Potency assignment of biotherapeutic reference standards.

The role of biotherapeutic proteins in the prevention and treatment of diseases such as cancers, infectious diseases, and autoimmune disorders continues to grow. The biological activity or "potency" of a biotherapeutic reflects its mechanism of action and thus its efficacy. The potency of these complex biomolecules cannot be quantitatively correlated to chemical and physical properties and thus must be determined by comparison to a reference standard, typically using a cell-based bioassay. This lack of an absolute method for determining potency, along with test method variability and potential for bias make assignment and monitoring of reference standard potency a major challenge during pharmaceutical development and manufacturing. The reference standard links the potency of dosages administered to the patient with those of original clinical studies. Therefore, the assignment of potency to biotherapeutic reference standards is vital for assuring the quality of medicines for patients. In this work, we propose a comprehensive roadmap for assigning potency to reference standards that is compliant with the two-tier system of standards as recommended in regulatory guidance. The roadmap includes statistical approaches for study design and acceptance criteria that are risk-based and phase-appropriate. It also provides mitigation approaches for potential assay bias.

Establishment of the First National Reference Standard for Insulin Lispro: Report of a collaborative study.

The present study was aimed to establish the First National Reference Standard (NRS) for Insulin lispro to allow stakeholders including manufacturer's laboratories, drug testing laboratories, drug regulatory authorities and academic institutions to demonstrate accuracy of the test results and to enable comparison and validation of analytical methods. The candidate standard for Insulin lispro was evaluated in a collaborative study to assign the vial content in order to serve it as NRS to support the Indian Pharmacopoeia (IP) monograph. The candidate standard was calibrated against the Ph. Eur. Insulin lispro reference standard by each of six participant laboratories in India using HPLC assay method as per the requirements of IP monograph. The results indicate that the candidate standard has an average content of 5.79 mg per vial with purity of 99.87%. Based on the study results the candidate standard was judged suitable to serve as the first NRS for Insulin lispro.