# Presentation: 679411

## The Food and Drug Administration

## FDA Today

## FDA is part of DHHS

## FDA Mission

- To promote and protect the public health by helping safe and effective products reach the market in a timely way;
- To monitor products for continued safety after they are in use; and
- To help the public get the accurate, science-based information needed to improve health.

**Notes:**
The Food and Drug Administration is one of the nation's oldest and most respected consumer protection agencies. 
This presentation will provide information on:
(1) FDA's responsibilities;
(2) The tools it use to fulfill those responsibilities;
(3) Its priorities for improving the way it serves the public.

## Brief History

- Pre-history
- “Poison Squads” of federal employees used to determine safety of food additives.
- Food and Drug Act of 1906
- First nationwide consumer protection law made it illegal to distribute misbranded or adulterated foods, drinks and drugs across state lines.
- Federal Food, Drug, and Cosmetic Act of 1937
- Public health disaster (Sulfanilamide)
- •Congress has continued to give FDA new responsibilities over the years, including the requirement that drugs and medical devices be proven effective as well as safe before they can be sold.
- Congress has continued to give FDA new responsibilities over the years, including the requirement that drugs and medical devices be proven safe and effective before they can be sold.
- Work is a blending of law and science aimed at protecting consumers.

**Notes:**
Sulfanilamide  first "wonder drug" and popular/effective treatment for strep throat and gonorrhea
Formulated into an Elixir of Sulfanilamide and marketed for use in children. 
But the liquid formulation contained a poison, the same chemical used in antifreeze, and it killed 107 people, most of them children. 
FFDCA 1937
The earlier law did not require the drug's manufacturer to test the formulation for safety before it was sold.Law required companies to prove the safety of new drugs before putting them on the market. 
The new act also added the regulation of cosmetics and therapeutic devices, and generally updated the law to improve consumer protection.

## Broad Responsibilities

- Varied products
- Every day, every American comes in contact with a host of FDA-regulated products, amounting to $1 trillion per year.
- FDA-regulated products account for about 25 cents of every consumer dollar spent.
- Everything from the most common food ingredients to complex medical and surgical devices, lifesaving drugs, and radiation-emitting consumer and medical products.
- Varied approaches
- Some products (e.g., new drugs and complex medical devices) must be proven safe and effective before companies can put them on the market.
- Other products (e.g., x-ray machines and microwave ovens) must measure up to performance standards.
- Other products (e.g., cosmetics and dietary supplements) can be marketed with no prior approval.
- Differences are dictated by the laws we enforce and the relative risks that the products pose to consumers.

## Benefits versus Risks

- At the heart of all FDA's regulatory activities is a judgment about whether a new product's benefits to users will outweigh its risks.
- Science-based, efficient risk management allows FDA to provide the most health promotion and protection at the least cost to the public.
- No regulated product is totally risk-free, so these judgments are important.
- FDA will allow a product to present more of a risk when its potential benefit is great -- especially for products used to treat serious, life-threatening conditions.

## US Food and Drug Administration

- 5 Regional Offices
- 20 District Offices
- 140 Resident Posts

## Safe, Wholesome, Sanitary Food

- FDA safeguards the nation's food supply by making sure that all ingredients used in foods are safe, and that food is free of contaminants
- Like disease-causing organisms, chemicals, or other harmful substances.
- FDA must approve new food additives before they can be used in foods.•FDA also monitors the safety of dietary supplements and the content of infant formulas and medical foods.
- Meat and poultry products are regulated by the Department of Agriculture (USDA).

## US Food and Drug Administration

- 5 Regional Offices
- 20 District Offices
- 140 Resident Posts

## Safe and Effective Medicines and Biologics

- Medicinal products need to be proven safe and effective before they can be used by patients.
- The product categories covered by this requirement include:
- Medicines – used for the treatment and prevention of disease.
- Biologics – vaccines, blood products, biotechnology products and gene therapy.

## US Food and Drug Administration

- 5 Regional Offices
- 20 District Offices
- 140 Resident Posts

## Safe and Effective Animal Drugs and Medical Devices

- FDA regulates drugs and medical devices used for animals, both pets and animals that produce food.
- Veterinary Drugs
- Before manufacturers can market animal drugs (including drugs used in animal feeds), they must gain FDA approval by providing proof of their safety and effectiveness.
- Livestock Drugs
- Evaluated for their safety to the environment and to the people who eat the animal products.
- FDA makes sure that any drug residues that remain in these foods aren’t harmful to the consumers who eat them.
- Veterinary Medical Devices
- Veterinary medical devices do not have to be pre-approved by FDA before marketing, but they still must be safe, effective, and properly labeled.

## US Food and Drug Administration

- 5 Regional Offices
- 20 District Offices
- 140 Resident Posts

## Safe Consumer Medical Devices and Medical Radiation Products

- Medical products need to be proven safe and effective before they can be used by patients.
- From simple (tongue depressors, thermometers, etc.) to complex technologies (heart pacemakers, dialysis machines, etc.).
- Only the most complex are reviewed by FDA before marketing.
- FDA also protects the public from unnecessary exposure to radiation from electronic products.
- Microwave ovens, cell phones, x-ray equipment, lasers, medical ultrasound and MRI machines.
- Many other consumer, industrial, and medical products.

## US Food and Drug Administration

- 5 Regional Offices
- 20 District Offices
- 140 Resident Posts

## Safe Cosmetics

- FDA monitors cosmetic products to be sure that they are safe and properly labeled.
- But these products and their ingredients are not reviewed or approved by FDA before they are sold to the public.
- And FDA cannot require safety testing.

## US Food and Drug Administration

- 5 Regional Offices
- 20 District Offices
- 140 Resident Posts

**Notes:**
FDA employs some 9,000 people who work in locations around the country.
The network of field offices is generally the first point of contact for the public and regulated manufacturers. 
The employees in these offices focus on inspection and surveillance, laboratory work, and public and industry education.
The FDA staff who work in the greater Washington, D.C., area focus on product review and regulatory policy.

## Truthful and Informative Labels

- Consumers rely on product labels to know what the product is and how to use it.
- FDA regulates what is on these labels to ensure that they are truthful and that they provide useable information that helps consumers make healthy, safe decisions when using the product.
- In recent years FDA has redesigned labeling for foods, over-the-counter medicines and dietary supplements, making them much more informative and easy to read.
- FDA also oversees the labeling for drugs and medical devices used by health professionals to ensure that the products have the information needed for proper use.

## OFFICE OF REGULATORY AFFAIRS

**OFFICE OF REGULATORY AFFAIRS**
**13 FIELD LABORATORIES**
**CURRENT FY 2004**

**NORTHEAST**

**PACIFIC**

**CENTRAL**

**SOUTHEAST**

**SOUTHWEST**

- 10/02

- Division of Planning, Evaluation & Mgmt
- ORALABSCurr.PPT

**  ****5 MULTI-PURPOSE LABS**** **

**  ****8 ORA LABS**

**SEATTLE**

**SAN FRANCISCO**

**LOS ANGELES**

- `

**DENVER**

**KANSAS CITY**

**JEFFERSON**

**DETROIT**

**FORENSIC**
**CHEMISTRY**
**CENTER**

**PHILADELPHIA**

**NEW YORK**

**WINCHESTER**

**ATLANTA**

**SAN JUAN**

**Notes:**
Information on Lab Closing Dates
As of 10/27/98
In discussions with Larry D’Hoostelaere, DFS:

Baltimore - September 1999;

Detroit - December 1999;

Minneapolis - February 2000;

Dallas - January 2000.

## OFFICE OF REGULATORY AFFAIRS

**OFFICE OF REGULATORY AFFAIRS**
**190 OFFICES IN FY 2004**

**NORTHEAST**

**PACIFIC**

**CENTRAL**

**SOUTHEAST**

**SOUTHWEST**

- 3/03

- Division of Planning, Evaluation, & Mgmt
- ORA Offices.ppt

**REGIONAL OFFICES - 5**
**DISTRICT OFFICES - 20**
**RESIDENT INSPECTION POSTS - 140**
**OCI FIELD OFFICES - 6**
**OCI RESIDENT OFFICES - 6**
**OCI DOMICILES - 13**

**CA**

**NV**

**WA**

**MT**

**OR**

**ID**

**AL**

**HI**

**AZ**

**UT**

**WY**

**CO**

**NM**

**TX**

**OK**

**AR**

**MO**

**IA**

**NE**

**KS**

**TN**

**NC**

**GA**

**AL**

**MS**

**LA**

**FL**

**SC**

**PR**

**ME**

**VT**

**NY**

**NH**

**MA**

**CT**

**RI**

**MN**

**WI**

**IL**

**MI**

**IN**

**OH**

**PA**

**WV**

**KY**

**VA**

**NJ**

**ND**

**SD**

**MD**

**DE**

**VI**

**Notes:**
Information on Lab Closing Dates
As of 10/27/98
In discussions with Larry D’Hoostelaere, DFS:

Baltimore - September 1999;

Detroit - December 1999;

Minneapolis - February 2000;

Dallas - January 2000.

## Cost to Consumers

- A relative bargain for United States taxpayers.
- Dividing FDA's budget by the number of people it protects  Just over a penny (1 cent) per day per person.
- Most of FDA's budget goes toward paying its highly skilled and internationally respected work force.
- Employees are drawn from a wealth of science and public health professions (e.g., biologists, chemists, physicians, biomedical engineers, pharmacologists, veterinarians, toxicologists, and specialists) in public health education and communication.

## FDA Activities

- New Product Review
- Safe Manufacturing and Handling
- Standards and Regulation
- Research
- Enforcement

## FDA New Product Review

- FDA reviews the results of laboratory, animal and human clinical testing done by companies to determine if the product they want to put on the market is safe and effective.
- FDA does not develop or test products itself.
- FDA conducts this pre-market review for new human drugs and biologics, complex medical devices, food and color additives, infant formulas, and animal drugs.

## IND Review Process

## IND Review Process (cont’d)

## NDA Review Process

## NDA Review Process (cont’d)

## Drug Development Process

- Pre-approval (preclinical, toxicology, carcinogenicity, reproductive,) and clinical (pk/pd, phases II and III).
- Post-approval (post-marketing clinical and non-clinical studies and post-marketing surveillance).

## FDA Approval Process

## Phase 1 Clinical Studies

- Involves initial introduction of an IND into humans.
- Closely monitored and may be conducted in patients, but are usually conducted in healthy volunteer subjects.
- Designed to determine the metabolic and pharmacologic actions of the drug in humans, side effects, and, if possible, early evidence on effectiveness.
- Sufficient information about the drug's pharmacokinetics and pharmacological effects should be obtained to permit the design of well-controlled, scientifically valid, Phase 2 studies.
- Phase 1 studies also evaluate drug metabolism, structure-activity relationships, and the mechanism of action in humans.
- Studies determine which investigational drugs are used as research tools to explore biological phenomena or disease processes.
- Total number of subjects included in Phase 1 studies varies with the drug, but is generally in the range of twenty to eighty.

## Phase 2 Clinical Studies

- Phase 2 includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness of the drug for a particular indication or indications in patients with the disease or condition.
- This phase of testing also helps determine the common short-term side effects and risks associated with the drug.
- Phase 2 studies are typically well-controlled, closely monitored, and conducted in a relatively small number of patients, usually involving several hundred people.

## Phase 3 Clinical Studies

- Phase 3 studies are expanded controlled and uncontrolled trials.
- Performed after preliminary evidence suggesting effectiveness of the drug has been obtained in Phase 2
- Intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug.
- Provide an adequate basis for extrapolating the results to the general population and transmitting that information in the physician labeling.
- Phase 3 studies usually include several hundred to several thousand people.

## Sponsor/FDA Meetings (Pre-NDA) 

- Purpose is to discuss the presentation of data (both paper and electronic) in support of the application.
- A summary of clinical studies to be submitted in the NDA;
- Proposed format for organizing the submission, including methods for presenting the data; and
- Other information needed to be discussed.
- Meeting goals
- Uncover any major unresolved problems or issues.
- Identify studies the sponsor is relying on as adequate and well controlled in establishing the effectiveness of the drug.
- Help reviewers become acquainted with the general information to be submitted
- Discuss the presentation of the data in the NDA to facilitate its review.
- Once the NDA is filed, a meeting may also occur 90 days after the initial submission of the application in order to discuss issues that are uncovered in the initial review.

## Advisory Committees 

- CDER uses advisory committees to obtain outside advice and opinions from expert advisors so that final agency decisions will have the benefit of wider national expert input.
- Committee recommendations are not binding on CDER, but the agency considers them carefully when deciding drug issues.

## Accelerated Development/Review 

- Accelerated development/review (*Federal Register, April 15, 1992*) speeds development of drugs that promise significant benefit over existing therapy for serious or life-threatening illnesses for which no therapy exists.
- Can be used under two special circumstances:
- When approval is based on evidence of the product's effect on a “surrogate endpoint”.
- When the FDA determines that safe use of a product depends on restricting its distribution or use.
- Manufacturers must continue testing after approval to demonstrate that the drug indeed provides therapeutic benefit to the patient.

## Treatment IND

- Treatment Investigational New Drugs (*Federal Register, May 22, 1987*) are used to make promising new drugs available to desperately ill patients as early in the drug development process as possible.
- An immediately life-threatening disease means a stage of a disease in which there is a reasonable likelihood that death will occur within a matter of months or in which premature death is likely without early treatment.
- Examples are advanced cases of AIDS, herpes simplex encephalitis, and subarachnoid hemorrhage.
- Treatment INDs are made available to patients before general marketing begins (typically during Phase 3 studies).
- Treatment INDs also allow FDA to obtain additional data on the drug's safety and effectiveness.

## Parallel Track 

- Another mechanism to permit wider availability of experimental agents is the "parallel track" policy (*Federal Register of May 21, 1990*) developed by the U.S. Public Health Service in response to AIDS.
- Under this policy, patients with AIDS whose condition prevents them from participating in controlled clinical trials can receive investigational drugs shown in preliminary studies to be promising.

## Subpart E 

- Subpart E in *Section 312 of the Code of Federal Regulations* establishes procedures to expedite the development, evaluation, and marketing of new therapies intended to treat people with life-threatening and severely-debilitating illnesses, especially where no satisfactory alternatives exist (*Federal Register, October 21, 1988*).

## FDA Safe Manufacturing and Handling

- FDA keeps track of marketed products, in terms of how they are manufactured and responds to problems or newly identified risks.
- Safe manufacturing and handling
- Inspects domestic and foreign manufacturers, checks shipments of imported products, and collects and tests product samples for signs of contamination.
- Makes more than 16,000 facility visits per year.
- Maintains cooperative arrangements with many state governments to help increase the number of facilities that are checked.
- Monitor for new risks
- Keeps careful watch on reports of adverse experiences with products **after** they are marketed.
- FDA receives more than 400,000 problem reports a year.
- Can ask manufacturers to recall products, withdraw approvals (of a drug, for example), require labeling changes, or send warnings to physicians or other health practitioners.

## FDA cGMPs

- current Good Manufacturing Practices (cGMPs) and supplements.
- FDA faces a statutory requirement to inspect facilities every two years.
- ORA (Office of Regulatory Affairs does domestic inspections for CDER and some from SBER).
- CDER performs foreign inspections
- CBER performs biologic inspections for some Biologic.
- Many supplements can require pre-approval inspections.

## FDA Standards and Regulation

- Uses regulations and product standards as the “yardsticks” that define specific requirements manufacturers must follow to assure product safety and to provide accurate information to health professionals and consumers.
- Works with foreign governments to encourage the safety and quality of imported products by making sure that **foreign** standards are equivalent to those enforced by FDA.

## FDA Research

- Research activities provide the scientific basis for its regulatory decisions and the tools needed to identify and assess risks.
- FDA uses research results to guide standard setting, evaluate new products, develop test methods and other support for product monitoring, and to study emerging risks.

## FDA Enforcement

- FDA can take a number of actions to protect the public health.
- Initially, the agency works with the manufacturer to correct the problem voluntarily.
- If that fails, legal remedies include asking the manufacturer to recall a product, having federal marshals seize products if a voluntary recall is not done, and detaining imports at the port of entry until problems are corrected.
- If warranted, FDA can ask the courts to issue injunctions or prosecute those that deliberately violate the law.

## FDA Challenges

- Scientific breakthroughs
- FDA scientists need to keep up with rapidly- advancing technologies in all product areas.
- More sophisticated products
- These technologies will translate into products with new complexities and risks.
- New public health threats
- FDA needs to be prepared to respond rapidly to unexpected health risks, such as the threat of terrorism, tougher strains of antibiotic-resistant bacteria or more dangerous food-borne illnesses.
- International commerce
- Monitoring of imports and cooperation with foreign regulators will become more important as international commerce continues to grow.
- Consumer information
- Today's sophisticated consumers and the wide availability of information about FDA-regulated products will challenge the Agency to be sure consumers are getting the information they need from the right sources.

## FDA Priorities

- Risk Management
- Target resources for enforcement, product approval, and monitoring domestic manufacturing and imports at the areas that present the greatest public health risks.
- Better Consumer Information
- Make sure people have the accurate, science-based information they need to make smarter health decisions.
- Post-marketing Safety
- Greatly enhance our ability to identify and correct risks from medical products that emerge after they are marketed
- Counterterrorism
- Strengthen our capability to identify, prepare for, and respond to terrorist threats
- Effective Regulation/Strong Workforce
- Recruit and retain a world-class professional workforce, build efficiency in operations, and have the resources needed to accomplish our mission.