1, the U.S. drug administration
The U.S. Food and Drug Admistraton (Food and Drug Admistraton referred to as FDA), under the U.S. Department of Health, Education, and Welfare, is responsible for the nation's medicines, foods, biological products, cosmetics, veterinary drugs, medical devices and diagnostic supplies. The FDA consists of the Bureau of Drugs, the Bureau of Foods, the Bureau of Veterinary Drugs, the Bureau of Radiological Health, the Bureau of Biological Products, the Bureau of Medical Devices and Diagnostic Supplies, and the National Center for Toxicological Research, and the regional work management agencies, i.e., 6 Bureaus (also known as the 6 Centers in some publications), a Center, and a regional management agency. The U.S. Food and Drug Administration*** has about 7,500 employees, 1,143 at FDA headquarters, including 350 in the Bureau of Drugs.
Drug Administration (also known as the Center for Drug Evaluation and Research) is responsible for the approval of medicines for human use, with eight divisions and a number of sections.1. Drug Administration. It consists of four sections: Drug Information, Information System Design, Administration and Budget, and Medical Library.2. Office of Drug Supervision. It has 7 sections including drug quality evaluation, drug labeling supervision, production and product quality, scientific research and investigation, and regulations. 3. Drug Standards Division. There are 2 sections for evaluation of commonly used drugs, drug listing and advertisement. 4. Drug Evaluation Division. There are five sections: cardiovascular and renal drugs, antineoplastic drugs, nutritional drugs, medical imaging surgery and dental drugs, gastrointestinal drugs and coagulants. 5. Drug Review Division II. It consists of three sections: anti-infective drugs, metabolic and endocrine drugs, and antiviral drugs. 6. Epidemiology and Biostatistics Division. It consists of two sections: Epidemiology and Investigation, and Biostatistics. 7. Research Division. There are 2 sections, namely, Research and Testing and Drug Analysis. 8) Generic Drugs Division. There are 2 sections: generic drugs and bioequivalence.
The U.S. Food and Drug Administration is located in Washington, D.C., and Rockville, Maryland, a huge organization, with branches all over the country. In order to strengthen the quality management of drugs, the FDA divided the country into six regions, namely, the Pacific Region (San Francisco, Seattle, Los Angeles muscle), the Southwest Region (Dallas, Denver, Kansas), the Midwest Region (Chicago, Minneapolis, Detroit), the Northeast Region (Boston, New York, Buffalo), the Mid-Atlantic Region (Philadelphia, Cincinnati, Newark, Baltimore), the Southeast Region (Atlanta, Nashville, New Orleans, Orlando, and St. Gian's in Porto Rico). Each district has a regional office, which in turn has a number of district offices. The Pacific Region has a regional office in San Francisco, the Southwest Region has a regional office in Dallas, the Midwest Region has a regional office in Chicago, the Northeast Region has a regional office in Boston, the Mid-Atlantic Region has a regional office in Philadelphia, and the Southeast Region has a regional office in Atlanta. The regional office is responsible for the supervision and inspection of food, drugs, cosmetics, devices, blood banks, etc. in the region. Each regional office has a number of workstations as needed to ensure coverage of the region. There are currently 143 workstations throughout the United States***. Regional institutes, district institutes and workstations are all directly under the FDA at all levels. The size of the district depending on the workload, the United States, more than 65% of the drugs produced in the Mid-Atlantic region, so the district's strength is stronger, *** there are 525 employees, of which 250 supervisors, accounting for about 1/4 of the supervisors of the FDA headquarters, analyzing and inspecting personnel 150.
The management of drugs in each state is carried out in accordance with the local drug management regulations, the main tasks are: examination and registration of pharmacists, supervision and inspection of drug departments and pharmacies, the issuance or renewal of licenses, revocation of licenses of illegal households, evaluation of local pharmacy colleges and universities, review of trainee pharmacies and so on.
2, the United States of America's drug review
In the United States from the development of new drugs to the approval of the production takes 8 to 10 years, costing 65-800 million U.S. dollars. the FDA approval of a new drug is generally 2 years, an average of 2,000 new drugs per year, only 10% of the production. The U.S. drug application is divided into three categories: 1. investigational drug application p. new drug application; 3. simple new drug application. A new drug development and review of the average cycle for: preclinical studies 1 ? years, the FDA safety review 1 month, phase III clinical trials 5 years, the FDA new drug review 2 years. Only one-fourth of the new drugs declared pass the review at the end of the process. 17 years after the new drug is patented, other pharmaceutical companies can copy it. Applications to manufacture generic drugs must be approved by the Generic Drugs Branch before a Simplified New Drug Application can be used.
A new drug application often contains 5,000-100,000 pages of information. To facilitate the review, the FDA has developed a series of guidelines on the format and content of the application. For example, the Guidelines for Method Validation and Analytical Data Applications state that the applicant should prepare four samples, two of which should be sent to two laboratories designated by the Office of Drug Review, and the other two for backup. The samples should be accompanied by test controls (including miscellaneous controls) and less commonly used reagents and materials. The attached information should indicate the purification method of the control product, the spectrum and other test data. Another example is the submission of new drug applications, which stipulates that two kinds of documents should be submitted. One is the complete and permanent main document, and the other is the review of the sub-volume. These two kinds of documents should be attached to the application form and application letter. The contents of the master file are: 1. summary; 2. chemical, manufacturing and quality testing; 3. non-clinical pharmacology and toxicology; 4. human metabolism kinetics and bioavailability; 5. microbiology; 6. clinical data; 7. statistical data. In addition, the FDA has clear regulations on the size of the paper to be used for filing documents, as well as the specifications and colors of the folders to be used. The content of the main document can also be used to specify the specifications of the microfilm, in order to facilitate the review process and the preservation of review information.
3, the U.S. drug supervision
FDA's Office of Drug Supervision has a staff of 150. The division of labor is fine. The main tasks of each section are: 1. Returns Section. Tracking information on drug company returns; 2. Counterfeit Section. Cleans up deceptive drug information; 3. Labeling Oversight Section. Manages the labeling of commonly used and prescription drugs; 4. Pharmaceutical and Product Quality Section. In this section, the Supervision and Evaluation Office reviews the supervision reports of regional institutes, the Policy Guidance Office reviews the policy of the reports, the Sterilized Drug Office focuses on the production and quality of I.V. fluids, and the Generic Drug Office is responsible for the supervision of generic drugs; 5. Pharmaceutical Quality Evaluation Section. The Product Investigation Office is responsible for reviewing the certification of insulin, etc. and formulating a national drug quality research plan, the Drug Catalog Office is responsible for the registration of pharmaceutical companies and product catalogs, the Statutory Methods Research Office is responsible for researching disputes over statutory test methods, and the Pharmaceutical Investigation Office is responsible for collecting information on reported pharmaceuticals; 6. Scientific Research Section. It is responsible for finalizing and investigating new drug application information, and the Research Section consists of four rooms, namely, Regulatory Management, Research Review, Clinical Research, and Non-clinical Research; 7. Regulatory Section. Responsible for drafting relevant regulations and resolving disputes over the interpretation of regulations.
Supervision of the Office of each regional institute have a person responsible for the supervision of drugs, the region's supervisor is responsible for the supervision of drug manufacturers in the region. U.S. drug manufacturers must re-register with the FDA annually. Enterprises receive the FDA on the re-registration of the notification letter should be processed within 1 month. Companies should report changes in product catalogs to the FDA every six months. Foreign pharmaceutical companies exporting drugs to the United States are not required to register, but must be subject to supervision and inspection and submit product catalogs, imported product catalogs for use in customs inspection. Supervision of pharmaceutical factories is mainly to check whether the production activities of the factory is under control, i.e., the factory should have a set of management methods in line with the Food, Drug and Cosmetic Act and the current requirements of the Code of Practice for the Manufacture of Pharmaceutical Products, and should be implemented. The regional office prepares a supervision plan based on past supervision or reports and rework records, etc. Generally, pharmaceutical companies are inspected once every two years. Inspections are divided into comprehensive and summary inspections, with comprehensive inspections generally conducted every 3-4 years. Comprehensive inspection is more in-depth, the main contents include: 1. plant and equipment, such as state marking, easy to cause uneven or cross-contamination factors; 2. personnel, such as training, quality and experience; 3. materials, such as storage, standards and sampling, water supply; 4. production operations; 5. laboratory management, such as detection capabilities, instrument suitability tests, records and results; 6. packaging and labeling, focusing on the possibility of confusion check Records and reports, such as batch records and sales records; 8. Process validation, such as the validation of process changes. At the end of a comprehensive inspection, an inspection report should be written, and the conclusions of the report should be accurate and appropriate. Simple inspection of the facilities of the pharmaceutical plant, representative of the batch records, such as a brief inspection, but should be packaged, labeled and production processes such as strict inspection. The key process of API production should also be checked according to the requirements of the current drug production management standard. Key process refers to the production of phase changes, such as dissolution, crystallization, evaporation, etc.; phase separation, such as centrifugation, filtration, etc.; chemical changes, such as acetylation. Salt formation, etc.; condition adjustment, such as acidity and alkalinity adjustment; material set; particle size changes, such as crushing, etc.; improve uniformity, such as mixing and other processes.
Pre-approval of drugs to monitor the program for the review of the approval of the Office of the first to seek the views of the regional office. The regional office may recommend not approving or delaying approval based on the information available. If approval is deferred, the pharmaceutical company may be re-inspected to verify the production facilities for the new product. A full comparative validation of the clinical trial batch samples and production scale products at the time of filing will be conducted. If the inspection reveals process changes, the pharmaceutical company should make a supplemental declaration for approval. Characteristics of the clinical trial lot samples have been obtained from the Drug Analysis Laboratory in St. Louis and the Regional Laboratory in New York and are stored in a computer for future checking. Characteristics of test lots include appearance, size, internal and external color, wave spectra, and differential thermal analysis data. For generic drugs, the characteristics should be consistent with the production-scale product. However, the characteristics should not be exactly the same as those of the product of the inventing plant.
State pharmacy agencies inspect drug establishments and pharmacies at least once a year, using a brief checklist, and re-register them once a year. The registration of pharmacists is also renewed once a year, with one of the conditions being the necessity of at least 10 hours of continuing pharmacy education in the past year.
4. U.S. Drug Legislation
The U.S. Congress passed the Food and Drug Act, the Pharmacy Act, in 1906. At that time, the management of drugs was not strict enough, only to adopt the method of after-the-fact sampling and testing, and prohibited to engage in interstate trading of adulterated or counterfeit drugs. 1912 Congress also passed an amendment to explicitly prohibit exaggerated publicity on the labeling of drugs.
In 1935 pharmacists discovered the antibacterial effect of sulfanilamide, a variety of sulfonamide tablets, capsules have come out. 1937 a U.S. pharmaceutical company's director of pharmacist Watkins in order to make the pediatric take convenient, with diethylene glycol and water as a solvent, the preparation of color, aroma and taste of the oral liquid system agent - that is, the sulfonamide spiritus ( Preparations containing grain and volatile oils or alcoholic solutions of the main drugs, referred to as spiritus), without animal testing (at that time the U.S. law was allowed). 1938 sulfanilamide spiritus caused the death of 107 people poisoned. Animal testing later proved that sulfanilamide itself was not toxic, and that it was the industrial diethylene glycol that caused the poisoning deaths. The U.S. Federal Court fined the pharmaceutical company $1,688 for substituting diethylene glycol for alcohol in spiritus, adulteration, and false labeling, and the chief pharmacist, Watkins, committed suicide in a fit of guilt and despair. This was the "Sulfanilamide Preparation" incident that shook the United States so much at the time. The U.S. Pharmaceutical Administration realized that there was a big loophole in the regulations for the clinical and market introduction of new drugs, and had to revise the regulations to strengthen the safety tests. The revised regulations require that new drugs must be safe, the old drugs to change the dosage form before entering the market, the prescription should be sent to the FDA for validation, labeling and advertising should also be strictly examined. 1962 Congress revised the regulations, that drugs not only to be safe, but also must be effective. At the same time, strict regulations were added for the approval of new drugs and 412 drugs were eliminated. After this, the states reflected that the regulation was too strict, and the approval time for new drugs was too long, Congress again in January 1979, re-amended the Drug, Food, and Cosmetic Statute. The statute stipulates that all drug manufacturers and wholesalers are required to register for review and approval. At the same time, it provides for a system of drug quality standards, a system of pharmacological inspectors, and the reporting of adverse drug reactions in order to monitor the quality of drugs. The current U.S. Food, Drug, and Cosmetic Act *** 9 chapters, 902 articles.