Pharmaceutical & Medical Packaging News staff

The work behind ASTM International Standard Test Method F2638.

By Paul F. Herman and Curtis L. Larsen, CPP, Fellow

Editor’s Note: Longer, more complete versions of Part I and Part II are being published in PMP News’s sister publication, MD&DI. To read these articles, please see the May 2008 and June 2008 issues online at www.devicelink.com/mddi. PMP News will publish a shorter version of Part II in its June 2008 issue.

In 1997, the European Committee for Standardization (CEN) and the International Organization for Standardization (ISO) introduced standards for packaging and materials for terminally sterilized medical devices. These standards highlighted the need for a universally recognized microbial barrier test for such materials. Both the CEN and ISO working groups decided that, without a widely accepted procedure for evaluating the integrity of the sterile package (sterile barrier system [SBS] def. ISO11607-01:2006), the best approach was to carry out separate tests for determining seal integrity, integrity of the package materials and films, and microbial barrier of porous materials.¹

Although there were a number of recognized tests for evaluating seal integrity, this was not the case for determining the microbial barrier of permeable or porous materials. Tests such as ASTM International F1608, DIN 58953 Part 6 subclauses 2.14 and 2.15, and BS 6256 Appendix C (methylene blue) were all used, but not universally recognized.² In addition, all of these tests take a long time to perform and often require several days to produce results.

FILTRATION THEORY

Challenges to sterile barrier systems used to protect medical devices from bacteria and viruses come in the form of aerosols of suspended particles. Microbial spores can exist as individual entities or clusters, or they can be attached to inert particles such as dust particles. The size of a particulate challenge can range from 0.002 µm for the smallest virus up to 100 µm for the largest dust particle that can remain suspended in air for a significant length of time.

Filtration theory explains why certain particles permeate certain materials. Three mechanisms occur at all flow rates and for all particle sizes: interception, inertial impaction, and diffusion. (For an in-depth discussion of these, please see the MD&DI articles.) In theory, larger particles moving at higher flow rates are more likely to be trapped by inertial impaction, whereas lighter ones moving at slower speeds are more likely to be caught by diffusion.

The BTC Project

Without an internationally recognized test to evaluate the microbial barrier of permeable or porous materials, a group of seven companies within the Sterile Barrier Association (SBA), previously known as ESPA (European Sterile Packaging Association), formed the Barrier Test Consortium Ltd. (BTC) in 1998 to develop a rapid, easy-to-use, microbial barrier test for porous medical packaging materials. BTC consists of the following companies:

BTC members agreed that the new test had to meet certain key requirements. Specifically, the test had to be:

Following a call for research proposals, the project was awarded to Air Dispersions Ltd. (ADL; Manchester, UK). The project tasks included:

To ensure that erroneous results were not obtained owing to variations in commercially available materials, the initial work was to prove a correlation existed using research-quality papers designed and produced by ADL. These papers had a high degree of uniformity and a wide range of porosity.

The next phase, a blind study, utilized 16 of 30 samples submitted by BTC members. The samples represented the range of porous packaging materials commercially available at the time. For the range of properties for these materials, please see the MD&DI articles.

The specialized microbiological test used for the project was developed by ADL several years before work began on the BTC project.³ This test challenges the sample with standardized dispersions of microorganisms at a range of pressure differentials corresponding to overall flow rates of 0.1 to 100.0 cm³/min/cm². This range encompasses typical conditions experienced by medical packages during normal conditions of handling, distri­bution, and storage.

The equipment used for this test was designed as a research instrument. It was highly specialized to allow for a wide operating range of flow rates. It also featured very sensitive control mechanisms for flow control, particle control, particle size, and enumeration. This test measures the extent of microbial penetration at each flow rate by measuring the concentration of air-dispersed microorganisms both before and after passing through the material. For a given test organism, the extent of penetration through the test sample strongly depends on the flow rate. This results in a maximum penetration value being obtained at a specific flow rate for a particular organism and packaging material. Endospores of bacillus subtilis var. niger are typically used. The maximum penetration value is a measure of the microbial barrier performance of the packaging material.

It is important to note that although this test gives an accurate result, it is a microbiological test and takes several days to complete. In addition, this test requires a high level of technical expertise and a dedicated microbiological laboratory. Although ADL considered the test to be a good research tool, it didn’t meet the criteria requirement of being rapid.

To reduce equipment cost, the particle generator, size classifier, and neutralizer were replaced by an atomizer and an aerosol of polystyrene beads measuring 1.0 µm in diameter. This modification simplified the process, allowing for variable airflow capacity and a single size, synthetic particle for the test medium.

The commercially available equipment selected for the BTC project was known to fulfill these criteria very well, enabling relatively inexperienced operators to obtain reproducible results for the physical particulate barrier performance of filter media in a matter of minutes. As with the microbiological test, a maximum penetration value is obtained.

To test medical packaging materials as opposed to filter media, it was necessary to design a special sample holder to use in conjunction with the equipment. Once the sample holder mechanism was available, it was then possible to identify percentage penetration of the most penetrating particle size (maximum particle penetration) for any material using synthetic substances as the test particle.

BASIS FOR NEW ASTM METHOD

The BTC project was successfully completed in 2000 and formed the basis of the new ASTM international standard test method F2638-07.4 ADL was able to demonstrate correlation between results obtained using commercially available equipment for testing the physical particulate barrier performance of fibrous filter media and those generated using ADL’s specialized microbiological test.³ Furthermore, the relationship extends over a wide range of commercially available packaging materials including coated and uncoated paper and coated and uncoated nonwovens (DuPont Tyvek for sterile packaging). This was not unexpected because both tests measure the effectiveness of materials to act as filter media.

Part II of this series will discuss the development of ASTM F2638-07, as well as provide a comparison of this new microbial barrier test method versus ASTM F1608, which is commonly called the log reduction value (LRV) test. The article will also look at the aerosol filtration equipment required to perform the new test method.

References

1. ISO 11607-1:2006 Packaging for terminally sterilized medical devices Part 1: Materials, sterile barrier systems and packaging systems.

2. ASTM International F1608-00(2004) Standard Test Method for Microbial Ranking of Porous Packaging Materials (Exposure Chamber Method).

3. Microbiological Barrier Testing of Porous Medical Packaging Materials, Alan Tallentire and Colin Sinclair at the Meeting of the Society of Plastics Engineers (Scandinavian Section), May 1994.

4. ASTM International F2638-07 Standard Test Method for Using Aerosol Filtration for Measuring the Performance of Porous Packaging Materials as a Surrogate Microbial Barrier.

Paul F. Herman is a nonwovens application consultant for DuPont Active, Medical, and Industrial Packaging (Richmond, VA). Curtis L. Larsen, a member of PMP News’s editorial advisory board, is a packaging consultant for DuPont Medical Packaging and Spartan Design Group LLC (Tonka Bay, MN).