FDA authentication

The food and Drug Administration (FDA) is one of the executive agencies set up 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 is responsible for ensuring the safety of food, cosmetics, drugs, biological agents, medical equipment and radiation products produced or imported in the United States. It was one of the first federal agencies to protect consumers.

brief introduction

This institution is closely related to the life of every American citizen. Internationally, FDA is recognized as one of the largest food and drug administration agencies in the world. Many other countries seek and receive FDA assistance to promote and monitor the safety of their products.

Food and Drug Administration (FDA) director: 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; also including cosmetics, radiation products, combination products and other electronic products and medical products related to personal health and safety. Testing, inspection and certification of the items that the ionizing and non-ionic radiation produced in the use or consumption of the product affects human health and safety. According to the regulations, the above products can only be sold on the market after they have passed the FDA inspection and proved to be safe.

FDA has the right to inspect the manufacturer and Sue the violator. According to the different product range of supervision, it can be divided into the following main regulators:

1. Center for food safety and practical nutrition (CFSAN):

The center is the FDA's largest department. It is responsible for food safety throughout the United States except for meat, poultry and eggs, which are under the jurisdiction of the United States Department of agriculture. Although the United States is the safest food supplier in the world, about 76 million foodborne diseases occur every year. 325000 people need to be hospitalized 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: to ensure the safety of substances and pigments added to food; to ensure the safety of food and ingredients developed through biological processes; to be responsible for the management activities in the correct identification of food (such as ingredients, nutritional health statements) and cosmetics; to formulate corresponding policies and regulations to manage dietary supplements, infant food formulas and medical foods; to ensure cosmetics Product ingredients and product safety, ensure correct identification; supervise and regulate the after-sales behavior of the food industry; conduct consumer education and behavior expansion; cooperate with state and local governments; coordinate international food standards and safety, etc.

2. Center for drug evaluation and Research (CDER):

The center aims to ensure the safety and effectiveness of prescription drugs and over-the-counter drugs, evaluate new drugs before they go on the market, and supervise more than 10000 kinds of drugs sold on the market to ensure that products meet the highest updated standards. At the same time, the center oversees the authenticity of advertisements for drugs 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 new medical devices. Because there are more than 20000 enterprises around the world that produce more than 80000 kinds of medical devices, from blood glucose monitor to artificial heart valve. These products are closely related to people's lives, so the center also supervises the after-sales service nationwide. For some products that can produce radiation, such as microwave ovens, TV sets, mobile phones, etc., the center has also determined some corresponding safety standards.

4. Center for biological products evaluation and Research (CBER):

The center supervises biological products that can prevent and treat diseases, so it is more complex than comprehensive chemical drugs. It includes scientific research on the safety and effectiveness of blood, plasma, vaccines, etc.

5. Veterinary Medicine Center (CVM):

Certification introduction

Food certification

The FDA's regulatory agency for food, agricultural products, and seafood is the food safety and Nutrition Center (cfasan), which is responsible for ensuring that American food supplies are safe, clean, fresh, and clearly labeled.

The annual import of food supervised by the center is US $240 billion, of which 15 billion is imported food. The main monitoring focuses of the center include:

1. Food freshness;

2. Food additives;

3. Other harmful components of food biotoxin;

4. Seafood safety analysis;

5. Food identification;

6. Follow up and warning after food listing

According to the anti-terrorism law passed by the U.S. Congress in 2003, food enterprises outside the U.S. must register with the FDA before exporting to the U.S. and notify the FDA of the shipment when exporting

The foreign food production and processing enterprises that must be registered with FDA in accordance with public law 107-188 of the United States are as follows:

1. Wine and alcoholic beverages;

2. Food for infants and children;

3. Bread and pastry;

4. Drinks;

5. Candy (including chewing gum);

6. Cereals and instant cereals;

7. Cheese and cheese products;

8. Chocolate and cocoa;

9. Coffee and tea products;

10. Food pigment;

11. Conventional diet food, medical food and meat substitutes;

12. Supplementary food (i.e. domestic healthy food, vitamin drugs and Chinese herbal medicine products);

13. Condiments;

14. Fish and seafood;

15. Materials and products placed in food and in direct contact with food;

16. Food additives and safe ingredients;

17. Food sugar substitute;

18. Fruit and fruit products;

19. Edible gum, lactase, pudding and filling;

20. Ice cream and related food;

21. Imitated dairy products;

22. Macaroni and noodles;

23. Meat, meat products and poultry products;

24. Milk, butter and dried milk products;

25. Meals, marinades, sauces and special products;

26. Dried fruits and nuts;

27. Shell eggs and egg products;

28. Snacks (flour, meat and vegetables);

29. Capsicum, specialty and salt, etc;

30. Soup;

31. Soft drinks and canned water;

32. Vegetables and vegetable products;

33. Vegetable oil (including olive oil);

34. Vegetable protein products (meat products);

35. Whole wheat food and flour processed food, starch, etc;

36. Main or all products for human consumption;

Medical authentication

FDA's management of medical devices is conducted through the device and radiation health center (CDRH), which supervises the production, packaging and distributors of medical devices to carry out business activities in accordance with the law.

The range of medical devices is very wide, ranging from medical gloves to cardiac pacemakers, all under the supervision of FDA. According to the medical use and possible harm to human body, FDA classifies medical devices into I, II and III categories, and the higher the category, the more the supervision

If the product is a novel invention that does not exist in the market, FDA requires manufacturers to conduct strict human experiments, and there is convincing medical and statistical evidence to prove the effectiveness and safety of the product.

FDA certification of medical devices, including: Manufacturer registration in FDA, product registration in FDA, product listing registration (510 form registration), product listing review and approval (PMA review), label and technical transformation, customs clearance, registration, and pre listing report of medical and health devices, shall submit the following materials: (1) five complete packaged finished products, (2) device structure drawing and text description, (3) ）Performance and working principle of the device; (4) safety demonstration or test materials of the device; (5) brief introduction of manufacturing process; (6) summary of clinical test; (7) product manual. If the device has radiation performance or releases radioactive substances, it must be described in detail.

Registration and certification procedures

FDA has a clear and strict definition of medical devices, which are 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 that meet the following conditions, including components, parts or accessories: those explicitly listed in the national formula or the United States pharmaceuticals or the appendixes of the two; intended use For the diagnosis of animal or human diseases or other physical conditions, or for the cure, alleviation and treatment of diseases; intended to affect the function or structure of animal or human body, but not through metabolism to achieve its main purpose. ".

Only products that meet the above definition can be regarded as medical devices. Under this definition, not only various instruments and tools in hospitals, but also fitness equipment such as spectacle frames, glasses, toothbrushes and massagers that can be purchased by consumers in general stores are under the management of FDA. It is slightly different from the recognition of medical devices in China.

According to the different risk levels, FDA classifies medical devices into three categories (I, II, III), with the highest risk level of category III. The 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 is necessary to clarify the classification and management requirements of the products to be put on the market.

FDA has formulated many bills for medical devices, which are revised and supplemented from time to time, but there are not many fundamental bills, including: Federal Food, drug and Cosmetics Act (FD & C act), public health service act, fair packaging and Labeling Act, health and safety radiation control act, safety medical device act, and Modernization Act. FDA has given a very detailed explanation to these bills, and has specific operation requirements. Before planning to enter the U.S. market, enterprises need to carefully evaluate the regulations and specific requirements (including the requirements of different U.S. product standards) related to their products.

After the above information is made clear, the enterprise can start to prepare relevant application materials and apply to FDA for approval according to certain procedures. For any product, enterprises need to register and list. For class I products (accounting for about 47%), general control is applied. Most of the products only need to be registered, listed and GMP standardized, so that they can enter the U.S. market (a few of them are exempt from GMP, and a few of the reserved products need to submit 510 (k) application to FDA, i.e. PMN (premarket notification)); for class II products (accounting for about 46%), general control is applied. ）After registration and listing, enterprises need to implement GMP and submit 510 (k) application (rarely 510 (k) exemption); for class III products (accounting for about 7%), enterprises need to implement GMP and submit PMA (premarket application) application (part of class III Application) to FDA after registration and listing Product or PMN).

For class I products, after the enterprise submits relevant materials to FDA, FDA will only make announcement without relevant certificates to the enterprise; for class II and III devices, the enterprise must submit PMN or PMA, and FDA will give the enterprise a formal market access approval letter (clearance) at the same time of announcement, that is to say, the enterprise is allowed to directly sell its products in the American Medical Device Market in its own name. Whether or not to conduct on-site GMP assessment in the application process is determined by FDA according to product risk level, management requirements, market feedback and other comprehensive factors.

It can be seen from the above contents that most of the products can be approved for listing by FDA after enterprise registration, product listing and GMP implementation, or after submitting 510 (k) application.

1.510 (k) document is also the document required by FDA for PMN. It is commonly referred to as 510 (k) document because of its corresponding section 510 of FD & C act.

2. Substantive equivalence comparison (SE)

3.510 (k) review procedure

Before application, it must be clear whether the product is recognized as a medical device by FDA, product category, management requirements, and the application work content;

Check whether the products applied for listing are in accordance with the US compulsory standards and whether the products meet the standards (the formal inspection report of the testing agency is generally required);

Before preparing the 510 (k) application documents, it is necessary to consider whether, when and what kind of 510 (k) applications need to be submitted: regular 510 (k), special 510 (k), simplified 510 (k);

In the process of application, FDA should give written and timely answers to the questions raised in time;

Letter size (21.5cm x 29.7cm) shall be used for all documents submitted to FDA.

All the data submitted to FDA should be kept as a backup, because FDA will scan and log in the application data after receiving it, and destroy the application data at the same time, which will not be returned to the enterprise.

For a small number of products, FDA will conduct on-site GMP assessment for enterprises. Enterprises need to refer to the requirements of GMP management in the United States, and provide appropriate translators who have a certain understanding of GMP and enterprises when FDA conducts on-site audit;

Inform the official contact person of FDA to have a certain understanding of FDA regulations and working procedures, and be able to communicate with FDA directly to facilitate timely feedback. The enterprise can make it clear that it or the entrusted consulting agency is responsible for the daily communication with FDA.

Cosmetics certification

Voluntary registration program 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 cosmetics manufacturers and declaration of cosmetics ingredients.

Benefits of participating in vcrp

The manufacturer's voluntary registration and obtaining the registration number does not mean the FDA's approval of the manufacturer or its products, nor does the FDA allow the manufacturer to use the registration number or listing number participating in the vcrp for commercial publicity; however, the manufacturer can directly obtain the following benefits by participating in the vcrp:

Obtain important information about cosmetic ingredients. FDA will input all information from vcrp into computer database. If a currently used cosmetic ingredient is considered harmful and should be banned, 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 vcrp, FDA will remind the manufacturer if it finds that the manufacturer uses unapproved pigment additives or other prohibited ingredients in the formula. In this way, the manufacturer can modify the product formula before the product is imported or sold, thus eliminating 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 if a cosmetics company has registered with the FDA. Although registration does not indicate FDA approval, it does indicate that your product has been reviewed by FDA and entered the government's database. FDA will notify you if you submit an incomplete product formulation, or if it contains a banned ingredient or an unapproved pigment additive.

The decision to collect samples is based on the nature of the product; FDA's key concerns; and the product's past history. FDA takes a physical sample and sends it to FDA regional laboratory for analysis

If FDA finds that the sample meets the requirements, it will send a "Release Notice" to the U.S. Customs and the importer respectively.

If the FDA determines that the sample 'shows a violation of 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 FDA or U.S. Customs Supervision

A hearing is the only opportunity for an importer to defend an imported article or to provide evidence that will make the article fit for entry after it has been trimmed.

If the case and underwriters, consignors, importers or a designated representative do not reply to the notice, FDA will send a 'notice of refusal' to the U.S. Customs and the case and importer. Then the products involved in the problem are returned or destroyed.

If the case and the Underwriters, consignors, importers or a designated representative reply to the 'notice of seizure and hearing', FDA will hold a hearing on the seized product when the importer provides evidence that the product 'meets the requirements' or submits an application to modify the product.

If the trade name provides evidence that the product meets the requirements, FDA will collect subsequent samples. After analysis, it is determined that the product is either released or denied entry.

FDA reviews the importer's proposed modification procedures and approves or disapproves them as appropriate. Once approved, FDA will conduct subsequent inspection / sample collection to determine its eligibility. If the sample is qualified, send a 'Release Notice' to the U.S. Customs and importer. If the hair sample is unqualified, a "Notice of rejection" will be issued.

Section 8 (c) of the FDCA requires the applicant to pay for all expenses, including the travel, daily use and wages of FDA officials or employees, in addition to the cost of updating the label or other expenses to make the seized goods conform to the relevant measures in the application form (fda-766). By submitting form fda-766, the applicant agrees to pay all regulatory fees in accordance with current regulations.

Drug Certification

FDA has a complete set of certification procedures for pharmaceutical products to ensure the safety and effectiveness of new drugs. The procedures are as follows:

1. Investigational new drug application (ind):

When the pharmaceutical company submits ind to FDA, FDA begins to monitor the new drug. 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 body experiment is divided into four stages. The first stage mainly tests the safety, main side effects, metabolism mechanism, etc. the number of samples is generally less than today's 00

The second phase mainly tests the effectiveness of drugs to determine whether the 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 the second phase is generally less than 300

If the second phase experiment is encouraging, a larger sample will be prepared for testing, and the experiment will enter the third phase. The third phase will include different age groups, different populations, and different dosage, so as to comprehensively study the safety and effectiveness of drugs. The number of samples in the third phase experiment varies from hundreds to thousands

Phase IV is mainly conducted 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 has completed the human body experiment and verified the safety and effectiveness of the new drug, it formally submits an NDA application to FDA. FDA reviews all the animal and human experimental data, as well as the data of the drug's surrogate mechanism, GMP data of drug production. If the data is incomplete or unreasonable, FDA will refuse to apply, or FDA will complete the application and approval within 10 months or so, and give consent or rejection opinions

The above content is extracted from the service manual of MTG FDA certification service center

FDA certification process

1. Preparation stage

Copy of the corporate license;

Production (hygiene) license, copy of certificate;

Company profile (time of establishment, technical strength, main products and their performance, asset status).

2. Application and acceptance of technical preliminary examination

Submit English translation documents of DMF (drug master document) and SOP (standard operation procedure) to the agent;

Modify the above documents according to the opinions of the agent.

3. DMF data review

FDA carefully reviews and visits the factory to check whether the DMF documents are true;

If FDA does not find any major error and considers it to meet the requirements, it shall propose a pre approval inspection plan.

4. FDA examination

FDA inspectors inspect the factory, ask questions, and the factory must answer them one by one;

In case of any doubt, the official will give a "483" form (rectification proposal). If the problem is serious, the official will not give a "483" form.

5. FDA issues "approval letter"

We must carefully answer the questions raised by the prosecutor on the "483" form. If there are any questions, we must immediately correct them and prove them;

If the prosecutor does not find out the problem, he needs to explain and prove it

Material certification

Food contact materials refer to all materials that can be contacted with food in the process of packaging, processing, production, storage and transportation of food. Common materials include all kinds of plastic, metal, ceramic, glass, bamboo and wood products, etc. the environmental protection and safety of these materials that can be contacted with food are directly related to the food safety and health of users. Therefore, such products need to be exported to the United States in accordance with FDA standards Conduct relevant test certification

The common inspection items of FDA certification for materials in contact with food are as follows:

Organic coatings, metals and electroplated products require U.S. FDA CFR 21 175.300

Deionized water extraction

8% alcohol extractives

N-heptane 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 requires U.S. FDA CFR 21 181.32 or 180.22

In water deionized water extraction

In 3% acetic acid 3% acetic acid leaching method

In 8% ethanol 8% alcohol extraction

In n-heptane extraction

Laser authentication

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 drawings; and product technical information, laser protection measures and working principle description.

3. Label

Label: English label conforming to regulations, including warning label, product label, conformity certification label (such as complies with 21 CFR 1040.10 & 1040.11), light outlet label, etc.

4. Laser information

Laser device information: laser generator type, medium, laser light path diagram, laser parameters, laser device certificate / test record (if purchased from other manufacturers, information of the manufacturer, 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 measurement and verification certificate and report of optical power meter.

6. Quality Control System

Quality control documents: mainly including internal quality control flow chart, inspection procedure, quality control specification / control of design modification; production line sampling table, incoming material inspection sheet, finished product inspection sheet, internal inspection report, etc. (including the sample of the form).

7. US Agent / Importer

U.S. agent and U.S. importer information: including contact full name, telephone / fax / email, U.S. detailed address / zip code, company name; and U.S. agent authorization agreement.