BIOL G200-Pharmacology lecture [ CH.2: Drug Regulation History & Background]

Why were drug regulations necessary?

(think before regulation (< 1900s), no quality control (QC), no testing.)

1. lack of efficacy; not all drugs did what they claimed to do

2. lack of purity; drugs may have contained other ingredients

3. improper dosage; meds may have had inconsistent concentrations → different batches had different amounts of active ingredients

4. lethality; meds may have contained dangerous ingredients (e.g., poisons, radioactive isotopes, cocaine, etc.)

What is the U.S. Pharmacopeia- National Formulary?

(USP-NF) established in 1975; private organization.

a reference that standardizes drug information; merging of the U.S. Pharmacopeia (covered all drug products of therapeutic value) + the National Formulary (included all other drugs not included in USP)

What does the U.S. Pharmacopeia- National Formulary include?

1. list of drugs, their purity, strength & formulations (how to synthesize them)

2. covers quality standards for drugs, inert/ inactive ingredients, dietary supplements; compliance with USP standards ensures medication’s labeling actually matches what’s in the bottle.

What was the 1902- Biologics Control Act (Virus-Toxin Law)?

standardized quality of serums & blood-related products (e.g.,vaccines, anti-toxins, etc.)

What historical event in 1906 gave the government control and regulation over labelling medicines?

The Pure Food and Drug Act

What act in 1906 required labelling of drug contents?

The Pure Food and Drug Act

What was The Pure Food and Drug Act passed in 1906?

The regulatory act that required labelling of drug contents and gave the government control and regulation over labelling medicines.

What was the Sherley Amendment passed in 1912?

Prohibited the sales of drugs labeled with false therapeutic claims intended to defraud the consumers.

What act did Congress pass in 1938 that prohibited sales of drugs not thoroughly tested before marketing?

Food, Drug & Cosmetic Act

What was the Food, Drug & Cosmetic Act that Congress passed in 1938?

prohibited sales of drugs not thoroughly tested before marketing

What did Congress pass in 1994 that requires clear labeling of dietary supplements and gave FDA the power to remove supplements if considered a significant risk to the public?

Dietary Supplement Health and Education Act (DSHEA)

What was the Dietary Supplement Health and Education Act (DSHEA) passed in 1994?

requires clear labeling of dietary supplements & gave FDA the power to remove supplements if considered a significant risk to the public

FDA (Federal Drug administration)

1. any private, public, or academic pharmaceutical lab MUST seek FDA approval before marketing a drug

2. Black Box Warnings → warnings on packaging of high risk meds to alert the consumers about “special issues” (e.g., adverse drug reactions discovered during or after FDA review process)

What are the different branches of the FDA?

1. Center for Drug Evaluation & Research (CDER)

2. Center for Biological Evaluations & Research (CBER)

3. Center for Food Safety and Applied Nutrition (CFSAN), renamed Humans Food Program (HFP)

What is the Center for Drug Evaluation & Research (CDER) responsible for?

1. Determine whether Rx drugs or OTCs can be used for therapy/treatment

2. Keep unsafe & ineffective drugs off the market

3. provide clear, easily understandable drug info for safe & effective use

What is the Center for Biological Evaluations & Research (CBER) responsible for?

1) Regulates use of biologics (i.e., sera/ serum, vaccines, blood products, gene therapies)

2) 1986 Childhood Vaccine Act→ authorized FDA to collect info abt pt’s taking vaccines, to recall biologics from market, recommend civil penalties for companies that don’t follow FDA guidelines

3) 1996 Health Insurance and Portability and Accountability (HIPAA)→ requires health-related organizations & schools to maintain confidentiality of all health-related info

What is the Humans Food Program (HFP) responsible for?

1. Regulates herbal & dietary supplements

2. Supplements products do not require prior FDA approval (no stringent testing), but package info & inserts are monitored after market release

What is the National Center for Complementary and Integrative Health (NCCIH)?

A part of the NIH (National Institutes of Health) NOT part of FDA that uses rigorous scientific investigation to evaluate efficacy & safety of CAM therapy

What is the drug approval process?

What are the 4 phases of FDA review?

1. Pre-clinical investigation: initial testing for dosage, efficacy, and safety

2. Clinical investigation: clinical trials; testing humans for dosage & adverse side effects ( New drug Application (NDA ) submitted)

What occurs during the Pre-Clinical Investigation phase?

1. testing done on cultured cells (human & bacterial cells)

2. animal testing for adverse effects (note:current trend with FDA, NIH, EPA, & CDC is to move away from animal testing for ethical and practical reasons & to use human-relevant, more accurate, more ethical alternatives)

What are some human-relevant ethical alternatives for testing?

1. Micro physiological systems→ organ on a chip = microfluidic devices that contain micrometer (1/1,000,000m) or nanometer (1/1,000,000,00) channels & use very small amounts of fluid for testing; create a biomimetic system with differentiated cells that physiological tissue in a 3D structure.

2. Biometric material→ reconstructed tissue = 3D tissue (e.g., skin, cornea) in-vitro culture (test tubes/ petri dishes) of multiple layers of cells

3. Organoids → small portions of 3D organs

4. AI computer-based modeling to make predictions about a physiological system

What are some examples of micro physiological systems (organ on a chip)?

liver on a chip, kidney on a chip, brain on a chip, heart on a chip, intestine on a chip, skin on a chip, pancreas on a chip

What are the 3 phases in the Clinical Investigation phase of the FDA review?

1. Phase I —> 20-100 healthy pre-screened individuals or pts with specific pathology/condition/illness (~several months) → safety & dosage

2. Phase II → up to several 100 pre-screened patients with the condition (several months -2 years) → efficacy & side effects/ adverse events

1. Phase III → several 100-1,000 pre-screened patients w condition (1-4 years) —> efficacy & monitoring for adverse events/ side effects

What are the “drugs” in “drug approval”?

Drugs = chemicals, biologics, biosimilar

physical dependency: body adapts to repeated use of substance