The U.S. Food and Drug Administration (FDA) is referred to as FDA. FDA is one of the executive agencies established by the U.S. government in the Department of health and human services (DHHS) and the Department of public health (PHS). As a scientific regulatory agency, FDA's responsibility is to ensure the safety of food, cosmetics, drugs, biological agents, medical equipment and radioactive products produced or imported in the United States. It was one of the first federal agencies whose main function was to protect consumers.
The agency is closely related to the life of every American citizen. Internationally, FDA is recognized as one of the largest food and drug regulatory agencies in the world. Many other countries seek and receive FDA help to promote and monitor the safety of their products.
Food and Drug Administration (FDA): Supervision and inspection of food, drugs (including veterinary drugs), medical devices, food additives, cosmetics, animal food and drugs, wine drinks with alcohol content less than 7% and electronic products; It also includes cosmetics, radiation products, combination products and other electronic products and medical products related to human health and safety. Testing, inspection and certification of items in which the ionic and non-ionic radiation generated during the use or consumption of the product affects human health and safety. According to the regulations, the above products can be sold on the market only after they have been inspected and proved safe by FDA. FDA has the right to inspect manufacturers and prosecute violators. According to the different product scope of supervision, it can be divided into the following main supervision institutions:
1. Center for food safety and practical nutrition (CFSAN):
The center is the FDA department with the largest workload. It is responsible for food safety throughout the United States except meat, poultry and eggs under the jurisdiction of the United States Department of agriculture. Although the United States has the safest food supply in the world, about 76 million foodborne diseases occur every year, 325000 people need hospitalization for foodborne diseases, and about 5000 people die of foodborne diseases. The center for food safety and nutrition is committed to reducing foodborne diseases and promoting food safety. And promote various plans, such as the promotion and implementation of HACCP plan. The functions of the center include: ensuring the safety of substances and pigments added to food; Ensure the safety of foods and ingredients developed through biological processes; Be responsible for the management activities in correctly labeling food (such as ingredients, nutrition and health statements) and cosmetics; Develop appropriate policies and regulations to manage dietary supplements, infant food formulas and medical foods; Ensure the safety of cosmetic ingredients and products and ensure correct identification; Supervise and standardize the after-sales behavior of the food industry; Conduct consumer education and behavior development; Cooperation projects with state and local governments; Coordinate international food standards and safety.
2. Center for drug evaluation and Research (CDER):
The center aims to ensure the safety and effectiveness of prescription and over-the-counter drugs, evaluate new drugs before they go on the market, and supervise more than 10000 drugs sold on the market to ensure that products meet the highest standards that are constantly updated. At the same time, the center also supervises the authenticity of drug advertisements on television, radio and publications. Strictly supervise drugs and provide consumers with accurate and safe information.
3. Equipment safety and radiation protection health center (CDRH):
The center is ensuring the safety and effectiveness of newly listed medical devices. More than 20000 enterprises around the world produce more than 80000 types of medical devices, from blood glucose monitors to artificial heart valves. These products are closely related to human life, so the center also supervises after-sales service nationwide. For some products that can produce radiation, such as microwave ovens, televisions and mobile phones, the center has also determined some corresponding safety standards.
4. Biological products evaluation and Research Center (CBER):
The center supervises biological products that can prevent and treat diseases, so it is more complex than chemical comprehensive drugs. It includes scientific research on the safety and effectiveness of blood, plasma and vaccines.
5. Veterinary Medicine Center (CVM):
The FDA's regulatory agency for food, agricultural products and seafood is the center for food safety and nutrition (cfasan), whose responsibility is to ensure that American food supply is safe, clean, fresh and clearly marked.
The food import supervised by the center is 240 billion US dollars every year, of which 15 billion are imported food. The main monitoring focuses of the center include:
1. Food freshness;
2. Food additives;
3. Food biotoxin and other harmful ingredients;
4. Seafood safety analysis;
5. Food identification;
6. Tracking and warning after food marketing
According to the anti-terrorism law passed by the U.S. Congress in 2003, food enterprises outside the United States must register with the FDA before exporting to the United States and notify the FDA of the shipment at the time of export
Foreign food production and processing enterprises that must register with FDA in accordance with public law 107-188 of the United States are as follows:
1. Alcohol and alcoholic beverages;
2. Food for infants and children;
3. Bread and pastry;
5. Candy (including chewing gum);
6. Cereals and cereals ready to eat;
7. Cheese and cheese products;
8. Chocolate and cocoa food;
9. Coffee and tea products;
10. Food pigments;
11. Weight loss conventional food, medicinal food and meat substitutes;
12. Supplementary food (i.e. domestic health food, vitamin drugs and Chinese herbal medicine products);
14. Fish and seafood;
15. Materials, substances and products placed in food and in direct contact with food;
16. Food additives and safe ingredients;
17. Food sugar substitute;
18. Fruits and fruit products;
19. Edible gum, lactase, pudding and stuffing;
20. Ice cream and related foods;
21. Imitation dairy products;
22. Macaroni and noodles;
23. Meat, meat products and poultry products;
24. Milk, butter and dry dairy products;
25. Dinner food, brine, sauce and special products;
26. Dried fruits and nuts;
27. Eggs with shells and egg products;
28. Snacks (flour, meat and vegetables);
29. Pepper, special flavor and salt;
31. Soft drinks and canned water;
32. Vegetables and vegetable products;
33. Vegetable oil (including olive oil);
34. Vegetable protein products (square meat food);
35. Whole wheat food, flour processed food, starch, etc;
36. Products mainly or entirely for human consumption;
FDA's management of medical devices is carried out through the device and radiation health center (CDRH), which supervises the production, packaging and dealers of medical devices to conduct business activities in compliance with the law.
A wide range of medical devices, ranging from medical gloves to cardiac pacemakers, are under the supervision of FDA. According to medical uses and possible harm to human body, FDA divides medical devices into categories I, II and III. The higher the category, the more supervision
If the product is a novel invention that does not exist in the market, FDA requires the manufacturer to conduct strict human experiments and have convincing medical and statistical evidence to show the effectiveness and safety of the product.
For FDA certification of medical devices, including: Manufacturer's registration with FDA, product FDA registration, product listing registration (510 form registration), product listing review and approval (PMA review), label and technical transformation, customs clearance, registration and pre marketing report of medical and health devices, the following materials must be submitted: (1) five finished products with complete packaging, (2) device structure drawing and its text description, (3) Performance and working principle of the instrument; (4) Safety demonstration or test materials of the device, (5) introduction to manufacturing process, (6) summary of clinical test, (7) product specification If the device has radioactive properties or releases radioactive substances, it must be described in detail.
Registration and certification procedures
FDA has a clear and strict definition of medical devices, It is defined as follows: "The so-called medical devices refer to the instruments, devices, tools, machinery, appliances, insertion tubes, in vitro reagents and other related articles, including components, parts or accessories that meet the following conditions: those explicitly listed in the appendix of national formula or the United States Pharmacopeia or both; those expected to be used in the diagnosis of animal or human diseases or other physical conditions, or For the cure, mitigation and treatment of diseases; Those who are expected to affect the physical function or structure of animals or human bodies, but do not achieve their main purpose through metabolism ".
Only products that meet the above definition can be regarded as medical devices. Under this definition, not only various instruments and tools in the hospital, but also fitness equipment such as spectacle frames, spectacle lenses, toothbrushes and massagers that consumers can buy in general stores belong to the management scope of FDA. It is slightly different from the identification of medical devices in China.
According to different risk levels, FDA divides medical devices into three categories (I, II and III), and category III has the highest risk level. FDA has clearly defined the product classification and management requirements for each medical device, and the FDA medical device product catalog has included more than 1700 products. If any medical device wants to enter the U.S. market, it must first clarify the product classification and management requirements for listing.
FDA has formulated many bills for medical devices, which are revised and supplemented from time to time, but there are few basic bills, mainly including the federal food, drug and Cosmetics Act (FD & C act); Public health services act; Fair packaging and Labeling Act; Health and safety radiation control act; Safe medical devices act; Modernization Act. The FDA has given a very detailed explanation of these bills, with specific operational requirements. Before planning to enter the U.S. market, enterprises need to carefully evaluate the regulations and specific requirements related to their products (including different U.S. product standard requirements).
After clarifying the above information, enterprises can start to prepare relevant application materials and report to FDA according to certain procedures to obtain approval. For any product, the enterprise needs to carry out enterprise registration and product listing. For class I products (accounting for about 47%), general control is implemented. Most products can enter the U.S. market only by registering, listing and implementing GMP specifications (very few products are exempted from GMP, and very few reserved products need to submit 510 (k) application to FDA, namely PMN (premarket notification)); For class II products (about 46%), special control is implemented. After registration and listing, enterprises also need to implement GMP and submit 510 (k) application (510 (k) exemption for very few products); For class III products (accounting for about 7%), pre marketing license is implemented. After registration and listing, enterprises must implement GMP and submit PMA (premarket application) application to FDA (some class III products are still PMN).
For class I products, after the enterprise submits relevant materials to FDA, FDA only makes an announcement and does not issue relevant certificates to the enterprise; For class II and III devices, enterprises must submit PMN or PMA. While announcing, FDA will give enterprises a formal market access approval letter (clearance), that is, enterprises are allowed to directly sell their products in the American Medical Device Market in their own name. Whether to go to the enterprise for on-site GMP assessment during the application process is determined by FDA according to comprehensive factors such as product risk level, management requirements and market feedback.
From the above, it can be seen that most products can be approved by FDA for listing after enterprise registration, product listing and GMP implementation, or after submitting 510 (k) application.
1.510 (k) document, that is, the document required by FDA for PMN, is usually called 510 (k) document because of its corresponding FD & C act chapter 510.
2. Substantive equality comparison (SE)
3.510 (k) review procedure
Before the application, it must be clear whether the product is recognized as a medical device by FDA, product category, management requirements, and the content of the application;
Check whether there is a mandatory American Standard for the products applying for listing and whether the products meet the standard (generally, the formal inspection report of the testing organization is required);
Before preparing 510 (k) application documents, it is necessary to consider whether it is really necessary to submit, when to submit and what kind of 510 (k) application to submit: regular 510 (k), special 510 (k) and simplified 510 (k);
Written and timely answers shall be given to the questions raised by FDA during the application process;
The paper size of all materials submitted to FDA shall be letter size (21.5cm x 29.7cm);
All data submitted to FDA shall be kept in backup by the enterprise, because FDA will electronically scan and log in after receiving the application data, destroy the application data at the same time, and will not return it to the enterprise.
For a small number of products, FDA will conduct on-site GMP assessment for enterprises. Enterprises shall refer to the GMP management requirements of the United States, and provide appropriate translators with a certain understanding of GMP and enterprises during FDA on-site audit;
Inform the official contact person of FDA that they need to have a certain understanding of FDA regulations and working procedures, and can communicate directly with FDA to facilitate timely feedback. The enterprise can clarify itself or entrust a consulting agency to be responsible for daily communication with FDA.
Voluntary registration scheme for cosmetics (vcrp)
The FDA Office of cosmetics and pigments has developed a voluntary registration plan for cosmetics at the request of the cosmetics industry. The plan includes two parts: voluntary registration of cosmetic manufacturers and declaration of cosmetic ingredients.
Benefits of participating in vcrp
A manufacturer's voluntary registration and obtaining a registration number does not mean that FDA Approves the manufacturer or its products, and FDA does not allow the manufacturer to use the registration number or listing number obtained by participating in vcrp for commercial publicity; However, manufacturers can directly obtain the following benefits by participating in vcrp:
Obtain important information about cosmetic ingredients. FDA inputs all information obtained from vcrp into the computer database. If a cosmetic ingredient currently used should be banned once it is considered harmful, FDA will notify the manufacturer or seller of the product through the address book in the vcrp database. If your product is not in the registration database, FDA will not be able to notify you.
Avoid product recall or import detention due to ingredient problems. If the cosmetics manufacturer files the product formula in the vcrp, as long as FDA finds that the manufacturer uses unapproved pigment additives or other prohibited ingredients in the formula, it will remind the manufacturer to pay attention. In this way, the manufacturer can modify the product formula before the product is imported or sold, so as to eliminate the risk of product recall or detention due to the use of improper ingredients. Help retailers identify safety conscious manufacturers. Retailers (such as department stores) sometimes ask the FDA whether a cosmetics company has been registered with the FDA. Although registration does not mean FDA approval, it indicates that your product has been reviewed by FDA and entered the government database. If the product formula you submit is incomplete, or contains a prohibited ingredient or unapproved pigment additive, FDA will notify you.
The decision to collect samples is based on the nature of the product; Key concerns of FDA; History of the product. The FDA takes a physical sample and sends it to the FDA regional laboratory for analysis
If FDA finds that the sample meets the requirements, it will send a "Release Notice" to U.S. Customs and importer respectively.
If FDA determines that the sample "has violated FDCA and other relevant laws", it will send "Notice of seizure and hearing" to the U.S. Customs and the case and the importer respectively. The notice specifies the illegality and nature, and gives the case and the importer 10 working days to provide evidence that the goods can be permitted.
Seized imports must be repaired, returned or destroyed under the supervision of FDA or U.S. Customs
The hearing is the only opportunity for the importer to defend the imported goods or provide evidence to make the goods suitable for entry after modification.
If the case and the underwriter, owner, importer or a designated representative do not respond to the notice, FDA sends a "Notice of refusal" to the U.S. Customs and the case and importer. Then the products involved in the problem are transported back or destroyed.
If the case and the underwriter, owner, importer or a designated representative reply to the "Notice of seizure and hearing", FDA will hold a hearing on the seized products when the importer provides evidence that the products "meet the requirements" or submits an application for repairing the products.
If the firm provides evidence that the product meets the requirements, FDA will collect subsequent samples. After analysis, it is decided that the product is either released or refused entry.
FDA reviews the importer's proposed trimming procedures and approves or disapproves them as appropriate. Once approved, FDA will conduct follow-up inspection / sample collection to determine its eligibility. If the sample is qualified, a "Release Notice" shall be sent to the U.S. Customs and importer. If the fruit sample is unqualified, a "refusal notice" shall be issued.
Section 8 (c) of the FDCA requires the applicant to pay all expenses, including the travel, daily expenses and wages of FDA officials or employees, in addition to the cost of updating the label or other measures to make the seized goods comply with the provisions of the application (form fda-766). By submitting form fda-766, the applicant agrees to pay all regulatory fees in accordance with current regulations.
FDA has a complete set of certification procedures for pharmaceutical products to ensure the safety and effectiveness of new drugs The procedure is as follows:
1. Application for approval of investigational new drugs (ind):
When pharmaceutical companies submit ind to FDA, FDA's monitoring of new drugs begins At this time, the human experiment of the new drug has not yet started. FDA mainly reviews the in vitro safety data and animal experiment data to determine whether the drug is safe enough to enter the human experiment stage
2. Human experiment:
The human experiment is divided into four stages Phase I mainly tests the safety, main side effects, metabolic mechanism, etc. of the drug, and the number of samples is generally less than 00
Phase II mainly tests the effectiveness of drugs to determine whether drugs can effectively act on the human body At the same time, the safety and side effects of drugs are also closely observed The number of samples in phase II experiment is generally less than 300
If the phase II experiment is encouraging, a larger sample will be ready for testing and the experiment will enter phase III Phase III will include different age groups, different populations and different dosage to comprehensively study the safety and effectiveness of drugs The number of samples in phase III experiment ranges from hundreds to thousands
Phase IV is mainly carried out after the approval of new drugs, mainly testing the long-term safety of drugs, new populations, etc
3. New drug application (NDA):
When the pharmaceutical company completes the human experiment and verifies the safety and effectiveness of the new drug, it formally submits an NDA application to FDA FDA reviews all animal and human experimental data, as well as the data of drug metabolism mechanism and GMP data of drug production. If the data are incomplete or unreasonable, FDA will refuse to apply for approval, otherwise FDA will complete the application and give consent or rejection opinions within about 10 months
The above contents are extracted from the service manual of MTG FDA certification service center
FDA certification process
1. Preparation stage
Copy of enterprise legal person license;
Copies of production (hygiene) license and qualification certificate;
Company profile (establishment time, technical strength, main products, performance and asset status).
2. Acceptance of application for preliminary technical review
Submit the English translation documents of DMF (drug master document) and SOP (standard operating procedure) to the agent;
Modify the above documents according to the opinions of the agent.
3. Review of DMF data
FDA carefully reviewed and visited the factory to check whether the DMF documents are true;
If FDA finds no major errors and considers that the requirements are met, it will propose a pre-approval inspection plan.
4. FDA inspection
FDA inspectors inspect the factory and answer questions one by one;
If there is any doubt, the official will give the "483" form (rectification proposal). If the problem is serious, the "483" form will not be given.
5. FDA issues "approval letter"
The questions raised by the inspector on the "483" form must be answered carefully. If there are any questions, they must be corrected immediately and proved;
If the prosecutor does not understand the problem, it needs to be explained and proved
Food contact materials refer to all materials that can come into contact with food during food processing, production, packaging, storage and transportation Common materials include various plastics, metal ceramics, glass, bamboo and wood products. The environmental protection and safety of these materials that can be contacted with food is directly related to the dietary safety and health of users. Therefore, the export of such products to the United States needs to be tested and certified in accordance with FDA standards
The FDA certification test items of common materials in contact with food are as follows:
Requirements for organic coatings, metals and electroplated products U.S. FDA CFR 21 175.300
Deionized water extraction
8% alcohol extractives
Paper product requirements U.S. FDA CFR 21 176.170
Net chloroform soluble extracts for water fraction
Net chloroform soluble extracts for 8% alcohol fraction
Net chloroform soluble extracts for 50% alcohol fraction
Net chloroform soluble extracts for n-heptane fraction
Wood requirements U.S. FDA CFR 21 178.3800
Pentachlorophenol and its salt PCP
ABS requirements U.S. FDA CFR 21 181.32 or 180.22
In water deionized water leaching method
In 3% acetic acid
In 8% ethanol 8% alcohol extraction method
In n-heptane n-heptane leaching method
1. Application Form
Application form: including company information, product information, etc
2. Product File / Technology Specification
Product documents / technical data: mainly including preparation of detailed instructions / sales manuals, installation manuals, maintenance manuals, etc; Product assembly drawing; And product technical information, whether there are laser protection measures and their working principle description.
Labels: English labels conforming to regulations, including warning labels with warning signs, product labels, compliance certification labels (such as complies with 21 CFR 1040.10 & 1040.11), and light outlet label, etc.
4. Laser Information
Laser device information: type of laser generator, medium, laser optical path diagram, laser parameters, laser device certificate / test records (if purchased from other manufacturers, the manufacturer's information, laser device parameters / datasheet or instructions, and whether the laser device has FDA certification / if any, FDA number shall be provided).
5. Calibration Report of Power Meter
Annual metrological verification certificate and report of optical power meter.
6. Quality Control System
Quality control documents: mainly include internal quality control flow chart, inspection procedures, quality control specifications / such as control of design modification; Production line sampling table, incoming material inspection sheet, finished product inspection sheet, internal inspection report, etc. (including samples of the table).
7. US Agent / Importer
Information of U.S. agent and U.S. importer: including contact person's full name, telephone / fax / e-mail, U.S. detailed address / postal code and company name; And U.S. agent principal-agent authorization agreement.