Preclinical studies and clinical trials of drugs
(1) Pre-clinical research content
1. Literature research includes drug name and naming basis, the purpose and basis of the topic.
2. Pharmacy research. Raw material technology research, formulation prescription and technology research, confirmation of chemical structure or component test, drug quality test, drug standard drafting and description, sample inspection, auxiliary materials, stability test, packaging material and container related test, etc.
3. Pharmacology and Toxicology Research. General pharmacology tests, main pharmacodynamic tests, acute toxicity tests, long-term toxicity tests, allergic, hemolytic and local irritation tests, mutagenicity tests, reproductive toxicity tests, carcinogenic toxicity tests, dependence tests, animals Pharmacokinetic tests, etc.
The drug safety evaluation research must implement the “Pharmaceutical Non-Clinical Research Quality Management Standards” (GLP)
2. naming of drugs
1. The main types of drug names
Generic name of medicine
Official name of drug
Drug brand name (brand name)
Patent name (proprietary name)
“International Nonproprietary Name for Pharmaceutical Substances (INN)”.
2. Items included in the drug name
Chemical names include common names, chemical names, English names, and pinyin
The names of Chinese medicinal materials include Chinese names, Pinyin, Latin names
The names of traditional Chinese medicine preparations include Chinese names, Pinyin, and English names
The names of biological products include common names, pinyin, and English names
3. Principles for naming drugs
Scientific, systematic and simplified
① The pronunciation of the drug name should be clear and legible, the whole word should not be too long, and it should be avoided to be similar to the currently used drugs;
②The names of drugs belonging to the same pharmacodynamic category should strive to display this relationship in an appropriate way; any name that makes it easy for patients to guess the pharmacodynamic effects from the perspective of anatomy, physiology, pathology and therapeutics should not generally be used .
If it has already been used as a generic name for a drug, the name shall not be used as a drug trademark.
3. Other requirements for preclinical research
1. Requirements for institutions engaged in drug research and development
2. Regulations for research APIs
The research drug must have a drug approval number, “Imported Drug Registration Certificate” or “Pharmaceutical Product Registration Certificate”, and the drug substance must be obtained through legal channels. Research APIs that do not have a drug approval number, “Imported Drug Registration Certificate” or “Pharmaceutical Product Registration Certificate” must be approved by the State Food and Drug Administration.
3. Processing of overseas drug trial research data
Drug clinical research must be conducted after approval by SFDA.
Drug clinical research includes clinical trials and bioequivalence trials.
Clinical research must implement the “Guidelines for the Quality Control of Drug Clinical Trials” (GCP).
(1) Staging of clinical trials and minimum number of cases
Clinical trials are divided into phases I, II, III, and IV.
Phase Ⅰ clinical trial
Preliminary clinical pharmacology and human safety evaluation test. Observe the human body’s tolerance to new drugs and pharmacokinetics to provide a basis for formulating dosing regimens.
Number of cases: 20-30 cases
Phase Ⅱ clinical trial
Initial evaluation stage of treatment effect. The initial evaluation of the therapeutic effect and safety of the drug on the target indication patients also includes providing a basis for the design of the phase III clinical trial study and the determination of the dosage regimen.
Number of cases: ≥ 100 cases
Phase III clinical trials
Confirmation of treatment effect. To further verify the therapeutic effect and safety of drugs on target indication patients, evaluate the relationship between benefits and risks, and ultimately provide a sufficient basis for the review of drug registration applications.
Number of cases: ≥ 300 cases
Phase III clinical trials can be applied for new drug production
Phase IV clinical trials
The stage of applied research conducted by the applicant after the launch of the new drug. Its purpose is to investigate the efficacy and adverse reactions of drugs under widely used conditions, to evaluate the relationship between the benefits and risks of use in ordinary or special populations, and to improve the dosage of drugs.
Number of cases: ≥2000 cases
Bioequivalence test
Using bioavailability research methods, using pharmacokinetic parameters as indicators, comparing the preparations of the same or different dosage forms of the same drug, under the same test conditions, there is no statistical difference in the degree and speed of absorption of active ingredients test.
Number of cases: 18-24 cases
(2) Clinical research needs to be conducted in drug registration
1. Apply for new drug registration
Clinical trials
2. Apply for drug registration with existing national standards
Clinical trials are generally not required;
Need to conduct clinical trials: chemical drugs are generally tested for bioequivalence;
Drugs that require technology and standards to control the quality of drugs should undergo clinical trials.
3. Application for import drug registration
Clinical trials are conducted in accordance with the requirements of corresponding domestic drug registration categories.
4. Drug supplement application
If there is a major change in the addition of new indications or production processes for drugs already on the market, clinical trials are required.
(3) Drug clinical trial site
After the drug clinical trial is approved, the applicant shall select the institution that undertakes the drug clinical trial from the institutions that have the qualification for drug clinical trial, and agree on the responsible unit of the clinical trial, the main investigator and the unit participating in the clinical trial.
(4) Recording of drug clinical trial programs
Before the drug clinical trial is implemented, the applicant should submit the confirmed clinical trial plan and the name of the main investigator of the clinical trial responsible unit, the list of participating research institutions and their investigators, the ethics committee review consent, the sample of informed consent, etc. The State Food and Drug Administration shall file for the record and copy it to the location of the clinical trial unit and the provincial drug supervision and administration department accepting the application.
(5) Preparation and use management of drugs for clinical research
Clinical trial drugs should be prepared in GMP-compliant workshops, and the preparation process should strictly comply with GMP requirements. The applicant is responsible for the quality of the drugs used in clinical trials.
Vaccine products, blood products, other biological products prescribed by the State Food and Drug Administration, and drugs for clinical trials produced overseas must be inspected by a drug inspection office designated by the State Food and Drug Administration.
The drugs used in clinical trials can only be used in clinical trials after passing the inspection.
(6) Implementation of clinical research
After the clinical study of the drug is approved, it should be implemented within 3 years. If it is overdue, it should be reapplied. After completing the clinical trial, the applicant should submit the clinical trial summary report and statistical analysis report to SFDA.
(7) Guarantee the safety of the subjects
Clinical research institutions and clinical researchers are obliged to take necessary measures to ensure the safety of the subjects. Pay close attention to adverse drug reactions, and report and handle in accordance with regulations.
Large-scale, unexpected drug adverse reactions, or confirmation of serious quality problems in clinical trial drugs, SFDA or provincial FDA can take emergency control measures and order to suspend or terminate clinical research, applicants and clinical trial units must immediately stop clinical trials .
(8) Provisions for overseas applicants to conduct international multi-center clinical drug research in China
1. Drugs for clinical research should be drugs that have been registered overseas or have entered Phase II or Phase III clinical trials; international multi-center clinical drug research applications for new preventive vaccine drugs submitted by overseas applicants that have not been registered overseas will not be accepted .
2. SFDA may require applicants to conduct Phase I clinical trials in China as needed.
3. When conducting clinical research, if any serious adverse reactions or unexpected adverse reactions related to the drug are found in any country, the applicant should report to the SFDA in time according to the relevant regulations.
4. After the clinical research is completed, the applicant should submit the complete clinical research report to SFDA.
5. The data obtained from the international multi-center clinical drug research for the application for drug registration in China must comply with the relevant clinical trial regulations, and the applicant must submit all the research data of the multi-center clinical research.
