U.S. FDA - Structure and Roles

Public Health Service Act (1944)

included the regulation of biological products to the FD&C Act

What is else is under Food and Dietary Supplements in CFSAN

labeling safety of all food products (except meat and poultry) Bottled water

Transfer from CBER to CDER

(need to know this slide??)

Product Classes Defined by the FD&C (7)

Food Dietary Supplement Cosmetic Drug Device Biologic Tobacco

Misbranded

false labeling (imitation, inaccurate quantity)

CVM: 3 functional areas

premarketing post-marketing safety monitoring food safety resarch

Center for Tobacco Products

regulates tobacco products

Biologics License Application (BLA) (this slide was glossed over)

similar to new drug application (NDA), but includes more info on mfg facility

Durham-Pumphrey Amendment (1951)

*Defined prescription drugs* -drugs that require a physician's oversight

Who does premarketing in CVM

*Office of New Animal Drug Evaluation* Investigational New Animal Drug exemption = (INAD) New Animal drug application = NADA

Definition of a drug (need to know slide 17.5?)

*intended for use* to treat, prevent, diagnose, mitigate, or cure disease and affects structure and function 1) disease claims 2) structure and fxn claims

Thalidomide Scandal -What happened and what was the result

-a tranquilizer for morning sickness caused severe birth defects (mostly in Europe) -led to a review of our regulatory frameworks so that it wouldn't happen here -led to Kefauver-Harris Drug Amendment (1962)

Prescription Drug User Fee Act (PDUFA) - 1992 (?????)

-allowed the FDA to collect fees from drug manufacturers to fund the new drug approval process companies pay the FDA to review the product, which the FDA uses to hire reviewers -PDUFA must be reauthorized every 5 years

Hatch-Waxman Act (1984) (???)

-allows ANDA process for generics for off-patent drugs; generics don't have to show safety and efficacy --> just bioequivalency (similar to a 510k) *patent extension and period of market exclusivity* encouraged the mfg of generic drugs and established the modern system of generic drug regulation generic drugs are granted a 180-day period of exclusivity. Generic drugs cannot go on to the market until the branded patent has expired. ANDA = abbreviated new drug application

Elixir of Sulfanilamide Scandal (1937) -what happened, what were the effects

-an antibiotic was reformulated in antifreeze, led to 105 deaths -led to FD&C Act in 1938 (replaced 1906 law)

How do we determine who reviews combination products?

-based on the primary mode of action (i.e. a drug eluting stent's primary mode is mechanical; the drug is secondary --> regulated by CDRH under device provisions) Ask yourself: "Can I use one without the other?"

Harvey Wiley and his "Poison Squad": Why is he called the "Father of FDA"

-he was one of the first consumer advocates -him and his squad would analyze products in their lab -- for example, how high are preservative levels, and what should they be? -an early version of clinical testing (Wiley was also first commissioner of the FDA)

What does the Center for Veterinary Medicine regulate

-livestock feeds -pet foods -veterinary drugs and devices

1938: Federal Food, Drug, and Cosmetic Act -what did it do?

-new drugs must show *safety before marketing* (pre-market review) -drugs to be *labeled with adequate directions* -*Cosmetics and devices* now under FDA control -authorized FDA factory *inspections* -Court *injunctions* in addition to seizures and prosecutions

The Food and Drug Act of 1906 -what did it do

-prohibits interstate commerce of *misbranded* and *adulterated* food, drinks and drugs -it was a deficient law, but it was a good start, as there was at least something in place -no safety of efficacy data needed -unapproved claims: claims must be false AND fraudulent in intent, so they were hard to prove wrong

Kefauver-Harris Drug Amendment (1962)

-required *premarket approval* based on *efficacy* and greater safety -*labeling approval* -Informed consent -Adverse events reporting -preclinical testing (before clinical trials) -GMP -prescription drug ads must include side effects info (main idea = efficacy of drugs)

Cosmetics (part of CFSAN) -how are they regulated/approved?

-the FDA does not have a pre-market approval system for cosmetic products/ingredients (exception = color additives) -safety and labelling

Office of Regulatory Affairs (ORA)

1) oversees inspections of facilities for G(M/C/L)P compliance 2) can investigate issues of fraud and criminal conduct 3) represents 1/3 of FDA's personnel

Sales of products regulated by FDA constitute X amount of the US economy

1/4 of the US economy ($1.5 trillion a year)

In what year was the FDA established?

1931

Insulin Amendment (1941) and Penicillin Amendment (1945)

Amendment to FD&C; they were regulations to make sure processes of making those 2 compounds were safe

What Center is responsible for Food, Dietary Supplements, and Cosmetics

Center for Food Safety and Applied Nutrition *(CFSAN)*

What department is FDA in?

Dept of health and human services

What does the Center for Devices and Radiological Health Regulate

Devices xray machines televisions in vitro diagnostics

Industry Guidance

FDA has guidance documents because they *want* companies to comply -Proactive (rather than reactive) approach

Adulterated

Impure (filthy, poisonous, or substitute with inferior components)

The FDA is a science-based law enforcement agency -- what does this mean?

It looks at scientific *data* to evaluate safety and efficacy - in order to protect public health and safety -helps public get accurate, science-based information to use meds and foods to improve their health

Food Additives (1958) and Color Additives (1960) Amendments

Required the safety of both of those additiives

Upton Sinclair and The Jungle (1906): role in evolution of FDA

The Jungle described the unsanitary conditions in slaughterhouses --> led to the concept of inspection, truth in labeling, etc (food safety laws) increase in public awareness and concern

Definition of a medical device

an *instrument, apparatus, implement, mahcine, implant, etc...* -DOES NOT acheive its primary intended purposes through chemical action; not dependent on being metabolized same intended use to diagnose, treat, or prevent disease

Difference btw biologic and drug (??)

biologic: any virus, serum, toxin/antitoxin, blood, blood component or derivative.... (similarity: intended to treat, prevent, cure, etc)

What branch does the FDA fall under?

executive branch

Center for Drug Evaluation and Research (CDER) - what do they regulate 2 products they govern

drug approvals OTC and rx drug labeling drug mfg standard Drugs (RX, generics, and OTC) Some biologics (well-characterized proteins and antibodies)

Center for Biologics Evaluation and Research (CBER)

vaccines gene therapy with vectors blood clotting factors engineered tissues blood products