Overview of Drug Safety Evaluation, its Importance and Content

The safety issues caused by drugs have been widely and highly valued by the drug administration departments of various countries, and the technology and methods of drug safety evaluation are the hotspots of scholars from all over the world. In recent years, with the continuous development of science and technology, new safety evaluation techniques and methods have emerged, including evaluation techniques and methods for liver, kidney, heart and other target organ toxicity, developmental and reproductive toxicity, genotoxicity and carcinogenicity, etc. .

In the early 1960s, Australian doctor Mcbride reported that short-limb deformities were related to mothers taking Thalidomide (Thalidomide) during pregnancy. People realized and gradually paid attention to the adverse reactions caused by drugs that could cause serious harm to humans. On the other hand, the historical experience of global innovative drug research and development also shows that 35% to 40% of new drugs fail to be developed due to safety reasons. The later drug toxicity is discovered, the greater the economic loss to pharmaceutical companies. Therefore, the safety of drugs has always been widely and highly valued by drug administrations and new drug developers in various countries.

Drugs refer to substances that are used to prevent, treat, and diagnose diseases, purposefully regulate human physiological functions, and specify indications or functional indications, usage, and dosage, including Chinese medicinal materials, Chinese herbal pieces, Chinese patent medicines, chemical raw materials, and other substances. Preparations, antibiotics, biochemical drugs, radiopharmaceuticals, serum, vaccines, blood products and diagnostic drugs, etc.

New Drug Development Program

1. Exploration and screening: Apply conventional pharmacological methods to detect the pharmacological activity of the compound, if it exceeds the activity standard, it can be considered active; try to exclude potentially problematic compounds through early toxicity screening, thereby increasing the number of test compounds and reducing experimental animals dosage and expand the range of dosage.

2. Non-clinical research: Carry out toxicological safety evaluation, bioavailability evaluation and pharmacokinetics research in compliance with GLP standards.

3. Clinical research: Phase I: To prove the human tolerance to the drug and to determine its pharmacokinetic properties in the human body. Phase II: Determine the dose-response relationship of the drug. Phase III: clinical pharmacodynamics trials (comprehensive, multi-center, and involving a large number of patients) Phase 1, Phase II, and Phase III clinical trials should meet GCP standards.

4. Application for new drug registration: "Drug Administration Law", "Measures for the Administration of Drug Registration"

5. Launching of new drugs: monitor adverse drug reactions and conduct Phase W clinical trials in compliance with GCP standards

The Importance of Safety Research

"Thalidomide" Thalidomide Thalidomide Incident (1960s, Germany) a. In October 1957, Thalidomide was officially put on the market as an "anti-pregnancy drug without any side effects" and became "the ideal choice for pregnant women". b. In 1960, some doctors found that the incidence of neonatal malformations was related to the sales volume of thalidomide. Later toxicological studies showed that thalidomide was highly teratogenic to primates sex. c. In November 1961, all thalidomide was withdrawn from the Federal German market, and soon other countries also stopped the sale of thalidomide. During this period, more than 10,000 deformed fetuses were born due to thalidomide. 

Medicilon has a quality management system for drug safety evaluation based on the internationally certified AAALAC quality standard and compliance with international and domestic GLP regulations.

Since 2008, we have continued to meet international standards and completed high-quality GLP safety evaluation services, establishing a long-term brand effect. Medicilon can perform systematic evaluation services covering multiple toxicity endpoints and has internationally recognized pathology studies to support our safety evaluation studies.

The concept and research content of safety evaluation

Drug safety evaluation is to elucidate the toxicity and potential hazards of drugs through animal experiments and observations on the population, so as to determine whether they can enter the market or to clarify the conditions for safe use, so as to minimize their harmful effects and protect human health. The research content of drug safety evaluation includes preclinical safety evaluation, clinical safety evaluation and post-marketing safety re-evaluation.

The concept, purpose and significance of GLP

GLP is the abbreviation of Good Laboratory Practice in English, good laboratory practice, or good laboratory practice or standard laboratory practice. It is a regulatory document formulated for a series of management of laboratory experimental research from planning, experimentation, supervision, recording to experiment report. Purpose: The main purpose of formulating GLP is to strictly control all aspects of drug safety evaluation trials, improve the quality of drug non-clinical safety evaluation studies (i.e. toxicology studies), ensure the authenticity, integrity and reliability of experimental data, and Guarantee the safety of people's medicines.

Significance: Promoting the GLP process can avoid errors and errors caused by human factors to the greatest extent, improve the quality of non-clinical research on drugs, and ensure the safety of people's medication. Therefore, safety evaluation research plays a decisive role in determining whether a drug can enter clinical research, predicting the degree of risk of its clinical research, and whether the final evaluation has development value. In order to improve the market competitiveness of our province's pharmaceutical products and ensure the sustainable development of the pharmaceutical industry in Heilongjiang Province, we must solve the problem from the source of pharmaceutical products and seek development by enhancing the research and development capabilities of innovative drugs.

Toxicity studies of systemic drugs

Acute toxicity test, long-term toxicity test, systemic toxicity test of preparation, vascular stimulation test; in vitro hemolysis test; allergy test. Acute toxicity refers to the toxic effects that occur within a short period (up to 14 days) after the body (human or experimental animal) is exposed to a chemical once or multiple times within 24 hours, including changes in general behavior, appearance, Gross morphological changes and death effects. Long-term toxicity test refers to a toxicity test in which animals are repeatedly dosed continuously. In the case of repeated administration, the toxic reaction, dose-effect relationship, main target organs, degree of damage and its reversibility in experimental animals. Under the condition of repeated administration, the dose range that the experimental animals can tolerate and the safety range of complete non-toxic reaction are obtained.

General Pharmacology Research

General pharmacological research: refers to the research on the extensive pharmacological effects of new drugs other than the main pharmacological effects. Include studies of secondary pharmacodynamics and safety pharmacology. Secondary pharmacodynamics (side effects) are the study of undesired, unrelated effects and mechanisms of action of a drug. Safety pharmacology studies the potential undesired adverse effects of a drug at doses within or above the therapeutic range. Additional and/or supplementary safety pharmacology studies may be conducted as needed. It mainly studies the effects of drugs on the spirit, nervous system, cardiovascular system, respiratory system and other systems.

Toxicity Studies of Topical Drugs

Including skin irritation test, skin absorption test, skin photosensitivity test, eye irritation test, muscle irritation test, blood vessel irritation test,

Special Toxicity Studies

Drugs have some toxic reactions, which are often only exposed after a long incubation period or under special conditions. The incidence rate is low, but the consequences are often serious and irreparable. This is mutagenicity, Carcinogenicity, reproductive toxicity (teratogenicity) and dependence, these types of toxicity tests are usually called specific toxicity tests.

1. Mutagenic effect.

     Ames test; Escherichia coli reverse mutation test; mammalian in vitro cytogenetic test; micronucleus test; mammalian in vivo bone marrow cell genetic test; mammalian in vitro cell gene mutation test; test

2. Carcinogenicity test

Cultured cell malignant transformation test; comet test; mammalian short-term carcinogenicity test; mammalian long-term carcinogenicity test

3. Reproductive toxicity and developmental toxicity test

     General reproductive toxicity test; teratogenicity sensitive period toxicity test (teratogenicity test); perinatal toxicity test

4. Evaluation of Drug Dependence

     physical dependence test; mental dependence test