1、BS ISO 4802-2:2016Glassware Hydrolyticresistance of the interiorsurfaces of glass containersPart 2: Determination by flamespectrometry and classificationBSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06BS ISO 4802-2:2016 BRITISH STANDARDNational forewordThis British S
2、tandard is the UK implementation of ISO 4802-2:2016. Itsupersedes BS ISO 4802-2:2010 which is withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/212, IVDs.A list of organizations represented on this committee can beobtained on request to its secretary.This publi
3、cation does not purport to include all the necessaryprovisions of a contract. Users are responsible for its correctapplication. The British Standards Institution 2016. Published by BSI StandardsLimited 2016ISBN 978 0 580 88546 4ICS 71.040.20Compliance with a British Standard cannot confer immunity f
4、romlegal obligations.This British Standard was published under the authority of theStandards Policy and Strategy Committee on 30 June 2016.Amendments issued since publicationDate Text affectedBS ISO 4802-2:2016 ISO 2016Glassware Hydrolytic resistance of the interior surfaces of glass containers Part
5、 2: Determination by flame spectrometry and classificationVerrerie Rsistance hydrolytique des surfaces internes des rcipients en verre Partie 2: Dtermination par spectromtrie de flamme et classificationINTERNATIONAL STANDARDISO4802-2Third edition2016-06-15Reference numberISO 4802-2:2016(E)BS ISO 480
6、2-2:2016ISO 4802-2:2016(E)ii ISO 2016 All rights reservedCOPYRIGHT PROTECTED DOCUMENT ISO 2016, Published in SwitzerlandAll rights reserved. Unless otherwise specified, no part of this publication may be reproduced or utilized otherwise in any form or by any means, electronic or mechanical, includin
7、g photocopying, or posting on the internet or an intranet, without prior written permission. Permission can be requested from either ISO at the address below or ISOs member body in the country of the requester.ISO copyright officeCh. de Blandonnet 8 CP 401CH-1214 Vernier, Geneva, SwitzerlandTel. +41
8、 22 749 01 11Fax +41 22 749 09 47copyrightiso.orgwww.iso.orgBS ISO 4802-2:2016ISO 4802-2:2016(E)Foreword ivIntroduction v1 Scope . 12 Normative references 13 Terms and definitions . 14 Principle 45 Reagents 46 Apparatus . 67 Sample preparation . 67.1 Sample size . 67.2 Determination of the filling v
9、olume 77.2.1 Flat-bottomed containers 20 mm outer flange diameter (except ampoules, syringes and cartridges) 77.2.2 Flat-bottomed containers 20 mm outer flange diameter 77.2.3 Round-bottomed containers 77.2.4 Lipped containers . 87.2.5 Ampoules 87.2.6 Syringes and cartridges . 88 Procedure. 88.1 Gen
10、eral . 88.2 Cleaning of samples 98.3 Filling and heating . 98.4 Analysis of the extraction solutions . 108.4.1 Containers of hydrolytic resistance container classes HCF1, HCF2 and HCFB or those known to be made from borosilicate glass 108.4.2 Containers of hydrolytic resistance container classes HCF
11、3 and HCFD, or those known to be made from soda-lime-silica glass .108.5 Testing to determine whether the containers have been surface-treated .119 Expression of results .119.1 Determination 119.2 Classification 129.3 Distinction between containers of hydrolytic resistance container class HCF1 and h
12、ydrolytic resistance container class HCF2 129.4 Designation . 1210 Test report 1211 Reproducibility .13Bibliography .14 ISO 2016 All rights reserved iiiContents PageBS ISO 4802-2:2016ISO 4802-2:2016(E)ForewordISO (the International Organization for Standardization) is a worldwide federation of natio
13、nal 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. Internati
14、onal 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.The procedures used to develop this document and those intended
15、 for its further maintenance are described in the ISO/IEC Directives, Part 1. In particular the different approval criteria needed for the different types of ISO documents should be noted. This document was drafted in accordance with the editorial rules of the ISO/IEC Directives, Part 2 (see www.iso
16、.org/directives).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. Details of any patent rights identified during the development of the document will
17、be in the Introduction and/or on the ISO list of patent declarations received (see www.iso.org/patents).Any trade name used in this document is information given for the convenience of users and does not constitute an endorsement.For an explanation on the meaning of ISO specific terms and expression
18、s related to conformity assessment, as well as information about ISOs adherence to the World Trade Organization (WTO) principles in the Technical Barriers to Trade (TBT) see the following URL: www.iso.org/iso/foreword.html.The committee responsible for this document is ISO/TC 76, Transfusion, infusi
19、on and injection, and blood processing equipment for medical and pharmaceutical use.This third edition cancels and replaces the second edition (ISO 4802-2:2010), which has been technically revised in particular by amending the subclauses on water (test water and purified water), the test procedure,
20、and the subclause on autoclave and steam sterilizer respectively.ISO 4802 consists of the following parts, under the general title Glassware Hydrolytic resistance of the interior surfaces of glass containers: Part 1: Determination by titration method and classification Part 2: Determination by flame
21、 spectrometry and classificationiv ISO 2016 All rights reservedBS ISO 4802-2:2016ISO 4802-2:2016(E)IntroductionThis part of ISO 4802 is largely based on a method of test approved by the International Commission on Glass (ICG), Technical Committee 2, Chemical Durability and Analysis, for measuring th
22、e hydrolytic resistance of the interior surfaces of glass containers.This part of ISO 4802 contains a classification which is related to but not equivalent to the classification set up in ISO 4802-1 for the titration method. ISO 2016 All rights reserved vBS ISO 4802-2:2016BS ISO 4802-2:2016Glassware
23、 Hydrolytic resistance of the interior surfaces of glass containers Part 2: Determination by flame spectrometry and classification1 ScopeThis part of ISO 4802 specifies:a) methods for determining the hydrolytic resistance of the interior surfaces of glass containers when subjected to attack by water
24、 at (121 1) C for (60 1) min. The resistance is measured by determining the amount of sodium and other alkali metal or alkaline earth oxides in the extraction solution using flame atomic emission or absorption spectrometry (flame spectrometry);b) a classification of glass containers according to the
25、 hydrolytic resistance of the interior surfaces determined by the methods specified in this part of ISO 4802.The test method specified in this part of ISO 4802 might not be applicable to containers whose surfaces have been treated with silicon (e.g. containers that are ready for direct filling).2 No
26、rmative referencesThe following documents, in whole or in part, are normatively referenced in 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
27、) applies.ISO 385, Laboratory glassware BurettesISO 719, Glass Hydrolytic resistance of glass grains at 98 degrees C Method of test and classificationISO 720, Glass Hydrolytic resistance of glass grains at 121 degrees C Method of test and classificationISO 1042, Laboratory glassware One-mark volumet
28、ric flasksISO 3819, Laboratory glassware BeakersISO 9187-1, Injection equipment for medical use Part 1: Ampoules for injectables3 Terms and definitionsFor the purposes of this document, the following terms and definitions apply.3.1ampoulesmall, normally flat-bottomed container having stems in many d
29、ifferent formsNote 1 to entry: Ampoules are usually thin-walled and have a capacity normally up to 30 ml. They are intended to be closed, after filling, by flame sealing.INTERNATIONAL STANDARD ISO 4802-2:2016(E) ISO 2016 All rights reserved 1BS ISO 4802-2:2016ISO 4802-2:2016(E)3.2bottleflat-bottomed
30、 container, made from moulded glassNote 1 to entry: Bottles are normally thick-walled and have a capacity usually of more than 5 ml. They may be of circular or other geometric cross-section. Bottles are sealed with a closure made from a material other than glass, and not by flame-sealing.3.3brimful
31、capacityvolume of water required to fill a container, placed on a flat, horizontal surface3.4containerarticle made from glass to be used as primary packaging material intended to come into direct contact with the pharmaceutical preparationsEXAMPLE Bottles, vials, syringes, ampoules and cartridges. S
32、ee also Figure 1.Note 1 to entry: These containers are made from borosilicate or soda-lime-silica glass.3.5filling volumedefined volume of water to fill the test specimenNote 1 to entry: For the determination of the filling volume, see 7.2. The filling volume is a test specific quantity that is used
33、 to compare container sets from different sources or lots. It has no relation to the nominal product volume.3.6borosilicate glasssilicate glass having a very high hydrolytic resistance due to its composition containing significant amounts of boric oxideNote 1 to entry: Borosilicate glass contains a
34、mass fraction of boric oxide between 5 % and 13 %. This glass type may also contain aluminium oxide and/or alkaline earth oxides.Note 2 to entry: Neutral glass is a borosilicate glass having a very high hydrolytic resistance and a high thermal shock resistance. When tested according to ISO 720, it m
35、eets the requirements of class HGA 1. Containers properly made from this glass comply with hydrolytic resistance container class HCF1 of this part of ISO 4802.3.7soda-lime-silica glasssilicate glass containing a mass fraction up to approximately 15 % of alkali metal oxides, mainly sodium oxide, and
36、a mass fraction up to about 15 % of alkaline earth oxides, mainly calcium oxideNote 1 to entry: Containers made from this glass will have a moderate hydrolytic resistance due to the chemical composition of the glass, and comply with hydrolytic resistance container class HCF3.2 ISO 2016 All rights re
37、servedBS ISO 4802-2:2016ISO 4802-2:2016(E)a) Example of a glass cylinder for pen-injectors (see ISO 13926-1)b) Example of an injection vial made of glass tubing (see ISO 8362-1)c) Example of a glass barrel (see ISO 11040-4)d) Example of a stem cut ampoule with constriction (see ISO 9187-1)Figure 1 E
38、xamples of containers ISO 2016 All rights reserved 3BS ISO 4802-2:2016ISO 4802-2:2016(E)3.8surface treatmenttreatment of the internal surface of glass containers with reagents in order to achieve a de-alkalized surface and to produce a significantly lower release of alkali metal ions (and alkali ear
39、th metal ions)Note 1 to entry: Surface treatment is used, for example, in order to change a soda-lime-silica glass container of hydrolytic resistance class HCF3 to a container of hydrolytic resistance class HCF2 container. Treated containers are rinsed before use.3.9vialsmall, flat-bottomed containe
40、r, made from tubing or from moulded glassNote 1 to entry: Vials are normally thick-walled and have a capacity up to 100 ml. They are normally sealed with a closure made from a material other than glass, and not by flame-sealing.4 PrincipleThis method of test is a surface test applied to glass contai
41、ners as produced and/or as delivered.The containers to be tested are filled with specified water to a specified capacity. They are loosely capped and then heated under specified conditions. The degree of the hydrolytic attack is measured by flame spectrometric analysis of the extraction solutions.5
42、ReagentsDuring the test, unless otherwise stated, use only reagents of recognised analytical grade.5.1 Test water, to be prepared as follows:Prepare the test water from distilled water (5.6) by multiple distillations. Remove the carbon dioxide by boiling for at least 15 min before use in a boiling f
43、lask (6.3) of fused silica or borosilicate glass and cool.NOTE 1 Any other suitable method can be used.When tested immediately before use, water prepared as described above shall produce an orange-red (not violet-red or yellow) colour corresponding to the neutral point of methyl red indicator of pH
44、5,5 0,1 when 0,05 ml of methyl red indicator solution (5.5) is added to 50 ml of the water to be examined.This water may also be used as the reference solution (see 8.4).The conductivity of the water shall not exceed 1 S/cm, determined at 25 C by an in-line conductivity meter.NOTE 2 This description
45、 is based on the European Pharmacopoeia 3.2.112. In the European Pharmacopoeia, water prepared as described above is designated water R1.NOTE 3 Water of Grade 2 according to ISO 36962is suitable for this test.5.2 Hydrochloric acid, solution, c(HCl) 2 mol/l.5.3 Hydrochloric acid, solution, c(HCl) 6 m
46、ol/l ( 1 + 1).5.4 Hydrofluoric acid, c(HF) 22 mol/l (i.e. 400 g HF/l solution).CAUTION Hydrofluoric acid is very toxic and highly corrosive. Consider material safety data sheet!4 ISO 2016 All rights reservedBS ISO 4802-2:2016ISO 4802-2:2016(E)5.5 Purified water prepared by distillation, by ion excha
47、nge, by reverse osmosis or by any other suitable method from water having drinking water quality.NOTE 1 See national or regional regulation on water intended for human consumption.NOTE 2 Water that corresponds to Grade 3 according to ISO 3696 is suitable.NOTE 3 In the European Pharmacopoeia 3.2.112,
48、 water as described above is designated water R.5.6 Spectrochemical buffer solution (caesium chloride solution, CsCl).Dissolve 80 g of caesium chloride in approximately 300 ml of test water (5.1), add 10 ml of hydrochloric acid (5.3) and transfer to a 1 000 ml volumetric flask (6.3). Dilute to the m
49、ark with the test water (5.1) and mix.5.7 Stock solutions.5.7.1 Dry sodium chloride, potassium chloride and calcium carbonate at (110 5) C for 2 h. Prepare aqueous stock solutions, using the test water (5.1), directly from the chlorides and from the calcium carbonate, after dissolving in the minimum amount of hydrochloric acid so that all solutions have concentrations of 1 mg/ml, calculated as sodium oxide, potassium oxide and calcium oxide.5.7.2 Commercially available standard solutions
