1、BRITISH STANDARDBS EN ISO 22442-3:2007Medical devices utilizing animal tissues and their derivatives Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agentsICS 11.100.20g49g50g3g38g50g51g60g44g49g42g3g58g44g55g43g50g56g55g3g37g54g
2、44g3g51g40g53g48g44g54g54g44g50g49g3g40g59g38g40g51g55g3g36g54g3g51g40g53g48g44g55g55g40g39g3g37g60g3g38g50g51g60g53g44g42g43g55g3g47g36g58BS EN ISO 22442-3:2007This British Standard was published under the authority of the Standards Policy and Strategy Committee on 29 February 2008 BSI 2008ISBN 978
3、 0 580 54189 6National forewordThis British Standard is the UK implementation of EN ISO 22442-3:2007. It supersedes BS EN 12442-3:2000 which is withdrawn. The UK participation in its preparation was entrusted by Technical Committee CH/194, Biological evaluation of medical devices, to Subcommittee CH
4、/194/1, Medical devices utilizing tissues.A list of organizations represented on this committee can be obtained on request to its secretary.This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application.Compliance with a Bri
5、tish Standard cannot confer immunity from legal obligations.Amendments/corrigenda issued since publicationDate CommentsEUROPEAN STANDARDNORME EUROPENNEEUROPISCHE NORMEN ISO 22442-3December 2007ICS 11.100.20 Supersedes EN 12442-3:2000 English VersionMedical devices utilizing animal tissues and their
6、derivatives -Part 3: Validation of the elimination and/or inactivation of virusesand transmissible spongiform encephalopathy (TSE) agents(ISO 22442-3:2007)Dispositifs mdicaux utilisant des tissus animaux et leursdrivs - Partie 3: Validation de llimination et/ou delinactivation des virus et autres ag
7、ents responsablesdencphalopathie spongiforme transmissible (EST) (ISO22442-3:2007)Tierische Gewebe und deren Derivate, die zur Herstellungvon Medizinprodukten eingesetzt werden - Teil 3:Validierung der Eliminierung und/oder Inaktivierung vonViren und Erregern der bertragbaren spongisenEnzephalopathi
8、e (TSE) (ISO 22442-3:2007)This European Standard was approved by CEN on 14 December 2007.CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this EuropeanStandard the status of a national standard without any alteration. Up-to-date list
9、s and bibliographical references concerning such nationalstandards may be obtained on application to the CEN Management Centre or to any CEN member.This European Standard exists in three official versions (English, French, German). A version in any other language made by translationunder the respons
10、ibility of a CEN member into its own language and notified to the CEN Management Centre has the same status as theofficial versions.CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland,France, Germany, Greece, Hungary, Iceland
11、, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal,Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMIT EUROPEN DE NORMALISATIONEUROPISCHES KOMITEE FR NORMUNGManagement Centre: rue de Stassar
12、t, 36 B-1050 Brussels 2007 CEN All rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN ISO 22442-3:2007: EForeword This document (EN ISO 22442-3:2007) has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices“
13、 in collaboration with Technical Committee CEN/TC 316 “Medical devices utilizing tissues” the secretariat of which is held by NBN. This European Standard shall be given the status of a national standard, either by publication of an identical text or by endorsement, at the latest by June 2008, and co
14、nflicting national standards shall be withdrawn at the latest by June 2008. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. CEN and/or CENELEC shall not be held responsible for identifying any or all such patent rights. This docum
15、ent supersedes EN 12442-3:2000. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and supports essential requirements of EC Directive(s). This European Standard has been developed for medical devices regulated by the Medi
16、cal Device Directive 93/42/EC as amended by 2003/32/EC (see Annex ZA). By analogy, it could be applied for active implantable medical devices regulated by the Active Implantable Medical Device Directive 90/385/EC. For relationship with EC Directive(s), see informative Annex ZA, which is an integral
17、part of this document. According to the CEN/CENELEC Internal Regulations, the national standards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ic
18、eland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland and the United Kingdom. Endorsement notice The text of ISO 22442-3:2007 has been approved by CEN as a EN ISO 22442-3:2007 without any modificati
19、on. BS EN ISO 22442-3:2007Reference numberISO 22442-3:2007(E)INTERNATIONAL STANDARD ISO22442-3First edition2007-12-15Medical devices utilizing animal tissues and their derivatives Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) a
20、gentsDispositifs mdicaux utilisant des tissus animaux et leurs drivs Partie 3: Validation de llimination et/ou de linactivation des virus et autres agents responsables dencphalopathie spongiforme transmissible (EST) BS EN ISO 22442-3:2007ii iiiContents Page Introduction v 1 Scope . 1 2 Normative ref
21、erences . 1 3 Terms and definitions. 2 4 General requirements. 3 4.1 Risk management . 3 4.2 Sourcing and manufacturing process 3 4.3 General requirements related to validation . 3 5 Literature review . 4 5.1 Conduct of the literature review 4 5.2 Application of literature review output. 4 5.3 Virus
22、es . 4 5.4 TSE agents 4 6 Elimination and/or inactivation study of viruses and TSE agents 5 6.1 General. 5 6.2 Protocol . 5 6.3 Conduct of the study 6 6.4 Interpretation of data 6 7 Final report 6 8 Review of final report . 6 9 Routine monitoring and control of critical process parameters . 6 Annex
23、A (normative) Requirements related to literature review. 7 Annex B (informative) Guidance on the elimination and/or inactivation study for viruses . 11 Annex C (informative) Guidance on the elimination and/or inactivation study for TSE agents 16 Annex D (informative) Guidance on scaling down . 17 An
24、nex E (informative) Statistical evaluation of virus titres and reduction factors and assessment of their validity . 18 Annex F (informative) Calculation of reduction factors . 19 Annex G (informative) Probability of detection of agents at low concentrations 20 Bibliography . 21 BS EN ISO 22442-3:200
25、7Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of Directive 93/42/EEC as amended by Commission Directive 2003/32/EC .23 iv Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO
26、 member bodies). The work of preparing International Standards is normally carried out through ISO technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented on that committee. International organizations, gover
27、nmental and non-governmental, in liaison with ISO, also take part in the work. ISO collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. International Standards are drafted in accordance with the rules given in the ISO/IEC D
28、irectives, Part 2. The main task of technical committees is to prepare International Standards. Draft International Standards adopted by the technical committees are circulated to the member bodies for voting. Publication as an International Standard requires approval by at least 75 % of the member
29、bodies casting a vote. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. ISO shall not be held responsible for identifying any or all such patent rights. ISO 22442-3 was prepared by Technical Committee ISO/TC 194, Biological evaluat
30、ion of medical devices, Subcommittee SC 1, Tissue product safety. ISO 22442 consists of the following parts, under the general title Medical devices utilizing animal tissues and their derivatives: Part 1: Application of risk management Part 2: Controls on sourcing, collection and handling Part 3: Va
31、lidation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents BS EN ISO 22442-3:2007vIntroduction Certain medical devices utilize materials of animal origin. Animal tissues and their derivatives are used in the design and manufacture of medical d
32、evices to provide performance characteristics that were chosen for advantages over non-animal based materials. The range and quantities of materials of animal origin in medical devices vary. These materials can comprise a major part of the device (e.g. bovine/porcine heart valves, bone substitutes f
33、or use in dental or orthopaedic applications, haemostatic devices), can be a product coating or impregnation (e.g. collagen, gelatine, heparin), or can be used in the device manufacturing process (e.g. tallow derivatives such as oleates and stearates, foetal calf serum, enzymes, culture media). It i
34、s important to be aware that the exposure to a properly validated and accurately controlled method of viral and TSE inactivation/elimination is not the only factor associated with demonstrating product safety. Attention has also to be given to a number of factors including sourcing, collecting, hand
35、ling, storage, processing, testing of tissues and/or cells of animal origin, and to the control of the environment in which the product is manufactured, assembled and packaged. The manufacturer should consider the fact that each manufacturing phase can contribute to contamination as well as eliminat
36、ion and/or inactivation of viruses and TSE agents. For the safety of medical devices there are two complementary approaches (see ISO 22442-1) that can be adopted to control the potential contamination of tissues. These typically are: a) selecting source material for minimal contamination with viruse
37、s and/or TSE agents (see ISO 22442-1 and ISO 22442-2); b) providing valid scientific evidence to demonstrate the ability of the production processes to eliminate or inactivate viruses and/or TSE agents (this part of ISO 22442). Requirements for a quality system for medical devices for regulatory use
38、 are specified in ISO 13485. The standards for quality management systems recognize that, for certain processes used in manufacturing, the effectiveness of that process cannot be fully verified by subsequent inspection and testing of the product. The elimination and/or inactivation of viruses and TS
39、E agents is an example of a special process because process efficacy cannot be verified by inspection and testing of the product. For this reason, the following need to be considered in particular: definition of the process(es) and materials to be used; adequate inactivation validation before routin
40、e use; performance monitoring of the process during manufacture; appropriate equipment maintenance; staff training, etc. Historically there have been many instances of unknown or unsuspected viral contamination during manufacture. For this reason, evaluation of the manufacturing process can provide
41、a measure of confidence that a wide number of viruses, including unknown pathogenic viruses are eliminated. Similar principles may apply to TSE agents. NOTE To show compliance with this part of ISO 22442, its specified requirements should be fulfilled. The guidance given in the Notes and informative
42、 annexes is not normative and is not provided as a checklist for auditors. BS EN ISO 22442-3:2007blank1Medical devices utilizing animal tissues and their derivatives Part 3: Validation of the elimination and/or inactivation of viruses and transmissible spongiform encephalopathy (TSE) agents 1 Scope
43、This part of ISO 22442 specifies requirements for the validation of the elimination and/or inactivation of viruses and TSE agents during the manufacture of medical devices (excluding in vitro diagnostic medical devices) utilizing animal tissue or products derived from animal tissue, which are non-vi
44、able or have been rendered non-viable. It applies where required by the risk management process as described in ISO 22442-1. It does not cover other transmissible and non-transmissible agents. NOTE 1 Analysis and management of risk is described in ISO 22442-1. Conventional processes used for sterili
45、zation, when used for the treatment of animal tissues for medical devices, have not been shown to be completely effective in inactivating the causative agents of transmissible spongiform encephalopathy. Selective sourcing is extremely important (see ISO 22442-1 and ISO 22442-2). NOTE 2 ISO 11135, IS
46、O 11137, ISO 11737-1, ISO 13408, ISO 14160, ISO 14937 and ISO 17665 may be relevant for bacteria, moulds and yeast (see Bibliography). This part of ISO 22442 does not cover the utilization of human tissues in medical devices. This part of ISO 22442 does not specify a quality management system for th
47、e control of all stages of production of medical devices. NOTE 3 It is not a requirement of this part of ISO 22442 to have a full quality management system during manufacture, but it does specify requirements for some of the elements of a quality management system. Attention is drawn to the standard
48、s for quality management systems (see ISO 13485) that control all stages of production or reprocessing of medical devices. The quality management system elements that are required by this part of ISO 22442 can form part of a quality management system conforming to ISO 13485. This part of ISO 22442 d
49、oes not consider the effect of any method of elimination and/or inactivation on the suitability of the medical device for its intended use. 2 Normative references The following referenced documents are indispensable for the application of this document. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. ISO 22442-1:2007, Medical devices utilizing animal tissues and their derivatives Part 1: Application of risk management ISO 22442
