Navigating The Food and Drug Administration by Weaver & Amin

Navigating The Food and Drug Administration

The Food and Drug Administration (FDA) is more than just one regulatory body. The FDA consists of several Offices and Centers that can work independently, jointly, or with local or state authorities, depending on the actions. Although most of the policies and programs are developed internally by each individual Office or Center, the effective regulation and enforcement of foods, drugs and related products require a group effort. The FDA shows the cohesiveness of the various Offices and Centers best when it implements multi-center programs.

In this article, the roles of the Office of the Commissioner, the Office of Regulatory Affairs, and the five Centers will be discussed. The five Centers of the FDA are the following: (1) Center for Food Safety and Applied Nutrition; (2) Center for Drug Evaluation and Research; (3) Center for Biologics Evaluation and Research; (4) Center for Veterinary Medicine; and (5) Center for Devices and Radiological Health.

Office of the Commissioner

The Commissioner of the FDA assures that the Offices and Centers under its control abide by their applicable laws and regulations. The power granted to the commissioner is broad, and it essentially grants the commissioner the power to make the final decision on whether regulatory initiatives, priorities or programs will be implemented. The commissioner also has the power to determine the priority of enforcement activity.

Throughout the years, the structure of the Office of the Commissioner has evolved. Currently, the office consists of one deputy commissioner and four senior associate commissioners. Each of the five Center directors and the associate commissioner for regulatory affairs report directly to the commissioner.

Office of Regulatory Affairs

This Office is responsible for the agency’s law enforcement activities. Currently, four offices make up the Office of Regulatory Affairs. They are the Office of Enforcement, the Office of Regional Operations, the Office of Criminal Investigations, and the Office of Resource Management. The associate commissioner, who has final authority over individual enforcement actions, is the director of the Office of Regulatory Affairs.

The associate commissioner’s duties range from establishing enforcement programs and procedures to chairing the Compliance Policy Council. Some examples of establishing programs and procedures include the issuance of Warning Letters and reviewing injunctions and criminal cases involving clear instances of fraud.

For more information on the Office of Regulatory Affairs, please go to

The Five Centers of the FDA

As mentioned above, the FDA consists of five regulatory centers. These Centers are responsible for regulating various foods, drugs and related products. Each Center regulates a different area, but sometimes products overlap resulting in a multi-Center approach to regulation.

1. Center for Food Safety and Applied Nutrition (CFSAN)

CFSAN is responsible for the regulation of approximately 48,500 food establishments. This means that nearly half of the firms regulated by the FDA are monitored by CFSAN.

Most products regulated by CFSAN, except food additives and color additives, do not require FDA approval prior to marketing the products. Because of this, most of the Center’s enforcement activities result from post-market surveillance and investigations. CFSAN has provided the FDA with approximately 45 compliance program guides to help evaluate the regulatory compliance of various foods. Because most of the FDA’s import regulations deal with food, CFSAN also provides regulatory guidance for most of the FDA’s import activities and reviews most of the FDA’s Import Alerts.

In order to enforce its regulations, CFSAN works closely with other departments and Centers. For example, the U.S. Department of Agriculture (USDA), which regulates meat, poultry and eggs, interacts regularly with CFSAN. The Center also works closely with the Center for Veterinary Medicine (CVM) when looking into residues of animal drugs that may appear in human food.

The large number of establishments regulated by CFSAN places a tremendous amount of responsibility on the Center. A few years ago, a number of high-profile food-pathogen outbreaks occurred, which caused the government to increase its emphasis on ensuring food safety. An initiative was designed to reduce food-borne illnesses and improve the safety of the U.S. food supply, and to achieve the initiative’s goals, the FDA, USDA, Centers for Disease Control and the U.S. Environmental Protection Agency joined resources. The collaboration included education, surveillance and research, which have all helped to result in an increased number of inspections at food establishments.

As part of the initiative, CFSAN implemented in December 1997 the Hazard Analysis and Critical Control Point (HACCP) program to regulate the seafood industry. Under the HACCP, all seafood processors, repackers and warehouses must identify potential hazards and critical control points. They must also establish preventive measures, including critical limits, for each control point. In January 2001, CFSAN expanded the program to include fresh and processed fruit and vegetable juices, and it is considering whether to expand the program into other areas. HACCP pilot programs currently involve manufacturers of cheese, frozen dough, breakfast cereals and salad dressing, as well as a pilot program for retail establishments. In response to the program expansions, the National Conference on Interstate Milk Shipments implemented a voluntary HACCP pilot program for Grade A Dairy products.

For more information on CFSAN, please go to

2. Center For Drug Evaluation and Research (CDER)

CDER, the largest agency, is responsible for all drugs for human use except biological drugs, which are regulated by the Center for Biologics Evaluation and Research. This means that all companies (approximately 17,500) that manufacture, package, test or distribute drug products are regulated by CDER. It is mandatory that all manufacturers and importers of drugs register with the FDA and list the drugs they manufacture.

There are three types of products that the Center regulates: (1) new drugs, which are regulated under an approval system commonly called NDAs (new drug applications); (2) generic drugs, which are regulated under an abbreviated approval system commonly called ANDAs (abbreviated new drug applications); and (3) over-the-counter (OTC) drugs, which are regulated under a monograph system that establishes which active ingredients can be formulated for OTC drug products without pre-market approval, and for what recommended uses.

As part of its duties, CDER also makes sure companies comply with the labeling and good manufacturing practice (GMP) provisions of the Federal Food, Drug and Cosmetic Act, as well as other regulations. CDER has implemented more than 30 compliance programs for various drug products and areas such as bioresearch, drug quality and health fraud.

For more information about CDER, please go to

3. Center for Biologics Evaluation and Research (CBER)

CBER regulates biological products, including products derived from human blood, vaccines, and serums, toxins and antitoxins, allergenics and tissues derived from living animals. CBER monitors the activities of approximately 4,150 companies.

In order to market biological products, these products must obtain a license. It is this licensing requirement that grants CBER most of its power to regulate biological products. Enforcement actions, such as seizure and injunction, are typically not necessary because of the following: (1) FDA regulations authorize the immediate suspension of licenses; (2) strict “how to” regulations called “additional standards” are applied to licensed vaccines; and (3) the FDA is authorized to test individual lots of products before manufacturers can distribute them. These powers greatly reduce the chance that a defective licensed product will enter the market.

CBER also enforces standards for the nation’s blood supply, including the Red Cross and thousands of unlicensed, local blood banks and plasma collection centers, but the Center’s monitoring of compliance in this case is not as proactive as other areas. The Center typically relies on enforcement tools that correct problems in products already on the market, such as the GMP regulations for hepatitis and HIV testing.

A slightly different enforcement standard is also applied to manufacturers of vaccines and other similar products. Typically, CBER will assume a participatory, problem-solving role when monitoring vaccines because of the limited number of manufacturers. Actions concerning synthetic drugs will probably affect 10 to 15 manufacturers, but actions concerning vaccines may affect only one or two companies. The limited number of vaccine manufacturers subject to enforcement actions not only has a regulatory impact, but more importantly, they also threaten the nation’s supply of a particular vaccine. For this reason, CBER has adopted the participatory, problem-solving role.

CBER, like the other Centers, is also concerned with improving its procedures. In an attempt to address concerns regarding inconsistencies in inspections and to increase the depth of biological products inspections, CBER started an inspection partnership called Team Biologics with the Office of Regulatory Affairs. The coordinated inspections have led to longer inspection times and to more thorough FDA reviews of good manufacturing practices, but Team Biologics is not involved with prelicensing and preapproval inspections. These functions are still handled by CBER.

For more information about CBER, please go to

4. Center for Devices and Radiological Health (CDRH)

CDRH is responsible for regulating medical devices and radiation emitting products. Approximately 31,890 establishments that manufacture, package or import medical devices are monitored by this Center, and the CDRH also monitors another 4,700 establishments that manufacture, process or distribute radiation-emitting products.

CDRH is the fastest growing Center due to the large number of new medical devices and expanded regulatory powers over medical devices. The Medical Device Amendments of 1976 and the Safe Medical Devices Act of 1990 are two laws that have helped expand CDRH’s regulatory powers over the marketing of medical devices.

Medical devices are marketed under a very detailed system. This system consists of product classifications, approvals, notifications, performance standards, recognized standards and general controls. Different procedures apply depending on the type of device marketed.

One type of device is a device that is new to the market. In this case, if the FDA has stated that existing standards or controls are insufficient to ensure safety and efficacy of the new device, then the manufacturer will be required to apply for a Premarket Approval (PMA).

Another type of device is one that has the same intended use as an already-existing device. Here, the manufacturer can notify the FDA of its intent to market the device, and if the FDA confirms that the device is substantially equivalent to an already-existing device, then manufacturer will be able to market it. This process is known as a “510(k)”.

A third type of device is one that was already on the market before the Medical Device Amendments of 1976 were enacted. In this case, the device may be exempt from the licensing and notification scheme due to so-called “grandfather clauses”.

Of the different types of medical devices, 510(k) and grandfathered devices make up more than 95% of the products regulated by the CDRH. Because most devices fall under these two categories, the Center’s enforcement activities typically only involve labeling, good manufacturing practices and other mechanisms, rather than withdrawal of approvals or other similar sanctions.

As of late, the CDRH has increased its enforcement activities. Several reasons exist for the increased enforcement, but the most likely causes are the following: (1) new enforcement tools given to the Center under the Safe Medical Devices Act of 1990; (2) a large increase in prelicensing inspections for medical devices marketed under a PMA; (3) a more aggressive review of advertising, labeling and promotional activities; and (4) congressional criticism that the CDRH did not actively seek compliance.

With an increase in enforcement activities, the CDRH attempted to improve its procedures by implementing a three-part pilot program in March 1996. The first part consisted of preannouncing inspections for eligible firms. The second part consisted of annotating the FDA’s Lists of Inspectional Observations (FDA Form 483s) to note promised or completed corrections, and the third part consisted of issuing post-inspection notices to firms where no objectionable conditions or practices were found or where objectionable conditions existed but the likelihood the firm would produce nonconforming or defective products were minimal. In November 1998, the FDA expanded the program to other areas of regulated industry, but it eliminated the post-inspection notice in January 2001.

Another pilot program instituted by the CDRH was a two-part Warning Letter pilot program, which started in August 1998. The first part covers GMP violations, and the other part covers 510(k) and labeling deficiencies. This program only covers non-serious health risk violations and deficiencies.

If a firm receives a 483 for either GMP violations or 510(k) or labeling deficiencies, the firm will have 15 working days to respond. No Warning Letter will be issued if the FDA considers the response to be acceptable. Instead, the FDA will classify the matter as “voluntary action indicated”, but if it is later determined that the firm did not comply with the promised remedies, the FDA can proceed with appropriate enforcement actions as if a Warning Letter had been issued.

For more information about CDRH, please go to

5. Center For Veterinary Medicine (CVM)

CVM regulates drugs and medicated feeds used for animals, as well as residues of drugs in the edible tissue of animals, and approximately 4,600 establishments come under the control of CVM. A major emphasis relative to its regulatory role deals with food-producing animals.

Most of the CVM’s regulatory efforts come in the form of a premarket licensing system, which allows the CVM to control most problems through its licensing activities. CVM is also responsible for enforcing good manufacturing practice and labeling requirements for licensed and unlicensed products.

The Center’s duties sometimes coincide with the duties of other Centers. For example, the regulation of the edible tissue of animals deals with human food safety, and therefore the CVM and CFSAN will work together to regulate this area. Like CFSAN, CVM works closely with state and local authorities that perform inspections under the authority of the FDA.

For more information about CVM, please go to

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