Position statement on methods to evaluate decontamination technologies for surgical instruments
1. The Engineering and Science Advisory Committee into the decontamination of surgical instruments including prion removal, requested SEAC’s advice (SEAC 93)a on scientific principles to consider in developing strategies to evaluate and validate new technologies for the decontamination of surgical instruments, particularly the most appropriate prions and experimental systems to use.
2. Residual biological material, including protein, can remain adherent to the surface of surgical instruments following current recommended cleaning, disinfection and sterilisation procedures 1. Prions adsorbed onto stainless steel surfaces are unusually resistant to normal decontamination practices 2,3 and, although achieving very significant reductions in prion load, conventional procedures do not completely remove or inactivate prions on surgical instruments 4. Therefore, infectious material may be transferred from an infected patient to other patients via surgical instruments. A small number of cases of sporadic Creutzfeldt-Jakob disease (sCJD) transmission via contaminated surgical instruments have been reported 5.
3. To date, no cases of variant Creutzfeldt-Jakob disease (vCJD) transmission via surgical instruments have been reported. However, the risks of vCJD transmission may be significant for surgical procedures involving the central nervous system (CNS), posterior eye and lymphoid tissue 6. Effective instrument decontamination is critical to reducing these risks.
4. A number of new decontamination technologies are claimed to remove, degrade and/or deactivate prions adsorbed onto surgical instruments. These claims are based on extrapolation of results from laboratory studies using experimental systems to model the clinical situation, commonly bioassays to detect the infectivity remaining on contaminated stainless steel following the application of a decontamination treatment 7. However, a standardised system to evaluate and compare the effectiveness of decontamination technologies has not yet been defined.
a. SEAC paper and minutes available here.
Key criteria for an evaluation system
5. Key criteria for evaluation of decontamination technologies include (i) quantitation, over a wide dynamic range, of the reduction in contamination due to application of a specific technology, (ii) standardisation of experimental approaches to allow direct comparisons of different technologies and (iii) reliable prediction of the effectiveness of the technology when applied to removal of human prion infectivity from surgical instruments.
6. Comparison of infectivity before and after the application of the decontamination technology against a titration curve generated from known dilutions of the infective agent allows reductions in contamination to be quantified. To ensure accurate and precise quantitation, the material used to generate the titration curve should be identical to, and prepared in the same way as the contaminated test material, for example contaminated stainless steel, to which the decontamination technology is applied. The reduction in infectivity required to reduce transmission risks to acceptably low levels is uncertain and depends on the level of contamination of instruments and the infectivity of the contaminating tissue. On the basis that at least a five log reduction in infectivity would be necessary to appreciably improve existing decontamination practice 6, any evaluation system will need to quantify reductions in contamination over at least this, or preferably a larger, dynamic range.
7. Infectivity bioassays in animal models provide the most relevant and robust system to quantify the effectiveness of a decontamination treatment. Biochemical assays may not provide an accurate measure of the removal, degradation or deactivation of prions as, in some circumstances, abnormal prion protein (PrPSc) concentrations correlate poorly with the titre of infectivity 8. Furthermore, should a decontamination treatment alter prion phenotype, infectivity bioassays could detect such alterations whereas biochemical assays may not. Due to the relative resistance of prions and PrPSc to chemical and enzymatic degradation, measurement of protein concentrations provide an unreliable indicator of the effect of a decontamination treatment on prions or PrPSc.
8. Accurate comparison of the effectiveness of decontamination technologies can only be made when the same experimental system is applied to different decontamination technologies. Therefore the evaluation system, including the analytical test(s), the contaminant as well as the method of preparation of the test material and the material used to generate the titration curve, should be standardised.
9. Evaluation should assess the effectiveness of the decontamination technology when applied to a system that models the clinical situation as closely as possible. As adsorption of prions onto a metal surface may increase their resistance to chemical or enzymatic treatments 2,9-11 and may enhance their infectious properties 12, assessments should examine the effectiveness of technologies in removing and/or deactivating infectivity adhering to stainless steel rather than infectivity in liquid suspension. There are differences in the physico-chemical and infectious properties of prion strains 13-15 that may give rise to differences in their resistance to decontamination 14,16,17. Assessments should include vCJD, or closely related, prion strains to mimic most closely the clinical situation and bioassays that provide the most sensitive detection system for infectivity. The risks of vCJD transmission appear significant for procedures involving CNS, posterior eye and lymphoid tissue. Therefore valuation including prion strains with tissue distribution that includes the lymphoreticular system, as well as CNS, would provide some assurance about the likely efficacy of technologies when applied to instruments that come into contact with peripheral tissues.
10. As no single animal model is a perfect mimic of the human situation or may closely mimic the human situation and allow quantitation of sufficiently large reductions in infectivity, it may be advisable to use more than one animal model in any comparative evaluation.
11. In addition to evaluation of the effectiveness of new decontamination technologies, it is important to establish that these technologies do not compromise the removal of other infectious agents or add residues that would affect patient safety. Consideration of these aspects is outside the remit of SEAC.