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High-throughput assays for testing
degradation
For clarifying the effects that various conditions
have on antibody stability, researchers can use
high-throughput testing. This is particularly useful
in the early stages of mAb development when
degradation studies may be constrained by limited
material and time. High-throughput testing is also
preferable for screening multiple drug candidates
before lead candidate selection. Scientists should
use methods that are sensitive to degradation
products, including aggregation, deamidation, and
oxidation products. Examples of high-throughput
methods include capillary electrophoresis-SDS
(CE-SDS) to measure purity, CE-isoelectric focusing
(CE-IEF) to measure changes in charge profile, and
nanoDSF to measure aggregation and unfolding
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.
capsule, or solution, that contains a drug
substance, generally, but not necessarily, in
association with one or more other ingredients
[21 CFR 314.3]
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. Forced degradation means
degrading the new drug substance or product
at conditions more severe than those typically
encountered.
Commonly used forced degradation conditions
include high temperature, freeze-thaw, agitation,
high pH, low pH, light exposure, oxidation, and
glycation. These are all conditions that may be
present during processing, packaging, shipping,
and handling. Although these conditions are
relatively severe compared to real-life storage
and manufacturing conditions, they bring about
degradation products and elucidate degradation
trends within a fairly short time period
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.
