Large Molecule Bioanalysis

• LBA and LC-MS/MS analytical method development and validation
• Quantitative analysis in biological fluids and tissues for pharmacokinetic (PK), pharmacodynamic (PD) and toxicokinetic (TK) studies, including:
  • Peptides
  • Monoclonal antibodies
  • Bispecific antibodies
  • Proteins
  • Oligonucleotides
• Biomarker assays
• Immunogenicity assays:
  • Anti-drug antibodies (ADAs): Safety assessment using a tiered approach including ADA screening and positive ADA confirmation.
  • Neutralizing antibodies (NAbs) by non-cell based (CLBA) and cell-based assays (CBA).

FDA Guidance Documents

The U.S. Food and Drug Administration (FDA) has issued several guidance documents specific to large molecule bioanalysis, addressing various aspects of method validation, immunogenicity testing, and pharmacokinetic assessments. Some key FDA guidance documents include:

• Bioanalytical Method Validation: This guidance outlines the requirements and recommendations for validating bioanalytical methods used to quantify drugs and their metabolites in biological matrices. It covers method specificity, sensitivity, accuracy, precision, and stability, providing a framework for ensuring the reliability of bioanalytical data.
• Immunogenicity Assessment for Therapeutic Protein Products: This guidance focuses on the evaluation of immunogenicity risks associated with therapeutic protein products, such as monoclonal antibodies and recombinant proteins. It provides recommendations for assessing anti-drug antibody (ADA) and neutralizing antibody (NAb) responses, including assay development, validation, and interpretation of results.

EMA Guidance Documents

The European Medicines Agency (EMA) also issues guidance documents pertaining to large molecule bioanalysis, harmonizing regulatory requirements across the European Union and facilitating global drug development efforts. Some notable EMA guidance documents include:

• Guideline on Bioanalytical Method Validation: Similar to the FDA guidance, this document provides recommendations for validating bioanalytical methods used to quantify drugs and their metabolites in biological samples. It emphasizes the importance of method selectivity, sensitivity, accuracy, precision, and reproducibility in generating reliable pharmacokinetic and pharmacodynamic data.
• Guideline on Immunogenicity Assessment of Biotechnology-Derived Therapeutic Proteins: This guideline offers specific recommendations for assessing the immunogenicity of biotechnology-derived therapeutic proteins, including monoclonal antibodies, cytokines, and growth factors. It addresses assay validation, sample handling, and interpretation of immunogenicity data, aiming to minimize the potential risks associated with immune responses to biologic therapeutics.