Specific method validation and sample analysis approaches for biocomparability studies of denosumab addressing method
Ramak Pourvasei1, Ed Lee, Michael Eschenberg
1Department of Pharmacokinetic and Drug Metabolism, Amgen Inc., One Amgen Center Dr, Thousand Oaks, CA 91320, USA. ramakp@amgen.com
Abstract:
Manufacturing changes during a biological drug product life cycle occur often; one common change is that of the manufacturing site. Comparability studies may be required to ensure that the changes will not affect the pharmacokinetic properties of the drug. In addition, the bioanalytical method for sample analysis may evolve during the course of drug development. This paper illustrates the scenario of both manufacturing and bioanalytical method changes encountered during the development of denosumab, a fully human monoclonal antibody which inhibits bone resorption by targeting RANK Ligand. Here, we present a rational approach to address the bioanalytical method changes and provide considerations for method validation and sample analysis in support of biocomparability studies. An updated and improved ELISA method was validated, and its performance was compared to the existing method. The analytical performances, i.e., the accuracy and precision of standards and validation samples prepared from both manufacturing formulation lots, were evaluated and found to be equivalent. One of the lots was used as the reference standard for sample analysis of the biocomparability study. This study was sufficiently powered using a parallel design. The bioequivalence acceptance criteria for small molecule drugs were adopted. The pharmacokinetic parameters of the subjects dosed with both formulation lots were found to be comparable.
More Related Videos
10:50Purification and Analytics of a Monoclonal Antibody from Chinese Hamster Ovary Cells Using an Automated Microbioreactor System
Published on: May 1, 2019
07:25In Vitro Methods for Comparing Target Binding and CDC Induction Between Therapeutic Antibodies: Applications in Biosimilarity Analysis
Published on: May 4, 2017
Related Concept Videos
Therapeutic Drug Monitoring: Drug Analysis Methods
Clinically Relevant Drug Product Specifications: Methods of Establishment
Drug Products: Biologics, Biosimilars and Interchangeables
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast, controlled...
Bioequivalence studies: Biowaivers
FDA Approved Drugs: Changes to Approved Drugs
