Teriparatide, a recombinant human parathyroid hormone, is a highly utilized therapeutic agent in the treatment of osteoporosis. With the increasing development of biosimilars, there is a growing demand for robust bioanalytical methods that can accurately assess the pharmacokinetics, pharmacodynamics, and immunogenicity of Teriparatide and its biosimilar counterparts.
In response to this industry need, Lambda Therapeutic Research has developed a comprehensive bioanalytical package for Teriparatide, encompassing PK analysis, PD analysis, and immunogenicity assessment.
Pharmacokinetic Analysis:
- Utilizes a sandwich enzyme-linked immunosorbent assay (ELISA) approach.
- Involves removing endogenous parathyroid hormone (PTH) from samples and capturing Teriparatide with polyclonal antibodies.
- The resulting complex is then detected using horseradish peroxidase (HRP)-conjugated detection antibodies, with measurement through a colorimetric substrate.
- This Highly sensitive method enables quantification of Teriparatide at concentrations as low as 10 pg/mL.
Pharmacodynamic Analysis:
- To evaluate the pharmacodynamic effects of Teriparatide, Lambda employs the measurement of corrected serum calcium levels, a biomarker for its activity.
- The analysis includes measuring serum albumin and calcium levels, followed by the application of a correction formula to obtain corrected calcium levels.
- The methods used for calcium and albumin measurement are based on established in-vitro diagnostic platforms commonly employed in diagnostic laboratories for assessing biochemistry parameters.
Immunogenicity Assessment:
- Immunogenicity assessment plays a crucial role in biosimilar development. Lambda follows the Multi-Tiered Testing Approach recommended by the US Food and Drug Administration (FDA) for immunogenicity assessment.
- The bioanalytical package includes screening, confirmatory, and titer assays, all utilizing a direct ELISA format. Teriparatide is used as the capturing agent for anti-Teriparatide antibodies (ADA), and different reagents are employed for the detection of ADA subclasses. The read-out is obtained through absorbance measurements.
- Additionally, a neutralizing antibody assay is incorporated, which measures the inhibition of Teriparatide-induced cAMP generation in UMR 106 cells. The assay read-out is based on luminescence, specifically relative luminescence units (RLU).
Validation and Regulatory Approval:
The bioanalytical package developed by Lambda has undergone rigorous validation procedures to ensure reliability and reproducibility. The data obtained from three Phase-I clinical studies of a biosimilar Teriparatide were reviewed by regulatory bodies such as the European Medicines Agency (EMA) and the Medicines and Healthcare products Regulatory Agency (MHRA). Consequently, the biosimilar product has received Marketing approval in the European Union (EU) and the United Kingdom (UK).
The development of a comprehensive bioanalytical package for Teriparatide by Lambda represents a significant advancement in biosimilar development and assessment. The validated methods for PK analysis, PD analysis, and immunogenicity assessment enable accurate characterization of Teriparatide and its biosimilar counterparts.
As a Leading Global CRO, Lambda Therapeutic Research offers a wide range of bioanalytical capabilities specializing in cell-based assays, biomarkers, immunogenicity, and pharmacokinetics (PK). With state-of-the-art facilities and a team of experienced scientists, Lambda provides comprehensive solutions for the analysis of small molecules, biomarkers, biologics, and therapeutic elemental drugs. To know more, please click here.
