BS-EN-ISO-8871-3-2004.pdf

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 ? licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi bs en iso 8871-3:2004 this british standard was 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 it partially supersedes bs en iso 8871:1997 which will be withdrawn on publication of bs en iso 8871 parts 1 and 2.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 secretary. 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 catalogue 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 understand 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 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 issued since publication amd. no. datecomments licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi european standard norme europenne europische norm en iso 8871-3 may 2004 ics 11.040.20supersedes en iso 8871:1997 english version elastomeric parts for parenterals and for devices for pharmaceuticals use - part 3: determination of released-particle count (iso 8871-3:2003) lments en lastomre pour administration parentrale et dispositifs usage pharmaceutique - partie 3: dnombrement des particules libres (iso 8871-3:2003) elastomere teile fr parenteralia und fr gerte zur pharmazeutischen verwendung - teil 3: bestimmung von herausgelsten partikeln (iso 8871-3:2003) this european standard was approved by cen on 1 april 2004. 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 national standards may be obtained on application to the 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 management centre has the same status as the official versions. 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 standardization comit europen de normalisation europisches komitee fr normung management centre: rue de stassart, 36 b-1050 brussels 2004 cenall rights of exploitation in any form and by any means reserved worldwide for cen national members. ref. no. en iso 8871-3:2004 e licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi foreword the text of iso 8871-3:2003 has been prepared by technical committee iso/tc 76 “transfusion, infusion and injection equipment for medical and pharmaceutical use“ of the international organization for standardization (iso) and has been taken over as en iso 8871- 3:2004 by cmc. 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 november 2004, and conflicting national standards shall be withdrawn at the latest by november 2004. this document supersedes en iso 8871:1997. 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. endorsement notice the text of iso 8871-3:2003 has been approved by cen as en iso 8871-3:2004 without any modifications. en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi reference 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 partie 3: dnombrement des particules libres en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi dplcsid fremia ihts pdf file mya ctnoian emdebt dedyfepcaes. in ccacnadrow eita hebods licnesilop gnic,y tihs file mirp eb yatnde iv roweb detu slahl ton ide ebtlnu deess teh typfecaes wihce era hml era deddebicsnede ti dna onstlalde t noeh comuptfrep reromign tide ehtin.g in wodlnidaot gnihs fil,e trapise atpecc tiereht nser ehnopsiiblity fo nto ifnriigngn aebods licnesilop gnic.y eht iso tneclar secrteirata caceptl on siibality in this .aera ai ebods a tedarmfo kra aebod systemi snctaropro.de tedials fo teh sfotwcudorp erats sut deo crtaee tihs pdf file cna f ebi dnuon tlareneg eh ifnler oatit evt oeh file; tp ehdc-frtaeino marapterew stpo ereimizde fro irptni.gn evyre cera neeb sah takne tsne oeru taht teh file is siutlbae fosu re yb iso memdob rebeis. in tlnu ehikletneve y ttah lborp aem lertait gno it is f,dnuo plsaee ifnrom ttnec ehlar secterirata ta teh serddaig sleb nevwo. iso 3002 all 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national standards bodies (iso member bodies). the work of 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, 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 task 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. attention 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 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 pharmaceutical 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 en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi v introduction when elastomeric closures are 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 specified in clauses 3 and 4 make it possible to meet this request. en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi intenrational tsandadr is-1788 o3:(3002e) 1 elastomeric parts for parenterals and for devices for pharmaceutical use part 3: determination of released-particle count 1 scope elastomeric closures may be superficially contaminated 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 methods 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 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 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 classes 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. en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi 2 3.3 apparatus and materials 3.3.1 shaking machine, moving in a horizontal circle of 12 mm 1 mm diameter at 300 min1 to 350 min1. 3.3.2 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 medium 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 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 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 that 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 14644-1 (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 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. no more than five particles of class i and no more than one particle of class ii shall be found. no particles of class iii shall be present. en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi 3 if 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 values 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 cm2 into a conical flask. add 50 ml of filtered rinse fluid. shake for 20 s. immediately filter 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 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 cm2 of 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 presence can be detected by means of electrical or optical instruments. this method evaluates the potential of elastomeric parts to release such particles by bringing the parts in contact with water and examining the contact fluid with a suitable particle counter operating on the light extinction principle. en iso 88713:2004 licensed copy: sheffieldun sheffieldun, na, fri nov 17 10:00:39 gmt+00:00 2006, uncontrolled copy, (c) bsi 4 4.2 classification for the purpose of this method, particles are divided into size classes as follows, using the equivalent sphere diameter as the classifying parameter: w 2 m but 5 m; w 5 m but 10 m; w 10 m but 25 m; w 25 m. 4.3 apparatus and materials 4.3.1 shaking machine, moving in a horizontal circle of 12 mm 1 mm diameter at 300 min1 to 350 min1. 4.3.2 clean, wide-mouthed conical flasks, of capacity 300 ml. 4.3.3 particle-free water, containing not more than 100 particles larger than 2 m per 5 ml. 4.3.4 particle counter, operating on the light extinction (light obscuration or light blockage) principle, capable of classifying particles in the rinse fluid into the categories defined in 4.2. 4.4 preparations 4.4.1 ensure that 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 14644-1 (class 100,000 of us federal standard 209e), as well as suitably decontaminated tools and sample-handling equipment. 4.4.2 carry out a blank test as follows: place 100 ml of particle-free water into a conical flask. sha