Biopharmaceutical Regulatory Compliance

CHEN 5550

Homework

1. FMEA analysis for removal of a detergent from a protein preparation using an ion-
exchange chromatography method is shown in Table 3.3. This type of analysis can be
used to exclude non-key parameters.

a. Determine which variables need to be investigated further for characterization

b. Devise an experimental plan to determine the Design Space for detergent

removal.

Parameters not specified in Table 3.3:

Start collect early 10 CV (column volume)

Start collect late 20 CV

Stop collect early 20 CV

Stop collect late 30 CV

Flow rate low 30 cm/hr

Flow rate high 120 cm/hr
 (50 pts) The following DOE is an eight run Plackett-Burman Design for testing the
ruggedness of an analytical method. Variable A thru G were determined to be potentially
important. Determine if the method is rugged.

A B C D E F G
1 98.13 98.13 98.13 -98.13 98.13 -98.13 -98.13
- - -
2 110.57 110.57 110.57 110.57 110.57 110.57 110.57
- - -
3 107.83 107.83 107.83 107.83 107.83 107.83 107.83
4 95.87 -95.87 -95.87 95.87 95.87 95.87 -95.87
5 -97.23 97.23 -97.23 -97.23 97.23 97.23 97.23
6 91.07 -91.07 91.07 -91.07 -91.07 91.07 91.07
7 99.33 99.33 -99.33 99.33 -99.33 -99.33 99.33
8 -99.97 -99.97 -99.97 -99.97 -99.97 -99.97 -99.97
Sum/4 -7.8 2.63 3.8 6.8 -0.47 -2.63 -2.27

For each column, use sign from each row with test result number and sum up the
numbers.
+98.13-110.57
Divide resulting number by half the number of runs (4)