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Standard substances and reference substances refer to standard substances used in drug identification, inspection, and content determination, that is, those with definite characteristics or values used in drug standards, which are used to assign value, qualitatively, and evaluate measurement methods or calibrate instruments and equipment for test drugs. The standard substance refers to the standard substance used for the determination of content or potency in biological assays, antibiotics or biochemical drugs. The "Administrative Measures for Drug Registration" stipulates that "The National Institute for the Control of Pharmaceutical and Biological Products shall be responsible for the calibration and management of national standard materials." "Applicants shall provide the China Institute for the Control of Pharmaceutical and Biological Products with the raw materials for the preparation of the drug standard materials when applying for the production of new drugs, and Submit research data of relevant reference materials". However, in the research of new drugs, it is common for the application of reference substances (standards) to be prepared and calibrated ahead of the National Inspection Institute. In view of the continuity of new drug research and the reference materials involved in new drug research involving value traceability, product characterization, and impurity control And its importance in drug quality control. There is a close relationship between the preparation and calibration of reference materials and drug quality studies, stability studies and even the determination of doses in pharmacology and toxicology studies, and other preclinical basic research. Therefore, drug reference materials The research (preparation and calibration) of (standard products) is also an important content of drug review. Annex II of the "Administrative Measures for Drug Registration" clearly stipulates that "The standard or reference substance provided should be accompanied by additional information, indicating its source, physical and chemical constants, purity, content, and its measurement methods and data." However, in the application materials for the purpose, this part of the content has not been paid enough attention, the research level is uneven, or even ignored. In order to effectively do the overall evaluation of drug registration, especially the overall evaluation of preclinical basic research, some thoughts are put forward. Colleagues in the industry discuss and exchange together.

1. The reference substance (standard substance) used has been issued and provided by the China National Institute of Inspection and Quarantine (refer to Appendix XVG of the Chinese Pharmacopoeia 2000 Edition), and when the method of use is the same, the current batch reference substance (standard substance) provided by the China National Institute of Inspection and Quarantine should be used. And provide its label and instructions for use, stating that its batch number should not be from other sources; if the method of use is different from that of the instructions (e.g. qualitative reference substance is used for quantification, potency determination standard substance is used for physical and chemical determination method, UV method or volumetric method reference substance used for chromatographic quantification, etc.), should be re-calibrated by an appropriate method, and the calibration method and data should be provided; if the reference substance for chromatographic content determination is used as UV method or volumetric method, the quantitative reference substance should be used For qualitative, etc., it can be directly applied without re-calibration.

2. When applying for clinical research, if there is no supply from the CCIC, in order not to affect the registration progress, you can contact the CCIC for preparation and calibration in advance, and provide a calibration report and label (should indicate the potency or content, batch number, use Validity period) and instructions for use; it can also be calibrated in cooperation with the provincial institute. When reporting, provide standard or reference substance research data, "explain its source, physical and chemical constants, purity, content, and measurement methods and data"; when calibration is difficult, Reference substances (standard substances) issued by foreign drug regulatory authorities or pharmacopoeia committees or working reference substances (standard substances) of foreign pharmaceutical companies can be used for standard setting and other basic research, but its label should be provided (its content should be indicated) And the instruction manual can ensure the traceability of its value; the reference substance (standard substance) provided by foreign reagent companies (such as sigma company, etc.) can also be used, but the test report of the batch of reference substances (standard substance) of the reagent company should be provided ( When used for content determination, there should be definite content data), if it is a high-purity reagent, when a foreign reagent company's test report is provided (when used for content determination, there should be a definite content data), it can also be used and should be able to To ensure the traceability of its value, the applicant should contact the China Inspection Institute in a timely manner about the calibration of the reference substance (standard substance), and complete this work during the clinical study.

　　3. Directly declare the production varieties. If there is no supply from the CCIC, please refer to the requirements in 2 and provide corresponding research materials. However, the applicant should contact the CCIC during the standard trial period and complete the calibration matters.

　　 Put forward some preliminary views on its calibration work, in order to discuss and exchange with colleagues in the industry; and hope that in the process of drug research and development, the research unit should pay attention to the preparation and calibration matters with the National Inspection Institute in time to ensure the continuity of the research and development work.

The importance of standard substance (reference substance) in drug development