Actemra/RoActemra (tocilizumab) is a humanized IgG1 antibody targeted against the Interleukin-6 (IL-6) receptor (IL-6R). Actemra is approved for the treatment of several inflammatory diseases. Most recently, researchers have demonstrated that Actemra improves outcomes in patients with severe COVID-19, renewing the global interest in the production of Actemra biosimilars.
The demand for more affordable monoclonal antibody biosimilars is on the rise. However, their development and manufacture are not without challenges; complicated manufacturing procedures and stringent regulatory requirements on similarity mean the development of biosimilars can be a complex process.
At Sartorius, an expert team of scientists have created both off-the-shelf and custom analysis packages to support the detailed characterization and testing of your Actemra biosimilar. Our integrated programs include binding assays, bioassays, and physicochemical and structural characterization to simplify your comparability studies.
Simplify Your Biosimilar Characterization
Sartorius offers a comprehensive package of prequalified assays suitable for the development and manufacture of Actemra 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 Actemra
Actemra targets both soluble and membrane-bound IL-6 receptors, blocking the attachment of IL-6, a cytokine involved in the development of the body's inflammatory and immunological reactions.
IL-6 is implicated in the pathogenesis of many diseases. For example, abnormally high levels of IL-6 are observed in autoimmune disorders.
Actemra is currently approved for the treatment of rheumatoid arthritis in cases where other therapies have been unsuccessful. It is also widely used in the management of systemic juvenile idiopathic arthritis, and Japan has approved Actemra for use in the treatment of Castleman's disease.
The IL-6 signaling system is compelling because although IL-6R specifically binds IL-6, it does not directly transduce a signal. There are two signaling pathways through which IL-6 signaling functions.
Classical signaling pathway - IL-6 binds to IL-6R on the cell membrane and forms a complex with the transmembrane glycoprotein, gp130. Once in this trimeric form, gp130 forms a disulfide-linked homodimer with another gp130 protein to initiate intracellular signal transduction via the JAK/STAT pathway.
Trans-signaling pathway - The trans-signaling pathway does not require the localization of IL-6R to the cell membrane; soluble IL-6R, which can be present at relatively high levels in the circulation of even healthy individuals, can also bind IL-6. This soluble IL-6/IL-6R complex can associate with cell-associated gp130, resulting in signal transduction.
Actemra (tocilizumab) works through a dual mechanism: preventing the formation of the IL-6/IL-6R complex and subsequent signaling via both pathways and disrupting existing IL-6/IL-6R complexes. Therefore, Actemra inhibits robust IL-6 signaling inhibition by several complementary mechanisms acting in concert.
Our range of analytical services gives you reliable data to support the detailed characterization of your product.
Physicochemical and structural assays reveal detailed insights into the composition of your biosimilar
Binding assays allow you to quantify and evaluate the binding of your Actmera biosimilar to IL-6R as well as other components of the immune system.
Bioassays directly measure the biological activity of your biosimilar in both classical and trans pathways of IL-6 signaling.
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.
Bioassays provide the means to directly assess the fundamental biological activity of Actemra biosimilars. As such, they represent a significant component of a product characterization study.
Our extensive experience in developing novel bioassays to assess a wide range of monoclonal antibodies has enabled us to create cell-based platforms to measure the blocking activity of Actemra biosimilars. Our assays include:
Actemra Classical (cis-) Signaling IL-6R Neutralization Bioassay
Actemra Trans-Signaling IL-6R Neutralization Bioassay
These functional assays allow us to determine the biological activity of your Actemra biosimilar in both classical and trans pathways, building a comprehensive picture of the behavior of your product.
If you require an Actemra bioassay method that is not listed, please contact us.
Sartorius has developed an optimized Actemra IL-6R binding assay to support process development, characterization, and comparability studies.
Using a traditional ELISA method, our platform reports the relative binding of the biosimilar molecule to IL-6R compared to a designated reference lot, along with comprehensive parallelism assessments.
Fc-Receptor Binding Assays
The Fc-Gamma Receptors (FcR) are members of the immunoglobulin super-family and play a critical role in antibody function.
Our Fc binding platforms allow you to determine immune interactions. We can assess the full range of Fc gamma receptors using sensitive label-free SPR technology, to determine potential Fc function:
Fc-Gamma Receptor I (FcRI)
Fc-Gamma Receptor IIa (both R and H variants) (FcRIIa)
Fc-Gamma Receptor IIb (FcRIIb)
Fc-Gamma Receptor IIIa (V) (FcRIIIa V)
Fc-Gamma Receptor IIIa (F) (FcRIIIa F)
Fc-Gamma Receptor IIIb (FcRIIIb)
Additionally, we offer off-the-shelf assays for the neonatal Fc receptor (FcRn) using SPR, and C1q (using ELISA or SPR) to complete our comprehensive Fc comparability package. C1q is the first mediator of the classical complement system, and thus helps to determine the initiation point for complement-dependent cytotoxicity.