[Zum Stand der Viruzidie-Prüfung in Deutschland]
Jochen Steinmann 1Manfred H. Wolff 2
1 MikroLab GmbH, Bremen, Germany
2 Institute for Microbiology and Virology at the University Witten/Herdecke, Witten, Germany
Abstract
Several chemical disinfectants have been tested in a quantitative suspension test for virucidal activity as per the test method devised by the German Society for Control of Viral Diseases (DVV) and the former German Federal Health Office (BGA, now the Robert Koch-Institute, RKI) drafted in 1982. The introduction of the term “limited virucidal activity” (effective against enveloped viruses) in addition to the existing term “virucidal activity” (effective against non-enveloped and enveloped viruses) by the Robert Koch Institute has led to enormous expansion of these tests. However, there are no definitions to determine when a disinfectant with virucidal activity as apposed to a disinfectant with limited virucidal activity is to be used. The 1982 guideline was recently revised, while bringing it into line to reflect the latest insights. The BSA challenge has been omitted, while other controls such as verification of the sustained effect and interference control with which cell susceptibility is verified have been incorporated. A new requirement is that all tests be conducted in at least two independent batches, followed by biometric evaluation of the test results with calculation of the 95% confidence interval. The new guideline differs from DIN EN 14476, which in the meantime has been published in Europe, in that it does not feature the statistics now required. This guideline has introduced the parvovirus for chemothermal inactivation as well as the Bovine Viral Diarrhea Virus (BVDV) as test virus for the limited virucidal activity (in addition to vaccinia virus which serves as a surrogate virus for hepatitis C virus – HCV). A second important example is Feline Calicivirus (FCV), which serves as a surrogate for noroviruses. In the USA efficacy testing of surface disinfectants against noroviruses is conducted with FCV in a carrier test (practice-related test). The third surrogate virus is the Duck Hepatitis B Virus (DHBV), used as a surrogate for hepatitis B virus (HBV).
Today evaluation of the virus-inactivating properties is often conducted in parallel with bacteriological evaluation, so as to avoid any subsequent surprises in respect of viral efficacy. The DVV has failed over the past 24 years to formulate guidelines for practice-oriented tests. The future challenge is to define these as quickly as possible. Here similar approaches should be used for e.g. process challenge devices, challenge, exposure time as for bacteriological evaluation, so that the resultant application recommendations have equivalent status. The term “limited virucidal activity” should be expanded to disinfectant efficacy at European level.
Text
In addition to vaccinations, isolation and cohort formation, disinfection measures play a pivotal role in the hospital setting and in medical practice in the interruption of viral chains of infection. For that reason chemical disinfectants must be endowed with virus-inactivating properties, and this must be demonstrated in corresponding tests.
Several of the chemical disinfectants presently available on the German market have been tested in a quantitative suspension test for virucidial activity as per the test method devised by the German Society for Control of Viral Diseases (DVV) and the former German Federal Health Office (BGA, now the Robert Koch-Institut, RKI) drafted in 1982 [1], [2].The test viruses used are the Elstree vaccinia strain, poliovirus vaccination strain type I, LSc-2ab strain, adenovirus type 5 and polyomavirus (formerly, papovavirus) SV 40 strain 777. The introduction of the term “limited virucidal activity” (effective against enveloped viruses; test viruses: Elstree vaccinia strain and Bovine Viral Diarrhea Virus strain NADL) in addition to the existing term “virucidal activity” (effective against non-enveloped and enveloped viruses) by the Robert Koch Institute [3] has led to enormous expansion of these tests in the past year and a half. However, at present there are no definitions to determine when a disinfectant with virucidal activity as apposed to a disinfectant with limited virucidal activity is to be used.
The 1982 guideline was recently revised by the specialist committee “Viral Disinfection” at the DVV under the direction of Prof. Rabenau, while bringing it into line to reflect the latest insights [4]. The version of the newly named guideline (name changed for legal reasons) first published in December 2005 by the DVV and RKI dates back to 15 June 2005.
The most important differences relate to the omission of the BSA load as well as the incorporation of other controls such as verification of the sustained effect and interference control with which cell susceptibility is verified. A new requirement is that all tests be conducted in at least two independent batches, followed by biometric evaluation of the test results with calculation of the 95% confidence interval. The new guideline differs from DIN EN 14476, which in the meantime has been published in Europe and does not call for biometric evaluation, in particular in respect of the statistical calculations now specified [5]. This guideline has introduced parvovirus for chemothermal inactivation. For the first time this guideline also cites Bovine Viral Diarrhea Virus (BVDV) as test virus for the limited virucidal activity (in addition to vaccinia virus), which serves as a surrogate virus for hepatitis C virus (HCV). The approach taken here is to introduce a virus that is pathogenic to animals for testing products intended for use in human medicine since at present no corresponding human-pathogenic test viruses can be adequately grown in cell culture. In the USA, too, BVDV is also being used in the meantime in everyday tests by the Environmental Protection Agency (EPA) as a surrogate for HCV (http://www.epa.gov/oppad001/pdf_files/hepcbvdvpcol.pdf). A second important example is Feline Calicivirus (FCV), which serves as a surrogate for noroviruses. In the USA efficacy testing of surface disinfectants against noroviruses is conducted with FCV in a carrier test (practice-related test; http://www.epa.gov/oppad001/pdf_files/fcv2_confirm_surf_pcol.pdf). Even evaluation of swabs for efficacy against noroviruses is carried out on the basis of an EPA protocol (http://www.epa.gov/oppad001/pdf_files/fcv3_towel_ini_pcol.pdf). The third very important surrogate virus is the Duck Hepatitis B Virus (DHBV), used as a surrogate for hepatitis B virus (HBV). The committee “Viral Disinfection” at the DVV in Germany is planning to appoint DHBV as test virus, once a multicenter trial has been successfully completed at a later date. Here, too, the USA is ahead of us. There investigation results obtained with DHBV (http://www.epa.gov/oppad001/pdf_files/hbvprotocol.pdf) can already be extrapolated to HBV.
Often today, evaluation of virus-inactivating properties is already a component of development activities in parallel to bacteriological tasks following a situation whereby in the past many chemical disinfectants were optimized only for efficacy against bacteria and fungi, giving rise to later surprises in respect of viral efficacy when testing the products available on the market. However, over the past 24 years the DVV has failed to formulate guidelines for practice-oriented tests since in the last analysis quantitative suspension tests have merely an orientational character and the application recommendations must be tailored to the results of practical tests.
Here it should be borne in mind that in many respects, e.g. process challenge devices, challenge, exposure times, similar approaches are used as for bacteriological evaluation so that the resultant application recommendations have equivalent status.
Top priority for the time being must be accorded to the formulation of practice-oriented test guidelines, and attempts must be made to achieve this as soon as possible. This will give the user of chemical disinfectants a greater sense of security in his efforts to interrupt viral infection chains in the hospital and medical practice and to provide better protection to patients and staff. Surrogate viruses can play an important role in testing and be integrated into test guidelines. Once the corresponding indications have been defined, the term “limited virucidal activity” should be expanded to disinfectant efficacy at European level.
Curriculum Vitae
Dr. Jochen Steinmann
Figure 1 [Abb. 1]
Associate and technical-scientific head of MikroLab GmbH (Laboratory for Applied Microbiology) in Bremen.
Jochen Steinmann was reading Microbiology at the Christian-Albrecht University, Kiel (CAU), and started out after his dissertation as scientific assistant at the Institute for Hygiene (later: Department for Medicinal Microbiology) of the CAU in 1974. Main focus of his research at that time is improvements of the virological diagnostics.
After changing to head of the Clinical Virology at that Federal Institute for Hygiene Bremen in 1981 he was engaged in nosocomial virus infections, especially of rota- and enterovirus infections in pediatrics. The identification and prevention of virus infections in hospitals are henceforth his scientific main interest. A publication on hygienical hand disinfection has been rewarded with the Düsseldorf Hygiene Award in 1996. At the beginning of 2002 he left the civil service and founded the MikroLab GmH in Bremen. MicroLab GmbH understands itself as a service organisation for the chemical-pharmaceutical industry on all issues of applied virology.
Jochen Steinmann is a member of numerous scientific associations and German and international committees dealing with questions of virus inactivation.
Prof. Dr. rer. nat. habil. Manfred H. Wolff
Figure 2 [Abb. 2]
Director of the Chair for Microbiology and Virology, University Witten/Herdecke.
Manfred H. Wolff was reading biology at the Rheinische Friedrich-Wilhelm University Bonn, but wrote his dissertation at the Institute for Medical Microbiology and Immunology (Virus Department) of the University Bonn and gets his doctors degree for Dr. rer. nat. Here he staid as Scientific Assistant. In 1975 he moved to USA for one year (Department of Microbiology, Committee on Virology, University of Chicago) but moved back to Bonn, where he finally decided for Virology. In 1981 he habilitated at the Medicinal Faculty of the Bonn University and was appointed professor in 1982. He received the call to the Chair of Microbioloy and Virology of the University Witten/Herdecke in 1986.
His scientific focus is on the Varicella-Zoster-Virus, its pathogenesis and molecular-scientific tests for transcription-regulation. Besides that, he deals with problems of virus infections. He is a member of numerous scientific associations and boards.
Literatur
[1] Richtlinien des Bundesgesundheitsamtes und der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten e.V. zur Prüfung von chemischen Desinfektionsmitteln auf Wirksamkeit gegen Viren. Bundesgesundheitsblatt. 1982;25:397-8.[2] Kommentar zur Richtlinie des Bundesgesundheitsamtes und der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten e.V. zur Prüfung von chemischen Desinfektionsmitteln auf Wirksamkeit gegen Viren. Bundesgesundheitsblatt. 1983;26:413-4.
[3] Anonym. Prüfung und Deklaration der Wirksamkeit von Desinfektionsmitteln gegen Viren. Stellungnahme des Arbeitskreises Viruzidie beim Robert Koch-Institut (RKI) sowie des Fachausschusses Virusdesinfektion der Deutschen Gesellschaft zur Bekämpfung der Viruskrankheiten (DVV) und der Desinfektionsmittelkommission der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM). Bundesgesundheitsblatt. 2004;47(1):62-6.
[4] Anonym. Leitlinie der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e. V. und des Robert Koch-Instituts zur Prüfung von chemischen Desinfektionsmitteln auf Wirksamkeit gegen Viren in der Humanmedizin (Fassung vom 15. Juni 2005). Hyg Med. 2005;30:460-7.
[5] E DIN EN 14476. Chemische Desinfektionsmittel und Antiseptika - Quantitativer Suspensionsversuch Viruzidie für in der Humanmedizin verwendete Desinfektionsmittel und Antiseptika - Prüfverfahren und Anforderungen (Phase2/Stufe1). Berlin, Wien, Zürich: Beuth Verlag; 2005.
