Uncertainty estimates of purity measurements based on current information: toward a "live validation" of purity methods.
OBJECTIVE
To predict precision and other performance characteristics of chromatographic purity methods, which represent the most widely used form of analysis in the biopharmaceutical industry.


METHODS
We have conducted a comprehensive survey of purity methods, and show that all performance characteristics fall within narrow measurement ranges. This observation was used to develop a model called Uncertainty Based on Current Information (UBCI), which expresses these performance characteristics as a function of the signal and noise levels, hardware specifications, and software settings.


RESULTS
We applied the UCBI model to assess the uncertainty of purity measurements, and compared the results to those from conventional qualification. We demonstrated that the UBCI model is suitable to dynamically assess method performance characteristics, based on information extracted from individual chromatograms.


CONCLUSIONS
The model provides an opportunity for streamlining qualification and validation studies by implementing a "live validation" of test results utilizing UBCI as a concurrent assessment of measurement uncertainty. Therefore, UBCI can potentially mitigate the challenges associated with laborious conventional method validation and facilitates the introduction of more advanced analytical technologies during the method lifecycle.
Amgen, Analytical Sciences, Thousand Oaks, California 91320, USA. iapostol@amgen.com
Izydor
I
Apostol
Drew
D
Kelner
Xinzhao Grace
XG
Jiang
Gang
G
Huang
Jette
J
Wypych
Xin
X
Zhang
Jessica
J
Gastwirt
Kenneth
K
Chen
Szilan
S
Fodor
Suminda
S
Hapuarachchi
Dave
D
Meriage
Frank
F
Ye
Leszek
L
Poppe
Wojciech
W
Szpankowski
D002845:Chromatography / Q000379:methods*; D008956:Models, Chemical; D015233:Models, Statistical; D012984:Software; D035501:Uncertainty