1、February 2017 English price group 11No part of this translation may be reproduced without prior permission ofDIN Deutsches Institut fr Normung e. V., Berlin. Beuth Verlag GmbH, 10772 Berlin, Germany,has the exclusive right of sale for German Standards (DIN-Normen).ICS 11.100.99; 71.040.20!%_z“260879
2、7www.din.deDIN ISO 4802-1Glassware Hydrolytic resistance of the interior surfaces of glass containers Part 1: Determination by titration method and classification (ISO 48021:2016),English translation of DIN ISO 4802-1:2017-02Glasartikel Wasserbestndigkeit der inneren Oberflche von Glasbehltern Teil
3、1: Bestimmung nach der Titrationsmethode und Klasseneinteilung (ISO 48021:2016),Englische bersetzung von DIN ISO 4802-1:2017-02Verrerie Rsistance hydrolytique des surfaces internes des rcipients en verre Partie 1: Dtermination par analyse titrimtrique et classification (ISO 48021:2016),Traduction an
4、glaise de DIN ISO 4802-1:2017-02SupersedesDIN ISO 48021:201212www.beuth.deDocument comprises 19 pagesDTranslation by DIN-Sprachendienst.In case of doubt, the German-language original shall be considered authoritative.02.17 A comma is used as the decimal marker. Introduction 61 Scope . 72 Normative r
5、eferences 73 Terms and definitions . 74 Principle . 105 Reagents . 106 Apparatus 117 Sample preparation 117.1 Sample size 117.2 Determination of the filling volume . 117.2.1 Flat-bottomed containers 20 mm outer flange diameter (except ampoules, syringes and cartridges) . 117.2.2 Flat-bottomed contai
6、ners 20 mm outer flange diameter . 117.2.3 Round-bottomed containers. 137.2.4 Lipped containers 137.2.5 Ampoules . 137.2.6 Syringes and cartridges 138 Procedure 148.1 General 148.2 Cleaning of samples . 148.3 Filling and heating 148.4 Analysis of the extraction solutions . 158.5 Test to determine wh
7、ether the containers have been surface treated 169 Expression of results .169.1 Determination 169.2 Classification 169.3 Distinction between containers of hydrolytic resistance container class HCT1 and hydrolytic resistance container class HCT2 .169.4 Designation . 1710 Test report 1711 Reproducibil
8、ity .18Bibliography .19Contents PageNational foreword 3 Nationaler Annex NA (informative) Bibliography 5 DIN ISO 4802-1:2017-02 2 National foreword This document (ISO 4802-1:2016) has been prepared by Technical Committee ISO/TC 76 “Transfusion, infusion and injection, and blood processing equipment
9、for medical and pharmaceutical use” with the active participation of German experts. The responsible German body involved in its preparation was DIN-Normenausschuss Medizin (DIN Standards Committee Medicine), Working Committee NA 063-02-03 AA Verpackungssysteme fr die Befllung und Applikation von me
10、dizinischen Produkten. Attention is drawn to the possibility that some of the elements of this document may be the subject of patent rights. DIN shall not be held responsible for identifying any or all such patent rights. The DIN ISO 4802 series consists of the following parts, under the general tit
11、le Glassware Hydrolytic resistance of the interior surfaces of glass containers: Part 1: Determination by titration method and classification Part 2: Determination by flame spectrometry and classification The DIN Standards corresponding to the International Standards referred to in this document are
12、 as follows: ISO 385 DIN EN ISO 385 ISO 648 DIN EN ISO 648 ISO 719 DIN ISO 719 ISO 720 DIN ISO 720 ISO 1773 DIN ISO 1773 ISO 3585 DIN ISO 3585 ISO 3819 DIN EN ISO 3819 ISO 8362-1 DIN EN ISO 8362-1 ISO 8362-4 DIN EN ISO 8362-4 ISO 8536-1 DIN EN ISO 8536-1 ISO 9187-1 DIN EN ISO 9187-1 ISO 13926-1 DIN
13、ISO 13926-1 ISO 11040-1 DIN ISO 11040-1 ISO 11040-4 DIN ISO 11040-4 ISO 11418-1 DIN ISO 11418-1 ISO 11418-4 DIN ISO 11418-4 ISO 11418-7 DIN ISO 11418-7 Amendments This standard differs from DIN ISO 4802-1:2012-12 as follows: a) subclauses on water (test water and purified water) have been revised; b
14、) test methods have been revised; c) the subclause on autoclaves and steam sterilizers has been revised; d) the text of the standard has been editorially revised. DIN ISO 4802-1:2017-02 3 Previous editions DIN 52329: 1967-04 DIN 52339-1:1980-12 DIN EN ISO 4802-1: 2012-12 DIN ISO 4802-1:2017-02 4 Nat
15、ional Annex NA (informative) Bibliography DIN EN ISO 385, Laboratory glassware Burettes DIN EN ISO 648, Laboratory glassware Single-volume pipettes DIN EN ISO 3819, Laboratory glassware Beakers DIN EN ISO 8362-1, Injection containers and accessories Part 1: Injection vials made of glass tubing DIN E
16、N ISO 8362-4, Injection containers and accessories Part 4: Injection vials made of moulded glass DIN EN ISO 8536-1, Infusion equipment for medical use Part 1: Infusion glass bottles DIN EN ISO 9187-1, Injection equipment for medical use Part 1: Ampoules for injectables DIN ISO 719, Glass Hydrolytic
17、resistance of glass grains at 98 C Method of test and classification DIN ISO 720, Glass Hydrolytic resistance of glass grains at 121 C Method of test and classification DIN ISO 1773, Laboratory glassware Narrow-necked boiling flasks DIN ISO 3585, Borosilicate glass 3.3 Properties DIN ISO 3696, Water
18、 for analytical laboratory use Specification and test methods DIN ISO 11040-1, Prefilled syringes Part 1: Glass cylinders for dental local anaesthetic cartridges DIN ISO 11040-4, Prefilled syringes Part 4: Glass barrels for injectables DIN ISO 11418-1, Containers and accessories for pharmaceutical p
19、reparations Part 1: Drop-dispensing glass bottles DIN ISO 11418-4, Containers and accessories for pharmaceutical preparations Part 4: Tablet glass bottles DIN ISO 11418-7, Containers and accessories for pharmaceutical preparations Part 7: Screw-neck vials made of glass tubing for liquid dosage forms
20、 DIN ISO 4802-1:2017-02 5 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 the hydrolytic resistance of the interior surfaces of glass containers.The
21、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 this part of ISO 4802. In addition, this part of ISO 4802 contains a classification of containers ot
22、her 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 in order to increase the reproducibility of the test results. In particular, the autoclaving cycle
23、 is described in detail.DIN ISO 4802-1:2017-02 6Glassware Hydrolytic resistance of the interior surfaces of glass containers Part 1: Determination by titration method and classification1 ScopeThis part of ISO 4802 specifies:a) a method for determining the hydrolytic resistance of the interior surfac
24、es 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 the extraction solution produced with hydrochloric acid solution, in which case the resistance is inversely proportional to the volume of acid
25、 required;b) a classification of glass containers according to the hydrolytic resistance of the interior surfaces determined by the methods specified in this part of ISO 4802.2 Normative referencesThe following documents, in whole or in part, are normatively referenced in this document and are indis
26、pensable for its application. For dated references, only the edition cited applies. For undated references, the latest edition of the referenced document (including any amendments) applies.ISO 385, Laboratory glassware BurettesISO 648, Laboratory glassware Single-volume pipettesISO 719, Glass Hydrol
27、ytic 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 1773, Laboratory glassware Narrow-necked boiling flasksISO 3819, Laboratory glassware BeakersISO 9187-1, Injecti
28、on 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 different formsNote 1 to entry: Ampoules are usually thin-walled and
29、 have a capacity normally up to 30 ml. They are intended to be closed, after filling, by flame sealing.DIN ISO 4802-1:2017-02 7 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 ci
30、rcular 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 capacityvolume of water required to fill a container, placed on a flat, horizontal surface3.4containerarticle made from glass to be used as primary pa
31、ckaging material intended to come into direct contact with the pharmaceutical 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 fi
32、ll 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 to compare container sets from different sources or lots. It has no relation to the nominal product volume.3.6borosilicate glasssilicate glass having
33、 a very high hydrolytic resistance due to its composition, containing significant 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 en
34、try: Neutral glass is a borosilicate glass having a very high hydrolytic resistance 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 o
35、f 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 a mass fraction up to about 15 % of alkaline earth oxides, mainly calcium oxideNote 1 to entry: Containers made from this glass have a mo
36、derate hydrolytic resistance due to the chemical composition of the glass, and comply with hydrolytic resistance container class HCT3.DIN ISO 4802-1:2017-02 8 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) Exam
37、ple of a glass barrel (see ISO 11040-4)d) Example of a stem cut ampoule with constriction (see ISO 9187-1)Figure 1 Examples of containersDIN ISO 4802-1:2017-02 9 3.8surface treatmenttreatment of the internal surface of glass containers with reagents in order to achieve a de-alkalized surface and to
38、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 container. Tre
39、ated 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-sealin
40、g.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 attack
41、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 dioxide b
42、y 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 correspond
43、ing 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 25 C b
44、y 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, standard volu
45、metric 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!DIN ISO 4802-1:2017-02 10 5.5 Methyl red, indicator
46、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 quality.NOTE 1 See national or regional regulat
47、ion 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 and those specified in 6.1 to 6.6.6.1 Autoclave or steam sterilizer, capable of withstanding a pressure of at
