Abstract

Drug immunogenicity and the detection of anti-drug antibodies
(ADA) have an important role in the drug discovery process for
potential new therapeutics. The clinical effects of these immune
responses can affect pharmacokinetics, pharmacodynamics,
safety, or efficacy. Detection and analysis of ADA formation is
crucial for any therapeutic protein product development program.
Consequently, regulatory agencies are looking to understand the
implications of immunogenicity and are directing the industry to
integrate programs for immunogenicity risk management starting
in early phase drug development in clinical and pre-clinical.
Agencies are stipulating that screening and confirmatory IgG and
IgM ADA assays should achieve a sensitivity of at least 100
nanograms per millilitre (ng/mL). Assays developed to assess IgE
ADA should have sensitivity in the high picograms per millilitre
(pg/mL) to low ng/mL range.
Merck’s propriety Single Molecule Counting (SMC™) immunoassay
technology SMC™ technology can support all phases of
immunogenicity testing using digital counting on the SMCxPRO™
high-sensitivity instrument for low-level protein detection.
SMC™ advantages include, ultrasensitivity down to pg/mL
detection for low-affinity ADA and reduced need for dilutions as
well as a wide dynamic range for detection of high-affinity ADA
with minimal matrix interference. All ADA subtypes can be
detected including IgM and IgE and tolerance to high drug
concentrations in sample is well tolerated. Reduced wash steps for
detection of low-affinity antibodies offers advantages and helps
reduce assay time.