Preclinical Research and Clinical Trials of Drugs

1. Drug Preclinical Research

(1) Preclinical research content

1. Literature research, including the name of the drug and the basis for naming, and the basis for establishing the title.

2. Pharmaceutical research: API process research, preparation formulation and process research, test to confirm chemical structure or composition, drug quality test, drug standard drafting and description, sample test, excipients, stability test, packaging material and container related tests, etc.

3. Pharmacology and Toxicology Research General pharmacology test, main pharmacodynamic test, acute toxicity test, long-term toxicity test, allergy, hemolytic and local irritation test, mutagenicity test, reproductive toxicity test, carcinogenic toxicity test, dependence test, animal Pharmacokinetic test, etc.

Drug safety evaluation research must implement the “Non-clinical Drug Research Quality Management Practice” (GLP)

(2) Name of Drugs

1. The main types of drug names

Generic name of the drug

Official name of the drug

Drug product name (brand name)

Patent name (proprietary name)

“International Nonproprietary Name for Pharmaceutical Substances” (INN).

2. Items included in the name of the drug

The names of chemical drugs include common name, chemical name, English name, Chinese pinyin

The names of Chinese medicinal materials include Chinese names, Chinese pinyin, and Latin names

The names of Chinese medicine preparations include Chinese name, Chinese pinyin, and English name

The names of biological products include common names, Chinese pinyin, and English names

3. Principles of Drug Naming

Scientific, systematic, and simplified

① The pronunciation of the name of the drug should be clear and easy to distinguish, 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 drug effect category should be used to show this relationship in an appropriate way; any name that is easy to make patients guess the drug effect from the anatomy, physiology, pathology, and therapeutic perspectives should generally not be used .

If it has been used as a generic name for a drug, the name may not be used as a drug trademark.

(3) Other requirements for pre-clinical research

1. Requirements of institutions engaged in drug research and development

2. Regulations on APIs for Research

The API for research must have a drug approval number, “Imported Drug Registration Certificate” or “Registration Certificate for Pharmaceutical Products”, and the API must be obtained through legal channels. APIs for research use that do not have a drug approval number, “Imported Drug Registration Certificate” or “Medicinal 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 implemented after SFDA approval.

Drug clinical research includes clinical trials and bioequivalence trials.

Clinical research must implement the “Quality Management Practices for 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

The initial evaluation stage of the therapeutic effect. Preliminary evaluation of the therapeutic effect and safety of the drug on patients with target indications, including providing a basis for the design of phase III clinical trials and the determination of dosage regimens.

Number of cases: ≥ 100 cases

Phase III clinical trial

Confirmation stage of therapeutic effect. Further verify the therapeutic effect and safety of the drug on patients with target indications, evaluate the relationship between benefits and risks, and finally provide sufficient basis for the review of drug registration applications.

Number of cases: ≥ 300

Application for new drug production after phase III clinical trial

Phase IV clinical trial

The applied research stage conducted by the applicant after the new drug is marketed. Its purpose is to investigate the efficacy and adverse reactions of drugs under widely used conditions, evaluate the relationship between benefits and risks used in general or special populations, and improve dosages.

Number of cases: ≥2000 cases

Bioequivalence test

Using the method of bioavailability research, using pharmacokinetic parameters as an indicator to compare the same or different formulations of the same drug, under the same test conditions, whether there is a statistical difference in the degree and speed of absorption of the active ingredients test.

Number of cases: 18-24

(2) Circumstances Where Clinical Research is Required in Drug Registration

1. Apply for new drug registration

Clinical trials must be conducted

2. Apply for drug registration with national standards

Generally, clinical trials are not required;

Need to conduct clinical trials: chemicals generally undergo bioequivalence testing;

Drugs that require the use of technology and standards to control the quality of drugs should undergo clinical trials.

3. Application for registration of imported drugs

Conduct clinical trials in accordance with the requirements of the corresponding domestic drug registration categories.

4. Drug supplement application

If new indications are added to the marketed drugs or there are major changes in the production process, clinical trials are required.

(3) Drug Clinical Trial Sites

After the drug clinical trial is approved, the applicant shall select the institution that undertakes the drug clinical trial from the institutions with drug clinical trial qualifications, and agree on the responsible unit of the clinical trial, the main investigator and the clinical trial participating unit.

(4) Filing of Drug Clinical Rrial Programs

Before the implementation of the drug clinical trial, the applicant shall submit the determined clinical trial protocol and the name of the main investigator of the clinical trial responsible unit, the list of participating research units and their investigators, the ethics committee review consent form, and samples of the informed consent form, etc. The State Food and Drug Administration puts it on record and sends a copy to the location of the clinical trial unit and the provincial drug regulatory authority that accepted the application.

(5) Preparation and Use Management of Clinical Research Drugs

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 specified by the State Food and Drug Administration, and drugs for clinical trials produced overseas must be inspected by a drug inspection institute designated by the State Food and Drug Administration.

Drugs used in clinical trials can be used in clinical trials only after they are qualified.

(6) Implementation of Clinical Research

Drug clinical research should be implemented within 3 years after it is approved, and it should be invalidated if it is overdue, and a new application should be made. After completing the clinical trial, the applicant shall submit the clinical trial summary report and statistical analysis report to SFDA.

(7) Ensure the Safety of Subjects

Clinical research institutions and clinical researchers are obliged to take necessary measures to ensure the safety of subjects. Pay close attention to adverse drug reactions, report and handle them in accordance with regulations.

In the event of a large-scale and unexpected adverse drug reaction, or it is confirmed that the clinical trial drug has serious quality problems, SFDA or the provincial FDA can take emergency control measures and order the suspension or termination of the clinical trial. The applicant and the clinical trial unit must immediately stop the clinical trial .

(8) Provisions for Overseas Applicants to Conduct International Multi-center Drug Clinical Research in China

1. Drugs for clinical research should be drugs that have been registered overseas or drugs that have entered phase II or phase III clinical trials; international multi-center drug clinical research applications for new preventive vaccine drugs that have not been registered overseas are not accepted by foreign applicants .

2. SFDA may require applicants to conduct Phase I clinical trials in China as needed.

3. In conducting clinical research, if any serious or unexpected adverse reaction related to the drug is found in any country, the applicant should report to SFDA in time in accordance with relevant regulations.

4. After the clinical study is over, the applicant should submit the complete clinical study report to SFDA.

5. The data obtained from international multi-center drug clinical research is used for drug registration application in China and must comply with the relevant clinical trial regulations. Applicants must submit all research materials for multi-center clinical research.