Herceptin (Trastuzumab) Biosimilars

Herceptin Biosimilars

Herceptin (trastuzumab) is one of the most well-known antibody therapies. Herceptin is a humanized IgG1 monoclonal antibody targeting the human epidermal growth factor receptor 2 (HER2/ERBB2). HER2 is a member of the human epidermal growth factor family and is found at increased levels in certain tumor cells, particularly in breast cancers.

Access to life-saving biopharmaceuticals - like Herceptin - is enhanced by the release of biosimilars. However, for biosimilars to be approved by regulatory bodies, they must undergo extensive characterization to demonstrate comparability to the Innovator product. These requirements can be a hurdle to the efficient development of new biosimilars.

Sartorius offers an integrated package of assays for comparability studies of Herceptin biosimilars. Our analysis solutions are designed to meet strict approval criteria and are valuable at all project stages, from process development to commercial production.

Simplify Your Biosimilar Characterization

Sartorius offers a panel of ready-to-use assays for the comprehensive characterization of your Herceptin 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 

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Characteristics of Herceptin

HER2 is the protein target of Herceptin’s clinical actions. HER2 is a transmembrane oncoprotein found on the surface of many cell types. When overactive, HER2 can cause uncontrolled cell proliferation, a hallmark of tumorigenesis. 

HER2 overexpression is observed in up to 30% of breast cancers and is associated with a poor prognosis. HER2 upregulation has also been observed in other cancers, including esophageal, stomach, and ovarian cancer.  Breast cancers with HER2 overexpression are called HER2-positive. Compared to HER2-negative tumors, HER2-positive tumors are more likely to grow faster, spread, and return after treatment.  

Therefore, HER2 presents an attractive target for cancer therapies. Herceptin is frequently employed in the treatment of HER2-positive tumors with a high degree of success; a combination of Herceptin with standard chemotherapy has been shown to achieve a better response rate than chemotherapy alone. 

HER2 is a growth factor receptor that triggers intracellular signaling in response to extracellular factors. HER2 is a ligandless receptor; instead, it is activated by dimerization with itself or other receptors.  

When functioning normally, the HER2 pathway promotes cellular proliferation, survival, migration, invasion, and differentiation. When HER2 is overexpressed, the cell receives constant proliferative signals, causing uncontrolled proliferation and tumor formation. The overexpression of HER2 also causes the deactivation of checkpoints, further increasing cellular proliferation.  

Herceptin acts through a variety of complementary mechanisms. Amplified HER2 signaling activates various downstream pathways required for the aberrant proliferation of cancer cells, including MAPK and PI3K/Akt pathways. One of the primary modes of action of Herceptin is in blocking HER2 downstream signaling, leading to cell cycle arrest and cell death.    

Herceptin’s antitumor effect is also mediated by its ability to prevent dimerization of HER2 receptors with other members of the HER family. This dimerization can also promote cell cycle progression and induce pro-angiogenic proteins such as vascular endothelial growth factor (VEGF). 

Finally, Herceptin acts on the immune system by mediating antibody dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), which direct immune cells to target the HER2-positive cancer cells for destruction.

Sartorius can support your Herceptin biosimilar project from cell line development through to comprehensive analysis of your product. Our off-the-shelf characterization solutions were designed to meet regulatory requirements for comparability. 

  • Physicochemical and structural assays reveal detailed insights into the composition of your Herceptin biosimilar. 

  • Binding assays quantify and evaluate the binding of your biosimilar to HER2 and other components of the immune system. 

  • Herceptin has a number of different mechanisms of action. Therefore, a range of bioassays are required to fully characterize the product and demonstrate comparability with the Innovator.  

Our Herceptin comparability assays are complemented by our integrated services for biologics, including cell banking and biosafety analysis. 

Assay Types

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.   

A critical quality attribute of Herceptin is the glycan structure. Matching your biosimilar to the innovator product is crucial in creating a product that gains regulatory approval.  Sartorius offers in-depth glycan profiling and can link this to your functional characterization using ADCC assays. 

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The potency of Herceptin biosimilars is a critical quality attribute and must be assessed in detail.  Sartorius offers a comprehensive selection of assays to comprehensively analyze the biological activity of your biosimilar.  

Herceptin inhibition of proliferation assay – When it binds to HER2, Herceptin should induce cell cycle arrest. Using BT474 cells overexpressing HER2, our proliferation assay evaluates the ability of Herceptin’s Fab region to bind to HER2 and inhibit the proliferation of cells. Using a marker of live cells, the results are reported as the relative potency of your biosimilar against a designated reference standard. 

ADCC, ADCP, and CDC assays – Sartorius provides off-the-shelf assays to study your biosimilar’s ability to induce ADCP, ADCC, and complement-dependent cytotoxicity (CDC). One of Herceptin’s modes of action is to target HER2-positive cells for elimination by phagocytosis (ADCP) or chemical/enzyme-mediated destruction (ADCC). Herceptin can activate the complement cascade; however, no Herceptin complement-mediated cell lysis has been reported.  Our assays use a reporter-based system to characterize the effector functions of your Herceptin biosimilar, helping you to meet acceptance criteria for comparability to the Innovator product.  

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Sartorius has improved the traditional Herceptin HER2 binding ELISA and offers an enhanced assay that significantly increases the understanding of the Herceptin-HER2 binding during comparability studies. This SPR-based assay reports full kinetic analysis, including Affinity Constants (KD), with the association or “on” rate (Ka) and dissociation rate or “off” rate (Kd). The assay also generates relative binding and parallelism assessments. 

To complement our selection of bioassays, we also offer full Fc characterization for Herceptin biosimilars assessing the following binding interactions: 

  • Herceptin Fc-gamma Receptor I (FcRI) binding assay by SPR 

  • Herceptin Fc-gamma Receptor IIa (R and H variants) (FcRIIa) binding assay by SPR 

  • Herceptin Fc-gamma Receptor IIb (FcRIIb) binding assay by SPR 

  • Herceptin Fc-gamma Receptor IIIa (V) (FcRIIIa V) binding assay by SPR 

  • Herceptin Fc-gamma Receptor IIIa (F) (FcRIIIa F) binding assay by SPR 

  • Herceptin Fc-gamma Receptor IIIb (FcRIIIb) binding assay by SPR 

  • Herceptin neonatal Fc receptor (FcRn) binding assay by SPR 

  • Herceptin C1q binding assay 

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