BioPharmaSpec provides a complete solution for Infliximab/ Remsima/ Inflectra/ Remicade comparability, biosimilarity and characterization studies.
Infliximab (trade names Remicade/ Remsima/ Inflectra) is a chimeric monoclonal antibody, meaning it is a combination of mouse and human antibody amino acid sequences. Similar to Enbrel and Humira, Infliximab targets tumor necrosis factor alpha (TNF-α) and is used to treat autoimmune diseases such as Crohn’s disease, ulcerative colitis, psoriasis, ankylosing spondylitis, and arthritis.
Remsima/ Inflectra became the first biosimilar monoclonal antibody to be approved by the EMA and FDA, with the notes from these regulatory submissions (i.e. comparability to Remicade in terms of safety, efficacy and quality) providing valuable guidance for other biosimilar developers.
Biosimilar Characterization Considerations
The guidelines state that Infliximab/ Remsima/ Inflectra/ Remicade comparability and characterization studies should include determination of physicochemical and structural properties, purity, impurities and quantity in line with ICH Topic Q6B:
Structural Characterization
- Primary (de novo) Amino Acid Sequence
- Amino Acid Composition
- Terminal Amino Acid Sequence
- Peptide Map
- Disulfide Bridges
- Carbohydrate Structure
- Secondary and Tertiary Structure
Physicochemical Characterization
Functional Testing by Custom Biologics
- Cell Proliferation Assays
- TNFα Neutralization Assay
- Antibody-dependent cell cytotoxicity (ADCC) Reporter Bioassay
- Complement-dependent Cytotoxicity (CDC) Assays
- Binding Assays– TNFα, Fc-Receptors, C1q, FcRn
- ELISA
- MSD
- BLI
Product Specific Technical Considerations
Particular attention should be paid to the Post Translational Modifications (PTMs) including:
- Levels of Pyroglutamination
- Disulfide bridges
- Heavy chain C-terminal Lysine
- Glycosylation (in particular, levels of galactosylation and fucosylation)
- Deamidation
- Oxidation
