Drug Development and Regulation Flashcards
Preclinical Drug Development
1) Pharmacological Profile (Potential Efficacy):
a. *Molecular and Cellular Systems:
- -e.g. Receptor binding, Enzyme Inhibition
b. *Isolated Tissue or Organ:
- -Direct Effects on intact Tissue
c. *Whole Animal Studies:
–Effects on Systems
(Systemic Effects)
–Models of Disease.
2) Safety:
a. Acute Toxicity (Single Dose):
- -Lethal Dose Determination
b. *Chronic Toxicity (1-2 yr):
(Daily Dose)
–Determine Effects on Clinical Chemistry
–Target Organ Toxicity
c. *Reproductive Performance:
- -Effects on Fertility
- -Prenatal and Postnatal Effects
- -Teratology
d. *Carcinogenic Activity and Mutagenic Activity
Clinical Testing:
Phase 1
How Many:
–20-100 subjects
Who:
- -Normal, Healthy Volunteers
- -Patients with Serious Illness (AIDS, Cancer)
Why:
- -Effects
- -Phamacokinetics
Clinical Testing:
Phase 2
How Many:
–100-200 patients
Who:
–Small pop of Selected Patients
Why:
- -Efficacy
- -Dose-response
Clinical Testing:
Phase 3
How Many:
–1000-6000 patients
Who:
–*Large Sample of Selected Patients (in multiple clinical sites)
Why:
- -Safety
- -Efficacy
Clinical Testing:
Phase 4
Performed *After NDA (New Drug Application) approved
Who:
–All Patients Treated with Drug
= *Post-Marketing Surveillance
Why:
- -Evaluate Adverse Reactions
- -New Indications
Pure Food and Drug Act (1906)
Proper Labeling of what is actually inside.
In response to food contamination.
Food, Drug, and Cosmetic Act (1938)
Required SAFETY.
The major regulation affecting what drugs are available in the USA
and how they may be dispensed, and requiring that SAFETY be established
Durham-Humphrey Amendment (1952)
Designated some drugs as “legend” drugs, to be dispensed only through Prescription Order by a Licensed Practitioner.
Kefauver-Harris Amendments (1962)
Required Proof of EFFICACY to be established prior to marketing.
Orphan Drug Amendments
Enabled government to assist companies in development and marketing of drugs used in treating rare (Less Than 200,000 patients nationwide) disorders.
Dietary Supplement Health and Education Act (DSHEA)
Provided Guidelines for Marketing and Labeling (but Not testing or quality assurance) of Dietary Supplements, such as herbal preparations.
**Label Cannot make Specific Therapeutic or Health Claims
**Can Describe Role in Affecting “Structure or Function in Humans”
**Labels must state that product has *Not been Evaluated by FDA
**Labels must state that is Not Intended “to Diagnose, Treat, Cure, or Prevent Any Disease.”
Problems in Evaluation and Use of Herbal Products:
1) Lack of Well-designed, Well-controlled, Blinded studies of safety and effectiveness.
- -*Natural does not mean Safe.
- -Lack of Long-term Studies in children, elderly, chronic disease
- -Lack of Reproductive studies in pregnant and nursing women
2) Identification of Active Constituents
3) Quality Control
Controlled Substances Act (1970)
Established Schedules of controlled substances, *According to Abuse Potential Relative to Medical Use.
Schedule I
High Abuse Potential
No Accepted Medical Use in U.S.
- Heroin
- Hallucinogens
Schedule II
High Abuse Potential
Acceptable Medical Use
- Narcotics (or *Opiates)
e. g. *Morphine; - Amphetamines
- Cocaine
**May NOT be Refilled.
Requires Written prescription signed, for each fill.
Schedule III
Less Abuse Potential
Medical Use
- Codeine in *Analgesic Combinations
- Anabolic Steroids
- THC
- *Refill Requirements:
- -Signed Prescription
- -New prescription after 5 refills or 6 months (whichever comes first)
