EUROPEAN PHARMACOPOEIA 9.0 3.2.2.1.

Plastic containers for aqueous solutions (parenteral)

The nature and amount of the additives are determined by 01/2008:90003

the type of the polymer, the process used to convert the corrected 6.0
polymer into the container and the intended purpose of the
container. Additives may consist of antioxidants, stabilisers,
plasticisers, lubricants, colouring matter and impact modifiers.
Antistatic agents and mould-release agents may be used only
for containers for preparations for oral use or for external 3.2.2.1. PLASTIC CONTAINERS FOR
use for which they are authorised. Acceptable additives are
indicated in the type specification for each material described AQUEOUS SOLUTIONS FOR INFUSION
in the Pharmacopoeia. Other additives may be used provided DEFINITION
they are approved in each case by the competent authority Plastic containers for aqueous solutions for infusion are
responsible for the licensing for sale of the preparation. manufactured from one or more polymers, if necessary
with additives. The containers described in this section
For selection of a suitable plastic container, it is necessary to are not necessarily suitable for emulsions. The polymers
know the full manufacturing formula of the plastic, including most commonly used are polyethylene, polypropylene and
all materials added during formation of the container so poly(vinyl chloride). The specifications of this text are to be
that the potential hazards can be assessed. In justified cases, read in conjunction with section 3.2.2. Plastic containers and
further detailed information may be necessary to assess the closures for pharmaceutical use.
impact on chronic use and for vulnerable patient groups. The
The containers may be bags or bottles. They have a site
plastic container chosen for any particular preparation should
suitable for the attachment of an infusion set designed to
be such that :
ensure a secure connection. They may have a site that allows
an injection to be made at the time of use. They usually
– the ingredients of the preparation in contact with the plastic have a part that allows them to be suspended and which will
material are not significantly adsorbed on its surface and withstand the tension occurring during use. The containers
do not significantly migrate into or through the plastic, must withstand the sterilisation conditions to which they will
be submitted. The design of the container and the method of
– the plastic material does not release substances in quantities sterilisation chosen are such that all parts of the containers
sufficient to affect the stability of the preparation or to that may be in contact with the infusion are sterilised. The
present a risk of toxicity. containers are impermeable to micro-organisms after closure.
The containers are such that after filling they are resistant to
Using material or materials selected to satisfy these criteria, a damage from accidental freezing which may occur during
number of identical type samples of the container are made by transport of the final preparation. The containers are and
a well-defined procedure and submitted to practical testing in remain sufficiently transparent to allow the appearance of the
conditions that reproduce those of the intended use, including, contents to be examined at any time, unless otherwise justified
where appropriate, sterilisation. In order to confirm the and authorised.
compatibility of the container and the contents and to ensure The empty containers display no defects that may lead to
that there are no changes detrimental to the quality of the leakage and the filled and closed containers show no leakage.
preparation, various tests are carried out such as verification of For satisfactory storage of some preparations, the container
the absence of changes in physical characteristics, assessment has to be enclosed in a protective envelope. The initial
of any loss or gain through permeation, detection of pH evaluation of storage has then to be carried out using the
changes, assessment of changes caused by light, chemical tests container enclosed in the envelope.
and, where appropriate, biological tests.
TESTS
The method of manufacture is such as to ensure reproducibility Solution S. Use solution S within 4 h of preparation. Fill a
for subsequent bulk manufacture and the conditions of container to its nominal capacity with water R and close it,
manufacture are chosen so as to preclude the possibility of if possible using the usual means of closure ; otherwise close
contamination with other plastic materials or their ingredients. using a sheet of pure aluminium. Heat in an autoclave so
The manufacturer of the product must ensure that containers that a temperature of 121 ± 2 °C is reached within 20 min
made in production are similar in every respect to the type to 30 min and maintain at this temperature for 30 min. If
samples. heating at 121 °C leads to deterioration of the container, heat
at 100 °C for 2 h.
For the results of the testing on type samples to remain valid, Blank. Prepare a blank by heating water R in a borosilicate-glass
it is important that : flask closed by a sheet of pure aluminium at the temperature
and for the time used for the preparation of solution S.
– there is no change in the composition of the material as
defined for the type samples, Appearance of solution S. Solution S is clear (2.2.1) and
colourless (2.2.2, Method II).
– there is no change in the manufacturing process as defined Acidity or alkalinity. To a volume of solution S corresponding
for the type samples, especially as regards the temperatures to 4 per cent of the nominal capacity of the container add
to which the plastic material is exposed during conversion 0.1 mL of phenolphthalein solution R. The solution is
or subsequent procedures such as sterilisation, colourless. Add 0.4 mL of 0.01 M sodium hydroxide. The
solution is pink. Add 0.8 mL of 0.01 M hydrochloric acid and
– scrap material is not used. 0.1 mL of methyl red solution R. The solution is orange-red
or red.
Recycling of excess material of well-defined nature and Absorbance (2.2.25). Measure the absorbance of solution S
proportions may be permitted after appropriate validation. from 230 nm to 360 nm, using the blank (see solution S) as the
compensation liquid. At these wavelengths, the absorbance is
Subject to satisfactory testing for compatibility of each not greater than 0.20.
different combination of container and contents, the materials Reducing substances. To 20.0 mL of solution S add 1 mL
described in the Pharmacopoeia are recognised as being of dilute sulfuric acid R and 20.0 mL of 0.002 M potassium
suitable for the specific purposes indicated, as defined above. permanganate. Boil for 3 min. Cool immediately. Add 1 g

General Notices (1) apply to all monographs and other texts 429
3.2.3. Sterile plastic containers for human blood EUROPEAN PHARMACOPOEIA 9.0

of potassium iodide R and titrate immediately with 0.01 M capacity is the volume of blood to be collected in the container.
sodium thiosulfate, using 0.25 mL of starch solution R as The containers are of a shape such that when filled they may
indicator. Carry out a titration using 20.0 mL of the blank. be centrifuged.
The difference between the titration volumes is not greater The containers are fitted with a suitable device for suspending
than 1.5 mL. or fixing which does not hinder the collection, storage,
Transparency. Fill a container previously used for the processing or administration of the blood.
preparation of solution S with a volume equal to the nominal The containers are enclosed in sealed, protective envelopes.
capacity of the primary opalescent suspension (2.2.1)
diluted 1 in 200 for a container made from polyethylene CHARACTERS
or polypropylene and 1 in 400 for other containers. The
The container is sufficiently transparent to allow adequate
cloudiness of the suspension is perceptible when viewed
visual examination of its contents before and after the taking
through the container and compared with a similar container
of the blood and is sufficiently flexible to offer minimum
filled with water R.
resistance during filling and emptying under normal
LABELLING conditions of use. The container contains not more than 5 mL
of air.
The label accompanying a batch of empty containers includes
a statement of : TESTS
– the name and address of the manufacturer,
Solution S1. Fill the container with 100 mL of a sterile,
– a batch number which enables the history of the container pyrogen-free 9 g/L solution of sodium chloride R. Close the
and of the plastic material of which it is manufactured to container and heat it in an autoclave so that the contents are
be traced. maintained at 110 °C for 30 min.
If the container to be examined contains an anticoagulant
solution, first empty it, rinse the container with 250 mL of
01/2008:30203 water for injections R at 20 ± 1 °C and discard the rinsings.
Solution S2. Introduce into the container a volume of water
for injections R corresponding to the intended volume of
anticoagulant solution. Close the container and heat it in an
autoclave so that the contents are maintained at 110 °C for
3.2.3. STERILE PLASTIC CONTAINERS 30 min. After cooling, add sufficient water for injections R to
FOR HUMAN BLOOD AND fill the container to its nominal capacity.
BLOOD COMPONENTS If the container to be examined contains an anticoagulant
solution, first empty it and rinse it as indicated above.
Plastic containers for the collection, storage, processing and Resistance to centrifugation. Introduce into the container a
administration of blood and its components are manufactured volume of water R, acidified by the addition of 1 mL of dilute
from one or more polymers, if necessary with additives. hydrochloric acid R, sufficient to fill it to its nominal capacity.
The composition and the conditions of manufacture of Envelop the container with absorbent paper impregnated with
the containers are registered by the appropriate competent a 1 in 5 dilution of bromophenol blue solution R1 or other
authorities in accordance with the relevant national legislation suitable indicator and then dried. Centrifuge at 5000 g for
and international agreements. 10 min. No leakage perceptible on the indicator paper and no
When the composition of the materials of the different parts permanent distortion occur.
of the containers correspond to the appropriate specifications, Resistance to stretch. Introduce into the container a
their quality is controlled by the methods indicated in those volume of water R, acidified by the addition of 1 mL of
specifications (see 3.1. Materials used for the manufacture of dilute hydrochloric acid R, sufficient to fill it to its nominal
containers and subsections). capacity. Suspend the container by the suspending device at
Materials other than those described in the Pharmacopoeia the opposite end from the blood-taking tube and apply along
may be used provided that their composition is authorised by the axis of this tube an immediate force of 20 N (2.05 kgf).
the competent authority and that the containers manufactured Maintain the traction for 5 s. Repeat the test with the force
from them comply with the requirements prescribed for Sterile applied to each of the parts for filling and emptying. No break
Plastic Containers for Human Blood and Blood Components. and no deterioration occur.
In normal conditions of use the materials do not release Leakage. Place the container which has been submitted to
monomers, or other substances, in amounts likely to be the stretch test between two plates covered with absorbent
harmful nor do they lead to any abnormal modifications of paper impregnated with a 1 in 5 dilution of bromophenol
the blood. blue solution R1 or other suitable indicator and then dried.
The containers may contain anticoagulant solutions, Progressively apply force to the plates to press the container
depending on their intended use, and are supplied sterile. so that its internal pressure (i.e. the difference between the
Each container is fitted with attachments suitable for the applied pressure and atmospheric pressure) reaches 67 kPa
intended use. The container may be in the form of a single unit within 1 min. Maintain the pressure for 10 min. No signs of
or the collecting container may be connected by one or more leakage are detectable on the indicator paper or at any point of
tubes to one or more secondary containers to allow separation attachment (seals, joints, etc.).
of the blood components to be effected within a closed system. Vapour permeability. For a container containing an
The outlets are of a shape and size allowing for adequate anticoagulant solution, fill with a volume of a 9 g/L solution of
connection of the container with the blood-giving equipment. sodium chloride R equal to the volume of blood for which the
The protective coverings on the blood-taking needle and on container is intended.
the appendages must be such as to ensure the maintenance For an empty container, fill with the same mixture of
of sterility. They must be easily removable but must be anticoagulant solution and sodium chloride solution. Close
tamper-proof. the container, weigh it and store it at 5 ± 1 °C in an atmosphere
The capacity of the containers is related to the nominal with a relative humidity of (50 ± 5) per cent for 21 days. At
capacity prescribed by the national authorities and to the the end of this period the loss in mass is not greater than 1 per
appropriate volume of anticoagulant solution. The nominal cent.

430 See the information section on general monographs (cover pages)