Regulation and Development of Drugs Flashcards
Drug Enforcement Administration (DEA)
Enforces laws that regulate controlled substances
Part of Department of Justice
The DEA requires the prescribing physician or PA to register with the Attorney General.
The assigned DEA registry number for that physician or PA must be included on all prescriptions for scheduled drugs.
Schedule I Drugs
High potential for abuse and no approved medical use
Cannot be prescribed (research use only)
Strict penalties for possession and trafficking
Examples: narcotics (heroin), hallucinogens (LSD, PCP), marijuana
Schedule II Drugs
High potential for abuse but has accepted medical use
Examples: morphine, oxycodone, methylphenidate (Ritalin)
Regulations:
No automatic refills
At the federal level, no time limit for filling prescription and no limit on amount dispensed
However, some states have a 10-day limit within which prescription must be filled with maximum 30-day supply
Phone orders can be placed only during an emergency
Physician and pharmacist must keep records of written prescriptions for 2 yrs
Schedule III Drugs
Moderate potential for abuse (may lead to dependence) and approved medical use
Regulations:
Prescription refills may be provided up to 5 times but must be dispensed within 6 months of the initial prescription date.
Example: hydrocodone (Vicodin)
Schedule IV Drugs
Lower potential for abuse and dependence and approved medical use
Regulations:
identical to Sch. III regulation
prescription refills allowed up to 5 times and must be dispensed within 6 months of initial prescription date
Examples: Some depressants, anti-anxiety medications- benzodiazepines such as diazepam (Valium) and Xanax, long-acting barbiturates (phenobarbital)
Schedule V Drugs
Limited potential for abuse or dependence
Approved medical purpose
Dispense and refill as authorized
Examples: central-acting anti-diarrheal (diphenoxylate- Lomotil), anticonvulsant and pain modulator pregabalin (Lyrica)
For sch. III-V drugs: call-in or fax, dispense without written prescription if record kept by pharmacist
Food and Drug Administration (FDA)
The FDA regulates the approval process for new drugs, labeling and packaging of drugs, and manufacturing standards.
The FDA regulates advertising of prescription drugs. (The FTC regulates advertising of “over-the-counter” medications with certain requirements that are set by the FDA.)
Preclinical Evaluation
Preclinical tests are done in non-human models and include a range of molecular assays.
A new drug may be identified by rational drug design based on knowledge of important targets, mechanisms of disease, or modifying a known chemical structure (“lead” compound).
A new drug may be identified by randomly screening a “library” of compunds.
Preclinical studies can take ~10-20 years to complete.
Preclinical Evaluation Details
Preclinical studies must assess safety and efficacy of the drug in animal models.
Pharmacokinetics (what the body does to the drug), metabolism, absorption
Pharmacodynamics (what the drug does to the body), Non-specific toxicity, selectivity
Special carcinogenic, mutagenic, reproductive and teratogenic studies
Prior to Clinical Evaluation
Investigational New Drug (IND) application must include
Preclinical data; chemical synthesis and manufacturing information
Clinical trial design
Informed consent form
Explanation of purposes and procedures
Foreseeable risks
Statement of confidentiality
Compensation, treatment if injury occurs
Statement that participation is voluntary
IRB: certified to approve ethics of trial, ensure safety and protection of patient
Phase 0 Clinical Trial
FDA introduced these trials in 2006
They are also referred to as micro-dosing trials, because they use a single, sub-therapeutic dose
10 to 15 patients
May provide initial data on kinetics or dynamics
(how does the drug work in the body?)
May test biologic or molecular correlates
(does the drug reach the tumor/target tissue?)
May help rank multiple promising compounds
Cannot provide safety or efficacy data, because the dose is too low
Phase I Clinical Trial
20 to 100 volunteers (healthy volunteers in some settings; patients in cancer or HIV trials)
Tests safety, tolerability and dose, pharmacokinetics, pharmacodynamics
May test a single ascending dose, multiple ascending doses, or the effects of giving the drug with or without food
Phase II Clinical Trial
100 to 300 patient volunteers
Safety and efficacy
This is the 1st phase where efficacy starts to be a focus.
Phase I and II may be combined
Phase III Clinical Trial
Randomized, multi-center, controlled
300 to 3000 patient volunteers
Efficacy is compared to the standard treatment
NDA often filed while phase III ongoing
safety and efficacy, labeling (package insert), GMP and quality control
New Drug Application (NDA)
drug is safe and effective for intended purpose
appropriate labeling / package insert
good manufacturing practice (GMP); quality control
NDA established in 1930s after an antibiotic that was dissolved in diethylene glycol caused 105 deaths
Establishment of the NDA set standards for the safety of ingredients in a drug, and gave authority to the FDA to oversee the safety of food, drugs, cosmetics
