Module 9 2024

03/09/2024

MSD Platform – Example

A

100000.0

Assessment of clinical samples for presence of anti-adalimumab antibodies. Screening assay (A) and confirmatory assay (B).

10000.0

Blue and purple: Adalimumab-treated patient serum samples (T0, T3, T6) Green: negative controls Red: positive control

1000.0

100.0

Assay principle

10.0

B

Sulfo-tag adalimumab

100000.0

Left: Adalimumab-treated patient serum samples (T0, T3, T6) Middle: Adalimumab-treated patient serum samples (T0, T3, T6) pre-incubated with excess drug Right: Adalimumab-treated patient serum samples (T0, T3, T6) pre-incubated with excess irrelevant drug

ADA

10000.0

1000.0

biotin-adalimumab

100.0

10.0

The Organisation for Professionals in Regulatory Affairs

17

ECL Technology

Advantages: • Bridging format ensures high specificity

• Signal amplification and large dynamic range of detection • Increased sensitivity and drug tolerance over ELISAs (usually) • Detection of low affinity antibodies • Assays can be provided as single- or multiplex assays (with up to 10-plex in each well)

Disadvantages: • Dedicated equipment; single vendor • Requires labelled therapeutic - labelling could mask epitope

→ conjugation ratios must be optimized

• IgG4 ADA may not be detected in bridging format

The Organisation for Professionals in Regulatory Affairs

18

9