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1、INTERNATIONAL STANDARD INTERNATIONAL ORGANIZATION FOR STANDARDIZATION ORGANISATION INTERNATIONALE DE NORMALISATION MEKAYHAPOAHAR OPTAHM3AqMR no CTAHAAPTMSAUMM Injection containers for injectables and accessories - Part 2 : Closures for injection vials Rcbients et accessoires pour produits injectable
2、s - Partie 2: Bouchons pour flacons IS0 8362-2 First edition 1988- 12- 1.5 Reference number IS0 8362-2 : 1988 (E) Copyright International Organization for Standardization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo r
3、eproduction or networking permitted without license from IHS -,-,- IS0 8362-2 : 1988 (E) Contents Page Foreword ,. .,. , , ,. . . . i Introduction . . . . . . . . . , . . , . . . . . , . , . . . . I . . , . . , , . , . . , . , , . . . . . . . . . . . . . . . . . . . iv 1 Scope . . . 1 2 Normative re
4、ferences , . . , . , . , , . , . , . . , . . , . . . . . . . . , . , , . . . . , , . . , . . . . . . . . . . 1 3 Dimensions and designation . . . . . . . . . . . , . , , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 4 Material . , .,. . . . . 3 5 Requirements . . . , . . , . . . . . .
5、. . . . . . . . . . . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 6 Sample . ,., . , . . . . 4 7 Marking . 4 Annexes A Test method for fragmentation . . . . . , . , . , . , . . , . , . , . . , . . . . . . . . . . . , . . . . . . , 5 B Test method for penetrability. . . . . . .
6、. . . . . . , . , . . , . , . . , . , . , . . . . . . . . . . . . . . . 7 C Test method for closure/container integrity and self-sealing. . . . . . . . . . . . . . . . , 8 0 International Organization for Standardization, 1988 0 Printed in Switzerland Copyright International Organization for Standar
7、dization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without license from IHS -,-,- IS0 8362-2 : 1988 (E) Foreword IS0 (the International Organization for Standardization) is a wo
8、rldwide federation of national standards bodies (IS0 member bodies). The work of preparing International Standards is normally carried out through IS0 technical committees. Each member body interested in a subject for which a technical committee has been established has the right to be represented o
9、n that committee. International organizations, govern- mental and non-governmental, in liaison with ISO, also take part in the work. IS0 collaborates closely with the International Electrotechnical Commission (IEC) on all matters of electrotechnical standardization. Draft International Standards ado
10、pted by the technical committees are circulated to the member bodies for approval before their acceptance as International Standards by the IS0 Council. They are approved in accordance with IS0 procedures requiring at least 75 % approval by the member bodies voting. International Standard IS0 8362-2
11、 was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection equipment for medical use. IS0 8362 consists of the following parts, under the general title Injection containers for injectables and accessories : - Part I : Injection vials made of glass tubing Part 2: Closures for
12、 njection vials Part 3: Aluminium caps for injection vials Part 4: Injection vials made of moulded glass - - - Annexes A, B and C form an integral part of this parf of IS0 8362. . 111 Copyright International Organization for Standardization Provided by IHS under license with ISO Licensee=NASA Techni
13、cal Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without license from IHS -,-,- IS0 8362-2 : 1988 (E) Introduction The materials from which injection containers (including the elastomeric closures) are made are suitable primary packaging mater
14、ials for storing injectable products until they are administered. iv Copyright International Organization for Standardization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without l
15、icense from IHS -,-,- INTERNATIONAL STANDARD IS0 8362-2 : 1988 (E) Injection containers for injectables and accessories - Part 2 : Closures for injection vials 1 sc This part of IS0 8362 specifies the design, dimensions, material, performance, requirements and tests for closures for injection vials
16、covered by IS0 8362-1 and IS0 8362-4. Closures specified in this part of IS0 8362 are intended for single use only. The closure shall be made from the formulation originally tested and approved by the end-user. The closure manufacturer will certify identity of the closure as well as conformance of t
17、he closure to previously agreed functional parameters or compen- dium requirements. 2 Normative references The following standards contain provisions which, through reference in this text, constitute provisions of this part of IS0 8362. At the time of publication, the editions indicated were valid.
18、All standards are subject to revision, and parties to agreements based on this part of IS0 8362 are encouraged to investigate the possibility of applying the most recent editions of the standards listed below. Members of IEC and IS0 main- tain registers of currently valid International Standards. O
19、48 : 1979, Vulcanized rubbers - Determinai.vn of hardness (Hardness between 30 and 85 IRHDI. IS0 2859 : 1974, Sampling procedures and tables for inspec- tion by attributes. IS0 3302 : 1976, Rubber - Dimensional tolerances of solid moulded and extruded products. IS0 3696 : 1987, Water for analytical
20、laboratory use - Specification and test methods. IS0 7864 : 1984, Sterile hypodermic needles for single use. IS0 7886 : 1984, Steriie hypodermic syringes for single use. IS0 8362-1 : 1988, Injection containers for injectables and accessories - Part I : Injection vials made of glass tubing. IS0 8362-
21、4 : 1988, Injection containers for injectables and accessories - Part 4: Injection vials made of moulded glass. IS0 8871 : 1988, Elastomeric parts for aqueous parenteral preparations - Identification, requirements, test methods. 1 Copyright International Organization for Standardization Provided by
22、IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without license from IHS -,-,- IS0 8362-2 : 1988 (E) 3 Dimensions and designation 3.1 Dimensions The dimensions of closures shall be as shown in fi
23、gure 1 and as given in table 1. Figure 1 illustrates two types of closure, types A and B. Dimensions in millimetres 6 r 2 NOTE - Other dimensions are as indicated for type A closures. Figure 1 - Dimensions and configuration of types A and B closures 2 Copyright International Organization for Standar
24、dization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without license from IHS -,-,- IS0 8362-2 : I988 (E) Nominal di d2 d3=d4 d5 d6 d7 h, h2 h3 7 2 2,5 20 13,2 10 4,5 5,5 18,8 - 8
25、,8 3,3 2,5 f 0 . 1 max. min. max. +0,2 / I O mi Annex E N H ) 1,0 ml of cHCIi or cNaOH) = 5 mmol/l Annex G I per 20 ml Acidity/ alkalinity Residue on evaporation 4 mg/100 ml Annex H (total solids) Discoloration of lead acetate paper 50 pg Na,S/20 cm2 of rubber surface Annex I Volatile sulfides (at -
26、pH 2) Zinc (calculated as Zn2+ 30 Rg/lO mi Annex K Zn2+ 1 ConductivityJ 40 pS/cm Annex L Turbidity Not exceeding 3 Annex M 5.4 Biological requirements The elastomeric closure shall not release any substances which may adversely affect the therapeutic effectiveness of the injec- table products, inclu
27、ding those substances which may exhibit toxic, pyrogenic or haemolytic reactions. NOTE - Since biological tests are usually requested by most of the na- tional Pharmacopoeias or related regulations of health authorities, they are mandatory for producers and users in countries where they exist. If th
28、is is not the case, reference should be made to biological tests, e.g. as described in the United States Pharmacopoeia, European Phar- macopoeia or other Pharmacopoeias. 1) Purified water corresponds to grades 1 and 2 of IS0 3696. 4 6.1 Sample size The closures to be tested shall be taken from a sam
29、ple collected as described in IS0 8871; the sample size is deduced from the rules given in IS0 2859. The minimum sample size to produce a sufficient number of items for all physical and chemical tests is as follows : - nominal size 13 : 570 closures; - nominal size 20 : 395 closures, 6.2 Pre-conditi
30、oning for physical properties testing Pre-condition the samples for fragmentation, penetrability and integrity and self-sealing as follows. Estimate the total surface area, A, in square centimetres, of the quantity of closures to be treated. Wash the closures by placing them in a suitable glass cont
31、ainer and covering with (2A) ml of purified water). Boil the water for 5 min f 15 s, and rinse 5 times with cold purified water. Place the washed closures in a wide-necked flask and add ( 2 4 ml of purified water. Cover the mouth of the flask with aluminium foil or a borosilicate beaker. Heat in an
32、autoclave so that a temperature of 121 O C f 1 O C is reached in the flask within 30 min; maintain this temperature for 30 min. Allow the closures to cool to room temperature within 30 min. D r y the closures in hot air at 60 O C within 60 min. Store the closures in a closed glass container, 7 Marki
33、ng The packaging closures given shall be marked with the desig- nation given in 3.2. Copyright International Organization for Standardization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking per
34、mitted without license from IHS -,-,- IS0 8362-2 : 1988 (E) U Bevel type mm min. max. 3,21 3,78 2,70 3,9 L (long1 M (medium) Annex A (normative) rr nom. 130 220 t 10 15O30 26O C io Test method for fragmentation A.1 Principle The purpose of the test is to measure the relative coring tendencies of dif
35、ferent IS0 rubber closures. The values ob- tained can be significantly affected by many factors, such as prior processing of the closures, type of crimping device, seal- ing force, design of the hypodermic needle point, its sharpness, the amount of lubrication on the needle, the gauge of the needle
36、and the keenness of the operators sight. It is, therefore, necessary to control these variables in order to obtain comparable results. For this reason, the closures to be tested have to be compared to known samples. A.2 Apparatus A.2.1 50 injection vials, complying with IS0 8362-1 or IS0 8362-4. A.2
37、.2 Hand-operated capping device and aluminium caps with a central hole which fit the injection vials to be used in the test. A.2.3 Membrane filter set. A.2.4 Disposable syringe for single use (e.g. as specified in IS0 78861, of 1 ml capacity, fitted with a tip for an injection needle. A.2.5 10 injec
38、tion needles, having an outer diameter of 0,8 mm and complying with IS0 7864. The bevel types and dimensions shall be as given in figure A.l and table A.l; both the long and the medium bevel type are allowed. E O Figure A.l - Needle point A.3 Procedure A.3.1 of acetone or methyl-isobutylketone. Degr
39、ease 10 new injection needles (A.2.5) by means A.3.2 be tested. Place n ml of water into each of these vials, where II is 50 % of the nominal volume of the vials. Select 50 vials (A.2.1) in a size matching the closure to Place a closure of the type to be tested on each of 25 vials, and a closure wit
40、h known fragmentation properties on each of the remaining 25 vials. Seal all vials with an aluminium cap (A.2.2) using the hand- operated capping device. Arrange the vials in two rows as shown in figure A.2. A.3.3 Attach an injection needle (A.2.5) to the tip of the syringe (A.2.4) (see, however, A.
41、3.8). Fill the syringe with water. Remove any water adhering to the needle. A.3.4 Hold the syringe vertically by hand and pierce closure No. 1 within the marked area, leaving vial No. 1 standing firmly in a vertical position. Withdraw the needle. A.3.5 Repeat the procedure described in A.3.4 three m
42、ore times; however, before withdrawing the needle for the last time, inject the contents of the syringe (1 ml of water) into the vial. A.3.6 Repeat the procedures described in A.3.3 to A.3.5, using closure No. 26 fitted on vial No. 26 (.e. the first closurehial combination in the second row). A.3.7
43、Repeat all of the procedures described in A.3.3 to A.3.6, using, alternately, vials from the two rows, until all of the closures have each been pierced four times. 5 Copyright International Organization for Standardization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/99
44、72545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without license from IHS -,-,- - 8362 PT 2-88 I 4853903 0062359 A r IS0 8362-2 : 1988 (E) A,3.8 Use a new injection needle after every 20 piercings (see figure A,2). A.4 Expression of results A,3.9 Remove the clo
45、sures to be tested from the vials (first row). Pour the contents of all of them through one membrane filter. Ensure that no fragments remain in the vials. Count and record the number of fragments on the filter visible with the naked eye under normal conditions (distance between eye and filter: 25 cm
46、). A.3,10 Repeat the procedure described in A.3.9, using, however, the vials with closures having known fragmentation properties. The recorded numbers of fragments per 100 piercings for the two series shall be reported. A.5 Validity The results obtained on the test closures shall be considered inval
47、id if the results on the known closures lack consistency with previous results; the reason for such inconsistency shall be detected. First row: closures to be tested Second row : closures with known fragmentation properties n n Needle No.fJ Closure/vial combination No. 1 2 3 1; 26; 2; 27; 3 28; 4; 2
48、9; 5; 30 6; 31; 7; 32; 8 etc. etc. 1) Each needle is used for 20 piercings only (see A.3.8). Figure A.2 - Test sequence for fragmentation test 6 Copyright International Organization for Standardization Provided by IHS under license with ISO Licensee=NASA Technical Standards 1/9972545001 Not for Resale, 04/23/2007 22:22:24 MDTNo reproduction or networking permitted without license from IHS -,-,- IS0 8362-2 : 1988 (E) Annex B (normative) Test method for penetrability Fit the closure to be tested on an injection vial and seal with