Article 1 These measures are formulated in accordance with the requirements of Article 62 of the measures for the administration of drug registration (for Trial Implementation) promulgated by the State Drug Administration that "after completing the clinical study of a drug, the applicant shall submit the clinical study materials and other changed and supplementary materials to the drug administration of the province, autonomous region or municipality directly under the central government where it is located, with a detailed explanation of the basis and reasons, and at the same time, submit the raw materials for the preparation of the standard to the China Institute for the control of pharmaceutical and biological products" and article 173 that "when applying for the production of a new drug, 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 / biological product standard materials and submit the research materials related to the standard substances".
        Article 2 drug / biological product reference materials refer to the substances used for physical and chemical tests and biological method tests in the Pharmacopoeia of the people's Republic of China, the Chinese biological product regulations, the drug registration standards and other national drug / biological product standards, which have certain characteristic quantities and are used to calibrate equipment, evaluate measurement methods or assign values to the tested drugs, including biological standards, chemical references, traditional Chinese medicine reference materials, references and standard reagents.
        Article 3 the acceptance scope of pharmaceutical / biological reference materials is as follows:
        1. Varieties listed for sale in China for the first time.
        2. Varieties that have been put on the market but need to change the dosage form and route of administration, and there is no corresponding national reference material for drug / biological product inspection.
        3. If there are national standards, it is confirmed that there are no corresponding varieties of national drug / biological product reference materials.
        4. In the supplementary application, it is confirmed that there are no varieties of corresponding national drug / biological product reference materials.
        5. Apply for confirmation of the trial standards, and confirm that there are no varieties of corresponding national drug / biological product reference materials.
        Article 4 the acceptance procedures are as follows:
        1. The existing catalogue of national reference materials for drugs / biological products can be found on the website of the China Institute for the control of pharmaceutical and biological products（ http://www.nicpbp.org.cn/ ）Query and confirm.
        2. The applicant may download the "application form for pharmaceutical reference materials" (Annex 1) or "application form for biological reference materials" (Annex 2) from the website of the China Institute for the control of pharmaceutical and biological products, fill in the form as required and affix the official seal. (one copy)
        3. The applicant shall, according to the relevant provisions of these measures, submit the raw materials and technical data of drug / biological reference materials and the application form to the drug control office / health control office of the China Institute for the control of drug and biological products for preliminary review and filing.
        4. The heads of relevant professional departments shall review the raw materials and technical data of pharmaceutical / biological reference materials.
        5. The drug inspection division / health inspection division shall issue the "acceptance form for drug reference materials" or "acceptance form for biological product reference materials" for the varieties that meet the requirements.
        6. For the varieties of national pharmaceutical / biological products certified reference materials, the enterprise may not provide the raw materials and technical data for the preparation of certified reference materials for the time being, but shall bring the declaration form and the application for production raw materials
The quality standards of drugs / biological products of materials and preparations shall be filed with the drug inspection office or the health inspection office. The drug inspection office / health inspection office will issue the "national drug reference material confirmation form" or the "national biological product reference material confirmation form".
        7. The drug inspection division / health inspection division of China Institute for the control of pharmaceutical and biological products accepts the acceptance, filing and consultation of reference materials for pharmaceutical / biological products.
        Article 5 quality requirements for raw materials:
        1. The quality of raw materials used to prepare reference materials must comply with relevant quality standards.
        2. The raw materials submitted must be produced or refined in the same batch, with uniform and stable quality and single sealed packaging.
        3. Requirements for raw materials of chemical reference materials: generally, the purity of raw materials for preparation and content determination shall not be less than 99.5%; For thin layer identification only
Generally, the purity of raw materials used shall not be less than 90.0%; Generally, the purity of raw materials for infrared identification shall not be less than 98.0%; Generally, the purity of raw materials used for the preparation of relevant substances shall not be less than 95.0%.
        4. Requirements for raw materials of biological standards: the active components of raw materials for the determination of antibiotic potency shall be consistent with the clinical application samples; The raw materials of biological standard used for the inspection of biochemical, genetic engineering drugs and biological products shall be of the same quality with the products to be inspected, free of interfering impurities and with sufficient stability.
        5. Requirements for raw materials of chemical reference materials of traditional Chinese medicine: generally, the purity of raw materials for preparation and content determination shall not be less than 98.0%; The purity of raw materials for preparation and identification is generally not less than 95.0%.
        6. Requirements for raw materials of traditional Chinese medicine reference materials: the raw materials must be accurate in source, free from pollution, insects and mold, and be fresh medicinal materials (non prepared pieces) produced in the current year or in the recent 1-2 years.
        Article 6 quantity requirements of raw materials
        1. Generally, the quantity of biological standard / chemical reference material used for content determination shall not be less than 200g, and the quantity of raw material intermediates shall be 1-5g respectively.
        2. Generally, the quantity of raw materials for preparing chemical reference materials for identification and inspection shall not be less than 100g.
        3. Generally, the quantity of chemical reference materials of traditional Chinese medicine shall not be less than 10g.
        4. 3-5kg of traditional Chinese medicine (non decoction pieces) used to prepare the reference materials of traditional Chinese medicine, and three copies of wax leaf samples of corresponding traditional Chinese medicine (indicating the Chinese name, English name, Latin name, commonly used name, appraiser and identification date), a batch of Chinese patent medicines.
        5. The quantity of reference materials for drugs and biological products that are expensive and difficult to extract can be negotiated according to specific circumstances.
        Article 7 provision of technical data (one set)
        1. Inspection report of raw materials. The Chinese name, Latin name, species, origin, customary name of origin and medicinal part of the medicinal materials shall be indicated in the inspection report of Chinese medicinal materials.
        2. Raw material production process flow chart.
        3. Test data to confirm the chemical structure or components of raw materials.
        4. Test data of raw material quality research (physical and chemical properties, related substances, residual organic solvents, purity test, content determination and activity determination, etc.).
        5. Quality standards and drafting instructions for pharmaceutical raw materials and preparations (medicinal materials and their products, prepared prescriptions and single preparations) approved by the State Drug Administration. (in duplicate)
        6. Test data of raw material stability study.
        7. If the raw material has been refined, the detailed test report of raw material refining (including refining conditions, reagents and treatment steps) shall be provided.
        8. For the raw materials of the chemical reference materials of traditional Chinese medicine, the preparation report of the raw materials shall also be provided (such as: name \ structure confirmation \ source of raw materials \ medicinal part of raw materials \ extraction and preparation method of raw materials \ purity inspection of raw materials, including two different development systems, HPLC content determination conditions and atlas, etc.).
        9. The raw materials of traditional Chinese medicine reference materials also need to provide the preparation process.
        Article 8 other requirements:
        1. If the enterprise has prepared the standard / reference substance / reference drug for work, it is required to provide 2 pieces and attach the development and inspection report as a reference for preparing the national standard, reference substance and reference drug.
        2. If the same variety of the drug has been approved for marketing abroad, please provide the quality standards of the same variety abroad and the standards / references of the foreign pharmacopoeia or the standards / references of the original R & D factory as much as possible, and the quantity shall not be less than 2. (this clause is not a mandatory requirement)
        3. The imported drug reference materials for inspection shall be subject to the relevant provisions of the measures for the administration of drug import.