ISO 11137: The Real Cost of Compliance

By: Mark Botting, Isotron, Swindon, UK

Complete conformance
The publication of updated standard ISO 11137: 2006 “Sterilization of health care products -- Radiation -- Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices” has defined more clearly the validation requirements for manufacturers who label products sterile in accordance with Medical Devices Directive 93/42/EEC (MDD). This change has led to regulatory bodies requiring total conformance to this standard. 
 

Although the requirement to fully comply is viewed negatively by some manufacturers (because of increased costs), the evolution of the standard and industry over the last 15 years has brought cost benefits to other aspects of the manufacturing and sterilisation processes. New methods also have been designed to offer more cost-effective ways to reduce testing costs during a product’s lifecycle.

 

ISO 11137, the standard for “Sterilization of health care products – Radiation,” was first published in 1995 as an international standard clearly outlining “the requirements for development, validation and routine control of radiation sterilization for medical devices.” This standard progressed further than previous localised standards in detailing the methods that could be used to establish the required minimum dose of radiation for a product to conform to a sterility assurance level (SAL) of 10^-6.

 

The initial negative feedback from manufacturers focused on the costs to undertake microbiological testing in conformance with this standard, but also on the cost of product that would need to be tested (and hence destroyed) by implementing the methods described: 130 products in the case of Method 1 and 840 products in the case of Method 2.

 

In addition, the 1995 standard did not specify at what frequency the test should be undertaken to confirm maintenance of process effectiveness. It was sufficiently ambiguous to allow manufacturers to use historical data to conform to this standard without applying Method 1 or 2. In such cases, historical dose information—the use of minimum 25 kiloGray (kGy) for many years—regular and controlled bioburden and risk assessments meant that some manufacturers were able to undertake one initial Method 1 without subsequent audits, or in some cases to do no microbiological dose setting validation at all.

 

The latest version of ISO 11137 was published in 2006 after a number of years of standards development within ISO. The group working on this standard focused, in particular, on making a number of key changes to address some of industry’s concerns but also looked at areas of uncertainty for manufacturers and notified bodies. The key changes are outlined below.

 

Since the end of the transition period between the 1995 and 2006 standard, Isotron, from its vantage point as a supplier of radiation validation services, has seen a real shift in the regulatory environment within the United Kingdom. The key difference is the requirement from regulatory bodies to see the standard implemented in its entirety by all manufacturers of medical devices. As such, the cost of product, bioburden control and use of 25 kGy for many years are no longer acceptable reasons for avoidance.

 

 

The requirement to increase monitoring not only of product bioburden but also of irradiation dose efficacy will place greater emphasis on suppliers of raw materials and components to improve product microbial quality. In addition, a better understanding of cleanroom conditions and sources of contamination will lead to a reduction in quality-related issues and ultimately cost of manufacture.

 

The main benefit, however, should be in a reduction of the radiation dose. The historical use of 25 kGy as a minimum sterilisation dose is still the norm, even 15 years after ISO 11137 was first introduced. The introduction of Method 1 has shown that ultra clean products can be sterilised with doses as low as 11 kGy. The introduction of VDmax 15 and AAMI TIR33 allows the substantiation of sterilisation doses lower than historical standards. This reduction is a significant decrease in time within the irradiation cell, a high proportion of which can be passed along as cost reductions by sterilisation providers.

 

The clause outlining frequency of auditing (ISO 11137-1, clause 12.1.3) is a major benefit to manufacturers who are able to maintain a low and consistent bioburden. This now clearly outlines that auditing can be reduced from a quarterly frequency in the first year to six audits the second year and one annual audit from year three onwards, provided microbiological contamination is controlled and dose audits are successful. This means that the initial validation charges are not the norm throughout the product’s entire lifecycle.

 

In addition, dose reduction could lead to fewer damaged products, which may allow less expensive polymers to be used or product shelf life to be extended.

 

The use of VDmax as the test of choice by manufacturers also means that the cost of microbiological testing and product write off observed when the standard was first introduced are now significantly reduced and bring overall validation costs in line with the levels experienced by ethylene oxide (EtO) users for many years.

 

The standard also outlines how product families or master products can be used to reduce the need to test every product line. This means that some manufacturers making very similar products will only have to validate two or three product lines to be in compliance with the standard.

 

In conclusion, these standards have now been in place for 15 years and, as such, a consistent approach by the regulatory authorities should be seen as a positive move for industry. The standards and industry have evolved over the last 15 years to offer solutions that reduce costs associated with sterilisation and manufacturing, compensating for the increase in microbiological testing. This allows validation costs to be roughly equal to those experienced by users of EtO sterilisation. The introduction of more VDmax dose levels going forward is another positive move that industry should embrace. 

 

is UK Sales and Marketing Manager at Isotron Ltd, a division of Synergy Health.

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