Potency assignment of biotherapeutic reference standards

Area of Science:

• Biopharmaceutical development
• Drug quality control
• Protein therapeutics

Background:

• Biotherapeutic proteins are vital for treating cancers, infectious diseases, and autoimmune disorders.
• Potency, reflecting biological activity and efficacy, cannot be determined by physical properties alone.
• Cell-based bioassays against reference standards are used, but face challenges in variability and bias.

Purpose of the Study:

• To propose a comprehensive roadmap for assigning potency to biotherapeutic reference standards.
• To ensure compliance with the recommended two-tier system of standards.
• To address challenges in potency assignment during pharmaceutical development and manufacturing.

Main Methods:

• Development of a roadmap for potency assignment compliant with regulatory guidance.
• Integration of statistical approaches for risk-based, phase-appropriate study design and acceptance criteria.
• Inclusion of mitigation strategies for potential assay bias.

Main Results:

• A structured approach for potency assignment to biotherapeutic reference standards is presented.
• The roadmap incorporates statistical methodologies for robust study design and acceptance criteria.
• Methods for mitigating assay bias are provided to enhance reliability.

Conclusions:

• Accurate potency assignment to reference standards is vital for patient safety and drug quality.
• The proposed roadmap offers a systematic, statistically sound approach to potency determination.
• This framework supports reliable biotherapeutic manufacturing and quality assurance.