1、BS ISO 4802-1:2016Glassware Hydrolyticresistance of the interiorsurfaces of glass containersPart 1: Determination by titration methodand classificationBSI Standards PublicationWB11885_BSI_StandardCovs_2013_AW.indd 1 15/05/2013 15:06BS ISO 4802-1:2016 BRITISH STANDARDNational forewordThis British Sta
2、ndard is the UK implementation of ISO 4802-1:2016. Itsupersedes BS ISO 4802-1:2010 which is withdrawn.The UK participation in its preparation was entrusted to TechnicalCommittee CH/212, IVDs.A list of organizations represented on this committee can beobtained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 publica
3、tion 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 88545 7ICS 71.040.20Compliance with a British Standard cannot confer immunity fro
4、mlegal 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 4802-1:2016 ISO 2016Glassware Hydrolytic resistance of the interior surfaces of glass containers Part 1
5、: Determination by titration method and classificationVerrerie Rsistance hydrolytique des surfaces internes des rcipients en verre Partie 1: Dtermination par analyse titrimtrique et classificationINTERNATIONAL STANDARDISO4802-1Third edition2016-06-15Reference numberISO 4802-1:2016(E)BS ISO 4802-1:20
6、16ISO 4802-1:2016(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, including phot
7、ocopying, 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 22 74
8、9 01 11Fax +41 22 749 09 47copyrightiso.orgwww.iso.orgBS ISO 4802-1:2016ISO 4802-1:2016(E)Foreword ivIntroduction v1 Scope . 12 Normative references 13 Terms and definitions . 14 Principle 45 Reagents 46 Apparatus . 57 Sample preparation . 67.1 Sample size . 67.2 Determination of the filling volume
9、67.2.1 Flat-bottomed containers 20 mm outer flange diameter (except ampoules, syringes and cartridges) 67.2.2 Flat-bottomed containers 20 mm outer flange diameter 67.2.3 Round-bottomed containers 77.2.4 Lipped containers . 77.2.5 Ampoules 77.2.6 Syringes and cartridges . 78 Procedure. 88.1 General .
10、 88.2 Cleaning of samples 88.3 Filling and heating . 88.4 Analysis of the extraction solutions 98.5 Test to determine whether the containers have been surface treated 109 Expression of results .109.1 Determination 109.2 Classification 109.3 Distinction between containers of hydrolytic resistance con
11、tainer class HCT1 and hydrolytic resistance container class HCT2 .109.4 Designation . 1110 Test report 1111 Reproducibility .12Bibliography .13 ISO 2016 All rights reserved iiiContents PageBS ISO 4802-1:2016ISO 4802-1:2016(E)ForewordISO (the International Organization for Standardization) is a world
12、wide federation of 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 t
13、hat 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.The procedures used to develop this doc
14、ument and those intended 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 Directi
15、ves, Part 2 (see www.iso.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 developme
16、nt of the document will 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 speci
17、fic terms and expressions 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
18、 76, Transfusion, infusion and injection, and blood processing equipment for medical and pharmaceutical use.This third edition cancels and replaces the second edition (ISO 4802-1:2010), which has been technically revised in particular by amending the subclauses on water (test water and purified wate
19、r), the test procedure, 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
20、: Determination by flame spectrometry and classificationiv ISO 2016 All rights reservedBS ISO 4802-1:2016ISO 4802-1:2016(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 An
21、alysis, for measuring the hydrolytic resistance of the interior surfaces of glass containers.The European Pharmacopoeia Commission has adopted the principle of the determination by titration and has set up a classification for glass containers for injectable preparations which is now included in thi
22、s part of ISO 4802. In addition, this part of ISO 4802 contains a classification of containers other than for injectable preparations.According to many results of international interlaboratory tests, this part of ISO 4802 specifies the test conditions in more detail than the European Pharmacopoeia i
23、n order to increase the reproducibility of the test results. In particular, the autoclaving cycle is described in detail. ISO 2016 All rights reserved vBS ISO 4802-1:2016BS ISO 4802-1:2016Glassware Hydrolytic resistance of the interior surfaces of glass containers Part 1: Determination by titration
24、method and classification1 ScopeThis part of ISO 4802 specifies:a) a method for determining the hydrolytic resistance of the interior surfaces of glass containers when subjected to attack by water at 121 C 1 C for 60 min 1 min. The resistance is measured by titration of a known aliquot portion of th
25、e extraction solution produced with hydrochloric acid solution, in which case the resistance is inversely proportional to the volume of acid required;b) a classification of glass containers according to the hydrolytic resistance of the interior surfaces determined by the methods specified in this pa
26、rt of ISO 4802.2 Normative 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 (inclu
27、ding any amendments) applies.ISO 385, Laboratory glassware BurettesISO 648, Laboratory glassware Single-volume pipettesISO 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
28、 test and classificationISO 1773, Laboratory glassware Narrow-necked boiling 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
29、.3.1ampoulesmall, normally flat-bottomed container having stems in many different 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 4802-1:2016(E) ISO 2016 All ri
30、ghts reserved 1BS ISO 4802-1:2016ISO 4802-1:2016(E)3.2bottleflat-bottomed 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 ma
31、de from a material other than glass, and not by flame-sealing.3.3brimful 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
32、 preparationsEXAMPLE Bottles, vials, syringes, ampoules and cartridges. See 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 vol
33、ume, see 7.2. The filling volume is a test-specific quantity that is used 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 signifi
34、cant amounts of boric oxideNote 1 to entry: Borosilicate glass contains a mass fraction of boric oxide usually between 5 % and 13 %. This glass type can also contain aluminium oxide and/or alkaline earth oxides.Note 2 to entry: Neutral glass is a borosilicate glass having a very high hydrolytic resi
35、stance and a high thermal shock resistance. When tested in accordance with ISO 720, it meets the requirements of class HGA 1. Containers properly made from this glass comply with hydrolytic resistance container class HCT1 of this part of ISO 4802.3.7soda-lime-silica glasssilicate glass containing a
36、mass fraction up to approximately 15 % of alkali metal oxides mainly sodium oxide and a mass fraction up to about 15 % of alkaline earth oxides, mainly calcium oxideNote 1 to entry: Containers made from this glass have a moderate hydrolytic resistance due to the chemical composition of the glass, an
37、d comply with hydrolytic resistance container class HCT3.2 ISO 2016 All rights reservedBS ISO 4802-1:2016ISO 4802-1:2016(E)a) Example of a glass cylinder for peninjectors (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
38、-4)d) Example of a stem cut ampoule with constriction (see ISO 9187-1)Figure 1 Examples of containers ISO 2016 All rights reserved 3BS ISO 4802-1:2016ISO 4802-1:2016(E)3.8surface treatmenttreatment of the internal surface of glass containers with reagents in order to achieve a de-alkalized surface a
39、nd to produce a significantly lower release of alkali metal ions (and alkali earth 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 HCT3 to a container of hydrolytic resistance class HCT2 containe
40、r. Treated containers are rinsed before use.3.9vialsmall, flat-bottomed container, 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-
41、sealing.4 PrincipleThis method of test is a surface test applied to glass containers 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 a
42、ttack is measured by titration of the extraction solutions.5 ReagentsDuring the test, unless otherwise stated, use only reagents of recognized 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 dio
43、xide by boiling for at least 15 min before use in a boiling flask (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 corr
44、esponding to the neutral point of methyl red indicator of pH 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
45、25 C by an in-line conductivity meter.NOTE 2 This description 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, standar
46、d volumetric solution, c(HCl) = 0,01 mol/l.5.3 Hydrochloric acid, solution, c(HCl) 2 mol/l.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 4802-1:20
47、16ISO 4802-1:2016(E)5.5 Methyl red, indicator solution.Dissolve 25 mg of the sodium salt of methyl red (C15H14N3NaO2) in 100 ml of the test water (5.1).5.6 Purified water, prepared by distillation, by ion exchange, by reverse osmosis or by any other suitable method from water having drinking water q
48、uality.NOTE 1 See national or regional regulation on water intended for human consumption.NOTE 2 Water that corresponds to Grade 3 according to ISO 36962is suitable.NOTE 3 In the European Pharmacopoeia 3.2.112, water as described above is designated water R.6 ApparatusOrdinary laboratory apparatus a
49、nd those specified in 6.1 to 6.6.6.1 Autoclave or steam sterilizer, capable of withstanding a pressure of at least 250 kPa (2,5 bar) and of carrying out the heating cycle specified in 8.3. It shall be capable of maintaining a temperature of (121 1) C, equipped with a calibrated thermometer or a calibrated thermocouple recorder, a pressure gauge and a vent-cock.When necessary and appropriate, the autoclave vessel and ancillary equipment shall be thoroughly cleaned before use using t
