ISO 21881:2019

INTERNATIONAL ISO
STANDARD 21881
First edition
2019-10
Sterile packaged ready for filling glass
cartridges
Cartouches en verre préremplissables sous emballage stérile
Reference number
©
ISO 2019
© ISO 2019
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ii © ISO 2019 – All rights reserved

Contents Page
Foreword .iv
Introduction .v
1 Scope . 1
2 Normative references . 1
3 Terms and definitions . 1
4 Quality system . 3
4.1 General . 3
4.2 Testing . 3
5 Process description and requirements . 3
5.1 Washing . 3
5.2 Drying . 3
5.3 Lubrication . 3
5.4 Capping and crimping . 4
5.5 Plunger insertion . 4
5.6 Packaging . 4
5.7 Sterilization . 4
6 Requirements for glassware . 4
6.1 General . 4
6.2 Material . 4
6.3 Dimensions . 5
6.4 Particles . 5
6.4.1 Visible particles. 5
6.4.2 Sub-visible particles . 5
6.5 Bacterial endotoxin level . 5
7 Requirements for packaging system . 6
7.1 General . 6
7.2 Nest and tub configuration . 7
7.3 Tray configuration . 7
7.4 Nest . 7
7.5 Tub and tray . 8
7.6 Insert liner . 8
7.7 Sealing lid . 8
7.8 Protective bag . 8
7.9 Information to be provided by the manufacturer . 9
8 Marking of the tub or tray . 9
9 Labelling .10
Annex A (informative) Design of tub .11
Annex B (informative) Design of nest .12
Annex C (informative) Design of tray .13
Annex D (normative) Glide force test method to evaluate cartridge lubrication .14
Annex E (informative) Schematic illustrations of examples for the orientation of tubs or
trays within the protective bag .16
Annex F (normative) Closure systems liquid leakage .19
Annex G (informative) Sample preparation for endotoxin and particulate determination .21
Annex H (informative) Product and packaging configuration .25
Bibliography .28
Foreword
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This document was prepared by Technical Committee ISO/TC 76, Transfusion, infusion and injection, and
blood processing equipment for medical and pharmaceutical use.
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iv © ISO 2019 – All rights reserved

Introduction
In the last few years, following the more and more urgent request for ready for filling containers,
packaging manufacturers managed to offer to the pharmaceutical industry containers already washed
and sterilized. This category of products was born about 30 years ago with the appearance on the
market of ready for filling syringes.
Only recently, the sterilized sub-assembled ready for filling syringes have been standardized by
ISO 11040-4 and ISO 11040-7, including the corresponding packaging system. These two International
Standards define the performance requirements of the glass syringes and the related test methods, as
well as the ready for filling packaging system for these syringes, also including the test methods.
ISO 13926-1 specifies the design, dimensions, materials, performance and test methods for glass
cylinders used with pen-injectors for medical use.
Due to the increasing market presence of syringes ready for filling and the associated advantages of this
product for the pharmaceutical industry, the suppliers of packaging materials have started to develop
such systems of this type for cartridges.
The availability of two packaging configurations makes ready for filling glass cartridges suitable for
use both in clinical trials and in mass production. Nest and tub configuration has been conceived to
be used usually with automated filling machines, while tray configuration is usually suitable for small
batches filled manually or by means of semi-automated filling machines.
This duality of packaging configurations calls for a standardization of the production processes,
materials quality and analytical methods when launching these products on the market, in order to
avoid conceiving too highly customized processes.
INTERNATIONAL STANDARD ISO 21881:2019(E)
Sterile packaged ready for filling glass cartridges
1 Scope
This document specifies the characteristics of sterile and ready for filling empty glass cartridges for
injectable preparations, including the minimum requirements of materials, packaging systems and
analytical test methods.
2 Normative references
The following documents are refe
...