Analysis:
Brief Introduction of Food and Drug Administration (FDA)
1, US Drug Administration
The Food and Drug Administration (FDA) belongs to the US Department of Health, Education and Welfare, and is responsible for the management of medicines, food, biological products, cosmetics, veterinary drugs, medical devices and diagnostic supplies throughout the country. The FDA consists of drug bureau, food bureau, veterinary drug bureau, radiation health bureau, biological products bureau, medical equipment and diagnostic supplies bureau, national toxicology research center and regional work management institutions, namely, 6 bureaus (some publications are also called 6 centers), 1 center and 1 regional management institutions. The US Food and Drug Administration has about 7,500 employees, and the FDA headquarters has 1 143 employees, among which the Drug Administration has 350 employees.
The Drug Administration (also known as the Drug Evaluation and Research Center) is responsible for the examination and approval of drugs for human use, and consists of 8 departments and several departments. 1. Drug supervision department. It includes four departments: drug information, information system design, administration and budget, and medical library. 2. Drug supervision office. It consists of seven departments: drug quality evaluation, drug labeling supervision, production and product quality, scientific research and regulations. 3. Office of Drug Standards. There are two departments: evaluation of commonly used drugs, drug listing and advertising. 4. Drug Evaluation Department 1. It consists of five departments: cardiovascular and renal drugs, anti-tumor drugs, nutritional drugs, medical comparative surgery and dental drugs, gastrointestinal drugs and coagulation drugs. 5. Drug Evaluation Part II. There are three departments: anti-infective drugs, metabolic endocrine drugs and antiviral drugs. 6. Division of Epidemiology and Biostatistics. There are two departments: epidemiology, investigation and biostatistics. 7. Research room. There are two departments: research and testing and drug analysis. 8. Generic drug sector. There are two departments: generic drugs and bioequivalence.
The US Food and Drug Administration is located in Washington, D.C. and Rockwell, Maryland. It has a huge organization and branches all over the country. In order to strengthen drug quality management, FDA has divided China into six regions, namely, Pacific region (San Francisco, Seattle and Los Angeles), Southwest region (Dallas, Denver and Kansas), Midwest region (Chicago, Minneapolis and Detroit), Northeast region (Boston, new york and Buffalo), Mid-Atlantic region (Philadelphia, Cincinnati, Newark and Baltimore) and so on. Each district has a regional office, and there are several regional offices under the regional office. The Pacific region is located in San Francisco, the southwest region is located in Dallas, the midwest region is located in Chicago, the northeast region is located in Boston, the middle Atlantic region is located in Philadelphia, and the southeast region is located in Atlanta. The district is responsible for the supervision and inspection of food, medicines, cosmetics, equipment and blood banks in the region. Each area is equipped with several workstations according to work needs to ensure that the working face can cover the area. There are currently 143 workstations in the United States. Regional offices, regional offices and workstations are all directly under the FDA at all levels. The size of regional research institutes depends on the workload. More than 65% of drugs in the United States are produced in the mid-Atlantic, so the regional strength is strong. * * * has 525 employees, including 250 supervisors, accounting for about 65,438+0/4 of the FDA headquarters supervisors, and 65,438+050 analysts and inspectors.
The management of drugs in each state shall be implemented in accordance with local drug management laws and regulations. The main tasks are: pharmacist examination registration, supervision and inspection of drug administration departments and pharmacies, issuance or renewal of licenses, revocation of illegal household licenses, evaluation of local pharmaceutical colleges, and audit of trainee pharmacies.
2. Drug evaluation in America
In the United States, it takes 8 to 10 years for a new drug to be developed and approved for production, and it costs 65-80 million dollars. The FDA generally approves a new drug for two years, with an average of 2000 new drugs per year, and only 10% can be produced. Drug applications in the United States fall into three categories. 1. research drug application p. new drug application; 3. Simple new drug application. The average period of research, development and review of a new drug is: preclinical research 1.5 years, FDA safety review 1 month, phase III clinical trial for 5 years, and FDA new drug review for 2 years. Only 1/4 of the declared new drugs finally passed the review. After 0/7 years of new drug patent/kloc-,other pharmaceutical companies can copy it. The application for the production of generic drugs must be approved by the generic drug department before the application for the use of simple new drugs can be put forward.
A new drug application often has 5000- 100000 pages. In order to facilitate the examination, the FDA has formulated a series of guidelines on the format and content of the declaration. For example, the Application Guide for Method Verification and Analysis Data stipulates that the applicant shall prepare four samples, two of which shall be sent to two laboratories designated by the Drug Evaluation Office, and the other two shall be kept as samples. When sending samples, inspection standard materials (including miscellaneous standard materials) and uncommon reagents and materials should also be sent. The attached data should explain the verification data such as the purification method and spectrum of the reference substance. Another example is the new drug application submission method, which stipulates that two documents should be submitted. One is a complete and permanent master document, and the other is a divided review document. Both documents should be accompanied by an application form and an application letter. The content of the main document is: 1. Abstract; 2. Chemistry, manufacturing and quality inspection; 3. non-clinical pharmacology and toxicology; 4. Human metabolic kinetics and bioavailability; 5. Microbiology; 6. Clinical data; 7. statistics. In addition, the FDA has clear regulations on the size of paper used for declaration documents and the specifications and colors of folders used for volume division. The content of the main document can also be microfilm with specified specifications, so as to facilitate the review work and save the review data.
3. Drug supervision in the United States
The FDA Drug Administration Office has 150 staff. Fine division of labor. The main tasks of each department are: 1. Return part. Track the return information of pharmaceutical factory; 2. Counterfeiting commodity department. Clean up false drug information; 3. Label Supervision Section. Manage the labels of commonly used drugs and prescription drugs; 4. Pharmaceutical and product quality departments. Among them, the supervision and evaluation room reviews the supervision report of the district hospital, the policy guidance room reviews the policy of the report, the sterilization medicine room focuses on supervising the production and quality of large infusion, and the generic drug room is responsible for supervising generic drugs; 5. Drug Quality Evaluation Department. Among them, the product investigation room is responsible for reviewing the certification of insulin and drafting the national drug quality investigation plan, the drug catalogue room is responsible for the registration of pharmaceutical factories and product catalogues, the legal method research room is responsible for studying the disputes of legal inspection methods, and the drug investigation room is responsible for collecting drug report information; 6. scientific research section. Responsible for the review and investigation of new drug application materials, and the scientific research department has four rooms: regulatory management, scientific research review, clinical research and non-clinical research; 7. Part of regulations. Responsible for drafting relevant laws and regulations and resolving disputes over the interpretation of laws and regulations.
Each regional supervision office has a special person in charge of drug supervision, and the local supervisors are responsible for the supervision of drug production enterprises in the region. American pharmaceutical manufacturers must re-register with FDA every year. Enterprises should handle it within 1 month after receiving the FDA's notice of re-registration. Enterprises should report the change of product catalogue to FDA every six months. Although foreign pharmaceutical companies export drugs to the United States without registration, they must accept supervision and inspection and submit product catalogues. The customs shall go through customs clearance procedures with the catalogue of imported products. The supervision of pharmaceutical factories is mainly to check whether the production activities of pharmaceutical factories are under control, that is, pharmaceutical factories should have a set of management measures that meet the requirements of the Food, Drug and Cosmetics Law and the current pharmaceutical production management norms, and should be implemented. According to the previous supervision or reports and rework records, the regional office should make a good supervision plan. In general, pharmaceutical companies check 1 time every two years. Inspection is divided into comprehensive inspection and simple inspection, and comprehensive inspection is generally conducted once every 3-4 years. The comprehensive investigation is more in-depth, and the main contents include: 1. Factory equipment, such as status marks, may cause uneven or cross-contamination factors; 2. Personnel, such as training, quality and experience; 3. Materials such as storage, standards and sampling, and water supply; 4. Production and operation; 5. Laboratory management, such as testing ability, instrument suitability test, records and results; 6. Packaging bronzing, focusing on labels that may be confused; 7. Records and reports, such as batch records and sales records; 8. Process verification, such as verification when the process changes. After the comprehensive inspection, the inspection report should be written, and the conclusion of the report should be accurate and appropriate. Simple inspection is only a brief inspection of the facilities and representative batch records of the pharmaceutical factory, but strict inspection should be carried out on the packaging, labeling and production process. The key processes of API production should also be tested according to the requirements of the current pharmaceutical production management standards. The key process refers to the phase change in production, such as dissolution, crystallization and evaporation. Phase separation, such as centrifugation and filtration; Chemical changes, such as acetylation. Salt formation, etc. Conditional adjustment, such as pH adjustment; Material application; Particle size changes, such as crushing; Improve uniformity, such as mixing and other processes.
The regulatory procedure before drug approval is that the evaluation office first seeks the opinions of the region before approval. According to the local conditions, it may be suggested that the approval be denied or postponed. If the approval is delayed, it may be necessary to check the pharmaceutical factory again to verify the production facilities of new products. Comprehensive comparison and demonstration of clinical trial batches and production scale products at the time of declaration. If process changes are found during the inspection, the pharmaceutical factory shall make supplementary declaration and approval. The drug analysis room in St. Louis and the regional laboratory in new york have obtained the characteristics of clinical trial batches and stored them in computers for future verification. The characteristics of the test batch include appearance, size, internal and external colors, spectrum and differential thermal analysis. For generic drugs, their characteristics should be consistent with the products of production scale. But it should not be completely consistent with the product characteristics of the invention factory.
The national pharmaceutical institutions shall inspect the pharmaceutical business units and pharmacies at least once a year 1 time, use the concise checklist, and re-register 1 time every year. Pharmacists' registration is also updated 1 time every year, and one of the conditions is that they must receive continuing pharmaceutical education for more than 1 0 hours in the past1year.
4. American drug legislation
1906, the us congress passed the food and drug law-drug management regulations. At that time, the management of drugs was not strict enough, but after-the-fact sampling was adopted to prohibit interstate transactions of adulterated or counterfeit drugs. 19 12, the national assembly passed an amendment, which explicitly prohibited exaggerated publicity on drug labels.
1935 pharmacists discovered the antibacterial effect of sulfanilamide, and various sulfanilamide tablets and capsules came out one after another. 1937, Watkins, the chief pharmacist of a pharmaceutical company in the United States, used diethylene glycol and water as solvents to prepare an oral liquid preparation with good color, fragrance and taste, namely sulfanilamide (a preparation containing grain and volatile oil or alcoholic solution containing main medicine, referred to as fermented grains for short), without animal experiments (allowed by American law at that time). 1938 sulfanilamide caused 107 poisoning death. Later, animal experiments proved that sulfanilamide itself was not toxic, and industrial diethylene glycol was the cause of death. The U.S. federal court fined the pharmaceutical company 1.688 dollars on charges of diethylene glycol replacing alcohol, adulteration and false labeling, and chief pharmacist Watkins committed suicide in guilt and despair. This is the "sulfanilamide preparation" incident that shocked the United States at that time. American drug regulatory authorities are aware that there are big loopholes in the regulations on clinical application and marketing of new drugs, so it is necessary to revise the regulations and strengthen safety testing. The revised regulations require that new drugs must be safe. Before changing the dosage form of old drugs into the market, prescriptions should be sent to FDA for approval, and labels and advertisements should be strictly examined. 1962, the national congress revised the laws and regulations, and considered that drugs should be not only safe, but also effective. At the same time, strict regulations have been added to the approval of new drugs, and 4 12 drugs have been eliminated. Later, States complained that the management was too strict and the approval time for new drugs was too long. 1In June, 979, Congress revised the regulations on drugs, food and cosmetics again. According to the law, all kinds of drugs, pharmaceutical factories and wholesalers must be registered and approved. At the same time, the drug quality standard system, drug inspector system and adverse drug reaction reporting system are stipulated to monitor the drug quality. The current Food, Drug and Cosmetics Act in the United States consists of 9 chapters and 902 articles.