Guiding principles for the protection of varieties of traditional Chinese medicine Traditional Chinese medicine injections

Guiding principles of variety protection of traditional Chinese medicine

| 20 10-07-0 1

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Guiding principles of variety protection of traditional Chinese medicine

1 general rules

According to the relevant provisions of the Regulations on the Protection of Traditional Chinese Medicine Varieties, this guiding principle is formulated in order to inherit the tradition of traditional Chinese medicine, highlight the characteristics of traditional Chinese medicine, encourage innovation, promote improvement, protect the advanced, and ensure the scientific, fair and standardized protection of traditional Chinese medicine varieties.

2 General requirements

2. 1 Varieties that meet the provisions of Article 6 of the Regulations on the Protection of Traditional Chinese Medicine Varieties may apply for first-class protection.

2. 1. 1 has special curative effect on specific diseases, which means that a major breakthrough can be made in the therapeutic effect of a certain disease. For example, it has special curative effect on common diseases, frequently-occurring diseases and other diseases; It can achieve obvious curative effect on diseases that have no effective treatment in the past; Or make significant progress in improving the final results (mortality, disability rate, etc.). ) major and difficult diseases, critical diseases or rare diseases.

2. 1.2 is equivalent to the artificial products of national first-class protected wild medicinal materials, and refers to the artificial products listed as national first-class protected medicinal materials; Or medicinal artificial products of species whose wild resources are in an endangered state, although they are currently second-class protected species.

2. 1.3 Special diseases used for the prevention and treatment of special diseases refer to major and difficult diseases, critical diseases, serious infectious diseases and rare diseases that seriously endanger people's health and normal social and economic order. Such as malignant tumor, end-stage renal disease, stroke, acute myocardial infarction, AIDS, infectious atypical pneumonia, human avian influenza, phenylketonuria, thalassemia and other diseases.

The varieties of traditional Chinese medicine used to prevent and treat major and difficult diseases, acute and critical diseases and severe infectious diseases should be obviously superior to the existing treatment methods.

2.2 varieties that meet the provisions of article 7 of the regulations on the protection of varieties of traditional Chinese medicine may apply for secondary protection.

2.2. 1 has obvious curative effect on specific diseases, which means that it can highlight the characteristics of pharmacological methods used in TCM syndrome differentiation, has obvious clinical application advantages, or has good curative effect on the diseases, syndromes or symptoms.

2.2.2 Effective substances and special preparations extracted from natural medicines refer to preparations made from effective components and effective parts extracted from traditional Chinese medicines and natural medicines, which have advantages in clinical application.

2.3 Where there are intellectual property disputes such as patents, the varieties shall be protected after the dispute is resolved.

2.4 The enterprise shall ensure the authenticity, completeness, standardization and accuracy of the application materials and data. The test data shall indicate the source, completion date and storage place of the original documents, and the seal shall be consistent with the name of the test unit and signed by the main researchers so that the test data can be traced back.

2.5 The unit responsible for clinical trials should be the national drug clinical trial institution, and the diseases studied should be suitable for the professional departments identified by it. The participating units should be tertiary hospitals.

Secondary and primary hospitals can participate in clinical research aimed at widely used safety evaluation.

2.6 The test process shall meet the requirements of various quality management standards issued by the US Food and Drug Administration, and the original test data shall be kept until the protection period expires.

2.7 The reporting enterprise should have good production conditions and quality management system, and its production equipment and inspection instruments should match the production and quality inspection of the declared varieties and have a good reputation.

2.8 When necessary, the National Traditional Chinese Medicine Variety Protection Review Committee may organize on-site verification of the authenticity of the application materials, inspect and sample the production site and organize inspection.

2.9 producers of protected varieties of traditional Chinese medicine shall complete the improvement opinions and related requirements on time and as required during the protection period.

3 main protection

3. 1 The first application for protection refers to the first application for protection of traditional Chinese medicine varieties; Applications for protection filed by other production enterprises of the same variety before the announcement of the protection of this variety shall be managed according to the initial protection application.

3.2 The application materials shall be able to explain the insurability of the declared varieties and objectively and comprehensively reflect the production technology, quality research, safety evaluation, clinical application and other aspects of the varieties of traditional Chinese medicine.

3.3 The declared varieties shall generally complete the monitoring period, registration approval documents and other research work required by laws and regulations.

3.4 If the declared varieties are produced by several enterprises, the original research enterprise shall make the first declaration; If the quality standard cannot effectively control the product quality, the quality standard should be improved and unified.

3.5 review materials include an overview of clinical, pharmacological, toxicological and pharmaceutical contents, and explain the reasons for the applicable terms and application level.

3.6 Clinical data

3.6. 1 the clinical data of the varieties applying for first-class protection should be able to prove that they have made a major breakthrough in the therapeutic effect of a certain disease or used for the prevention and treatment of special diseases.

3.6.2 The clinical data of varieties applying for secondary protection should be able to prove that they have obvious clinical application advantages, or the curative effect on indications, syndromes or symptoms is better than that of similar varieties.

3.6.3 Clinical trial design should be scientific and reasonable, paying special attention to the acceptability of evaluation indexes, the rationality of reference drugs and sufficient sample size. Generally, positive control should be selected, and the selection of positive control drugs should follow the principle of "recognized, similar and preferred", and the selection basis should be explained in detail. If necessary, placebo control should be selected. The comparative advantage test should be conducted with the positive control drugs, or the advantages of the declared varieties should be reflected on the premise of confirming the effectiveness of the declared varieties. The number of experimental samples should meet the statistical requirements, and the number of cases in the experimental group is generally not less than 300; For a variety of diseases, the number of cases of each major disease in the experimental group is generally not less than 60 cases.

In safety evaluation, we should pay attention to routine safety observation, such as three routine examinations, liver and kidney function examination, electrocardiogram examination and so on. , as well as special safety observations related to the characteristics and indications of the varieties, such as incompatibility and preliminary research of the varieties.

Explain that there are special toxic varieties and injections.

3.7 pharmaceutical data

3.7. 1 Raw materials should have legal standards, complete contents and items, and complete testing items when necessary.

The origin of multi-base raw materials should be clear, and the main medicinal essence should be clear, with relatively stable supply channels and relevant certification materials; Raw materials for injection must have a fixed place of origin and production, and have corresponding safeguard measures.

Processing methods and standards for feeding Chinese herbal pieces shall be provided, and the production enterprises and supply channels for directly purchasing Chinese herbal pieces shall be defined.

3.7.2 Detailed production process (the whole process of raw material pretreatment, extraction, purification, concentration, drying and preparation molding), main process parameters and quality control indicators, process flow chart and process research data shall be provided. Process research data should be able to explain the rationality of the current production process and provide quality assurance measures taken in each link of the process.

3.7.3 The declared varieties must be those that implement the official national drug standards and can effectively control the drug quality. Fingerprint and safety inspection items must be established in the injection standard, and the quality inspection summary of the enterprise in the past three years and the inspection report of the provincial drug inspection institution should be provided to explain the implementation of the quality standard.

3.7.4 The main effective components of a single pharmaceutical preparation should be clear, and there should be corresponding specific quality control methods.

3.8 varieties with changed dosage forms should have experimental data to prove their advancement and rationality. Compared with the original dosage form, the common preparation with changed dosage form should prove its characteristics and advantages in drug stability, absorption and utilization, controllability, safety, effectiveness or patient compliance.

It should be compared with common preparations to prove its characteristics and advantages in drug release, bioavailability, effectiveness or safety.

Changes in dosage forms should also have significant clinical application advantages, or the curative effect on diseases, syndromes or symptoms is better than that of similar varieties.

3.9 Compared with the original varieties and similar varieties, the varieties that have undergone major technical improvements in Chinese patent medicines must have obvious advantages in dosage, preparation stability, controllability of quality standards, effectiveness or safety, and provide relevant information.

The varieties of improved technology should also have significant clinical application advantages, or the curative effect on diseases, syndromes or symptoms is better than that of similar varieties.

3. The prescription of10 contains incompatible medicinal tastes such as eighteen evils and nineteen fears, and contains medicinal tastes of heavy metals, toxic medicinal materials (toxic Chinese medicinal materials listed in the State Council's Measures for the Administration of Toxic Drugs for Medical Use), and the daily consumption of other toxic medicinal materials exceeds the pharmacopoeia standard, and the use of processed products or raw products is inconsistent with the traditional usage. The medicinal varieties with potential safety hazards reported in clinic or literature should be confirmed by experimental data.

3. 1 1 The technical requirements for applying for variety protection of traditional Chinese medicine injections shall not be lower than the current requirements for registration of traditional Chinese medicine injections, especially the safety research data must be carried out in the GLP laboratory recognized by the state, and there are adverse reaction retrieval reports.

3. 12 A compound preparation composed of traditional Chinese medicine, natural medicine and chemical medicine should have comparative research and clinical trial data on pharmacodynamic and toxicological interaction (synergy, attenuation or complementation) among traditional Chinese medicine, natural medicine and chemical medicine to prove the rationality of its prescription.

3. 13 The applicant enterprise shall propose specific steps to improve the varieties and implement them within the protection period. Such as further improving production process control, improving quality standards, strengthening basic and clinical research, and improving drug instructions.

3. 13. 1 Raw materials and medicinal materials used for production need to have a clear and fixed place of origin.

3. 13.2 further study the key links and technical parameters that affect the product quality in the whole production process, and improve the quality control and quality management in the production process.

3. 13.3 study the improvement and perfection of quality standards, enhance the specificity of detection items, study and establish detection indicators related to functional indications and safety, and complete the standard revision according to the national drug standard revision procedure.

3. 13.4 Further clinical and basic research, wider clinical observation, improved instructions and guidance on rational drug use. For example, according to the characteristics of varieties and the deficiency of existing research data, the indications, drug interaction, application in special populations, safety evaluation, dose-effect relationship, mechanism of action, drug in vivo process, adverse reactions, contraindications and matters needing attention are clarified.

4 protection of the same variety

4. 1 The same variety refers to the variety with the same drug name, dosage form and prescription. The application for protection of the same variety refers to the application for protection filed by other production enterprises of the same variety in accordance with the regulations after the announcement of the first application for protection.

4.2 For the varieties that have accepted the application for the same variety, the National Evaluation Committee for the Protection of Varieties of Traditional Chinese Medicine shall organize relevant experts and personnel of relevant units to evaluate the quality of the same variety. The quality evaluation of the same variety includes on-site inspection, sampling and inspection.

According to the needs of the work, you can entrust the provincial food and drug supervision department to conduct on-site inspection and sampling. 4.2. 1 On-site inspection The on-site inspection is to inspect the whole production process of the tested varieties according to national standards. 4.2.2 Sampling According to the Guiding Principles for Drug Sampling formulated by the US Food and Drug Administration, three batches of samples should be taken from the finished product warehouse of the enterprise, and the sampling amount is three times of the total inspection amount. If necessary, it can also be purchased in the market and confirmed by the enterprise. If the declared variety contains multiple specifications, one specification of the main production can be extracted, and if the quality standard involves qualitative and quantitative, the corresponding appropriate amount of medicinal materials should be extracted. 4.2.3 Sampling samples shall be inspected by the National Traditional Chinese Medicine Variety Protection Evaluation Committee entrusted by China Institute for the Control of Pharmaceutical and Biological Products or the provincial drug inspection institute according to the national drug standards implemented by the declared varieties. 5 extend the protection period

5. 1 The application for extension of protection period refers to the application for extension of protection period put forward by the producer of the protected variety of traditional Chinese medicine before the expiration of the protection period of the variety.

5.2 The variety applying for extended protection shall be able to prove that it has obvious clinical efficacy advantages over similar varieties in treating diseases, syndromes or symptoms.

5.3 The applicant enterprise shall complete all work and submit relevant materials according to the improvement opinions and relevant requirements.

5.4 The varieties with extended protection period should be significantly improved in clinical, pharmacological, toxicological and pharmaceutical aspects compared with those before protection, such as clear origin, fixed origin, clear process parameters, strict process control, controllable and perfect quality standards, exact indications and perfect drug instructions. The dose-effect relationship, mechanism of action and metabolic process in vivo of preparations made from effective components and effective parts should be basically clear.

5.5 The applicant enterprise shall propose a detailed plan and implementation plan for variety improvement during the extended protection period.