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11.3 CONTAINERS FOR HUMAN BLOOD AND BLOOD COMPONENTS

Appendix 11.3 should be read in conjunction with Appendix 11.2.

1. Sterile Plastic Containers for Human Blood and Blood Components

           Plastic containers for the collection, storage, processing, and administration of blood and blood components are supplied sterile. In normal conditions of use, the materials of the different parts of the containers do not release monomers or other substances in amounts likely to be harmful and do not lead to any abnormal modifications of the blood. The containers may contain anticoagulant solutions depending on their intended use.

           Each container is fitted with attachments suitable for its intended use. The container may be in the form of a single unit or the collecting container may be connected by one or more tubes to one or more secondary containers to allow separation of the blood components to be effected within a closed system. The outlets are of a shape and size allowing for adequate connection of the container with the blood transfusion equipment. The protective coverings on the blood-taking needle and on the appendages are designed to ensure that sterility is maintained. They are easily removable but are tamper-evident. The containers are fitted with a suitable device for suspending or fixing that does not hinder the collection, storage, processing, or administration of blood.

           The capacity of the containers is related to the nominal capacity, that is, to the volume of blood to be collected in the container and to the appropriate volume of anticoagulant solution. The containers are shaped in such a manner that when filled they may be centrifuged. They are enclosed in sealed, protective envelopes.

           Description The container is sufficiently transparent to allow adequate visual examination of its contents before and after taking the blood. It is also sufficiently flexible to offer minimal resistance during filling and emptying under normal conditions of use. The container contains not more than 5 ml of air.

           Resistance to centrifugation Introduce into the container a sufficient volume of water, previously acidified with 1 ml of 2 M hydrochloric acid, to fill it to its nominal capacity. Envelop the container with absorbent paper that has been impregnated with a fivefold dilution of aqueous bromophenol blue TS or other suitable indicator and then dried. Centrifuge at 5000 × g for 10 minutes. No leakage is detectable on the indicator paper and no permanent distortion occurs.

           Resistance to stretch Introduce into the container a sufficient volume of water previously acidified with 1 ml of 2 M hydrochloric acid to fill it to its nominal capacity. Suspend the container by the suspending device at the opposite end from the blood-taking tube, apply an immediate force of 20 N along the axis of the tube and maintain the traction for 5 seconds. Repeat the test with the force applied to each of the parts for filling and emptying. No break and no deterioration occur.

           Leakage Place the container that has been used in the test for Resistance to stretch between two plates covered with absorbent paper that has been impregnated with a fivefold dilution of aqueous bromophenol blue TS or other suitable indicator and then dried. Apply a force progressively to the plates to press the container so that its internal pressure (that is, the difference between the applied pressure and atmospheric pressure) reaches 67 kPa (about 502 Torr) within 1 minute. Maintain the pressure for 10 minutes. No signs of leakage are detectable on the indicator paper or at any point of attachment (seals, joints, etc.).

           Emptying under pressure Fill the container with a volume of water, at 4º to 6º, equal to the nominal capacity. Attach a transfusion set without an intravenous cannula to one of the connectors. Compress the container so as to maintain an internal pressure of 40 kPa (about 300 Torr) throughout the emptying. The container empties in less than 2 minutes.

           Speed of filling Attach the container by means of the blood-taking tube fitted with the needle to a reservoir containing a suitable solution having a viscosity equal to that of blood (a 33.5 per cent w/v solution of sucrose at 37º is suitable). Maintain the internal pressure of the reservoir at 9.3 kPa (about 70 Torr) with the base of the reservoir and the upper part of the container at the same level. The volume of liquid that flows into the container in 8 minutes is not less than the nominal capacity of the container.

           Resistance to temperature variations Place the container in a suitable chamber having an initial temperature of 20º to 23º. Cool rapidly to –80º and maintain at this temperature for 24 hours. Raise the temperature to 50º and maintain for 12 hours. Allow to cool to room temperature. The container complies with the test for Water Vapour Permeability described in 1.3.5 (Appendix 11.2) and the tests for Resistance to centrifugation, Resistance to stretch, Leakage, Emptying under pressure, and Speed of filling.

           Transparency Prepare a 16-fold dilution of the suspension prepared for Standard of opalescence (Method I, Appendix 4.1), so as to give an absorbance at 640 nm of 0.37 to 0.43 (Appendix 2.2). Fill the empty container to its nominal capacity with the diluted suspension. The cloudiness of the diluted suspension is detectable when viewed through the container, as compared with a similar container filled with water.

           Sterility Complies with the “Sterility Test” (Method I, Appendix 10.1) with the following modifications. Introduce aseptically into the container 100 ml of saline TS and shake the container to ensure that the internal surfaces have been entirely wetted. Filter the contents through a membrane filter and place the membrane in the appropriate culture medium.

           Pyrogens If the container being examined contains an anticoagulant solution, empty it, rinse the container with 250 ml of Sterile Water for Injection at 19º to 21º and discard the rinsings. Fill the container with 100 ml of pyrogen-free sodium chloride TS. Close the container and heat it in an autoclave so that the contents are maintained at 110º for 30 minutes (solution A). Solution A complies with the “Pyrogen Test” (Appendix 8.2), using 10 ml of the solution per kg of the rabbit’s weight.

           Abnormal toxicity Solution A complies with the “Abnormal Toxicity Test for Biological Products” (Appendix 8.1), using 0.5 ml of the solution.

           Packaging and storage Sterile plastic containers for human blood and blood components are packed in protective tamper-evident envelopes and stored at a temperature not exceeding 30º, protected from light. The protective envelopes are sufficiently robust to withstand normal handling.

           On removal from its protective envelope the container shows no signs of leakage and no growth of micro-organisms.

           Labelling The label states (1) the date after which the container is not intended to be used; (2) that, once withdrawn from its protective envelope, the container must be used within 10 days.

A part of the label is reserved for the information required concerning the blood or blood component for which the container is intended to be used. 

           The ink or other substance used to print the labels or the writing does not diffuse into the plastic material of the container and it remains legible up to the time of use. 

2. Empty Sterile Containers of Plasticized Polyvinyl Chloride for Human Blood and Blood Components 

           Unless otherwise authorized as described in Appendix 11.2; the nature and composition of the material from which the containers are made should contain not less than 55 per cent of polyvinylchloride. No colouring matter is added. 

           Empty sterile containers of plasticized polyvinyl chloride for human blood and blood components comply with the tests stated under Sterile Plastic Containers for Human Blood and Blood Components, and with the following tests. 

           Acidity or alkalinity Introduce into the container a volume of Sterile Water for Injection corresponding to the intended volume of anticoagulant solution. Close the container and heat in an autoclave so that the contents are maintained at 110º for 30 minutes. Cool and add sufficient Sterile Water for Injection to fill the container to its nominal capacity (solution A). To a volume of solution A corresponding to 4 per cent of the nominal capacity of the container add 0.1 ml of dilute phenolphthalein TS: the solution remains colourless. Add 0.4 ml of 0.010 M sodium hydroxide: the solution is pink. Add 0.8 ml of 0.010 M hydrochloric acid and 0.1 ml of methyl red TS: the solution is orange-red or red.

           Light absorption Heat Sterile Water for Injection in a borosilicate-glass flask in an autoclave at 110º for 30 minutes (solution B). Measure the light absorption of solution A (Appendix 2.2) in the range 230 to 360 nm using solution B in the reference cell. The absorbance is not more than 0.30 at any wavelength from 230 to 250 nm and not more than 0.10 at any wavelength from 251 to 360 nm. 

           Ammonium Place 10.0 ml of solution A in a comparison tube, add sufficient water to make 50.0 ml, add 2.0 ml of sodium hydroxide solution (1 in 3) and 1.0 ml of alkaline mercuric potassium iodide TS, and shake well. The solution has no more colour than the following control solution. 

           Control solution: Instead of solution A, use the solution prepared by the addition of water to 0.50 ml of ammonium standard solution (10 ppm NH4) to make 10.0 ml, and perform in the same manner. 

           Extractable di(2-ethylhexyl) phthalate Prepare five standard solutions containing 0.020 per cent w/v, 0.010 per cent w/v, 0.0050 per cent w/v, 0.0020 per cent w/v and 0.0010 per cent w/v of di(2-ethylhexyl) phthalate in Extraction Solvent ES and measure the absorbances at the maximum at 272 nm (Appendix 2.2). Plot a calibration curve of absorbance against concentration of di(2- ethylhexyl) phthalate.

           Using the donor tubing and the needle or adaptor, fill the empty container with a volume equivalent to half the nominal capacity with Extraction Solvent ES previously heated to 37º in a well-stoppered flask. Remove the air completely from the container and seal the donor tube. Immerse the filled container and seal the donor tube. Immerse the filled container in a horizontal position in a water-bath maintained at 36º to 38º for 59 to 61 minutes without shaking. Remove the container from the water-bath, invert it gently 10 times and transfer the contents to a glass flask. Immediately measure the absorbance at the maximum at 272 nm. The percentage of di(2-ethylhexyl) phthalate, calculated from the calibration curve, is not more than 0.010 per cent w/v.

           Reagent

           EXTRACTION SOLVENT ES Ethanol diluted to have a relative density (Appendix 4.9), of 0.9373 to 0.9378, verified with a pycnometer.

3. Sterile Containers of Plasticized Polyvinyl Chloride for Human Blood Containing an Anticoagulant Solution

           Unless otherwise authorized as described under Appendix 11.2, the nature and composition of the material from which the containers are made should meet the type specification as described under Empty Sterile Containers of Plasticized Polyvinyl Chloride for Human Blood and Blood Components.

           Sterile plastic containers containing an anticoagulant solution that complies with the monograph for Anticoagulant and Preservative Solutions for Blood are used for the collection, storage and administration of blood. Before filling they comply with the description and characteristics stated under Empty Sterile Containers of Plasticized Polyvinyl Chloride for Human Blood and Blood Components.

           After addition of the anticoagulant solution the containers comply with the tests stated under Sterile Plastic Containers for Human Blood and Blood Components and with the following tests.

           Light absorption Measure the light absorption (Appendix 2.2), of the anticoagulant solution from the container in the range 250 to 350 nm using in the reference cell an anticoagulant solution of the same composition that has not been in contact with a plastic material. The absorbance at the maximum at 280 nm is not more than 0.5.

           Extractable di(2-ethylhexyl) phthalate Carefully remove the anticoagulant solution by means of the flexible transfer tube. Using a funnel fitted to the tube, completely fill the container with water, leave in contact for 1 minute squeezing the container gently and empty completely. Repeat the rinsing. The container then complies with the test described under Empty Sterile Containers of Plasticized Polyvinyl Chloride for Human Blood and Blood Components.

           Volume of anticoagulant solution The volume does not differ by more than ±10 per cent from the stated volume when determined by emptying the container and collecting the anticoagulant solution in a graduated cylinder.