtration Efficiency Curves Face Velocity, cm/min Tyvek 2FS Tyvek 1059B Tyvek 1073B 9/23/14 Microbial Barrier Properties of Porous Sterile 28

29 Benefits of ASTM F2638 Method vs. ASTM F1608 Tests with polystyrene spheres vs. live spores No need to sterilize samples prior to testing No need to incubate and enumerate CFUs No need to maintain viable colonies of organisms Tests at multiple pressure differentials or flow rates Data generated during test is tabulated in Excel spreadsheet for fast, easy data reduction Tests performed at conditions closer to real-world for packages 9/23/14 Microbial Barrier Properties of Porous Sterile 29

30 ASTM F2638 Milestones Aug. 2007: ASTM F2638 received provisional approval pending completion of Repeatability and Reproducibility (R&R) testing for generation of Precision and Bias (P&B) statement Oct. 2011: U.S. FDA accepts ASTM F2638 test method as part of DuPont Medical Packaging Transition Project (MPTP) Feb. 2012: R&R testing completed; data submitted to ASTM May 2012: ASTM F2638 receives full approval June 2012: ASTM F2638 submitted for CDRH Recognition; received October 2012: Nelson Laboratories runs ASTM F2638 test for MPTP March 2014: Preliminary discussion with Chinese regulators regarding beginning the process of standard adoption in China September 2014: Update of ASTM standard; WI ID: WK /23/14 Microbial Barrier Properties of Porous Sterile 30

31 Summary The ability of the package to maintain device sterility from the point of sterilization until it is opened for use is a key factor in selecting packaging materials ASTM F2638 is a validated testing method that can for the first time provide more accurate measurement for microbial barrier of porous material under real-world conditions Selection of the proper packaging material can result in a decreased risk of package failure, protecting patients 9/23/14 Microbial Barrier Properties of Porous Sterile 31

32 Current Standard Overview 9/23/14 Microbial Barrier Properties of Porous Sterile 32

33 Proposed Changes WK47260 Change direction of flow rates to low flow to high flow; from high to low Define calibration procedure and material Addition of metal screen in a defined manner to prevent sample interference with air flow Pre-test method for determination of challenge concentration for a given material Addition of use of precision accumulators Add range of acceptable particle sizes for use 9/23/14 Microbial Barrier Properties of Porous Sterile 33

34 Thank You! Copyright 2012 DuPont. All rights reserved. The DuPont Oval Logo, DuPont and Tyvek are trademarks or registered trademarks of E.I. du Pont de Nemours and Company or its affiliates. 9/23/14 Microbial Barrier Properties of Porous Sterile 34