Integrity of sterile barrier systems

Risk-orientated validation of your sterile barrier systems (SBS)

Maintaining the sterility assurance level (S.A.L.) achieved through sterilization by the sterile barrier system (SBS) is a fundamental objective of the DIN EN ISO 11607 series. This is because the patient should be able to rely on a sterile medical device - achieved on the one hand through effective sterilization and on the other through reliable and germ tight sterile packaging.

Until recently, however, the validation obligation specified for critical processes in accordance with DIN EN ISO 13485 has not yet been implemented in a sufficiently risk-oriented manner, even though attempts have been made to improve this.

With the 2024-02 edition of the DIN EN ISO 11607 series, this has now been improved to such an extent that it was possible to include it to the list of harmonized standards in March 2024. Unfortunately, however, a number of aspects in the content of the standard are still not compatible with the risk-oriented approach.

Therefore, great care must also be taken when implementing the 2024-02 edition of the DIN EN ISO 11607 series to actually implement the required risk-oriented approach. And in some cases, this also involves deliberately choosing an interpretation of the series of standards, which contradicts some informative elements of the series of standards.

GBA Medical Device Services has almost 30 years of experience in risk-oriented planning and implementation of packaging validations. This experience is constantly growing thanks to our continuous involvement in relevant national and international standardization committees, as well as our many years of good cooperation with international companies. The test systems we offer cover all the issues required for risk-oriented implementation.

We would like to use two case studies to illustrate the problems described and to present our solutions.

Case study 1: Necessity of combining stability and performance testing

In the case of one customer, for example, we were only able to detect defects in his SBS that occurred in practice by means of a combination of stability and performance testing, which was deliberately not provided for in DIN EN ISO 11607-1.

This is because delamination of the two-layer film was observed. Here, only the inner film layer, which was very thin at 10 µm (= enabling the seal), was still connected to the porous part of the packaging, while the thicker outer film layer (= mechanical strength) was detached from it and therefore also from the seal seam. There was therefore an extremely high risk of critical leaks in the SBS.

The delamination of the SBS, in which 10 longer and heavier metal rods were packed, only occurred after the packaging had also been subjected to a mechanical load (= performance test) following the accelerated ageing (= stability test). With a deliberately sensitive test for germ tightness in the presence of moisture in the entire SBS, leaks could actually be detected in the area next to the sealed seam. The classic seal seam tests were not sensitive enough, due to the standardized minimum sensitivity (dye penetration test according to ASTM F1929: 50 µm) or the test approach averaging over small leaks in the tensile strength tests as well as the location of the defects.

This approach is also permissible, as the application of the risk-oriented approach specified in Chapter 4.2 and Annex F is normative, and the passage in Note 2 of Chapter 8.2 in DIN EN ISO 11607-1: 2024-02, which supposedly contradicts the approach described above, is only informative as a note (and therefore lower ranking). As, of course, it is also application-related, because which packaging is subjected either only to mechanical stress during transportation or only subject to ageing?

As we have had a whole series of comparable cases for almost 30 years now, we have long recommended (and now confirmed by the inclusion of the risk-oriented approach in the DIN EN ISO 11607 series) the risk-oriented combination of accelerated ageing (= stability test) and mechanical stress (= performance test) on the same packaging. This is followed by a deliberately sensitive test for germ tightness at the moisture of the entire SBS including visual assessment and dye test for homogeneity and integrity of the seal seam as an integrity test.

We also support our customers with a document that can be used as a basis for their own risk assessment and technical documentation when arguing their case to notified bodies or authorities with a formal approach.

Case study 2: Need for sensitive integrity testing of the entire SBS

In the case of another customer, for example, we were only able to detect defects in the SBS as a result of three SBS packed together in a product carton rubbing against each other by modifying the test for germ tightness in the presence of moisture in accordance with DIN 58953-6, which is not currently provided for in DIN EN ISO 11607-1.

This is because creases and whitish discolorations in the film had already been observed during the visual inspection. These could also be precisely assigned to the more strongly applied angular components of the products. It was unclear whether these were really still tight or whether there were already leaks.

However, a bubble test would have been far too insensitive for this, due to the standardized sensitivity (ASTM F2096: method sensitivity down to 250 µm) (usual microorganisms from the air or from the skin/hands are approx. 0.8-2 µm ...).

If the test for microbial resistance to moisture in accordance with DIN 58953-6 had only been carried out on randomly taken samples, there would have been a high probability that the samples or the 5 drops per sample would not have detected these areas of concern at all.

By using a modification of the test for germ tightness in the presence of moisture, in which the entire SBS was contaminated on the outside and then also tested for the presence of the test organisms on the inside, it was possible to prove that at least some of the whitish discolored (= highly stretched) areas were already leaking.

The modification made to DIN 58953-6 is not only permissible due to such cases and the risk-oriented approach that is now specified, but is in fact necessary. This modification has also been independently confirmed for more than two decades by official accreditation in accordance with DIN EN ISO/IEC 17025 (DAkkS, with ILAC Mutual Recognition Arrangement). As an integrity test, we carry out this test for germ tightness at the humidity of the entire SBS in conjunction with a visual assessment and the dye test for homogeneity and integrity of the sealing seams.

We also support our customers with a document that can be used as a basis of argumentation for their own risk assessment and technical documentation when presenting arguments to notified bodies or authorities with a formal approach.