1、BSI Standards PublicationBS EN 556-2:2015Sterilization of medical devices Requirements for medicaldevices to be designatedSTERILE“Part 2: Requirements for asepticallyprocessed medical devicesBS EN 556-2:2015 BRITISH STANDARDNational forewordThis British Standard is the UK implementation of EN 556-2:
2、2015. Itsupersedes BS EN 556-2:2003 which is withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/198, Sterilization and Associated Equipment andProcesses.A list of organizations represented on this committee can beobtained on request to its secretary.This publica
3、tion does not purport to include all the necessaryprovisions of a contract. Users are responsible for its correctapplication. The British Standards Institution 2015. Published by BSI StandardsLimited 2015ISBN 978 0 580 80961 3ICS 11.080.01Compliance with a British Standard cannot confer immunity fro
4、mlegal obligations.This British Standard was published under the authority of theStandards Policy and Strategy Committee on 30 September 2015.Amendments issued since publicationDate Text affectedBS EN 556-2:2015EUROPEAN STANDARD NORME EUROPENNE EUROPISCHE NORM EN 556-2 September 2015 ICS 11.080.01 S
5、upersedes EN 556-2:2003English Version Sterilization of medical devices - Requirements for medical devices to be designated STERILE“ - Part 2: Requirements for aseptically processed medical devices Strilisation des dispositifs mdicaux - Exigences relatives aux dispositifs mdicaux en vue dobtenir lti
6、quetage “ STRILE “ - Partie 2 : Exigences pour les dispositifs mdicaux soumis un traitement aseptiqueSterilisation von Medizinprodukten - Anforderungen an Medizinprodukte, die als STERIL gekennzeichnet werden - Teil 2: Anforderungen an aseptisch hergestellte Medizinprodukte This European Standard wa
7、s approved by CEN on 24 July 2015. CEN members are bound to comply with the CEN/CENELEC Internal Regulations which stipulate the conditions for giving this European Standard the status of a national standard without any alteration. Up-to-date lists and bibliographical references concerning such nati
8、onal standards may be obtained on application to the CEN-CENELEC 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 translation under the responsibility of a CEN member into its own langu
9、age and notified to the CEN-CENELEC Management Centre has the same status as the official versions. CEN members are the national standards bodies of Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece,
10、 Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey andUnited Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG CEN-
11、CENELEC Management Centre: Avenue Marnix 17, B-1000 Brussels 2015 CEN All rights of exploitation in any form and by any means reserved worldwide for CEN national Members. Ref. No. EN 556-2:2015 EBS EN 556-2:2015EN 556-2:2015 (E) 2 Contents Page European foreword 3 Introduction 4 1 Scope . 5 2 Normat
12、ive references . 5 3 Terms and definitions . 6 4 Requirements 8 4.1 Validation and routine control 8 4.2 Compliance 10 4.3 Documentation and records 10 Annex ZA (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on active implantable m
13、edical devices 11 Annex ZB (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on medical devices. 12 Annex ZC (informative) Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EC on in vitro
14、diagnostic medical devices 13 Bibliography 15 BS EN 556-2:2015EN 556-2:2015 (E) 3 European foreword This document (EN 556-2:2015) has been prepared by Technical Committee CEN/TC 204 “Sterilization of medical devices”, the secretariat of which is held by BSI. This European Standard shall be given the
15、 status of a national standard, either by publication of an identical text or by endorsement, at the latest by March 2016, and conflicting national standards shall be withdrawn at the latest by March 2016. Attention is drawn to the possibility that some of the elements of this document may be the su
16、bject of patent rights. CEN and/or CENELEC shall not be held responsible for identifying any or all such patent rights. This document supersedes EN 556-2:2003. This document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and support
17、s essential requirements of EU Directive(s). For relationship with EU Directive(s), see informative Annexes ZA, ZB and ZC, which are integral parts of this document. EN 556, Sterilization of medical devices Requirements for medical devices to be designated STERILE“, is currently composed with the fo
18、llowing parts: Part 1: Requirements for terminally sterilized medical devices; Part 2: Requirements for aseptically processed medical devices this document. The following amendments have been made in updating the document from EN 556-2:2003: a) normative references have been updated; b) terms and de
19、finitions have been aligned with ISO/TS 11139 and EN ISO 13408-1; c) requirements on validation and routine control have been revised; d) Table 1 and Table 2 on acceptance limits and actions for occurrence of non-sterile units in process simulations in initial performance qualification and in period
20、ic requalification, respectively, have been added; e) editorial revision according to the CEN Internal Regulations. Annexes designated informative are given only for information. In this standard Annexes ZA, ZB and ZC are informative. According to the CEN-CENELEC Internal Regulations, the national s
21、tandards organizations of the following countries are bound to implement this European Standard: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania
22、, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and the United Kingdom. BS EN 556-2:2015EN 556-2:2015 (E) 4 Introduction Medical devices designated STERILE are prepared using appropriate and validated methods. Whenever possi
23、ble, sterile medical devices are terminally-sterilized using a properly validated and controlled sterilization process (see EN 556-1, EN ISO 11135, EN ISO 11137-1, EN ISO 14160, EN ISO 14937, EN ISO 17665-1, EN ISO 20857 and EN ISO 25424). When a medical device is intended to be sterile but cannot b
24、e terminally-sterilized, aseptic processing is the method of manufacture (see EN ISO 13408-1). Aseptic processing necessitates that either: a) the entire product is sterilized and then introduced into a sterilized package; or b) components of the product are sterilized, then further processed/assemb
25、led, and the final product packed into a sterilized package. Processing/assembly and packaging are carried out in a manner that minimizes the opportunity for items to become re-contaminated by carrying out these operations in a controlled environment in which microbial and particulate levels are mai
26、ntained at or below defined limits and human intervention is minimized. NOTE EN ISO 15223-1 specifies the label applied to aseptically processed medical devices as STERILE A. BS EN 556-2:2015EN 556-2:2015 (E) 5 1 Scope This European Standard specifies the requirements for an aseptically processed me
27、dical device to be designated STERILE. NOTE For the purpose of the EU Directive(s) for medical devices (see Bibliography), designating that a medical device is STERILE is permissible when a validated manufacturing and sterilization process has been applied. Requirements for validation and routine co
28、ntrol of aseptic processes are specified in EN ISO 13408-1. Specific requirements for the aseptic processing of solid medical devices and combination products are specified in ISO 13408-7. 2 Normative references The following documents, in whole or in part, are normatively referenced in this documen
29、t and are indispensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies. EN ISO 11135:2014, Sterilization of health-care products Ethylene oxide Requirements for the de
30、velopment, validation and routine control of a sterilization process for medical devices (ISO 11135:2014) EN ISO 11137-1:2015, Sterilization of health care products Radiation Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices (ISO 1113
31、7-1:2006, including Amd 1:2013) EN ISO 13408-2:2011, Aseptic processing of health care products Part 2: Filtration (ISO 13408-2:2003) EN ISO 13408-5:2011, Aseptic processing of health care products Part 5: Sterilization in place (ISO 13408-5:2006) EN ISO 13485:2012, Medical devices Quality managemen
32、t systems Requirements for regulatory purposes (ISO 13485:2003) EN ISO 14160:2011, Sterilization of health care products Liquid chemical sterilizing agents for single-use medical devices utilizing animal tissues and their derivatives Requirements for characterization, development, validation and rou
33、tine control of a sterilization process for medical devices (ISO 14160:2011) EN ISO 14937:2009, Sterilization of health care products General requirements for characterization of a sterilizing agent and the development, validation and routine control of a sterilization process for medical devices (I
34、SO 14937:2009) EN ISO 17665-1:2006, Sterilization of health care products Moist heat Part 1: Requirements for the development, validation and routine control of a sterilization process for medical devices (ISO 17665-1:2006) EN ISO 20857:2013, Sterilization of health care products Dry heat Requiremen
35、ts for the development, validation and routine control of a sterilization process for medical devices (ISO 20857:2010) EN ISO 25424:2011, Sterilization of medical devices Low temperature steam and formaldehyde Requirements for development, validation and routine control of a sterilization process fo
36、r medical devices (ISO 25424:2009) BS EN 556-2:2015EN 556-2:2015 (E) 6 3 Terms and definitions For the purposes of this document, the following terms and definitions apply. 3.1 aseptic processing handling of sterile product, containers and/or devices in a controlled environment, in which the air sup
37、ply, materials, equipment and personnel are regulated to maintain sterility SOURCE: EN ISO 13408-1:2015, 3.4 3.2 bioburden population of viable microorganisms on or in product and/or sterile barrier system SOURCE: ISO/TS 11139:2006, 2.2 3.3 medical device instrument, apparatus, implement, machine, a
38、ppliance, implant, in vitro reagent or calibrator, software, material or other similar or related article, intended by the manufacturer to be used, alone or in combination, for human beings for one or more of the specific purpose(s) of: diagnosis, prevention, monitoring, treatment or alleviation of
39、disease, diagnosis, monitoring, treatment, alleviation of or compensation for an injury, investigation, replacement, modification or support of the anatomy or of a physiological process, supporting or sustaining life, control of conception, disinfection of medical devices, providing information for
40、medical purposes by means of in vitro examination of specimens derived from the human body and which does not achieve its primary intended action in or on the human body by pharmacological, immunological or metabolic means, but which may be assisted in its function by such means SOURCE: EN ISO 13485
41、:2012, 3.7 3.4 performance qualification PQ process of obtaining and documenting evidence that the equipment, as installed and operated in accordance with operational procedures, consistently performs in accordance with predetermined criteria and thereby yields product meeting its specification SOUR
42、CE: ISO/TS 11139:2006, 2.30 BS EN 556-2:2015EN 556-2:2015 (E) 7 3.5 process simulation exercise that simulates the manufacturing process or portions of the process in order to demonstrate the capability of the aseptic process to prevent biological contamination SOURCE: ISO 13408-7:2012, 3.2 Note 1 t
43、o entry: Other terms for process simulation include media fill, simulated process fill, simulated filling operation, broth trial, broth fill. 3.6 requalification repetition of part of validation for the purpose of confirming the continued acceptability of a specified process SOURCE: ISO/TS 11139:200
44、6, 2.40 3.7 sterility state of being free from viable micro-organisms SOURCE: ISO/TS 11139:2006, 2.45 3.8 sterile free from viable microorganisms SOURCE: ISO/TS 11139:2006, 2.43 3.9 terminally-sterilized condition of a medical device which has been exposed to a sterilization process in a packaged or
45、 assembled form that maintains the sterility of the medical device or a defined portion thereof SOURCE: EN 556-1:2001, 3.5 3.10 test for sterility technical operation defined in an official Pharmacopoeia performed on product following exposure to a sterilization process SOURCE: ISO/TS 11139:2006, 2.
46、53 Note 1 to entry: For the purpose of this document, the official Pharmacopoeia that applies is the European Pharmacopoeia. 3.11 validation documented procedure for obtaining, recording and interpreting the results required to establish that a process will consistently yield product complying with
47、predetermined specifications SOURCE: ISO/TS 11139:2006, 2.55 BS EN 556-2:2015EN 556-2:2015 (E) 8 4 Requirements 4.1 Validation and routine control For an aseptically processed medical device, the following shall apply: a) the manufacturing environment in which the aseptic process is conducted is spe
48、cified and records demonstrating compliance with the specification throughout the conduct of the process are prepared and maintained; b) the processes employed to sterilize product, components, equipment and packaging are validated and routinely controlled in compliance with EN ISO 11135:2014, EN IS
49、O 11137-1:2015, EN ISO 14160:2011, EN ISO 13408-2:2011, EN ISO 13408-5:2011, EN ISO 14937:2009, EN ISO 17665-1:2006, EN ISO 20857:2013, or EN ISO 25424:2011 as applicable; NOTE 1 Usually such sterilization processes are validated and routinely controlled to achieve a probability of a viable microorganism surviving on a sterilized item of 106or less. c) the requirements for the competence of personnel and methods for their training are specified and records demonstrating that t
