SIST EN 13824:2005
(Main)Sterilization of medical devices - Aseptic processing of liquid medical devices - Requirements
Sterilization of medical devices - Aseptic processing of liquid medical devices - Requirements
This document specifies requirements for the design and operation of aseptic processing facilities and the validation and routine control of aseptic processes for the preparation of sterile liquid medical devices. It is not applicable to those pharmaceutical products where the requirements of the relevant good manufacturing practices are applicable.
NOTE Many of the principles included in this document can be applied to certain aseptically processed sterile solid medical devices.
Sterilisation von Medizinprodukten - Aseptische Herstellung flüssiger Medizinprodukte - Anforderungen
Dieses Dokument legt Anforderungen an die Gestaltung und den Betrieb aseptischer Verarbeitungs-
einrichtungen und an die Validierung und Routinekontrolle der aseptischen Herstellungsverfahren für sterile
flüssige Medizinprodukte fest. Es gilt nicht für pharmazeutische Produkte, für die Anforderungen an die
einschlägige Gute Herstellungspraxis anzuwenden sind.
ANMERKUNG Viele der in diesem Dokument enthaltenen Prinzipien können auf bestimmte unter aseptischen
Bedingungen hergestellte Medizinprodukte im festen Zustand angewendet werden.
Stérilisation des dispositifs médicaux - Traitement aseptique des dispositifs médicaux liquides - Exigences
Le présent document spécifie les exigences relatives a la conception et au fonctionnement des installations de traitement aseptique et a la validation et au contrôle de routine des procédés aseptiques en vue de la préparation de dispositifs médicaux liquides stériles. Elle ne s'applique pas aux produits pharmaceutiques pour lesquels les exigences relatives aux bonnes pratiques de fabrication appropriées s'appliquent.
NOTE De nombreux principes spécifiés dans cette Norme peuvent etre appliqués a certains dispositifs médicaux solides traités dans des conditions d'asepsie.
Sterilizacija medicinskih pripomočkov – Aseptična proizvodnja tekočih medicinskih pripomočkov - Zahteve
General Information
Relations
Standards Content (Sample)
2003-01.Slovenski inštitut za standardizacijo. Razmnoževanje celote ali delov tega standarda ni dovoljeno.Sterilization of medical devices - Aseptic processing of liquid medical devices - RequirementsRþLKStérilisation des dispositifs médicaux - Traitement aseptique des dispositifs médicaux liquides - ExigencesSterilisation von Medizinprodukten - Aseptische Herstellung flüssiger Medizinprodukte - AnforderungenTa slovenski standard je istoveten z:EN 13824:2004SIST EN 13824:2005en11.080.01Sterilizacija in dezinfekcija na splošnoSterilization and disinfection in generalICS:SLOVENSKI
STANDARDSIST EN 13824:200501-marec-2005
EUROPEAN STANDARDNORME EUROPÉENNEEUROPÄISCHE NORMEN 13824November 2004ICS 11.080.01English versionSterilization of medical devices - Aseptic processing of liquidmedical devices - RequirementsStérilisation des dispositifs médicaux - Traitementaseptique des dispositifs médicaux liquides - ExigencesSterilisation von Medizinprodukten - Aseptische Herstellungflüssiger Medizinprodukte - AnforderungenThis European Standard was approved by CEN on 14 October 2004.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 lists and bibliographical references concerning such nationalstandards may be obtained on application to the Central Secretariat 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 responsibility of a CEN member into its own language and notified to the Central Secretariat has the same status as the officialversions.CEN members are the national standards bodies of Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France,Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia,Slovenia, Spain, Sweden, Switzerland and United Kingdom.EUROPEAN COMMITTEE FOR STANDARDIZATIONCOMITÉ EUROPÉEN DE NORMALISATIONEUROPÄISCHES KOMITEE FÜR NORMUNGManagement Centre: rue de Stassart, 36
B-1050 Brussels© 2004 CENAll rights of exploitation in any form and by any means reservedworldwide for CEN national Members.Ref. No. EN 13824:2004: E
EN 13824:2004 (E) 2 Contents page Foreword.5 Introduction.6 1 Scope.7 2 Normative references.7 3 Terms and definitions.8 4 Quality management systems.11 5 Personnel.12 5.1 Personnel management.12 5.2 Training for APA qualification.12 5.3 General employee health.13 5.4 Monitoring of personnel.13 5.5 Gowning.14 5.5.1 Gowning training.14 5.5.2 Gowning requirements.14 5.5.3 Control of gowned personnel.14 6 Premises.14 7 Process-related media.15 7.1 Water.15 7.1.1 Potable water.15 7.1.2 Treated potable water.15 7.1.3 Purified water.15 7.1.4 Water for Injections (WFI).16 7.2 Other media.16 7.2.1 Vacuum systems.16 7.2.2 Gases.16 7.2.3 Clean steam.17 8 Qualification of equipment and utilities, and process validation.17 8.1 General.17 8.2 Requalification and revalidation.18 9 Processes.18 9.1 Cleaning and disinfection of the APA.18 9.1.1 Disinfectants and cleaning agents.18 9.1.2 Validation of disinfection procedures.18 9.1.3 Monitoring of cleaning and disinfection effectiveness.19 9.2 Bioburden.19 9.3 Endotoxins.19 9.4 Sterilization, assembly and use of filling equipment and utensils.19 9.5 Clean in place (CIP).20 9.6 Steam in Place (SIP).20 9.7 Feeding sterilized container components and product to the filling line.21 9.8 Sterile filtration.21 9.8.1 Pore size rating.21 9.8.2 Liquid filtration.21 9.8.3 Gas filtration.23
EN 13824:2004 (E) 3 9.9 Aseptically-produced suspensions.23 9.10 Filling process: interventions, rejects.23 9.11 Freeze drying.23 9.12 Sealing and final packaging.23 10 Environmental monitoring and controls.24 10.1 Particulate monitoring programme.24 10.2 Microbiological monitoring programme.24 10.2.1 General.24 10.2.2 Alert and action levels.24 10.2.3 Review of data.25 10.3 Environmental monitoring trend analysis.25 10.4 Investigations and reports.25 10.4.1 Investigation action plans.25 10.4.2 Investigation testing.25 10.4.3 Investigation report.25 11 Media fills (process simulation tests).26 12 Finished product sterility testing.26 12.1 General.26 12.2 Investigation of sterility test positives.26 12.3 Sampling plans.26 13 Product release.26 Annex A (normative)
Conventional cleanrooms.28 A.1 Facility design features.28 A.2 Facility design review.29 A.3 Material flow.29 A.4 Aseptic processing area (APA).29 A.5 Critical processing zones.29 A.6 Other processing zones within the APA.30 A.7 Support areas outside the APA.30 A.8 Environmental air systems and controls.30 A.8.1 Temperature and humidity.31 A.8.2 Air.31 A.8.3 HEPA filter integrity.31 A.8.4 Air handling.32 A.9 Facility design.32 A.10 Preparation areas.32 Annex B (normative)
Isolator technology.33 B.1 Types of isolator.33 B.1.1 General.33 B.1.2 Transfer devices used with isolators.33 B.2 Transfer devices.33 B.2.1 General.33 B.2.2 Classification system for transfer devices.33 B.3 Surrounding area.34 B.3.1 General.34 B.3.2 Siting of Isolators.34 B.4 Gloves, gauntlets, half suits and full suits.35 B.4.1 General.35 B.4.2 Use of gloves/gauntlets.35 B.4.3 Changing gloves/gauntlets.36 B.4.4 Use of half suits, full suits.36 B.5 Pressure differentials.36 B.6 Cleaning of isolators.36 B.7 Filtration of air in isolators.36 B.8 Pressure differential.36 B.9 Air change rate.36
EN 13824:2004 (E) 4 B.10 Biodecontamination of isolator internal surfaces by microbicidal gas.37 B.10.1 Gas contact.37 B.10.2 Biodecontaminant residuals.37 B.10.3 Isolator biodecontamination: Validation.37 B.11 Qualification.38 B.12 Monitoring.39 B.12.1 Particulate monitoring.39 B.12.2 Microbiological monitoring.39 B.12.3 HEPA filters.39 B.13 Alarms.40 B.14 Maintenance and requalification (see also Clause 10).40 B.15 Product release.40 Annex C (informative)
Aseptically-prepared suspensions.41 C.1 General.41 C.2 Media fill considerations.41 Annex D (normative)
Freeze-drying.42 D.1 General.42 D.2 Validation.42 D.3 Gases used during the freeze-drying process.42 D.4 Process routing.43 D.5 Open containers and stoppers.43 D.6 Transport to freeze-dryer.43 D.7 Unloading and transport to sealing equipment.43 D.8 Cleaning and disinfection of freeze dryer.44 D.9 Biodecontamination of the freeze dryer.44 D.9.1 Frequency.44 D.9.2 Methods.44 D.10 Vent filter system.44 D.11 Environmental monitoring and controls.44 D.12 Media fills for freeze-drying.45 D.13 Maintenance.45 Annex E (normative)
Media fills (process simulation tests).46 E.1 Performance qualification.46 E.2 Performance requalification.47 E.3 Repeat of performance qualification.47 E.4 Media fill procedures.48 E.5 Media selection and growth support.48 E.6 Incubation and inspection of media filled units.48 E.7 Acceptance criteria.49 E.7.1 General.49 E.7.2 Acceptance criteria tables.49 E.8 Contamination with media.53 E.9 Data required for media fills.53 E.10 Media fill runs for which action levels are exceeded.54 E.10.1 Investigation.54 E.10.2 Further actions.55 Annex F (informative)
Contamination rate calculations for a given number of media filled units.56 Annex ZA (informative)
Clauses of this European Standard addressing essential requirements or other provisions of Council Directive 90/385/EEC relating to active implantable medical devices.59 Annex ZB (informative)
Clauses of this European Standard addressing essential requirements or other provisions of Council Directive 93/42/EEC relating to medical devices.60 Bibliography.61
EN 13824:2004 (E) 5 Foreword This document (EN 13824:2004) 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 status of a national standard, either by publication of an identical text or by endorsement, at the latest by May 2005, and conflicting national standards shall be withdrawn at the latest by May 2005. 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 EU Directive(s). For relationship with EU Directive(s), see informative Annexes ZA and ZB, which are integral parts 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, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Switzerland and United Kingdom.
EN 13824:2004 (E) 6 Introduction Medical devices that are labelled ‘sterile’ have to be prepared using appropriate and validated methods. CEN TC 204 has prepared standards relating to terminal sterilization of medical devices by irradiation (EN 552), by moist heat (EN 554), by liquid chemical sterilants (EN ISO 14160) and by ethylene oxide (EN 550). When a medical device is intended to be sterile and cannot be terminally sterilized, aseptic processing provides an alternative method. Aseptic processing requires the application of validated sterilization processes to all equipment components that come into contact with the aseptically processed material prior to the use of that equipment. This is also necessary for container components. The sterilized equipment and container components are then assembled in a manner that maintains their sterility. The product is processed in a controlled environment where microbial and particulate levels are maintained at defined levels and where human intervention is minimized. Sterilization practice is an exacting and demanding discipline. Manufacturers require validated systems, adequately trained personnel, controlled environments and well-documented systematic processes to ensure a sterile product. The application of this to aseptic processing is discussed below. While terminal sterilization involves the use of a process of known lethality, the assurance of sterility associated with aseptic processing can only be inferred, as facilities, equipment and people are all factors associated with the process and its control. Issues that need particular attention for aseptic processing include: a) personnel; b) layout and specifications for buildings, equipment and facilities; c) particulate and microbial environmental monitoring programmes; d) the satisfactory function of validated systems for production of water, steam and other process gases of appropriate quality; e) descriptions of and procedures for manufacturing operations including people, materials, material flow, solution preparation and associated acceptance criteria; f) validation and routine control of cleaning, disinfection and sterilization processes; g) validation methods and data requirements for media fills and container/closure systems and h) operating practices for acceptance criteria, investigation reviews and release/reject decisions.
EN 13824:2004 (E) 7 1 Scope This document specifies requirements for the design and operation of aseptic processing facilities and the validation and routine control of aseptic processes for the preparation of sterile liquid medical devices. It is not applicable to those pharmaceutical products where the requirements of the relevant good manufacturing practices are applicable. NOTE Many of the principles included in this document can be applied to certain aseptically processed sterile solid medical devices. 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. EN 980, Graphical symbols for use in the labelling of medical devices. EN 1174-1, Sterilization of medical devices — Estimation of the population of micro-organisms on product — Part 1: Requirements. EN 1174-2, Sterilization of medical devices — Estimation of the population of micro-organisms on product — Part 2: Guidance. EN 1174-3, Sterilization of medical devices — Estimation of the population of micro-organisms on product - Part 3: Guide to the methods for validation of microbiological techniques. EN 1822-1:1998, High efficiency air filters (HEPA and ULPA) — Part 1: Classification, performance testing, marking. EN 1822-2:1998, High efficiency air filters (HEPA and ULPA) — Part 2: Aerosol production, measuring equipment, particle-counting statistic
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