Guiding Principles for the Protection of Traditional Chinese Medicine Varieties
| 2010-07-01
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Guiding Principles for the Protection of Varieties of Traditional Chinese Medicines
1 General Principles
According to the relevant provisions of the "Regulations on the Protection of Varieties of Traditional Chinese Medicines", These guiding principles are 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 scientificity, fairness, and standardization of the protection of traditional Chinese medicine varieties.
2 General Requirements
2.1 Varieties that comply with the provisions of Article 6 of the "Regulations on the Protection of Traditional Chinese Medicine Varieties" can apply for first-level protection.
2.1.1 Having special curative effect on a specific disease means that a major breakthrough can be made in the treatment of a certain disease. For example, it has special effects on common diseases, frequently-occurring diseases, etc.; it can achieve obvious effects on diseases that have no effective treatments in the past; or it can improve the end-point outcomes (mortality rate, disability rate, etc.) of major difficult diseases, critical illness, or rare diseases. ) has made significant progress.
2.1.2 Artificial products equivalent to national first-level protected wild medicinal species refer to artificial products listed as national first-level protected species medicinal materials; or although they are currently second-level protected species, Artificial products of medicinal materials whose wild resources are in endangered status.
2.1.3 Special diseases used for the prevention and treatment of special diseases refer to major and difficult diseases, critical illness, severe infectious diseases and rare diseases that seriously endanger the health of the people and the normal social life and economic order. . Such as malignant tumors, end-stage renal disease, stroke, acute myocardial infarction, AIDS, SARS, human avian influenza, phenylketonuria, thalassemia and other diseases.
The efficacy of traditional Chinese medicines used to prevent and treat major and difficult diseases, critical illness, and severe infectious diseases should be significantly better than existing treatment methods.
2.2 Varieties that comply with the provisions of Article 7 of the "Regulations on the Protection of Varieties of Traditional Chinese Medicine" can apply for secondary protection.
2.2.1 Having significant curative effect on specific diseases means that it can highlight the characteristics of pharmacological methods for syndrome differentiation of traditional Chinese medicine, has significant clinical application advantages, or has a better curative effect on the main disease, syndrome or symptom than similar varieties. .
2.2.2 Effective substances and special preparations extracted from natural medicines refer to preparations made from active ingredients and effective parts extracted from traditional Chinese medicines and natural medicines, and have clinical application advantages.
2.3 For varieties with intellectual property disputes such as patents, the disputes should be resolved before handling protection matters.
2.4 Enterprises should ensure that the application materials and data are true, complete, standardized and accurate. The test data should indicate the source, completion date, and original file storage location. The seal should be consistent with the name of the test unit and signed by the main researcher. The test data can be traced to its source.
2.5 The unit responsible for clinical trials should be the national drug clinical trial institution, the diseases studied should be suitable for the professional departments recognized by it, and the participating units should be tertiary A hospitals.
Class II-A hospitals can participate in clinical research aimed at widely used safety evaluations.
2.6 The test process should comply with the requirements of various quality management specifications issued by the State Food and Drug Administration, and the original test data should be retained until the expiration of the protection period.
2.7 The applicant enterprise should have good production conditions and quality management systems, production equipment and inspection instruments that 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 can organize on-site verification of the authenticity of the application materials, conduct inspections and sampling of the production site, and organize inspections.
2.9 Enterprises producing protected varieties of traditional Chinese medicines should complete various improvements and related requirements on time and as required during the protection period.
3 Initial protection
3.1 The initial protection application refers to the first application for protection of a traditional Chinese medicine variety; applications for protection submitted by other manufacturers of the same variety before the announcement of the protection of the variety shall be treated as the first application. Protection application management.
3.2 The application materials should be able to explain the insurability of the applied variety, and objectively and comprehensively reflect the production technology, quality research, safety evaluation, clinical application, etc. of the traditional Chinese medicine variety.
3.3 The declared varieties should generally complete the monitoring period, registration approval documents and other research work required by laws and regulations.
3.4 If the declared variety is produced by multiple companies, the original research company should submit the first application; if the quality standards cannot effectively control the product quality, the quality standards should be improved and unified.
3.5 The review information includes an overview of clinical, pharmacological, toxicological, and pharmaceutical content, and explains the applicable terms and reasons for the application level.
3.6 Clinical data
3.6.1 The clinical data of the variety applied for first-level protection should be able to prove that it has made a major breakthrough in the treatment of a certain disease, or can be used for prevention. and treatment of specific diseases.
3.6.2 The clinical data of the variety applying for secondary protection should be able to prove that it has significant clinical application advantages, or that its curative effect on the main disease, syndrome or symptom is superior to similar varieties.
3.6.3 The design of clinical trials should be scientific and reasonable, with special attention to the recognition of evaluation indicators, the rationality of control drugs and sufficient sample size. Generally, a positive control should be selected. The selection of positive control drugs should follow the principle of "recognized, similar, and superior", and the basis for selection should be explained in detail. If necessary, a placebo control should be selected. A superiority test should be conducted compared with the positive control drug, or its advantages over the positive control drug should be demonstrated on the premise of confirming the effectiveness of the declared variety. The number of samples in the test should meet statistical requirements, and the number of cases in the test group is generally not less than 300; if there are multiple diseases and syndromes, the number of cases in the test group for each main disease syndrome is generally not less than 60.
In the safety evaluation, attention should be paid to routine safety observations, such as the three major routine examinations, liver and kidney function, electrocardiogram examination, etc., as well as special safety observations related to the characteristics of the species and the main indications. For example, it may contain incompatible species, early studies suggest that there are special toxic species, injections, etc.
3.7 Pharmaceutical Information
3.7.1 Raw materials should meet legal standards, and have complete content and complete items. If necessary, there should be more complete testing items.
Multi-base raw medicinal materials should have a clear base, the main medicinal flavor should have a clear origin, a relatively stable supply channel, and relevant supporting materials; injection raw materials must have a fixed base and origin, and provide corresponding safeguard measures.
Those who use traditional Chinese medicine pieces as ingredients should provide processing methods and standards. Those who purchase traditional Chinese medicine pieces directly should also specify the production companies and supply channels.
3.7.2 The detailed production process (raw material pre-treatment, extraction, purification, concentration, drying, preparation molding, etc.), main process parameters and quality control indicators, process flow chart and process research should be provided material. 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 comply with the national official drug standards. The drug standards should be able to effectively control drug quality. Fingerprints and safety inspection items must be established in the injection standards, and there should be nearly three Annual enterprise quality inspection summary table and inspection reports from provincial drug inspection agencies to illustrate the implementation of quality standards.
3.7.4 The main active ingredients of a single medicinal preparation should be clear, and there should be corresponding specific quality control methods.
3.8 Varieties with changed dosage forms should have test data to prove their advancement and rationality. A common preparation with a changed dosage form should be compared with the original dosage form to prove its characteristics and advantages in terms of drug stability, absorption and utilization, controllability, safety, effectiveness or patient compliance.
Changes to sustained-release preparations, controlled-release preparations, targeted preparations, etc. should be compared with ordinary preparations to prove their characteristics and advantages in drug release, bioavailability, effectiveness or safety, etc. .
Changing the dosage form variety should also have significant clinical application advantages, or be better than similar varieties in treating the main disease, syndrome or symptom.
3.9 Varieties that have undergone major process improvements on traditional Chinese patent medicines must have obvious advantages in dosage, preparation stability, quality standard controllability, effectiveness or safety compared with the original varieties and similar varieties. advantages and provide relevant information.
The varieties with improved technology should also have significant clinical application advantages, or be better than similar varieties in treating the main diseases, syndromes or symptoms.
3.10 Prescriptions contain incompatible medicinal flavors such as Shibafan and Shibawei, heavy metal-containing medicinal flavors, toxic medicinal materials (a series of toxic Chinese medicinal materials included in the "Measures for the Administration of Toxic Drugs for Medical Use" of the State Council), and other toxic materials If the daily dosage of medicinal materials exceeds the pharmacopoeia standard, the use of processed or raw products is inconsistent with traditional usage, and varieties with medicinal taste that have safety hazards reported in clinical or literature, there should be experimental data to confirm their drug safety.
3.11 When applying for variety protection of traditional Chinese medicine injections, the technical requirements shall not be lower than the current registration requirements for traditional Chinese medicine injections. In particular, the safety research data must be conducted in a nationally recognized GLP laboratory and must have adverse effects. Response search report.
3.12 Compound preparations composed of traditional Chinese medicines, natural medicines and chemical medicines should conduct comparative studies on the pharmacological effects and toxicological interactions (enhancement, attenuation or complementary effects) between traditional Chinese medicines, natural medicines and chemical medicines. and clinical trial data to confirm the rationality of its formulation.
3.13 The applicant enterprise should propose detailed plans and implementation steps for variety improvement during 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 The origin of raw materials for production must be clear and fixed.
3.13.2 Further study the key links and technical parameters that affect product quality in the entire production process, and improve the quality control and quality management of the production process.
3.13.3 Conduct research on improving and improving quality standards, enhance the specificity of testing items, research and establish testing indicators related to functional indications and safety, and complete standard revision work in accordance with the national drug standard revision procedures.
3.13.4 Further carry out clinical and basic research, conduct larger-scale clinical observations, improve instructions for use, and guide the rational application of drugs. For example, based on the characteristics of the variety and the shortcomings of existing research data, the scope of indications, drug interactions, applications for special groups, safety evaluation, dose-effect relationship, mechanism of action, in vivo processes of the drug, adverse reactions, contraindications, and precautions should be clarified. wait.
4 Protection of the same variety
4.1 The same variety refers to varieties with the same name, dosage form, and prescription. Applications for protection of the same variety refer to applications for protection submitted by other production enterprises of the same variety in accordance with regulations after the variety for which the initial application for protection is announced.
4.2 For varieties that have accepted applications for the same variety, the National Traditional Chinese Medicine Variety Protection Review Committee will organize relevant experts and personnel from relevant units to conduct quality assessments of the same variety. Quality assessment of the same variety includes on-site inspection, sampling and inspection.
According to work needs, provincial food and drug regulatory authorities can be entrusted to conduct on-site inspections and sampling. 4.2.1 On-site inspection On-site inspection is based on the national standards implemented by the variety to be assessed, and inspects the entire production process of the variety. 4.2.2 Sampling According to the "Guiding Principles for Drug Sampling" formulated by the State Food and Drug Administration, 3 batches of samples are taken from the company's finished product warehouse. The sampling volume should be three times the total inspection volume. If necessary, they can also be purchased in the market and collected by Enterprise confirmation. If the declared variety contains multiple specifications, one specification that is mainly produced can be selected. If the quality standards involve qualitative and quantitative aspects, the corresponding appropriate amount of medicinal materials should also be selected. 4.2.3 The samples taken for inspection shall be commissioned by the National Traditional Chinese Medicine Variety Protection Review Committee to be inspected by the National Institute for the Control of Pharmaceutical and Biological Products or provincial drug inspection institutes in accordance with the national drug standards implemented for the declared varieties. 5 Extension of the protection period
5.1 Application for extension of the protection period refers to an application for extension of the protection period submitted by the manufacturer of a protected variety of traditional Chinese medicine in accordance with regulations before the expiration of the protection period of the variety.
5.2 The variety applying for extension of protection should be able to prove that it has significant clinical efficacy advantages over similar varieties for the diseases, syndromes or symptoms it is intended to treat.
5.3 The applicant enterprise should complete various tasks and submit relevant information according to the improvement opinions and relevant requirements.
5.4 The clinical, pharmacological and toxicological, pharmaceutical and other aspects of the varieties with extended protection period should be significantly improved compared with those before protection. For example, the medicinal materials and decoction pieces used for production have clear bases, fixed origins, and clear process parameters. The process is strictly controlled, the quality standards are controllable and perfect, the scope of main treatments is precise, and the drug instructions are complete.
For preparations made from active ingredients and effective parts, the dose-effect relationship, mechanism of action and in vivo metabolic process should be basically clear.
5.5 The applicant enterprise should propose detailed plans and implementation plans for variety improvement during the extended protection period.