Table 2

Tests performed in the extraction study

TestMonographDescription/ acceptance limit
1. Clarity and degree of opalescence of the solutionPh. Eur. The clarity of the solution is the same as that of water R. The absence of any particles or inhomogeneties in a solution results in a clear solution
2. Degree of colouration of the solutionPh. Eur. 2.2.215 Examination of the degree of colouration of the solution in the range brown-yellow-red
3. pH of the solutionPh. Eur. 2.2.3Measurement of the pH
4. Absorbance (extractables and leachables)Ph. Eur The absorbance of the solution was measured from 230nm to 360nm. At these wavelengths the absorbance should not be not greater than 0.20
5. Reducing substancesPh. Eur. To 20.0 mL of solution S add 1 mL of dilute sulfuric acid R and 20.0 mL of 0.002M potassium permanganate. Boil for 3 min. Cool immediately. Add 1 g of potassium iodide R and titrate immediately with 0.01 M sodium thiosulfate, using 0.25 mL of starch solution R as indicator. Carry out a titration using 20.0 mL of the blank. The difference between the titration volumes is not greater than 1.5 mL.
6. TransparencyPh. Eur Fill a container previously used for the preparation of solution S with a volume equal to the nominal capacity of the primary opalescent suspension (2.2.1) diluted 1 in 200 for a container made from polyethylene or propylene and 1 in 400 for other containers. The cloudiness of the suspension is perceptible when viewed through the container and compared with a similar container filled with water R.
7. Weight lossLocal hospital standard≤2% wt loss compared with the initial weight.
8. Subvisible particlesPh. Eur. 2.9.1917 According to method 1. Light obscuration particle count test. The solution complies with the test if the average number of particles present in the units tested does not exceed 6000 per container equal to or greater than 10 µm and does not exceed 600 per container equal to or greater than 25 µm.
9. Closure integrity testPh. Eur. 3.2.9./ manipulated18 A dye immersion test with 0.1% methylene blue.
Immerse the syringes in a 1 g/L solution of methylene blue and reduce the external pressure by 27 kPa for 10 min. Restore atmospheric pressure and leave the vials immersed for 30 min. Rinse the outside of the syringes. None of the vials contains any trace of coloured solution
10. SterilityPh. Eur. 2.6.19 Sterility test with the membrane filtration method, with fluid thioglycollate medium (FTM) and Tryptic Soy Broth (Soybean-Casein Digest Medium) medium (TSB). Incubation during 14 days
11. Silicon*ICP- MS method (see method section for description)
  • *Silicon concentrations were only measured in the WFI batches.