1、Technical Information ReportMedical devices utilizing animal tissues and their derivativesPart 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and validation assays for those processesANSI/AAMI/ ISO TIR 22442-4: 2011 /(R)2016An ANSI Technical
2、 Report Prepared by AAMI ANSI/AAMI/ISO TIR22442-4:2011/(R)2016 Medical devices utilizing animal tissues and their derivativesPart 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and validation assays for those processes Approved 10 August 201
3、1 by Association for the Advancement of Medical Instrumentation Registered 6 March 2011 and reaffirmed 11 December 2016 by American National Standards Institute, Inc. Abstract: Adresses methods of elimination and inactivation of transmissible spongiform encephalopathies (TSE agents) from animal tiss
4、ues to be used in medical devices. The methods addressed will include those designed for: 1 inactivating infectivity (preferred method to reduce opportunities for cross-contamination); and 2 physically removing TSE agents (without complete inactivation). Includes inactivation and elimination methods
5、 to be used in the product manufacturing process and in facilities and equipment designed for utilizing animal tissue products. Keywords: TSE, elimination, inactivation, tissue, bovine, animalPublished by AAMI4301 N. Fairfax Dr., Suite 301 Arlington, VA 22203-1633 www.aami.org 2011 by the Associatio
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9、25-4890; Fax: +1-703-525-1067. Printed in the United States of America ISBN 978-1-57020-669-6AAMI Technical Information Report A technical information report (TIR) is a publication of the Association for the Advancement of Medical Instrumentation (AAMI) Standards Board that addresses a particular as
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18、nts on this technical information report are invited and should be sent to AAMI, Attn: Standards Department, 4301 N. Fairfax Drive, Suite 301, Arlington, VA 22203-1633. ANSI Technical Report This AAMI TIR has been registered by the American National Standards Institute as an ANSI Technical Report. P
19、ublication of this ANSI Technical Report has been approved by the accredited standards developer (AAMI). This document is registered as a Technical Report series of publications according to the Procedures for the Registration of Technical Reports with ANSI. This document is not an American National
20、 Standard and the material contained herein is not normative in nature. Comments on the content of this document should be sent to AAMI, Attn: Standards Department, 4301 N. Fairfax Drive, Suite 301, Arlington, VA 22203-1633. Contents PageGlossary of equivalent standards . v Committee representation
21、vii Background of US adoption of ISO/TR 22442-4:2010 ix Foreword x Introduction xi 1 Scope. 1 2 Normative references 1 3 Terms and definitions 2 4 Elimination of TSE agents: basic considerations 2 4.1 General 2 4.1.1 TSEs of concern . 2 4.1.2 Animal tissues of concern 2 4.1.3 Tissues infected with T
22、SE agents 3 5 Potential methods to eliminate TSE agents 3 5.1 Methods for inactivating infectivity 3 5.1.1 General 3 5.1.2 Physical methods for inactivating TSE infectivity 3 5.1.3 Chemical methods for inactivating TSE infectivity 4 5.2 Methods for removing TSE infectivity without inactivating infec
23、tivity 6 6 Experimental validation of methods for eliminating TSE agents from medical devices utilizing non-viable animal tissues . 6 6.1 General 6 6.2 Defining of product families for purposes of designing TSE process validation studies . 6 6.3 Selection and testing of product for establishing and
24、verifying the infecting dose of TSE agent 7 6.4 TSE agent spiking materials . 7 6.5 Availability of bioassay animals (conventional and transgenic mice, other rodents, farm animals) 7 6.6 Potential development of cell culture assays for infectivity . 8 6.7 Correlations between PrPTSEand infectivity a
25、ssays 8 6.8 Reductions in infectivity compared with failure to detect at limits of detection . 9 6.9 Determining numbers of replicate validations needed to support inferences of reduction in infectivity rather than variations in assay performance 9 6.10 Requirements for step-wise reductions in PrPTS
26、E and infectivity verses whole-process validation 9 Bibliography 10 2011 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO TIR22442-4:2011 v Glossary of equivalent standards International Standards adopted in the United States may include normative references to other Internat
27、ional Standards. For each International Standard that has been adopted by AAMI (and ANSI), the table below gives the corresponding U.S. designation and level of equivalency to the International Standard. NOTE: Documents are sorted by international designation. The code in the US column, “(R)20xx” in
28、dicates the year the document was officially reaffirmed by AAMI. E.g., ANSI/AAMI/ISO 10993-4:2002/(R)2009 indicates that 10993-4, originally approved and published in 2002, was reaffirmed without change in 2009. Other normatively referenced International Standards may be under consideration for U.S.
29、 adoption by AAMI; therefore, this list should not be considered exhaustive. International designation U.S. designation EquivalencyIEC 60601-1:2005 Technical Corrigendum 1 and 2 ANSI/AAMI ES60601-1:2005 and ANSI/AAMI ES60601-1:2005/A2:2010 ANSI/AAMI ES60601-1:2005/C1:2009 (amdt) Major technical vari
30、ations C1 Identical to Corrigendum 1 recently, sub-clinical infection with the vCJD agent was detected at autopsy in a patient with hemophilia and plausibly attributed to his treatment with processed human plasma-derived coagulation factor (UK Health Protection Agency 2009 at: http:/www.hpa.org.uk/w
31、ebw/HPAweb Peden, Head et al 2004; Peden, Ritchie and Ironside 2005). Exposure to the agent of bovine spongiform encephalopathy (BSE) has been responsible for more than 210 cases of vCJD worldwide, most of them thought to have resulted from dietary exposure to infected beef products. Although, excep
32、t for the iatrogenic vCJD infections just described, no transmissions of a BSE-derived agent via medical or veterinary products have been recognized, there is no reason to doubt that a medical device contaminated with BSE agent of ruminant origin could transmit infection to a susceptible subject. In
33、deed, two veterinary vaccines derived from non-viable ovine tissues transmitted the ovine/caprine TSE scrapie to sheep (World Health Organization 2006). Humans are not known to have been infected with the scrapie agent. This Technical Report generally uses terminology suggested by the World Health O
34、rganization (WHO Guidelines on Tissue Infectivity Distribution in Transmissible Spongiform Encephalopathies, 2006 (World Health Organization 2006), while recognizing that there is no international consensus regarding either preferred terminology, the probable molecular nature of the transmissible ag
35、ents (the all-protein or “prion” theory (Prusiner 1982) currently most widely held) or the precise role of various forms of the host-coded prion protein in the replication of the infectious agents or pathogenesis of disease. The sole intent of the xii 2011 Association for the Advancement of Medical
36、Instrumentation ANSI/AAMI/ISO TIR22442-4:2011 TR is to suggest strategies to validate the effectiveness of methods that might reduce the risk of accidentally transmitting TSEs by medical devices prepared using non-viable animal tissues. The following referenced documents are standards helpful for th
37、e proper interpretation of this document: ISO 22442-1, Medical devices utilizing animal tissues and their derivatives Part 1: Application of risk management ISO 22442-2, Medical devices utilizing animal tissues and their derivatives Part 2: Controls on sourcing, collection and handling ISO 22442-3,
38、Medical devices utilizing animal tissues and their derivatives Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents ISO 14160, Sterilization of health care products Liquid chemical sterilizing agents for single-use medical devi
39、ces utilizing animal tissues and their derivatives Requirements for characterization, development, validation and routine control of a sterilization process for medical devices These documents include both normative and informative annexes also directly relevant to the topic of this ISO TR. All term
40、s defined in those documents are used verbatim in this report. Due to the lack of consistent process steps that can reliably eliminate TSEs, it is important that one must use low-risk source animals and tissues. Although not directly applicable to validating methods purported to reduce the TSE risk
41、from medical devices manufactured from non-viable animal tissues, UK and US competent authorities have solicited expert advice on desirable features of validation studies for devices intended to remove TSE infectivity from human blood potentially contaminated with TSE agents, and this advice may be
42、helpful in evaluating methods for animal-derived tissues as well. These features included preliminary evaluation using TSE-spiked material with high titers of infectivity, selecting experimental agents relevant to the infection of concern, and accepting studies using assays for PrPTSEas a preliminar
43、y screening strategy to dismiss unpromising methods. These methods were required to indicate significant reduction in infectivity demonstrated by bioassays in known susceptible experimental animals. To qualify a method as potentially useful, the assay needed to demonstrate similar results for the sa
44、me candidate method with two TSE agent-bioassay combinations, whenever possible. These criteria should be met before concluding that the method offers sufficient promise to consider in practice. Demonstration that a method reduces TSE infectivity for tissues endogenously infected, and that the compl
45、ete manufacturing process eliminates all detectable infectivity, while desirable, are not currently feasible. Very low titers of infectivity in most tissues outside the nervous system and limited animals known to be susceptible to naturally occurring TSE agents without adaptation to a new species ar
46、e limiting factors. The lack of standard reference infected materials of known titer and biological properties from humans and animals with TSEs is thought to be an additional impediment to developing validation studies (World Health Organization (2006), Annex 2). Considering the extremely limited a
47、ttempted validation efforts for methods for improving TSE safety of human blood-derived and other human tissue-derived medical products products with demonstrated iatrogenic transmissions care must be taken not to discourage new efforts to validate methods that might improve the TSE safety of medica
48、l devices derived from animal tissues. It should be noted again that, as summarized above, animal tissues have not been directly implicated in causing any iatrogenic TSE infections of humans (Minor, Newham et al. 2004). However, experience with food-borne BSE and field transmissions of scrapie to sh
49、eep by ovine tissue-derived veterinary vaccines suggests that the risk of iatrogenic transmissions of TSEs (other than BSE) from animals to humans, while theoretical, remains worthy of continued attention. 2011 Association for the Advancement of Medical Instrumentation ANSI/AAMI/ISO TIR22442-4:2011 1 AAMI Technical Information Report ANSI/AAMI/ISO TIR22442-4:2011/(R)2016 Medical devices utilizing animal tissues and their derivativesPart 4: Principles for elimination and/or inactivation of transmissible spongiform encephalopathy (TSE) agents and
