1、November 2015 English price group 17No part of this translation may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).ICS 11.080.01!%GR:“2364723www.din.d
2、eDIN EN ISO 13408-7A s e p t i c p r o c e s s i n g o f h e a l t h c a r e p r o d u c t s P a r t 7 : A l t e r n a t i v e p r o c e s s e s f o r m e d i c a l d e v i c e s a n d c o m b i n a t i o n p r o d u c t s ( I S O 1 3 4 0 8 - 7 : 2 0 1 2 ) ;E n g l i s h v e r s i o n E N I S O 1 3
3、4 0 8 - 7 : 2 0 1 5 ,English translation of DIN EN ISO 13408-7:2015-11A s e p t i s c h e H e r s t e l l u n g v o n P r o d u k t e n f r d i e G e s u n d h e i t s f r s o r g e T e i l 7 : A l t e r n a t i v e V e r f a h r e n f r M e d i z i n p r o d u k t e u n d K o m b i n a t i o n s p
4、r o d u k t e ( I S O 1 3 4 0 8 - 7 : 2 0 1 2 ) ;E n g l i s c h e F a s s u n g E N I S O 1 3 4 0 8 - 7 : 2 0 1 5 ,Englische bersetzung von DIN EN ISO 13408-7:2015-11T r a i t e m e n t a s e p t i q u e d e s p r o d u i t s d e s a n t P a r t i e 7 : P r o c d s a l t e r n a t i f s p o u r l e
5、 s d i s p o s i t i f s m d i c a u x e t l e s p r o d u i t s d e c o m b i n a i s o n ( I S O 1 3 4 0 8 - 7 : 2 0 1 2 ) ;V e r s i o n a n g l a i s e E N I S O 1 3 4 0 8 - 7 : 2 0 1 5 ,Traduction anglaise de DIN EN ISO 13408-7:2015-11www.beuth.deDocument comprises 30 pagesDTranslation by DIN-S
6、prachendienst.In case of doubt, the German-language original shall be considered authoritative.11.15 DIN EN ISO 13408-7:2015-11 2 A comma is used as the decimal marker. National foreword This document (EN ISO 13408-7:2015) has been prepared by Technical Committee ISO/TC 198 “Sterilization of health
7、care products” (Secretariat: ANSI, USA) in collaboration with Technical Committee CEN/TC 204 “Sterilization of medical devices” (Secretariat: BSI, United Kingdom). The responsible German body involved in its preparation was DIN-Normenausschuss Medizin (DIN Standards Committee Medicine), Working Comm
8、ittee NA 063-01-12 AA Aseptische Herstellung. In the German version of this document, the word Verfahrenssimulation is used synonymously with Prozesssimulation. EN ISO 13408 consists of the following parts, under the general title Aseptic processing of health care products: Part 1: General requireme
9、nts Part 2: Filtration Part 3: Lyophilization Part 4: Clean-in-place technologies Part 5: Sterilization in place Part 6: Isolator systems Part 7: Alternative processes for medical devices and combination products The DIN Standards corresponding to the International Standards referred to in this docu
10、ment are as follows: ISO 11137-2 DIN EN ISO 11137-2 ISO 11737-2 DIN EN ISO 11737-2 ISO 13408-1 DIN EN ISO 13408-1 ISO 13485 DIN EN ISO 13485 ISO 14971:2007 DIN EN ISO 14971:2013-04 ISO 14644 (all parts) DIN EN ISO 14644 (all parts) ISO 14698 (all parts) DIN EN ISO 14698 (all parts) DIN EN ISO 13408-
11、7:2015-11 3 National Annex NA (informative) Bibliography DIN EN ISO 11137-2, Sterilization of health care products Radiation Part 2: Establishing the sterilization dose DIN EN ISO 11737-2, Sterilization of medical devices Microbiological methods Part 2: Tests of sterility performed in the definition
12、, validation and maintenance of a sterilization process DIN EN ISO 13408-1, Aseptic processing of health care products Part 1: General requirements DIN EN ISO 13485, Medical devices Quality management systems Requirements for regulatory purposes DIN EN ISO 14971, Medical devices Application of risk
13、management to medical devices DIN EN ISO 14644 (all parts), Cleanrooms and associated controlled environments DIN EN ISO 14698 (all parts), Cleanrooms and associated controlled environments Biocontamination control DIN EN ISO 13408-7:2015-11 4 This page is intentionally blank EUROPEAN STANDARD NORME
14、 EUROPENNE EUROPISCHE NORM EN ISO 13408-7 August 2015 ICS 11.080.01 English Version Aseptic processing of health care products - Part 7: Alternative processes for medical devices and combination products (ISO 13408-7:2012) Traitement aseptique des produits de sant - Partie 7: Procds alternatifs pour
15、 les dispositifs mdicaux et les produits de combinaison (ISO 13408-7:2012) Aseptische Herstellung von Produkten fr die Gesundheitsfrsorge - Teil 7: Alternative Verfahren fr Medizinprodukte und Kombinationsprodukte(ISO 13408-7:2012) This European Standard was approved by CEN on 30 July 2015. CEN memb
16、ers 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 national standards may be obtained on applicati
17、on 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 language and notified to the CEN-CENELEC Managem
18、ent 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, Hungary, Iceland, Ireland, Italy, Latvia,
19、Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and United Kingdom. EUROPEAN COMMITTEE FOR STANDARDIZATION COMIT EUROPEN DE NORMALISATION EUROPISCHES KOMITEE FR NORMUNG CEN-CENELEC Management Centre: Avenue Marnix 1
20、7, 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 ISO 13408-7:2015 EContents PageEuropean foreword 3Introduction 41 Scope 52 Normative references . 53 Terms and definitions . 54 Quality system elements . 65 As
21、eptic process definition 65.1 General . 65.2 Risk management 66 Manufacturing environment . 77 Equipment . 78 Personnel . 79 Manufacture of the product 710 Process simulation . 710.1 General . 710.2 Media selection and growth support 710.3 Simulation procedures . 710.4 Incubation and inspection of p
22、rocess simulation units . 1010.5 Initial performance qualification . 1010.6 Periodic performance requalification 1010.7 Repeat of initial performance qualification 1110.8 Documentation of process simulations 1110.9 Disposition of filled product . 1111 Test for sterility 1111.1 General . 1111.2 Inves
23、tigation of positive units from tests for sterility . 11Annex A (informative) Risk assessment for aseptic processing Quality risk management method 12Annex B (informative) Selection of a sample for testing for microbial contamination 19Annex C (informative) Testing options for process simulation .20
24、Bibliography .26Annex ZA Relationship between this European Standard and the Essential Requirements of EU Directive 90/385/EEC on active implantable medical devices 23 Annex ZB Relationship between this European Standard and the Essential Requirements of EU Directive 93/42/EEC on medical devices 24
25、Annex ZC Relationship between this European Standard and the Essential Requirements of EU Directive 98/79/EC on in vitro diagnostic medical devices 25 DIN EN ISO 13408-7:2015-11 EN ISO 13408-7:2015 (E) 2.(informative)(informative)(informative)European foreword The text of ISO 13408-7:2012 has been p
26、repared by Technical Committee ISO/TC 198 “Sterilization of health care products” of the International Organization for Standardization (ISO) and has been taken over as EN ISO 13408-7:2015 by Technical Committee CEN/TC 204 “Sterilization of medical devices” the secretariat of which is held by BSI. T
27、his 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 February 2016, and conflicting national standards shall be withdrawn at the latest by February 2016. Attention is drawn to the possibility that some
28、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 document has been prepared under a mandate given to CEN by the European Commission and the European Free Trade Association, and s
29、upports essential requirements of EU Directives. For relationship with EU Directives, see informative Annexes ZA, ZB and ZC, which are integral parts of this document. The following referenced documents are indispensable for the application of this document. For undated references, the edition of th
30、e referenced document (including any amendments) listed below applies. For dated references, only the edition cited applies. However, for any use of this standard within the meaning of Annex ZA, ZB or ZC, the user should always check that any referenced document has not been superseded and that its
31、relevant contents can still be considered the generally acknowledged state-of-art. When an IEC or ISO standard is referred to in the ISO standard text, this should be understood as a normative reference to the corresponding EN standard, if available, and otherwise to the dated version of the ISO or
32、IEC standard as listed below. NOTE The way in which these referenced documents are cited in normative requirements determines the extent (in whole or in part) to which they apply. Table Correlation between normative references and dated EN and ISO standards Normative references as listed in Clause 2
33、 of the ISO standard Equivalent dated standard EN ISO ISO 13408-1:2008 EN ISO 13408-1:2015 ISO 13408-1:2008 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, Cr
34、oatia, Cyprus, Czech Republic, Denmark, Estonia, Finland, Former Yugoslav Republic of Macedonia, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey and
35、 the United Kingdom. Endorsement notice The text of ISO 13408-7:2012 has been approved by CEN as EN ISO 13408-7:2015 without any modification. DIN EN ISO 13408-7:2015-11 EN ISO 13408-7:2015 (E) 3 IntroductionISO 13408 is the International Standard, published in a series of parts, for aseptic process
36、ing of health care products. Historically, sterile health care products that are aseptically produced have typically been liquids, powders or suspensions that cannot be terminally sterilized. More recently, medical devices and health care products have been developed that are combined with medicinal
37、 products, including biological and viable cells, that cannot be terminally sterilized.The application of ISO 13408-1 to these medical devices and combination products can require the development of alternative approaches to process simulation. This part of ISO 13408 specifies requirements and provi
38、des guidance for developing such alternative approaches for the qualification of aseptic processes through process simulation of medical devices and combination products that meet the requirements of ISO 13408-1.ISO 13408-1:2008, 10.1.2 permits the use of alternative process simulation approaches, b
39、ased on particular medical devices or combination products, where the substitution in full with sterile liquid media might not be possible.Medical devices and combination products that typically require aseptic processing might include, for example, the following.a) Medical devices that cannot be te
40、rminally sterilized and where the process simulation approach according to ISO 13408-1 cannot be applied: bioprostheses (e.g. heart valves, vascular implants); biodegradable implants (e.g. hernia meshes); artificial and/or non-viable biologically based matrixes; extracorporeal processing devices (e.
41、g. immuno-adsorbers); implantable osmotic pumps; hermetically sealed electromechanical devices and partially enclosed electronic devices (e.g. invasive and non-invasive diagnostic devices).b) Combination products (including viable cell-based combination products): implants coated with drug and/or bi
42、ologically derived substances (e.g. drug-coated stents, carrier materials with protein, bone-graft material with growth factors, biodegradable drug-coated stents); wound dressings (e.g. dressings with haemostatic agents, tissue sealants, or biologics); transdermal or injectable delivery systems (e.g
43、. drug-coated or biologics interstitial patches); kits containing a biological or drug component (e.g. demineralized bone matrices).For such products, a risk management strategy and method(s) can be used for the identification, evaluation and quantification (estimation) of contamination risks throug
44、hout the entire product/process life cycle. Environmental monitoring and microbiological studies can be performed on individual steps of the process to evaluate the effectiveness of contamination controls and risk mitigations. The design of the process simulation can then be driven by the results of
45、 the risk analysis. If the results of the process simulation are acceptable, this provides evidence that the aseptic process is in a state of contamination control (i.e. no extrinsic microbiological/microbial contamination has been introduced during the aseptic process).This part of ISO 13408 should
46、 be read in conjunction with ISO 13408-1. Within this International Standard, text that supplements ISO 13408-1 by providing additional requirements or guidance is identified by the prefix “Addition”.DIN EN ISO 13408-7:2015-11 EN ISO 13408-7:2015 (E) 4 1 ScopeThis part of ISO 13408 specifies require
47、ments and provides guidance on alternative approaches to process simulations for the qualification of the aseptic processing of medical devices and combination products that cannot be terminally sterilized and where the process simulation approach according to ISO 13408-1 cannot be applied.This part
48、 of ISO 13408 describes how risk assessment can be used during the development of an aseptic process to design a process simulation study for medical devices and combination products in those cases where a straightforward substitution of media for product during aseptic processing is not feasible or would not simulate the actual aseptic process.2 Normative referencesThe following referenced documents are indispensable for the application of this document. For dated references, only the edition cited appl
