versão On-line ISSN 2309-8309
versão impressa ISSN 1681-150X
SA orthop. j. vol.13 no.4 Pretoria Dez. 2014
TA du Plessis
MSc(Physics), DSc(Chem), Gammatron (Pty) Ltd, Modimolle, Limpopo
The issues of the shelf life of sterile medical devices and the concept of end-product sterility testing of a sample of devices to prove the sterility of a batch of sterile devices are discussed against the background of the probabilistic approach to sterility and sterilisation. The particular role that the sterilisation technique and the packaging materials used play in maintaining sterility are discussed against the background that sterility and the maintenance thereof is event- and not time-related, and the implications thereof on the shelf life of sterile medical devices.
Key words: sterile medical devices, sterility maintenance, shelf life
Manufacturers of sterile medical devices often give an expiry ('use by') date on the package, generally five years from the date of sterilisation. The question arises as to what limits the duration of the sterility of such devices? Why is the shelf life limited by manufacturers, and if so, why specifically five years and not three or ten years -probably relating to the accelerated or real-time testing of the packaging material? This becomes particularly relevant in the case of medical implants such as prostheses. If the implant is specified by the manufacturer to have a shelf life of five years prior to implantation, how does this relate to the in vivo performance of the device? It should be clearly pointed out that in this discussion the emphasis is put on the sterility of the implant and not on the mechano-clinical performance of such a device.
In order to get perspective on this issue, it is necessary that we clearly understand the underlying principles of the particular sterilisation technique and the associated packaging of sterile medical devices.
The concepts of sterile, sterilisation and sterility assurance levels
In many authoritative books in the field of sterilisation, the concept sterile is referred to as a state completely free of any viable microorganisms, and sterilisation is defined as the process which will destroy all viable microorganisms.1-3
What limits the duration of the sterility of sterile medical devices?
These concepts are thus used in the absolute sense where no viable microorganisms exist.
However, an inherent problem is that it is impossible in practice to prove either the complete absence or the destruction of these microorganisms.4 This will be discussed in more detail later.
The fact that the destruction of microorganisms through physical (radiation and steam) and chemical (ethylene oxide) sterilisation methods shows an exponential dependence on the various process parameters, clearly implies that the absence of microorganisms on a medical device following a properly validated sterilisation process can only be described in terms of a probability function.4-5 This exponential nature of sterilisation means that, although the probability may reach a very low value, it can never be lowered to a zero level in the absolute sense of the word.5-7
This probabilistic approach to sterility leads to the concept of sterility levels - a view which no doubt may have little room in the 'classical' approach to sterility. Such a probabilistic approach also implies the existence of certain 'sterility assurance levels' (SALs) - a concept that plays an important role in this field and is being used to quantify the level or probability of sterility achieved through a certain sterilisation process.8
The SAL indicates the expected probability of finding a viable microorganism on a medical device after subjecting such a device to an acceptable and properly validated sterilisation process in which all process specifications are strictly adhered to, and is usually expressed as an exponential function - 10-n.6 The use of SALs improves the understanding of the efficacy of a sterilisation process and its practical significance.
Field of application as a determinant of the required Sterility Assurance Level (SAL)
The Association for the Advancement of Medical Instrumentation (AAMI) in the USA in the early seventies recognised that different SALs can be specified for medical devices, depending on the locality of their application.9 In the ISO codes on sterilisation a similar distinction is made between two different medical device categories, depending on the intended field of application of such a device:
SAL 10-6: surgically implanted devices sterile fluid paths other products transgressing natural tissue barriers; implying that not more than one device in a million shall be non-sterile.
SAL 10-3: topical products mucosal devices non-fluid path surfaces of sterile devices; implying that not more than one device in a thousand shall be non-sterile.
With this approach, the contamination risk to the patient is the determining factor in selecting an SAL for a particular device. Those devices that are of an invasive nature will require a lower SAL than those that are non-invasive. Both categories will still be considered and classified as 'sterile' and appropriately labelled as such.
End-product sterility testing
The probabilistic approach to sterility and sterilisation has led to the concept and common practice of end-product sterility testing as proof of efficiency of a sterilisation process after completion. However, sterilisation is internationally recognised as an example of a process for which the efficacy cannot be verified by retrospective inspection and testing of the end product.6 This implies that sterility testing of the end product cannot be applied to verify a SAL of smaller than about 10-2, because the number of devices required as a representative sample for the sterility testing becomes both impractical and uneconomical.
To perform end product sterility testing to uniquely 'prove' an SAL of 10-6 will require the sterility testing of one million devices. To further complicate matters, it is accepted that the inherent limitations of sterility testing typically leads to 'false positives' at a level of about 10-3, which prevents end-product sterility testing to low SAL values.10-11
It clearly follows that end-product sterility testing of a few medical devices following sterilisation to 'demonstrate' or 'prove' that the entire batch is sterile, without a proper prior process validation, is without scientific foundation and can lead to erroneous conclusions with regard to the sterility of the batch as a whole.
However, it should be pointed out that the use of dosimeters (radiation) or biological indicators (steam and ethylene oxide) with a known accuracy and properly calibrated to monitor a properly validated sterilisation process, is completely acceptable and indeed essential, but they are employed to monitor the process parameters and not to prove the sterility of the resulting product.
The impact of sterilisation technique and packaging on the maintenance of sterility
Based on the basics of sterility and sterilisation, we return to our initial question on the shelf life of sterile medical devices - thus the maintenance of sterility prior to implantation. The sterilisation technique employed obviously plays a very important role on the nature and type of packaging that can be used.12,13
In the case of ethylene oxide gas sterilisation (EtO), the packaging material for both the primary and secondary packaging has to be selected to permit penetration by the sterilising gas to sterilise the devices, and its later removal at the end of the cycle. For this reason the polymer laminate packaging commonly used for radiation sterilisation cannot be used for gas sterilisation.
In the case of radiation sterilisation the device is hermetically sealed in double laminate pouches (polyethylene/polyester) - in general with a double seal and in the case of polymeric orthopaedic prostheses blanketed under ultra-pure nitrogen gas - the latter to protect the device or its polymeric components from radiation oxidative degradation during the radiation sterilisation cycle and subsequent storage. Radiation sterilisation has the advantage that the packaging integrity of these laminate pouches is particularly high and the author is not aware of any of such laminate pouches having failed during storage prior to use.
Radiation sterilisation has the advantage that the packaging integrity of these laminate pouches is particularly high
Sterility as a property of a medical device is recognised as event-related and not time-related
Provided a properly validated sterilisation process is used, and the integrity of the packaging is maintained, there is no reason to limit the shelf life of a sterile medical device - especially so in the case of radiation sterilisation. This clearly underlines the concept that sterility as a property of a medical device is recognised as event-related and not time-related. Should the packaging of a sterile medical device be compromised, it could lose its sterility directly after sterilisation. Similarly, if the packaging integrity is not compromised, the device will remain sterile.
The entire concept of the shelf life of medical devices is clearly still a topic that is hotly debated as follows from the international literature on the Internet, with the role of the packaging materials and the sterilisation techniques employed being the major points of discussion. Accelerated ageing of the packaging materials and seals that are generally used by manufacturers to set the shelf life are topics with their own inherent uncertainties.
No benefits of any form have been received from a commercial party related directly or indirectly to the subject of this article.
1. Medical Microbiology, Ed. R Cruickshank, p 680, E&S Livingstone Limited, London, 1968. [ Links ]
2. Borland's Illustrated Medical Dictionary, 24th Edition, p 1440, WB Saunders Company, London, 1965. [ Links ]
3. Sykes G. Disinfection and Sterilization, Second Edition, p 6, E and F N Spon Limited, London, 1967. [ Links ]
4. Whitby JL. Resistance of microorganisms to radiation and experience with dose setting, in Sterilization of Medical Products, Volume 5, p 346, Polyscience Publications Inc., Canada, 1991. [ Links ]
5. Medical Devices - Validation and routine control of ethylene oxide sterilization, Draft International Standard ISO/DIS 11135, p 2, International Organization for Standardization, 1992. [ Links ]
6. Sterilization of Health Care Products - Methods for validation and routine control - Gamma and electron beam radiation sterilization. ISO/TC 198 WG 2 N16, pp 1 and 5, International Organization for Standardization, 1991. [ Links ]
7. Tallentire A, Khann AA. The sub process in defining the degree of sterility assurance, in Sterilization by Ionizing Radiation, Volume 2, pp 65 66, Multiscience Publications Limited, Montreal, 1978. [ Links ]
8. Ibid, p 5.
9. Masefield J, et al. A North American Viewpoint on Selection of Radiation Sterilization Dose, in Sterilization by Ionizing Radiation, Volume 2, pp 322-325, Multiscience Publications Limited, Montreal, 1978. [ Links ]
10.Sterilization of Health Care Products - Methods for validation and routine control - Gamma and electron beam radiation sterilization. ISO/TC 198 WG 2 N16, p 99, International Organization for Standardization, 1991. [ Links ]
11.ISO 11137-1: Sterilization of health care products - Radiation - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices (2006). [ Links ]
12.ISO 11607-1: Packaging for terminally sterilized medical devices - Part 1: Requirements for materials, sterile barrier systems and packaging systems (2007). [ Links ]
13.ISO 11607-2: Packaging for terminally sterilized medical devices - Part 2: Validation requirements for forming, sealing and assembly processes (2007). [ Links ]
Dr TA du Plessis
PO Box 1271 Kokanje 0515