The Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) has released a draft proposal titled “Questions and Answers on Pharmaceutical Similarity Research of Biosimilars,” seeking public feedback until October 9th. This document, applicable to Category 3.3 biologics, provides clarity on common issues and technical requirements for the research and development of biosimilars.
- Research and Development and Production:
For clinical trial applications of biosimilars, pharmaceutical similarity studies and the production of clinical trial samples should align with processes and scales expected for commercial production. The candidate drug must be consistent with the reference drug in dosage form and specifications, and it is recommended to maintain consistency in formulation prescriptions. Deviations should be supported with comprehensive formulation prescription development research and risk assessment data. - Selecting Reference Drugs:
Priority should be given to selecting reference drugs from originators approved for marketing in China. In cases of difficulty obtaining reference drugs or for global filing preparations, it is permissible to use reference drugs from other sources, ensuring comparability. For reference drugs approved overseas and undergoing clinical trials in China, it is allowed to use reference drugs from other countries/regions for pharmaceutical similarity studies. - Similarity Evaluation:
Similarity research should encompass quality attribute similarity and stability similarity. During clinical trials, it is recommended to conduct quality attribute similarity studies with at least three batches of the candidate drug and six batches of the reference drug. For stability similarity, at least three batches of each should be used for accelerated stability and forced degradation comparison studies. For marketing applications, it is advised to use at least six batches of the candidate drug and ten batches of the reference drug for similarity evaluation. - Impurity Research:
When comparing impurity spectra, the residual level of impurities that may affect safety and/or immunogenicity in the candidate drug should not exceed that of the reference drug. For peptide-based biosimilars, the same impurity content should not be higher than that of reference drugs, with safety assessments conducted for new impurities. Complex molecules like antibodies and fusion proteins require detailed composition and biological activity analysis. - Post-Listing Quality Control:
Significant changes post-marketing approval of biosimilar drugs necessitate an evaluation of potential impacts on product quality. This may involve conducting similarity studies with reference drugs or analyzing test results from previous studies as supporting data for change studies. Quality standards for the proposed candidate drug solutions/raw materials and formulations must ensure quality control capabilities are not inferior to those of reference drugs. – Flcube.com
