1、BRITISH STANDARD BS EN ISO 8871-3:2004 Elastomeric parts for parenterals and for devices for pharmaceuticals use Part 3: Determination of released-particle count The European Standard EN ISO 8871-3:2004 has the status of a British Standard ICS 11.040.20 BS EN ISO 8871-3:2004 This British Standard wa
2、s published under the authority of the Standards Policy and Strategy Committee on 9 June 2004 BSI 9 June 2004 ISBN 0 580 43870 8 National foreword This British Standard is the official English language version of EN ISO 8871-3:2004. It is identical with ISO 8871-3:2003. It partially supersedes BS EN
3、 ISO 8871:1997 which will be withdrawn on publication of BS EN ISO 8871 Parts 1 and 2. The UK participation in its preparation was entrusted to Technical Committee CH/212, IVDs, which has the responsibility to: A list of organizations represented on this committee can be obtained on request to its s
4、ecretary. Cross-references The British Standards which implement international or European publications referred to in this document may be found in the BSI Catalogue under the section entitled “International Standards Correspondence Index”, or by using the “Search” facility of the BSI Electronic Ca
5、talogue or of British Standards Online. This publication does not purport to include all the necessary provisions of a contract. Users are responsible for its correct application. Compliance with a British Standard does not of itself confer immunity from legal obligations. aid enquirers to understan
6、d the text; present to the responsible international/European committee any enquiries on the interpretation, or proposals for change, and keep the UK interests informed; monitor related international and European developments and promulgate them in the UK. Summary of pages This document comprises a
7、front cover, an inside front cover, the EN ISO title page, the EN ISO foreword page, the ISO title page, pages ii to v, a blank page, pages 1 to 6, an inside back cover and a back cover. The BSI copyright notice displayed in this document indicates when the document was last issued. Amendments issue
8、d since publication Amd. No. Date CommentsEUROPEANSTANDARD NORMEEUROPENNE EUROPISCHENORM ENISO88713 May2004 ICS11.040.20 SupersedesENISO8871:1997 Englishversion Elastomericpartsforparenteralsandfordevicesfor pharmaceuticalsusePart3:Determinationofreleasedparticle count(ISO88713:2003) lmentsenlastomr
9、epouradministrationparentraleet dispositifsusagepharmaceutiquePartie3: Dnombrementdesparticuleslibres(ISO88713:2003) ElastomereTeilefrParenteraliaundfrGertezur pharmazeutischenVerwendungTeil3:Bestimmungvon herausgelstenPartikeln(ISO88713:2003) ThisEuropeanStandardwasapprovedbyCENon1April2004. CENmem
10、bersareboundtocomplywiththeCEN/CENELECInternalRegulationswhichstipulatetheconditionsforgivingthisEurope an Standardthestatusofanationalstandardwithoutanyalteration.Uptodatelistsandbibliographicalreferencesconcernings uchnational standardsmaybeobtainedonapplicationtotheManagementCentreortoanyCENmembe
11、r. ThisEuropeanStandardexistsinthreeofficialversions(English,French,German).Aversioninanyotherlanguagemadebytra nslation undertheresponsibilityofaCENmemberintoitsownlanguageandnotifiedtotheManagementCentrehasthesamestatusasthe official versions. CENmembersarethenationalstandardsbodiesofAustria,Belgi
12、um,Cyprus,CzechRepublic,Denmark,Estonia,Finland,France, Germany,Greece,Hungary,Iceland,Ireland,Italy,Latvia,Lithuania,Luxembourg,Malta,Netherlands,Norway,Poland,Portugal, Slovakia, Slovenia,Spain,Sweden,SwitzerlandandUnitedKingdom. EUROPEANCOMMITTEEFORSTANDARDIZATION COMITEUROPENDENORMALISATION EURO
13、PISCHESKOMITEEFRNORMUNG ManagementCentre:ruedeStassart,36B1050Brussels 2004CEN Allrightsofexploitationinanyformandbyanymeansreserved worldwideforCENnationalMembers. Ref.No.ENISO88713:2004EForeword ThetextofISO88713:2003hasbeenpreparedbyTechnicalCommitteeISO/TC76 “Transfusion,infusionandinjectionequi
14、pmentformedicalandpharmaceuticaluse“ofthe InternationalOrganizationforStandardization(ISO)andhasbeentakenoverasENISO8871 3:2004byCMC. ThisEuropeanStandardshallbegiventhestatusofanationalstandard,eitherbypublicationof anidenticaltextorbyendorsement,atthelatestbyNovember2004,andconflictingnational sta
15、ndardsshallbewithdrawnatthelatestbyNovember2004. ThisdocumentsupersedesENISO8871:1997. AccordingtotheCEN/CENELECInternalRegulations,thenationalstandardsorganizationsof thefollowingcountriesareboundtoimplementthisEuropeanStandard:Austria,Belgium, Cyprus,CzechRepublic,Denmark,Estonia,Finland,France,Ge
16、rmany,Greece,Hungary, Iceland,Ireland,Italy,Latvia,Lithuania,Luxembourg,Malta,Netherlands,Norway,Poland, Portugal,Slovakia,Slovenia,Spain,Sweden,SwitzerlandandUnitedKingdom. Endorsementnotice ThetextofISO88713:2003hasbeenapprovedbyCENasENISO88713:2004withoutany modifications. ENISO88713:2004 Referen
17、ce number ISO 8871-3:2003(E)INTERNATIONAL STANDARD ISO 8871-3 First edition 2003-08-01 Elastomeric parts for parenterals and for devices for pharmaceutical use Part 3: Determination of released-particle count lments en lastomre pour administration parentrale et dispositifs usage pharmaceutique Parti
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21、C ehlar Secterirata ta teh serddaig sleb nevwo. ISO 3002 All irthgs erse.devr lnUeto sswrehise specified, on trap fo this lbupictaion maeb y cudorperro de tuilizi den yna form ro na ybm ynae,s lecetrinoc ro mceinahcla, incliduntohp gcoiypodna gn micrfoilm, wittuoh repmissii now nritign from ietI reh
22、Sa Ot tsserdda eh ebolw or ISOs memreb i ydobn the cnuotfo yr ttseuqer ehe.r ISO cirypothg fofice saCe tsopale 65 eneG 1121-HC 02 av leT. 4 + 10 947 22 1 11 xaF0 947 22 14 + 9 74 E-mial coirypthgis.o gro We bwww.is.o groii ENISO88713:2004 iiiContents Page Foreword iv Introduction v 1 Scope 1 2 Norma
23、tive references . 1 3 Determination of visible-particle count 1 4 Determination of subvisible-particle count 3 Bibliography . 6 ENISO88713:2004iv Foreword ISO (the International Organization for Standardization) is a worldwide federation of national standards bodies (ISO member bodies). The work of
24、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, governmental and non-governmental,
25、 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 Directives, Part 2. The main t
26、ask 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 bodies casting a vote. Attent
27、ion 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 8871-3 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection equipment for
28、 medical and pharmaceutical use. Together with the other parts (see below), this part of ISO 8871 cancels and replaces ISO 8871:1990, which has been technically revised. ISO 8871 consists of the following parts, under the general title Elastomeric parts for parenterals and for devices for pharmaceut
29、ical use: Part 1: Extractables in aqueous autoclavates Part 2: Identification and characterization Part 3: Determination of released-particle count Part 4: Biological requirements and test methods Part 5: Functional requirements and testing ENISO88713:2004 vIntroduction When elastomeric closures are
30、 used as primary packaging materials in direct contact with pharmaceutical preparations, the pharmaceutical industry requires, to an increasing extent, definite details from the rubber manufacturer about the presence of particles the closures may release into an injectable. The test methods specifie
31、d in Clauses 3 and 4 make it possible to meet this request. ENISO88713:2004INTENRATIONAL TSANDADR IS-1788 O3:(3002E)1Elastomeric parts for parenterals and for devices for pharmaceutical use Part 3: Determination of released-particle count 1 Scope Elastomeric closures may be superficially contaminate
32、d with visible and subvisible particles, and fragments can also be produced when the closure is pierced by a needle. Such particles may be transferred to pharmaceutical preparations in contact with the elastomeric parts and affect the quality of such preparations. This part of ISO 8871 specifies met
33、hods for the determination of the number of visible and subvisible particles, respectively, detached from elastomeric parts by rinsing. It does not specify particle contamination limits. These will have to be agreed upon between manufacturer and user. 2 Normative references The following referenced
34、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 3696:1997, Water for analytical laboratory use Specification and test
35、methods 3 Determination of visible-particle count 3.1 Principle This method evaluates the potential for contamination by collecting and counting the particles detached from elastomeric parts on rinsing with water. 3.2 Classification For the purposes of this method, particles are divided into size cl
36、asses as follows, using the longest dimension as the classifying parameter: Class I: 25 m but u 50 m; Class II: 50 m but u 100 m; Class III: 100 m. ENISO88713:20042 3.3 Apparatus and materials 3.3.1 Shaking machine, moving in a horizontal circle of 12 mm 1 mm diameter at 300 min 1to 350 min 1 . 3.3.
37、2 Membrane filters, with a maximum pore size of 0,8 m, provided with grid lines dividing the surface into 3 mm 3 mm squares. NOTE The colour of the filter may significantly affect the test results. If no specific agreement has been made between the interested parties, the basic colour shall be mediu
38、m grey and lie within the following coordinate ranges in the CIE (International Commission on Illumination) system: L* between 60 % and 70 %; a* between 4,7 % and 3,7 %; b* between 4,7 % and 3,7 %. These specifications apply to the grid-imprinted surface of the filter, and assume this surface has a
39、3-mm- square grid made up of green lines. 3.3.3 Clean, wide-mouthed conical flasks, of capacity 300 ml. 3.3.4 Rinse fluid, prepared by dissolving 3 g of commercially available highly concentrated polysorbate 80 (Tween 80) in 10 l of purified water (grade 1 or grade 2 as specified in ISO 3696). 3.3.5
40、 Equipment for supplying the rinse fluid under a suitable pressure, including a terminal filter with a maximum pore size of 1,2 m. 3.3.6 Microscope, magnification about 50, with suitable direct illumination at an angle of 0 to 10 with the microscope stage. 3.4 Preparation for the test 3.4.1 Ensure t
41、hat the environment in which the test is to be carried out is free from extraneous particles which could cause interference. This involves wearing suitable garments and gloves and using a suitable clean-air work station, for example a laminar-flow cabinet meeting the requirements of Class 8 of ISO 1
42、4644-1 (Class 100,000 of US Federal Standard 209E), as well as suitably decontaminated tools and sample-handling equipment. 3.4.2 Carry out a blank test, as follows: Place 50 ml of filtered rinse fluid in a conical flask. Shake for 20 s. Immediately filter the fluid through a membrane filter. Add an
43、other 50 ml portion of rinse fluid to the flask, shake, and filter in the same way. Transfer the filter to the microscope, taking care not to contaminate it. Count the particles on the filter. No more than five particles of Class I and no more than one particle of Class II shall be found. No particl
44、es of Class III shall be present. ENISO88713:2004 3If these requirements are not met, investigate the possible causes of failure, rectify, and repeat the blank test until satisfactory results are obtained. Carry out a blank test both before and after each series of tests. Only when satisfactory valu
45、es are obtained both before and after the series of tests can the results of the tests be considered valid. 3.5 Test Place a number of complete elastomeric parts with a total surface area of approximately 100 cm 2into a conical flask. Add 50 ml of filtered rinse fluid. Shake for 20 s. Immediately fi
46、lter the fluid through a membrane filter. Add another 50 ml portion of rinse fluid to the flask, shake and filter in the same way. Transfer the filter to the microscope, taking care not to contaminate it. Count the particles on the filter. 3.6 Test report For each test, report the following: a) the
47、total surface area of the elastomeric parts tested, and the number of complete parts tested; b) the total particle count in each of the three particle-size classes; c) the particle counts in each of the three classes for the blank tests performed; d) the average particle count in each class per 10 cm 2of surface, rounded to one place of decimals. 4 Determination of subvisible-particle count 4.1 Principle In contact with liquid pharmaceutical preparations, elastomeric parts may release particles having dimensions of 25 m or smaller, and hence not visible to the naked eye. Their
