committee f02 on flexible barrier packaging - …...astm f2638 an evolution of testing committee f02...

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

Microbial Barrier Properties of Porous Sterile

Barrier Systems 9/23/14 2

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



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



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



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

../../../../../../../Local Settings/My Documents/NOW/health care/medical packaging/DuPont Presentations/DuPont Presentations/DuPont Standard Presentations rev 01/2009.10.27 Sterigenics/Bemis seminar 09/China Presentation Links/howbig.exe

http://www.microbe.org/microbes/bacterium.htm

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



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

9

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

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

12

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



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)



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



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



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



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



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



Particle Filtration Theory

Air Dispersions, Ltd. proved that

Flow rate is an

important factor

Microorganisms behave

like particles and follow the

filtration theory



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.



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



ASTM F2638 Particulate Barrier Test Equipment

Components:

• Aerosol generator

• Particle dryer

• Sample holder

• Particle counter

• Manometer



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



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


Barrier Systems

9/23/14 25

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



Breathable Materials

0

2

4

6

8

10

12

14

16

18

20

0 5 10 15 20 25

% P

enet

rati

on


ASTM F2638 Filtration Efficiency Curves

- Air Transportation 0.1 cm/min

- Handling 1.0 cm/min Microbial Barrier Properties of Porous Sterile


Tyvek® for Medical and Pharmaceutical Packaging

0

0.1

0.2

0.3

0.4

0.5

0 5 10 15 20 25

%P

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ASTM F2638 Filtration Efficiency Curves

Tyvek® 2FS™

Tyvek®

1059B

Tyvek®

1073B



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



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


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



Current Standard Overview



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

