Microbial Barrier Testing of
Porous Sterile Barrier Materials: ASTM F2638 An evolution of testing
Committee F02 on
Flexible Barrier
Packaging
ASTM F02 Meeting – Belfast September 2014
Jane Severin, PhD
Director, Regulatory Affairs – North America
DuPont Medical & Pharmaceutical Protection
Porous Sterile Barrier Systems – 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
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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
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Package Validation - ISO 11607-1:2006
5.2.3: 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
• 6.3.1 Integrity of the sterile barrier system shall be demonstrated
after sterilization and subsequent performance testing.
• 6.3.2 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.
• 6.3.3 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
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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
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A Review of Filtration Theory
Pictures from ASM.org
Amoebae Flu Virus
Borrelia burgdorferi
Pseudomonas
Streptococcus E. coli
Paramecium
Slime mold stack and spore cap Fungal spores
The size of the particle challenge varies:
from 0.002 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.)
Bacillus anthracis
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
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8
Inertial Impaction
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.
Circle = fiber Dashed line = air stream
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Interception
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)
Circle = fiber Dashed line = air stream
10
Diffusion
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
Circle = fiber
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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
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HOW BEST TO TEST ?
ASTM F1608 - 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
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ASTM F1608 - 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)
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How close is F1608 to the real world?
Method or Exposure
Face Velocity cm/min
Air Transport 0.10
Handling 1.00
ASTM F1608 143
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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
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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
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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
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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
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Particle Filtration Theory
Air Dispersions, Ltd. proved that
Flow rate is an
important factor
Microorganisms behave
like particles and follow the
filtration theory
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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, 2002. 56(1): p. 11-9.
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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
ASTM F2638-12 grew out of the results of this work
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ASTM F2638 Particulate Barrier Test Equipment
Components:
• Aerosol generator
• Particle dryer
• Sample holder
• Particle counter
• Manometer
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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
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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
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Curves with ASTM F1608 Flow Reference Point
0
5
10
15
20
25
0 20 40 60 80 100 120 140 160
% P
en
etr
ati
on
Face Velocity, cm/min
ASTM F2638 Filtration
Efficiency Curves
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Breathable Materials
0
2
4
6
8
10
12
14
16
18
20
0 5 10 15 20 25
% P
enet
rati
on
Face Velocity, cm/min
ASTM F2638 Filtration Efficiency Curves
- Air Transportation 0.1 cm/min
- Handling 1.0 cm/min Microbial Barrier Properties of Porous Sterile
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Tyvek® for Medical and Pharmaceutical Packaging
0
0.1
0.2
0.3
0.4
0.5
0 5 10 15 20 25
%P
en
etr
ati
on
Face Velocity, cm/min
ASTM F2638 Filtration Efficiency Curves
Tyvek® 2FS™
Tyvek®
1059B
Tyvek®
1073B
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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
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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: WK47260 Microbial Barrier Properties of Porous Sterile
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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
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Current Standard Overview
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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
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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.
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