Appendix XIX F. Sets for the Transfusion of Blood and Blood Components
DEFINITION
Sets for the transfusion of blood and blood components consist principally of plastic tubing to which are fitted the parts necessary to enable the set to be used for transfusion in the appropriate manner. Sets include a closure-piercing device, a blood filter, a drip chamber, a flow regulator, a Luer connector and, usually, a site that allows an injection to be made at the time of use. When the sets are to be used with containers requiring an air-filter, this may be incorporated in the closure-piercing device or a separate air-inlet device may be used. The chamber enclosing the blood filter, the drip chamber and the main tubing are transparent. The materials chosen and the design of the set are such as to ensure absence of haemolytic effects. The sets comply with current standards regarding dimensions and performance.
All parts of the set that may be in contact with blood and blood components are sterile and pyrogen-free. Each set is presented in an individual package that maintains the sterility of the contents. The sets are not to be re-sterilised or re-used.
Sets for the transfusion of blood and blood components are manufactured in accordance with the rules of good manufacturing practice for medical devices and any relevant national regulations.
TESTS
Carry out the tests on sterilised sets.
Solution S
Make a closed circulation system from 3 sets and a 300 mL borosilicate-glass vessel. Fit to the vessel a suitable thermostat device that maintains the temperature of the liquid in the vessel at 37 ± 1 °C. Circulate 250 mL of water for injections R through the system in the direction used for transfusion for 2 h at a rate of 1 L/h (for example using a peristaltic pump applied to as short a piece of suitable silicone elastomer tubing as possible). Collect the whole of the solution and allow to cool.
Appearance of solution
Solution S is clear (2.2.1) and colourless (2.2.2, Method II).
Acidity or alkalinity
To 25 mL of solution S add 0.15 mL of BRP indicator solution R. Not more than 0.5 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to blue. To 25 mL of solution S add 0.2 mL of methyl orange solution R. Not more than 0.5 mL of 0.01 M hydrochloric acid is required to reach the beginning of the colour change of the indicator.
Absorbance (2.2.25)
Maximum 0.30, determined between wavelengths of 230 nm and 250 nm on solution S; maximum 0.15, determined between wavelengths of 251 nm and 360 nm on solution S.
Reducing substances
Carry out the test within 4 h of preparation of solution S To 20.0 mL of solution S add 1 mL of dilute sulfuric acid R and 20.0 mL of 0.002 M potassium permanganate. Boil for 3 min and cool immediately. Add 1 g of potassium iodide R and titrate with 0.01 M sodium thiosulfate using 0.25 mL of starch solution R as indicator. Carry out a blank test using 20 mL of water for injections R. The difference between the titration volumes is not greater than 2.0 mL.
Ethylene oxide
Carrier gashelium for chromatography R.
Flow rate 20 mL/min.
Detection Flame ionisation.
Verify the absence of peaks interfering with the ethylene oxide peak by carrying out the test using an unsterilised set or using the same chromatographic system with the following modifications.
Ethylene oxide solutionPrepare in a fume cupboard. Place 50.0 mL of dimethylacetamide R in a 50 mL vial, stopper, secure the stopper and weigh to the nearest 0.1 mg. Fill a 50 mL polyethylene or polypropylene syringe with gaseous ethylene oxide R, allow the gas to remain in contact with the syringe for about 3 min, empty the syringe and fill again with 50 mL of gaseous ethylene oxide R. Fit a hypodermic needle to the syringe and reduce the volume of gas in the syringe from 50 mL to 25 mL. Inject these 25 mL of ethylene oxide slowly into the vial, shaking gently and avoiding contact between the needle and the liquid. Weigh the vial again: the increase in mass is 45 mg to 60 mg and is used to calculate the exact concentration of the solution (about 1 g/L).
Test Weigh the set after removing the package. Cut the set into pieces of maximum dimension 1 cm and place the pieces in a 250-500 mL vial containing 150 mL of dimethylacetamide R. Close the vial with a suitable stopper and secure the stopper. Place the vial in an oven at 70 ± 1 °C for 16 h. Remove 1 mL of the hot gas from the vial and inject it onto the column. From the calibration curve and the height of the peak obtained, calculate the mass of ethylene oxide in the vial.
Calibration curve In a series of 7 vials of the same type as that used for the test and each containing 150 mL of dimethylacetamide R, place respectively 0 mL, 0.05 mL, 0.10 mL, 0.20 mL, 0.50 mL, 1.00 mL and 2.00 mL of the ethylene oxide solution, i.e. about 0 µg, 50 µg, 100 µg, 200 µg, 500 µg, 1000 µg and 2000 µg of ethylene oxide. Stopper the vials, secure the stoppers and place the vials in an oven at 70 ± 1 °C for 16 h. Inject 1 mL of the hot gas from each vial onto the column and draw a calibration curve from the heights of the peaks and the mass of ethylene oxide in each flask.
Limit If the label states that ethylene oxide has been used for sterilisation:
Extraneous particles
Fill the set via the normal inlet with a 0.1 g/L solution of sodium laurilsulfate R, previously filtered through a sintered-glass filter (16) (2.1.2) and heated to 37 °C. Collect the liquid via the normal outlet. When examined under suitable conditions of visibility, the liquid is clear and practically free from visible particles and filaments (it is assumed that particles and filaments with a diameter equal to or greater than 50 µm are visible to the naked eye).
Flow rate
Pass through a complete set with the flow regulator fully open 50 mL of a solution having a viscosity of 3 mPa⋅s (3 cP) (for example a 33 g/L solution of macrogol 4000 R at 20 °C) under a static head of 1 m. The time required for passage of 50 mL of the solution is not greater than 90 s.
Resistance to pressure
Make tight the extremities of the set and any air-inlet device. Connect the set to a compressed air outlet fitted with a pressure regulator. Immerse the set in a tank of water at 20-23 °C. Apply progressively an excess pressure of 100 kPa and maintain for 1 min. No air bubble escapes from the set.
Transparency
Use as reference suspension the primary opalescent suspension (2.2.1) diluted 1 in 8 for sets having tubing with an external diameter less than 5 mm and diluted 1 in 16 for sets having tubing with an external diameter of 5 mm or greater. Circulate the reference suspension through the set and compare with a set from the same batch filled with water R. The opalescence and presence of bubbles are discernible.
Residue on evaporation
Evaporate 50.0 mL of solution S to dryness on a water-bath and dry to constant mass in an oven at 100-105 °C. Carry out a blank test using 50.0 mL of water for injections R. The difference between the masses of the residues is not greater than 1.5 mg.
Sterility (2.6.1)
The sets comply with the test for sterility. If the sets are stated to be sterile only internally, pass 50 mL of buffered sodium chloride-peptone solution pH 7.0 (2.6.12) through the set and use to carry out the test by the membrane filtration method.
If the sets are stated to be sterile both internally and externally, open the package with the necessary aseptic precautions and:
Pyrogens (2.6.8)
Connect together 5 sets and pass through the assembly at a flow rate not exceeding 10 mL/min 250 mL of a sterile, pyrogen-free 9 g/L solution of sodium chloride R. Collect the solution aseptically in a pyrogen-free container. The solution complies with the test for pyrogens. Inject per kilogram of the rabbit’s mass, 10 mL of the solution.
LABELLING
The label states, where applicable, that the set has been sterilised using ethylene oxide.