Drugs and the pharmaceutical sciences

400 Colton and Bestwick
This experiment demonstrated shaking is an acceptable extraction technique. It is
vigorous enough to promote extractables in a relatively short period of time. Shaking
may actually facilitate increased detection due to the lower volume required.
LEACHABLE TESTS
The goal of leachables testing is to determine what migrates out of the filter into the
pharmaceutical formulation when exposed to process conditions that are typical or that
test the extreme limits of acceptable conditions. Since leachables are typically a subset of
extractables, some filter users perform only leachable tests. Whenever possible, the
leachable tests should be performed with the same filter as is used in the process.
The conditions for leachables testing are determined by the maximum acceptable
range of the process conditions. The test conditions are then chosen based on worst case
conditions. Table 1 shows how this might be done.
Test Parameters and Extraction Conditions:
1. Filter Size: In the example shown in Table 1, the manufacturing process uses three
30 inch filters. It is acceptable to test with one 10 inch filter if the materials of
construction can be verified to be equivalent in the two sizes. The filter manufacturer
can usually provide a letter to this effect upon request.
2. Filtration/Extraction Product Volume: If the filter is used to process 2000 L, it is
considered advantageous for the extraction to be performed with a substantially
smaller volume because the concentration of leachables will be higher with a smaller
volume and therefore easier to detect and identify. The process volume and
extraction volume cannot be directly compared because the process uses a 30 inch
filter and the extraction will be performed with a 10 inch filter. To normalize the
difference in filter surface areas, it is necessary to determine the ratio of the
extraction volume to the surface area. In this case, testing a 10 inch filter in only 2 L
of formulation leads to a volume/surface area ratio approximately 100 that of
the process.
3. Rinsing: As mentioned previously, rinsing generally decreases the level of
leachables. The rinsing volume should be no more than is used for the process
TABLE 1 Comparison of Process Conditions to Leachables Test Conditions
Process conditions Test conditions
Filter part number Part number for 30 inch Part number for 10 inch
filter
filter
Filter area 3 filters 2.1 m 2 ¼ 6.3m 2
0.7 m 2
Product name API name API name
Filtration/extraction product
volume
2000 L ≤ 2L
Product volume/surface area 2000 L/6.3 m 2 ¼ 320 L/m 2
2 L/0.7 m 2 ¼ 2.9 L/m 2
Rinsing 20 L WFI 2 L WFI
Sterilization 125 C, 30 min 126 ± 1 C, 30 min
Contact time Up to 4 h At least 4 h
Temperature range 15–30 C 30± 5 C