Drug Approval Process Flashcards
T or F. movement of drugs from prescription to over-the-counter status leads to reduced costs
T, but the cost burden often shifts from the HMO to the consumer.
How does prescription use in the South compare to the rest of the nation?
the mid-south (TN-AR- MS) experiences a higher prescription drug use than does the population in general.
As a general rule, the more drugs a patient is taking concurrently, the greater the risk for adverse drug-drug interactions.
The Food and Drug Administration (FDA) falls under the aegis of the ____.
Department of Health and Human Services (DHHS)
Drugs are the responsibility of the ______.
Center for Drug Evaluation and Research (CDER)
What did the Pure Food and Drug Act of 1906 do?
prohibited mislabeling and adulteration of drugs
What did the Opium Exclusion Act of 1909 do?
prohibited importation of opium
What did the Amendment to the Pure Food and Drug Act in 1912 do?
prohibited false or fraudulent advertising claims
What did the Harrison Narcotic Act of 1914 do?
Established regulations for use of opium, opiates, and cocaine (marijuana added in 1937)
What did the Food, Drug, and Cometic act of 1938 do?
required that new drugs be safe as well as pure (no proof of efficacy). Enforcement by FDA
What did the Durham-Humphrey Act of 1952 do?
Vested in the FDA the power to determine which products could be sold without prescription
What did the Kefauver-Harris Amendments of 1962 to the Food, Drug, and Cosmetic Act do?
Required proof of efficacy as well as safety for new drugs and for drugs released since 1938; established guidelines for reporting of information about adverse reactions, clinical testing, and advertising of new drugs
What did the Comprehensive Drug Abuse Prevention and Control Act of 1970 do?
Outlined strict controls for habit-forming drugs; established drug schedules and programs to prevent and treat drug addiction
What did the Orphan Drug Amendments do?
Provided incentives for development of drugs that treat rare diseases (less than 200,000 in USA)
What did the Drug Price Competition and Patent Restoration Act of 1984 do?
Abbreviated NDAs for generic drugs (bioequivalence data). Patent life extended to account for FDA review process (max less than 5 extra years of 14 years post-NDA approval)
What did the Prescription Drug User Free Act of 1992 (and 2007) do?
Manufacturers pay use fees for certain NDAs
What did the Dietary Supplement Health and Education Act of 1994 do?
Established standards for dietary supplements prohibited full FDA review as drugs. Required specific ingredient and nutrient information labeling that defines dietary supplements and classifies them as part of the food supply but allows unregulated advertising
What did the Bioterrorism Act of 2002 do?
Enhanced controls on dangerous biologic agents and toxins. Seeks to protect safety of food, water, and drug supply
What did the FDA Amendments Act of 2007 do?
Grants FDA greater authority over drug marketing, labeling, and direct-to-consumer advertising; requires post-approval studies; established active surveillance systems, makes clinical trial operations and results more visible to the public
governs Phase IV studies and labeling issues and reporting adverse events
T or F. Drugs developed as antidotes to potential terrorism select agents are the one group of drugs that receive approval based solely upon animal tests.
T. Clearly it would be unethical to conduct trials of these lethal toxins in humans.
What is a risk/benefit profile?
whether or not the potential benefits of a potential drug choice outweigh the risks in that patient.
Are dosing recommendations typically personalized today?
Most drug dosing is still based upon the “one size fits all” concept. So dose recommendations try to balance risks/benefits across the patient spectrum. This is increasingly recognized as the wrong approach and a more individualized dosing profile will ultimately be adopted for many drug classes.
The first step in drug development is formulation of a correct, therapeutic compound. How does this work?
Developers begin with a standard compound and alter molecule characteristics including pks, metabolism, solubility, route of administration, etc.- to look at effects on activity. This is driven by modeling studies now and is becoming efficient
Preliminary techniques keep things simple and cheap, involving ___ systems.
in vitro.
Animal systems are no longer the first choice for ethical reasons and because they involve the use of larger quantities of the test agent. Synthesis is expensive; you don’t want the time and cost of producing large quantities of a “candidate” only to immediately find it is useless in your assay systems.
How did pharm products used to be made? How is that different today?
Once upon time, you began with compounds that produced an effect, then tried (sometime in an incomplete manner) to establish how they worked.
These days, with molecular modeling and molecular biology, one can synthesize “candidates” to specifically interact with a known receptor motif.
What are “first in class” drugs?
First the treat a specific thing.
Most often the result of phenotypic analysis, i.e. treating a recognized clinical condition.
However, once the new ‘target” is recognized and the drug comes to market, competitors hone in on the already defined receptor to develop their “me too” drugs.
What are some issues that still need to be figured out even once a drug candidate has been successful in in vitro testing?
Just because a “candidate” works in a cell assay or indeed in a cell- free system, it doesn’t mean that, from a physico-chemical perspective, the compound could be administered to patients. There are many considerations, such as solubility, metabolism, and potential drug-drug interactions
What is “high throughput screening” (HTS)?
many in vivo issues of a drug (solubility, drug-drug interactions, etc.) are highly automated and are therefore easily reproducible
Why must assays determine in vivo characteristics of a drug candidate such as solubility, etc. still be cheap and easy?
most of these “candidates” will fall by the wayside before the process is over!
What are Herg channels?
potassium channels in polarized membranes (potassium is an important regulator of membrane polarity-especially in the heart)
What happens if Herg channels are upset by a drug?
the membrane can become hyper-responsive, leading to cardiac arrhythmias (QT prolongation)
The most famous example in recent history was the antihistamine drug called terfenadine.
Is Herg channel interaction testing common?
In order to spare the financial burden, peer embarrassment and shareholder anger, drug copmanies now test for potential Herg channel interactions before the drug ever moves into clinical trials.
This is often done on a contract basis by specialist companies.
