BioOutsource offers a comprehensive range of services to support the biological evaluation of Humira including characterisation, comparability, lot release and clinical assessments. Our off-the-shelf binding assays and bioassays include binding measurements for TNF-Alpha and the Fc-Receptors, C1q binding as well as the Humira Complement Dependent Cytotoxicity assay (CDC assay) and Humira Antibody Dependent Cellular Cytotoxicity assay (ADCC assay). A number of different potency assays are also available reflecting the diverse mechanisms of action of Humira.
TNF-Alpha is a potent pro-inflammatory cytokine involved in a number of different diseases playing an integral role in autoimmune diseases. TNF-Alpha molecules are homotrimers and exist either as membrane TNF-alpha on cell surfaces (mTNF-alpha) or following cleavage of this membrane bound form by the TNF-alpha converting enzyme (TACE), exist as free molecules in solution (sTNF-Alpha). Two different classes of biological drug products that target TNF-Alpha have been approved; TNF-Alpha monoclonal antibodies (Infiximab and Adalimumab) and a soluble TNF-Alpha receptor (Etanercept). Each product class can bind to both the soluble and membrane-bound forms of TNF-Alpha.
Humira (Adalimumab) is a fully humanised monoclonal antibody and has been approved for the treatment of severe rheumatoid arthritis, ankolysing sponglylitis and Crohn’s disease amongst others. Humira possesses a wide range of distinct biological activities, mirroring the biology of TNF-alpha and it’s ability to function as both a ligand and as a receptor.
The Fab-related binding function of Humira (Adalimumab) allows the antibody to bind to both soluble and membrane TNF-Alpha with high affinity preventing activation of the TNF receptors on TNF-Alpha sensitive cells. Following binding to mTNF-Alpha, Humira mediates a range of additional biological responses including reverse signaling which results in apoptosis and cytokine suppression, Complement Dependent Cytotoxicity (CDC) and Antibody Dependent Cellular Cytoxicity (ADCC).
BioOutsource provides cutting edge methodologies using a range of novel cell lines allowing end to end support for Humira biosimilar manufacturers. We have extensive experience, working with over 10 different Humira biosimilar products across the clinical phases: