Remicade (infliximab) is a chimeric monoclonal antibody with potent anti-inflammatory activity. Remicade has been approved as a treatment for a range of chronic inflammatory conditions where its target - tumor necrosis factor-alpha (TNFα) - is an important disease mediator.
Remicade is an expensive drug, and there is a significant demand for more affordable alternatives. Biosimilars offer patients advanced therapeutics at a lower cost, without compromising on quality.
Successful biosimilar development requires reliable and detailed characterization studies to demonstrate sufficient comparability to the innovator product. Sartorius has supported the development of over 25 anti-TNF biosimilars, and our data has been a fundamental part of submissions for regulatory approval. Our experience has enabled us to develop a comprehensive panel of tests for comparability of the structure and function of Remicade biosimilars.
We offer pre-qualified, integrated characterization and comparability packages to support the development and production of your Remicade biosimilars.
Uncover valuable insights into your biosimilar
Accelerate development times
Meet regulatory requirements
Boost confidence in your product
Limit the risks associated with biosimilar development
Characteristics of Remicade
Remicade is indicated for the treatment of several autoimmune diseases, including severe rheumatoid arthritis, ankylosing spondylitis, moderate to severe Crohn’s disease, ulcerative colitis, and psoriasis.
Elevated levels of the inflammatory cytokine TNFα are observed in the tissues of patients with disorders associated with chronic inflammation. Remicade’s anti-inflammatory activity is due to its ability to bind and neutralize the effects of TNFα, improving many of the signs and symptoms of chronic inflammation.
Remicade is a monoclonal antibody consisting of approximately 75% human and 25% murine protein. It possesses murine variable regions with a human Fc-Gamma-1 isotype.
Remicade exerts its function by binding to both soluble and membrane bound TNFα, inhibiting its interactions with its receptors (TNFRs). TNFα is a central regulator of the immune response with diverse functions in cells and tissues. It interacts with its receptors and triggers biological pathways leading to the induction of proinflammatory cytokines, movement of white blood cells into the tissues, and increasing cell adhesion.
Therefore, by blocking TNFα signaling, Remicade can attenuate the inflammatory response.
Sartorius offers a comprehensive range of integrated services to support the biological, physicochemical, and structural evaluation of Remicade, including complete characterization and comparability testing.
Physicochemical and structural assays reveal detailed insights into the composition of your biosimilar
Binding assays quantify and evaluate the binding of your biosimilar to TNFα and other components of the immune system.
Our functional assays measure the biological activity of your Remicade biosimilar as well as measuring its ability to induce complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC).
Our bioanalytical comparability assays are complemented by a suite of methods to characterize our master, working, and end-of-production cell banks.
Physicochemical and structural characterization is a crucial step in determining the potential biological activity, stability, and safety of your biosimilar.
Our versatile platform of physicochemical methods provides the basis for your comparability study. With options suited for clone selection through to formal comparability, we can build detailed insights into the properties of your biosimilar.
The combination of our off-the-shelf physicochemical and structural analyses and our binding and bioassays allows you to evaluate the structure-function relationship and ticks the regulators’ box for orthogonal comparability.
Our Remicade TNFα neutralization bioassay measures the activity of Fab binding against TNFα, reporting the inhibition of the TNFα-mediated signal.
We currently offer six different versions of the Remicade TNFα neutralization assay:
Measurement of cell death/viability using L929 cells
Measurement of cell death/viability using U937 cells
Measurement of apoptosis using U937 cells
Measurement of ELAM-1 expression (a marker of adhesion) using HUVEC cells
Measurement of ICAM-1 expression (a marker of adhesion) using HUVEC cells
Measurement of VCAM-1 Expression (a marker of adhesion) using HUVEC cells
We also offer a range of ADCC and CDC assays using cell lines engineered to express TNFα. These assess the Fc effector function of Remicade biosimilars.
The binding of your Remicade biosimilar to its target is assessed using our Remicade TNFα binding assay, using an upgraded version of the traditional ELISA on the Mesoscale Discovery (MSD) platform. This assay reports the relative binding of biosimilar and innovator Remicade material as a percentage of a designated reference lot, with comprehensive parallelism assessments.
Fc Binding Characterization Assays
Fc characterization forms a critical part of the Remicade biosimilar comparability study and complements our ADCC and CDC bioassays.
We perform Fc-gamma receptor assays using surface plasmon resonance (SPR) instruments, which are versatile, label-free systems with exceptional sensitivity. We can access all Fc gamma receptors:
Remicade Fc-Gamma Receptor I (FcRI)
Remicade Fc-Gamma Receptor IIa (both R and H variants) (FcRIIa)
Remicade Fc-Gamma Receptor IIb (FcRIIb)
Remicade Fc-Gamma Receptor IIIa (V) (FcRIIIa V)
Remicade Fc-Gamma Receptor IIIa (F) (FcRIIIa F)
Remicade Fc-Gamma Receptor IIIb (FcRIIIb)
A key factor in the efficacy of therapeutic antibodies is the serum half-life, largely determined by the interaction between the antibody and the neonatal Fc receptor (FcRn). Evaluation and understanding of your antibody product’s ability to bind FcRn is critical in demonstrating comparability between Remicade biosimilar and innovator. Sartorius provides off-the-shelf FcRn binding assays by SPR.
The Fc region is also responsible for the CDC effector function through binding to C1q and activation of the classical complement pathway. We offer sensitive C1q binding assays by ELISA and SPR.