Drug regulation Flashcards
Drug regulation: Federal Government:
Controls what drugs may be prescribed or sold directly to the public through the Food and Drug Administration (FDA) of the Department of Health and Human Services.
FDA regulates:
- Evaluation process for determining safety and efficacy of new drugs prior to their public availability [1938 and 1962] and the removal of dietary supplements deemed unsafe, but only after their availability to public [1994]. [see below]
- Equivalency of brand name versus generic drugs [1984] [see below].
- Placement of drugs into prescription vs non-prescription categories [1951] and the determination of which prescription drugs are further restricted by the designation as Controlled Substances [1970]
Drug regulation: State Government:
Controls who may prescribe drugs through the licensing process of medical or dental boards. Exception is the prescribing of Controlled Substances which requires registration with the Drug Enforcement Administration (DEA) of the Department of Justice
Drug reguation: Local Governments
may also pass laws that concern drug use in their jurisdictions. Example: medical marijuana in Colorado
Phases of New Drug Development and the Approval Process in the United States
- Animal studies
- Clinical trials in humans (Phase I-III)
- Post-marketing surveillance (Phase IV)
Animal studies (number and types of subjects, approximate time involved, and limitations in pronouncing a new drug as “safe”):
- Pre-Clinical Testing [5-8 years]
- Detailed preclinical studies in rodent and non-rodent species; extensive studies of pharmacology, drug metabolism, and toxicity
- Attempts to determine safe dosage range for humans.
- Successful review of data leads to submission of Investigational New Drug (IND) application to the FDA. An NDA is filed for a specific indication (use)
Phase I studies (number and types of subjects, approximate time involved, and limitations in pronouncing a new drug as “safe”):
Clinical pharmacology (1 yr) [Is it safe, pharmacokinetics?]
- Very select normal volunteers (usually < 100, healthy males, 18-45 y/o)
- Toxicity (dose level of first appearance) and metabolism studies
- Determine if animal / human response differ significantly
Phase II studies (number and types of subjects, approximate time involved, and limitations in pronouncing a new drug as “safe”):
Clinical investigation (2 yrs) [Does it work in patients?]
- Select patient pool (200-300), preferably no other medical problems
- Comparison to placebo or existing treatment
- Safety and efficacy evaluated, final dosing and regimen adjustments, may detect broader range of toxicities
- Usually at university or government medical center under supervision of Institutional Review Board and with informed consent of patients
Phase III studies (number and types of subjects, approximate time involved, and limitations in pronouncing a new drug as “safe”):
- Full scale clinical trial (3 yrs) [Does it work, double blind?]
- 1000-6000 patients, in settings similar to those anticipated for ultimate use of drugs
- Efficacy measured against established therapy. Monitor adverse reactions from chronic use
- Sometimes omitted for drugs used in serious, life-threatening illnesses (AIDS, cancer). Drugs with the greatest potential benefit may obtain an accelerated or conditional approval that then requires more definitive clinical trials to be conducted after the initial approval.
- Positive results after unmasking of code may result in approval of New Drug Application (NDA)
Phase IV studies (number and types of subjects, approximate time involved, and limitations in pronouncing a new drug as “safe”):
- Manufacturers required to submit reports to the FDA of any adverse effects of their drugs on market
- Studies often continue after approval. Collect data on mortality / morbidity - monitor safety under actual conditions of use
- Study groups omitted during phases I and II due to increased risks (pregnancy, elderly, children); also patients with multiple disease
- FDA reserves the authority to revoke approval or restrict drug use (e.g., require certain lab tests to be performed) if unpredictable adverse effects become apparent when drug is made available to large, uncontrolled populations
Abbreviated New Drug Application (ANDA)
can be submitted for generic drugs allowing the manufacturer to bypass the expensive and time-consuming clinical trials for an already approved drug entity. Only bioequivalence standards must be met (FDA Orange Book).
Compare and contrast the differences between FDA regulation of drugs and dietary supplements
Drug: evidence required via clinical trials; must be studied, found acceptable and detailed in package insert; established via phase 1-3 clinical trials
Dietary supp: no proof required of efficacy; safety - burden of proof with FDA to show unsafe; guidelines based on tradition, occasionally with studies
Pharmaceutical Equivalents:
Drug products containing the same active ingredient (s) in the same dosage formulation (capsule, tablet, solution, etc.) that have the same route of administration, and are identical in strength or concentration
Bioequivalents
pharmaceutical equivalent formulations that display comparable bioavailability when studied under similar experimental conditions. Bioavailability refers to the rate and extent to which the active ingredient is absorbed from a drug formulation and becomes available at the site of action (i.e., drug molecule entering bloodstream)
Therapeutic Equivalents
Pharmaceutical equivalents that, when administered to the same individual in the same dosage regimen, provide the same efficacy and safety. Requires expensive, time-consuming human trials, so therapeutic equivalence of generic drugs is not usually determined and is NOT required by the FDA. It is assumed that, in the absence of any scientific evidence to the contrary, bioequivalent drugs will be therapeutically equivalent
