1、June 2014 Translation by DIN-Sprachendienst.English price group 22No 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 1
2、1.100.20!%2c;“2156424www.din.deDDIN ISO 13022Medical products containing viable human cells Application of risk management and requirements for processingpractices (ISO 13022:2012),English translation of DIN ISO 13022:2014-06Medizinische Produkte, die lebende Zellen menschlichen Ursprungs beinhalten
3、 Anwendung des Risikomanagements und Anforderungen an die Praxis der Handhabung(ISO 13022:2012),Englische bersetzung von DIN ISO 13022:2014-06Produits mdicaux contenant des cellules viables dorigine humaine Application du management du risque et exigences relatives aux pratiques de prparation(ISO 13
4、022:2012),Traduction anglaise de DIN ISO 13022:2014-06www.beuth.deDocument comprises pagesIn case of doubt, the German-language original shall be considered authoritative.5406.14 A comma is used as the decimal marker. Contents Page National foreword .3 National Annex NA (informative) Correction of F
5、igure B.1 .4 National Annex N (informative) Bibliography 5 Introduction .6 1 Scope 7 2 Normative references 8 3 Terms and definitions .8 4 Risk management process .12 4.1 General 12 4.2 Hazards associated with the cellular component 12 4.3 Risk analysis 14 4.4 Risk evaluation .15 4.5 Risk control 15
6、 4.6 Evaluation of overall residual risk acceptability 15 4.7 Production and post-production information system .16 Annex A (informative) Guidance on the application of ISO 13022 17 Annex B (informative) Graphic representation of the part of the risk management process for cell-based medical product
7、s 18 Annex C (normative) Requirements for donor selection and testing .19 Annex D (informative) Guidance for tissue procurement 23 Annex E (normative) Requirements for handling of cells and tissue during manufacture 26 Annex F (normative) Requirements for packaging and labelling .29 Annex G (informa
8、tive) Guidance for transport 32 Annex H (informative) Guidance for storage .37 Annex I (normative) Requirements for traceability .40 Annex J (normative) Risk reduction measures related to contamination with viruses and other infectious agents such as TSE .41 Annex K (informative) Guidance with regar
9、d to hazards caused by the tumorigenic potential of the human cells/tissues used for the production of medical products .44 Annex L (informative) Guidance with regard to microbiological contamination .45 Annex M (informative) Guidance with regard to potential adverse effects of non-cellular residues
10、 of the product .46 Annex N (normative) Requirements with regard to potential adverse effects of the cellular components of a medical product .47 Annex O (informative) Guidance for the characterization of the cellular components of a medical product .48 Annex P (informative) Clinical evaluation and
11、testing .51 Bibliography 52 DIN ISO 13022:2014-06 2 BNational foreword This document (ISO 13022:2012) has been prepared by Technical Committee ISO/TC 194 “Biological evaluation of medical devices”, Subcommittee SC 1 “Tissue product safety” (Secretariat: DIN, Germany) and has been adopted at national
12、 level as DIN ISO 13022:2014-06. The responsible German body involved in its preparation was the Normenausschuss Feinmechanik und Optik (Optics and Precision Mechanics Standards Committee), Working Committee NA 027-02-21 AA Medizinische Produkte auf Basis des Tissue Engineering. Figure B.1 in Annex
13、B showing the risk management process has been corrected in the National Annex to this standard (some arrows in the original flow chart are missing). This figure will be corrected in the next revision of ISO 13022. The DIN Standards corresponding to the International Standards referred to in this do
14、cument are as follows: ISO 7010 DIN EN ISO 7010 ISO 10993 (all parts) DIN EN ISO 10993 (all parts) ISO 13408 (all parts) DIN EN ISO 13408 (all parts) ISO 13485 DIN EN ISO 13485 ISO 14155 DIN EN ISO 14155 ISO 14971 DIN EN ISO 14971 ISO 22442-1 DIN EN ISO 22442-1 ISO 22442-2 DIN EN ISO 22442-2 ISO 224
15、42-3 DIN EN ISO 22442-3 DIN ISO 13022:2014-06 3 National Annex NA (informative) Correction of Figure B.1 During the process of translating ISO 13022 into German an error in Figure B.1 “Graphical representation of part of the risk management” was discovered: Some arrows are missing (there should be a
16、rrows connecting the squares listing the various Annexes with the rhombus containing the text “Risk / benefit acceptable?”). This error can lead to a misunderstanding of the risk management process. A decision was made to correct this figure in DIN ISO 13022. This figure will be corrected in the nex
17、t revision of ISO 13022. The corrected figure is shown below. Figure 1 Graphic representation of the part of the risk management process for cell-based medical products Corrected version DIN ISO 13022:2014-06 4 National Annex N (informative) Bibliography DIN EN ISO 7010, Graphical symbols Safety col
18、ours and safety signs Registered safety signs DIN EN ISO 10993 (all parts), Biological evaluation of medical devices DIN EN ISO 13408 (all parts), Aseptic processing of health care products DIN EN ISO 13485, Medical devices Quality management systems Requirements for regulatory purposes DIN EN ISO 1
19、4155, Clinical investigation of medical devices for human subjects Good clinical practice DIN EN ISO 14971, Medical devices Application of risk management to medical devices DIN EN ISO 22442-1, Medical devices utilizing animal tissues and their derivatives Part 1: Application of risk management DIN
20、EN ISO 22442-2, Medical devices utilizing animal tissues and their derivatives Part 2: Controls on sourcing, collection and handling DIN EN ISO 22442-3, Medical devices utilizing animal tissues and their derivatives Part 3: Validation of the elimination and/or inactivation of viruses and transmissib
21、le spongiform encephalopathy (TSE) agents DIN ISO 13022:2014-06 5 BIntroductionCertain medical products utilize materials of human origin. Depending on national regulatory requirements, these products are addressed as medicinal substances, medical devices or biologics. Materials of human origin are
22、used in the design and manufacture of medical products to provide performance characteristics that might be chosen for their advantages over non-human-based materials, particularly to improve regeneration of the patients own tissues or organs, or to replace or to supplement organ function.Medical pr
23、oducts utilizing human materials comprise a heterogeneous group. Examples include cell suspensions, cell/matrix constructs or cells combined with complex medical devices such as dialysis equipment.While the medical products utilizing human material are quite diverse, the hazards specifically related
24、 to all human materials are basically the same:a) the material can be contaminated with infectious agents e.g. bacteria, moulds, yeasts, viruses, Transmissible Spongiform Encephalopathy (TSE) infectious agents, parasites;b) the material can be contaminated with chemicals;c) the material can be unsui
25、table for the intended purpose due to unintended decomposition or degradation induced by inappropriate handling at any stage of the production process;d) the material can be hazardous for the patient due to tumorigenic potential;e) following application, unintended physiological and anatomical conse
26、quences can be hazardous, taking into account cell migration and release of biologically active substances;f) a failure of traceability;g) the material can cause harm for the patient by eliciting an immunogenic reaction.To address the hazards related to contamination, degradation, unintended modific
27、ation and/or mix-up of viable human cells and products, this International Standard was developed for the application of risk management on the manufacture of medical products utilizing viable human material.The hazards mentioned above have been related to the relevant manufacturing steps. The essen
28、tial aspects to be covered by this International Standard are as follows: terminology and definitions; donor selection and testing, addressing both living and deceased donors; human material procurement; human material handling (including production); human material packaging, storage and transport;
29、 human material labelling; risk related to handling of the product during application; consideration of risks and benefits in relation to intended use.This International Standard will assist manufacturers of products based on viable human materials that produce medicinal substances, medical devices
30、or biologics.Medical products containing viable human cells Application of risk management and requirements for processing practicesDIN ISO 13022:2014-06 6 1 ScopeThis International Standard specifies requirements and guidance for processing practices and managing risk associated with viable cellula
31、r components of products regulated as medicinal products, biologics, medical devices and active implantable medical devices, or combinations thereof. It covers viable human materials of autologous as well as allogeneic human origin, obtained from living or deceased donors.For manufacturers of medica
32、l products containing viable cells of human origin, this International Standard specifies procedures to be used in processing and handling, as well as those to be used in identifying the hazards and hazardous situations associated with such cells, in order to estimate and evaluate the resulting risk
33、s, to control these risks, and to monitor the effectiveness of that control. Furthermore, this International Standard outlines the decision process for the residual risk acceptability, taking into account the balance of residual risk and expected medical benefit as compared to available alternatives
34、.This International Standard provides requirements and guidance on risk management related to the hazards typical of medical products manufactured utilizing viable human materials, such as:a) contamination by bacteria, moulds, yeasts or parasites;b) contamination by viruses;c) contamination by agent
35、s causing Transmissible Spongiform Encephalopathies (TSE);d) contaminating material responsible for undesired pyrogenic, immunological or toxicological reactions;e) decomposition of the product and degradation products caused by inadequate handling;f) hazards related to the tumorigenic potential of
36、the cell types used;g) complications resulting from unintended physiological and anatomical consequences (this includes unintended migration of cells, unwanted release of biologically active substances such as hormones and cytokines, and unintended interactions between cellular and non-cellular comp
37、onents of the product);h) failure of traceability;i) complications resulting from the material eliciting an unintended immunogenic reaction.For the evaluation of contamination with other unclassified pathogenic entities, similar principles might be applicable.Hazards related to genetic modification
38、are outside the scope of this International Standard and are addressed elsewhere.NOTE 1 A definition of “genetically modified” can be found in ASTM F2312.NOTE 2 This International Standard does not specify a quality management system for the control of all stages of production of medical products as
39、 described above.If additional national or regional criteria beyond what is defined in this International Standard exist in the country where the medical product will be used, they are also applicable.NOTE 3 Regional requirements can be more stringent than requirements referenced in this Internation
40、al Standard, especially with regard to donor eligibility criteria.This International Standard is not applicable to: non-viable materials of human origin;DIN ISO 13022:2014-06 7 viable cells of non-human origin; blood and its components used for transfusion, germ cells, organs and bone marrow used fo
41、r transplantation, and other tissues that do not meet the definition of “medical product”; in vitro diagnostic devices.NOTE 4 For guidance on the application of this International Standard, see Annex A.2 Normative referencesThe following documents, in whole or in part, are normatively referenced in
42、this document 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.ISO 13485, Medical devices Quality management systems Requirements for regulatory pu
43、rposesISO 14971, Medical devices Application of risk management to medical devicesISO 22442-1, Medical devices utilizing animal tissues and their derivatives Application of risk managementASTM F2312, Standard Terminology Relating to Tissue Engineered Medical ProductsBSI PAS 84, Regenerative Medicine
44、 Glossary, June 20083 Terms and definitionsFor the purposes of this document, the terms and definitions given in ISO 13485, ISO 14971, ISO 22442-1, ASTM F2312, BSI PAS 84 and the following apply.3.1medical deviceinstrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calib
45、rator, 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 purposes of:a) diagnosis, prevention, monitoring, treatment or alleviation of disease;b) diagnosis, monitoring, treatment,
46、 alleviation of or compensation for an injury;c) investigation, replacement, modification, or support of the anatomy or of a physiological process;d) supporting or sustaining life;e) control of conception;f) disinfection of medical devices;g) providing information for medical purposes by means of in
47、 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 intended function by such meansNOTE 1 This definition has been developed b
48、y the Global Harmonization Task Force (GHTF).NOTE 2 Products which could be considered to be medical devices in some jurisdictions but for which there is not yet a harmonized approach are:a) aids for disabled/handicapped people;b) devices for the treatment/diagnosis of diseases and injuries in anima
49、ls;DIN ISO 13022:2014-06 8 c) accessories for medical devices (see NOTE 3);d) disinfection substances;e) devices incorporating animal and human tissues which can meet the requirements of the above definition but are subject to different controls.NOTE 3 Accessories intended specifically by manufacturers to be used together with a “parent” medical device to enable that medical device to achieve its intended purpose, should be subject to this Inte
