Standard and reference materials refer to the reference materials used for drug identification, inspection and content determination, that is, the materials with certain characteristics or quantities used in drug standards for the assignment, qualitative, evaluation and determination methods of the tested drugs or the calibration of instruments and equipment, in which the reference materials refer to the reference materials used for bioassay, antibiotic or biochemical drug content or potency determination. The measures for the administration of drug registration stipulates that "the China Institute for the control of pharmaceutical and biological products is responsible for the calibration and management of national reference materials", "when applying for the production of new drugs, the applicant shall provide the China Institute for the control of pharmaceutical and biological products with the raw materials for the preparation of the drug reference materials, and submit the research materials related to the reference materials". However, in the research of new drugs, the application of reference materials (standards) is generally ahead of the preparation and calibration of the Central Inspection Institute. In view of the continuity of the research of new drugs and the importance of reference materials in the research of new drugs, including quantity traceability, product characterization, impurity control and drug quality control, the preparation and calibration of reference materials are related to the quality research of drugs There is a close relationship between preclinical basic research such as dose determination in stability research and pharmacological toxicology research. Therefore, the research (preparation and calibration) of drug reference materials (standards) is also an important content of drug evaluation. Annex II of the measures for the administration of drug registration clearly stipulates that "the standard or reference substance provided shall be attached with additional information to explain its source, physical and chemical constants, purity, content and its determination methods and data". However, in the objective application materials, this part of the content has not been paid enough attention, and the research level is uneven, or even ignored. In order to do a good job in the overall evaluation of drug registration, especially the overall evaluation of preclinical basic research, this paper puts forward some thoughts, hoping to discuss and communicate with colleagues in the industry.

1. If the reference substance (standard substance) used has been issued and provided by the intermediate inspection institute (see Appendix XV g of Chinese Pharmacopoeia, 2000 edition, Part II), and the use methods are the same, the reference substance (standard substance) of the current batch number provided by the intermediate inspection institute should be used, and its label and operation instructions should be provided to state its batch number, and other sources should not be used; If the use method is different from the use method in the manual (for example, the qualitative reference material is used for quantification, the standard material for potency determination is used for physicochemical determination, UV method or volumetric method reference material is used for chromatography, etc.), appropriate methods should be used for recalibration, and calibration methods and data should be provided; If the reference substance for chromatographic content determination is used as UV method or volumetric method, and the reference substance for quantitative determination is used as qualitative method, it can be directly applied without recalibration.

2. When applying for clinical research, if there is no supply from the Central Inspection Institute, in order not to affect the registration progress, you can contact the Central Inspection Institute in advance for preparation and calibration, and provide calibration reports, labels (indicating potency or content, batch number, expiry date of use) and instructions when applying; It can also be calibrated in cooperation with the Provincial Institute, and provide the research data of the standard or reference substance when declaring, "explain its source, physical and chemical constants, purity, content, and its determination methods and data"; When it is difficult to calibrate, the reference substance (standard substance) issued by the foreign drug administration authority or Pharmacopoeia Committee or the working reference substance (standard substance) of foreign pharmaceutical enterprises can be used for standard formulation and other basic research, but its label (its content should be indicated) and instruction manual should be provided to ensure the traceability of its quantity value; The reference substance (standard substance) provided by foreign reagent companies (such as sigma company) can also be used, but the test report of the batch of reference substance (standard substance) of the reagent company (when used for content determination, there should be definite content data) should be provided. For high-purity reagents, when the test report of foreign reagent companies (when used for content determination, there should be definite content data) is provided, it can also be used, and the traceability of its quantity value should be ensured, However, the applicant should timely contact the Central Inspection Institute for the calibration of the reference (standard) and complete this work during the clinical study.

3. Directly declare the production varieties. If the intermediate inspection institute has not supplied them, it can refer to the requirements in 2 and provide the corresponding research materials. However, the applicant should contact the intermediate inspection institute and complete the calibration during the trial period of the standard.

Put forward some views on its calibration work, with a view to discussing and communicating with colleagues in the industry; It is hoped that in the process of drug research and development, the research and development unit should pay attention to the preparation and calibration with the Central Inspection Institute in time, so as to ensure the continuity of research and development work.