Overview of the FDA

Geoff Habiger, G Habiger Consulting, LLC

Topics

• Why do we have the FDA?– History of the agency.

• Role of the FDA– What’s Regulated– What’s Not Regulated

• cGMP Enforcement Tools• Other Organizations• Questions

• FDA has three basic responsibilities:– Protect the public health– Advancing the public health– Ensuring security of food supply and fostering development of

needed medical products to address public health threats.

• FDA protects the public health by assuring the safety, efficacy and security of human and veterinary drugs, biological products, medical devices, our nation’s food supply, cosmetics, tobacco, and products that emit radiation.

• FDA is over 100 years old!• How did we get here?

Why do we have the FDA?

1820 – United States Pharmacopeia (USP) Establishedcreate a system of standards and a national formulary

1848 – Congress passes Federal Drug Import Actrequires U.S. Customs Service inspection to stop entry of adulterated drugs from overseas. Federal legislation recognizes USP as the official compendium

1862 – Bureau of Chemistry EstablishedPresident Lincoln appoints a chemist, Charles M. Wetherill, to serve in the new Department of Agriculture. The Bureau of Chemistry is the forerunner of the FDA.

1902 – Harvey Wiley and the “Poison Squad”Wiley was head of the Bureau of Chemisrty. He studies common preservatives in food (borax, boric acid, copper sulfate, potassium nitrate, saccharin, sulfuric acid, benzoic acid and formaldehyde) and their affects in people.

History of the FDA

1905 – Collier’s Weekly publishes “The Great American Fraud”Articles by Samuel Adams on the evils of patent medicine, quackery, and fraud in drugs. The articles showed how many of these medicines actually harmed the people taking them.

1906 – Upton Sinclair publishes The JungleSinclair intended the book to show the deplorable conditions of immigrants in the US. However, most readers were more shocked by the unsanitary conditions he described in the meat-packing plants of the day.

1906 – FDA is created: Congress passes Pure Food and Drug Act which is enforced by Bureau of Chemistry through established USP requirementsFoundational law of the FDAs mission. Prohibits interstate commerce in misbranded and adulterated foods, drinks and drugs. Many of the provisions of the law were overturned and loopholes were created – 1911 Supreme Court ruled that provisions only applied to ingredients. Allowed companies to continue to make false claims about a product’s effectiveness.

History of the FDA

• Extending control to cosmetics and therapeutic devices.• Requiring new drugs to be shown safe before marketing.• Providing that safe tolerances be set for unavoidable poisonous substances.• Authorizing standards of identity, quality, and fill-of-container for foods.• Authorizing factory inspections.• Adding the remedy of court injunctions to the previous penalties of seizures and prosecutions.

1937 - Elixir of Sulfanilamide• containing the solvent diethylene glycol (poisonous solvent).• kills 107 people, many of whom are children.• dramatizes the need to establish drug safety before marketing and to enact the pending food and drug law.

1938 - The Federal Food, Drug and Cosmetic (FD&C) Act is passed and signed into law by President Franklin D. Roosevelt.

The Act contains new provisions:

History of the FDA

1950s/1960s – Thalidomide, a new sleeping pill, is found to have caused birth defects in thousands of babies born in western Europe. • News reports on the role of Dr. Frances Kelsey, FDA medical officer; she fought to keep the drug off the U.S. market. Gave rise to public support for stronger drug regulation.Kefauver-Harris Drug Amendments passed • ensures drug efficacy and greater drug safety. For the first time, drug manufacturers are required to prove to FDA the effectiveness of their products before marketing them.

1940s/1950s – Various court rulings and amendments to the 1938 FD&C Act clarified and enhanced enforcement authority of the FDA.• 1943 - In U.S. v. Dotterweich, the Supreme Court rules that the responsible officials of a corporation, as well as the corporation itself, may be prosecuted for violations. It need not be proven that the officials intended, or even knew of, the violations (culpable deniability).• 1953 - Factory Inspection Amendment clarifies previous law and requires FDA to give manufacturers written reports of conditions observed during inspections and analyses of factory samples.

History of the FDA

1941 – Sulfathiazole disaster• Tablets of sulfathiazole were contaminated with phenobarbital• Let to nearly 300 deaths nationwide• Prompted FDA to require detailed controls at manufacturer and throughout the industry. Birth of the modern GMPs

1982 - Tamper-resistant Packing Regulations• issued by FDA to prevent poisonings such as deaths from cyanide placed in Tylenol capsules. • The Federal Anti-Tampering Act passed in 1983 makes it a crime to tamper with packaged consumer products.

1976 - Medical Device Amendments • passed after the therapeutic disaster in which thousands of women were injured by the Dalkon Shield intrauterine device (IUD)• to ensure safety and effectiveness of medical devices, including diagnostic products following a U.S. Senate finding that faulty medical devices had caused 10,000 injuries, including 731 deaths.• The amendments require manufacturers to register with FDA and follow quality control procedures. Some products must have pre-market approval by FDA; others must meet performance standards before marketing.

1978 – GMPs finalized The regulations for drugs (21 CFR 210 and 211) and devices (21 CFR 820) became effective to ensure the safety and efficacy of products.

History of the FDA

1992 – Congress passes Generic Drug Enforcement Act• Imposes debarment and other penalties for illegal acts involving abbreviated drug applications • Resulted from bribery/fraud case in which executives at generic drug companies bribed FDA agents.• Companies tested name brand versions of drugs and submitted those results with their application.

2000s/2010s – Several new laws for regulation of Food/Drugs• 2002 – Best Pharmaceuticals for Children Act• 2003 – Pediatric Research Equity Act• 2004 – Food Allergy Labeling and Consumer Protection Act• 2009 – Family Smoking Prevention and Tobacco Control Act – gives FDA authority to regulate tobacco products• 2011 – Food Safety and Modernization Act• 2013 – Drug Quality and Security Act – followed outbreak of fungal meningitis from compounded pharmacy. Creates steps for an electronic and interoperable system to identify and trace certain prescription drugs throughout the U.S.

1997 – FDA creates Electronic Records Rule•Requires controls for security and integrity of electronic records (21 CFR 11)

History of the FDA

Role of the FDA

From earlier: •FDA has three basic responsibilities:

– Protect the public health– Advancing the public health– Ensuring security of food supply and fostering development of

needed medical products to address public health threats.

•The FDA accomplishes this mission by using the laws and regulations to verify that manufacturers are following cGMP.

The FDA has jurisdiction over many items that are regulated by law.

• Biologics (CBER – Center for Biological Evaluation and Research)– Biological products

• Blood/Blood Products• Cellular & Gene Therapy• Tissue/Tissue Products• Vaccines• Transplantation of non-human cells, organ transplants

• Drugs (CDER – Center for Drug Evaluation and Research)– OTC/Prescription drugs– Biological therapeutics & generic drugs– Not just medicine

• Fluoride toothpaste, antiperspirants, dandruff shampoo, sunscreen. All are considered “drugs” by FDA. (Look for Active Ingredients on label. If it lists one, it is regulated.

Role of the FDA

• Medical Devices (CDRH Center for Devices and Radiological Health)– Premarket approval of medical devices

• Class 1: ‘everyday’ items, like toothbrushes, tongue depressors, etc. • Class 2: require premarket notification (not approval) – device must be “substantially

equivalent” to an existing device.• Class 3: require premarket approval (PMA) – analogous to drug approval process.

Products that could cause serious injury/death if they don’t function properly (i.e., pacemakers, etc. )

– Manufacturing and performance standards for devices– Tracking reports of device malfunctioning and serious adverse reactions– Oversee radiation safety on non-medical devices that emit electromagnetic

radiation – cell phones, microwave ovens, laser pointers, sunlamps, etc. • Veterinary Products (CVM – Center for Veterinary Medicine)

– Drugs for animal use – companion animals and food animals.• For food animals, center makes sure food from treated animals is safe

– Animal foods – including food additives– Veterinary devices – but premarket approval is not required

Role of the FDA

• Foods (CFSAN – Center for Food Safety and Applied Nutrition)– Dietary supplements– Bottled water– Food additives– Infant formula– Food Products

• Cosmetics– Color additives in makeup/personal care products– Skin moisturizers/cleansers– Nail polish and perfume– Lipstick

• Tobacco Products (CTP – Center for Tobacco Products)– Cigarettes/cigars– Tobacco– Smokeless tobacco

Role of the FDA

Non-Regulated Items• Advertising: the Federal Trade Commission (FTC)• Alcohol: the Department of Treasury’s Alcohol and Tobacco Tax and Trade Bureau –

production, importation distribution, labeling, advertising• Consumer Products: the Consumer Product Safety Commission (CPSC)• Drugs of Abuse: Drug Enforcement Administration (DEA)• Health Insurance• Meat and Poultry: the U.S. Department of Agriculture (USDA) (FDA regulates game meats,

such as venison, ostrich and snake.) • Pesticides: shared between FDA, USDA, and EPA• Animal Vaccines: these are regulated by the USDA• Soap: As specifically defined by the FDA (if bulk is made from alkali salt of fatty acids and

labeled, sold, and represented solely as soap).• Restaurants and Grocery Stores• Water: shared between FDA and EPA. EPA has the responsibility for developing national

standards for drinking water from municipal water supplies. FDA regulates the labeling and safety of bottled water.

Role of the FDA

FDA Regulations• The Food, Drug, and Cosmetic Act• Code of Federal Regulations (CFR):

– 21 CFR 110: CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD

– 21 CFR 111: CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS

– 21 CFR 210: CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PROCESSING, PACKING, OR HOLDING OF DRUGS; GENERAL

– 21 CFR 211: CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS– 21 CFR 212: CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION

TOMOGRAPHY DRUGS – 21 CFR 225: CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS– 21 CFR 226: CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES – 21 CFR 606: CURRENT GOOD MANUFACTURING PRACTICE FOR BLOOD AND BLOOD

COMPONENTS – 21 CFR 820: QUALITY SYSTEM REGULATION (Subchapter H: Medical Devices)

• FDA & ICH Guidelines• Inspectional Manuals

cGMP Enforcement Tools

• FDA 483’s– Issued by FDA Inspector after an on-site inspection– 483 is the Form Number

• Establishment Inspection Report (EIR)– Inspection Conclusion: No Action Indicated (NAI), Correction Indicated (CI), Referred to

Center (RTC)– Decision Type: No Action Indicated (NAI), Voluntary Action Indicated (VAI), Official

Action Indicated (OAI), Referred to State (RTS), Referred to Center (RTC)

• Warning Letters– Issued by FDA for repeat 483’s – Issued by FDA for egregious violations

• Consent Decree– Judicial Action taken by the courts– Results in fines ($$) and may result in jail time

cGMP Enforcement Tools

cGMP Enforcement Tools

• International Conference on Harmonisation (ICH)– Organization works with industry and regulatory agencies– www.ICH.org

• Parenteral Drug Association (PDA)– Pharmaceutical trade organization – provides science, technology, regulatory info to industry– www.pda.org

• European Medicines Agency (EMA)– European regulatory agency– www.ema.europa.eu

• Pharmaceuticals and Medical Device Agency (PMDA)– Japanese regulatory agency– www.pmda.go.jp

• World Health Organization (WHO)– The United Nations health agency– www.who.int

Other Organizations

Questions?