Drug-substance uniformity is an important consideration for the final step in the manufacture of API. Uniformity validation
studies are necessary to ensure that the entire contents of the batch are homogenous and that the drug substance specification
and stability samples are representative of the batch in terms of critical quality attributes. Using risk-based approaches
and comprehensive process characterization studies, appropriate test parameters (e.g., protein concentration) and sample points
(beginning, middle, and end) can be selected. Scientifically sound strategies which may be used in combination for developing
uniformity acceptance criteria include those based on specification limits, measurement error, tolerance intervals of historical
data and equivalency of sample means. Additionally, operational considerations, such as filter weight checks, pre-processing
air drying, product flush, and the use of wet testing and/or engineering runs provide greater assurance of robust and consistent
drug substance filtration and uniformity.
Sushil Abraham* is director of process development, Eric Rydholm, is principal engineer, and Phil Wagner is senior engineer, all at Amgen, Longmont CO, firstname.lastname@example.org
PEER REVIEWED Article submitted: Oct. 20, 2010. Article accepted: Feb. 11, 2011.
1. 21 CFR 211 (Government Printing Office, Washington DC), section 110.
2. G.B. Limenati, Analy. Chem. 6, 1A–6A, (2005).
3. S. Richter and A. Richter, Qual. Engin. 14 (3), 375–380 (2002).