China’s Center for Drug Evaluation (CDE) has issued a notification outlining the “Guiding Principles for Pharmaceutical Research and Evaluation of Antibody Drug Conjugates (ADCs).” The document aims to standardize and guide the research, development, and regulatory submissions pertaining to ADCs.
The guidelines are applicable to ADC products that are created by linking antibodies or antibody fragments with payloads, such as small molecule cytotoxic drugs, through linkers. The document also covers other conjugated drugs like antibody conjugated nuclide drugs, peptide conjugated drugs, and antibody oligonucleotide conjugated drugs.
The notification highlights that while ADCs are generally classified as large-molecule drugs, they possess characteristics of both large and small molecules. Therefore, they must be comprehensively evaluated across various aspects, including targeting, in vivo circulation stability, and biological activity. The document calls for the establishment of a control strategy for the entire ADC production process based on risk analysis, at different stages. For instance, the development of small molecule components should adhere to the requirements for chemical raw materials, and the development of naked antibody production processes should refer to the Chinese Pharmacopoeia, the Technical Guidelines for Quality Control of Human Monoclonal Antibodies, as well as international technical requirements from ICH and WHO.
The document also offers recommendations for the formulation and selection of ADC prescriptions. Currently, freeze-dried formulations are generally preferred to enhance the convenience and safety of clinical medication, with the future development of liquid formulations being a研究方向 for ADC formulations. Moreover, the document emphasizes the process optimization of ADCs, particularly key quality attributes such as drug distribution, drug-antibody ratio (DAR) value, and the comparability of coupling sites, along with the impurity removal capability and biological activity in the production process of the original solution.- Flcube.com
