Part 2 Flashcards
What is the difference between USP/NF and PPI
USP is telling about individual compounds used to PRODUCE product. it is not the product itself. (ie: the compound amoxicillin)
PPI is information about the FINAL PRODUCT (the trade name. ie: amoxil)
A generic API would be shown on a….
USP/NF
What does NDA and IND stand for? Which is submitted first?
NDA= new drug application
IND= Investigational New Drug
IND is submitted first
When is an IND application submitted?
- new chemical entity discovered (API)
- Preclinical studies
THEN THE IND APPLICATION IS SUBMITTED AND REVIEWED BY THE FDA
Name 5 sources of a new chemical entity
-organic synthesis
-molecular modification
-isolation from plants
-extraction from animal tissue
-genetic engineering
Define further what “preclinical studies” means.
What happens after the preclinical studies are conducted?
preclinical studies is finding out the chemistry, physical and biological properties of the drug. ex: the pharmacology, the ADME, and the toxicology.
Preformulation
AFTER THE PRECLINICAL STUDIES ARE CONDUCTED, AN IND IS SUBMITTED AND REVIEWED BY THE FDA
PRECLINICAL STUDIES CONTINUE WHILE THE IND IS BEING REVIEWED:
-long term animal toxicity
-product formulation
-manufacturing and controls
-package and label design
When do clinical trials start being conducted?
phases 1-3 are conducted after the 30 day wait period after the IND is submitted
When is an NDA submitted?
After an IND has been approved by the FDA and phases 1-3 of clinical trials have been completed. All preclinical studies are complete
If the FDA approves an NDA, what is happening after the drug hits the market? (postmarketing)
-PHASE 4 CLINICAL STUDIES
(ie: clinical pharmacology/toxicology)
-adverse reaction reporting
-product defect reporting
-product line extension
WHERE are preclinical studies taking place?
in the setting of the company who discovered the new chemical entity (API)
When are issues like solubility of the API handled?
during preclinical studies
how long does the FDA take to review an IND? What happens if the FDA rejects an IND?
30 days
if the FDA rejects it, the company has to stop phases 1-3 of the clinical trials
How long does the FDA take to review and approve an NDA?
around 11/2 years
approximately how long does a drug take to be discovered and then finally hit the market
preclinical — 61/2 years
clinical —– 7 years
NDA review —- 11/2 years
approximately 15 years
What does the term “goal drug” mean
goal drug refers to a drug that has a good ADME (absorption, distribution, metabolism, excretion), no side effects, and good solubility without any modifications.
The “goal drug” is not yet discovered
In today’s age, are more drugs discovered or modified?
modified and designed. all the drugs that were “easy” to discover have already been discovered over the years
Name some methods of drug discovery
-random screening (luck)
-non-random screening
-biologic assays (not worried abt ADME–just if goal is accomplished)
-molecular modification
-mechanism-based drug design
What is a lead compound
a chemical compound that has pharmacological/biological activity but has suboptimal structure that requires it to be modified to fit better to the target
What are prodrugs?
prodrugs are inactive substances that do NOT HAVE THERAPEUTIC EFFECT. they are not drugs.
Prodrugs become biotransformed in the body to become a drug and gets activated
Are prodrugs drugs?
NO- they become drugs once they enter the body
What is the FDA’s definition of a new drug
-new formulation
-new manufacturing method
-new combination of drugs
-new indication for use. etc
Name 3 names of a drug
-generic name
-trade name
-empirical formula; synthetic chemical name; code number
The “name brand” of a medication could also be called the…
trade name
The generic name of a drug could also be referred to as the….
nonproprietary name
Who determines the generic/nonproprietary name of a drug?
USAN Council (United States adopted names council)
Name 3 branches of biological characterization of drugs
-Pharmacology
-Drug Metabolism
-Toxicology
Explain the biological characterization, “Pharmacology” further
pharmacokinetics and pharmacodynamics
pharmacokinetics = ADME
pharmacodynamics = mechanism of action, biochemical and physiological effects (therapeutic effect)
Clinical pharmacology
Give a subcategory of drug metabolism
First pass effect — Drug gets reduced in concentration (degraded by liver enzymes) before it can reach the site of action or systemic circulation
What are the 2 main concerns of toxicology
Carcinogenicity studies and reproduction studies
What are some lesser studies of toxicology (not carcinogenic or reproductive)
acute/short term toxicity studies
subacute/subchronic studies
genotoxicity/ mutagenicity studies
Explain the difference between acute, subacute and subchronic toxicology studies
acute — investigating the adverse events of a substance that result either from a single exposure or multiple exposures in a short period of time
subacute — investigating the effects of a drug following a treatment period of 2-4 weeks
subchronic – investigating the effects of a drug when taken from 90 days-12 months
Name 5 things that are determined in preformulation studies
-Drug solubility
-Partition coefficient
-Dissolution rate
-Physical form
-Stability
What will happen if a drug is not soluble in water
it most likely won’t have therapeutic effect
resolution = cosolvent
The partition coefficient is related to….
how much of the drug will cross the lipid membrane.
we want a 1:1 ratio
Which has a higher energy — crystalline form or amorphous form
AMORPHOUS — this higher energy means it has a better solubility
If a drug changes physical form, is this considered a new drug to the FDA?
YES (ie: crystalline to amorphous)
Amoxil contains…
the compound amoxicillin and inactive ingredients
Name things that can be found on a USP/NF monograph
Chemical name
Chemical structure
Cas #
Molecular weight (hydrous/anhydrous)
assay method
drug standard
packaging
storage
Does a USP/NF monograph contain information about the therapeutic effect of the compound?
NO!
This info is on “amoxil” handout. “physician’s desk reference”
USP/NF is not concerned with therapeutic effect, just with the compound itself (the pure API)
NOT the drug
Will a USP/NF contain pharmacology/microbiology information?
NO
What information can you find on PDR/PPI
-info related to the final PRODUCT
-brand name
-API
-description
-structure
-action (pharmacology)
-NDC #’s (NOT CAS NUMBER)
ALL INFO RELATED TO CLINICAL PRACTICE
Does the PDR contain the structure of the API
yes! both PDR and USP/NF contain the structure
Can the chemical name be found on a PDR
no – only the structure
Where can the inactive ingredients be found
PDR
Who reviews the IND of a DRUG
a division of the FDA called CDER
(center for drug evaluation and research)
Who reviews the IND of a new VACCINE
CBER
(center for biologics evaluation and research)
If an approved drug is converted to its salt or ester form, is it considered a new drug by the FDA?
YES
Explain thoroghly phase 1 of a clinical trial.
Include:
-# of patients
-length
-purpose
-% of drugs that successfully pass
phase 1…
# patients = 20-100
length: up to 1 year
purpose: mainly safety
% of drugs successfully passed = 70%
Explain thoroughly phase 2 of a clinical trial
include:
-# of patients
-length
-purpose
-% of drugs that pass
phase 2….
patients = 100-500
length = several months-2 years
purpose: some short term safety, but mainly effectiveness
% of drugs successfully passed = 33%
Explain thoroughly phase 3 of a clinical trial
include..
-# of patients
-length
-purpose
- % of drugs successfully tested
phase 3…
patients = 1,000-5,000
length = 1-4 years
purpose = safety, effectiveness, dosage
% of drugs that pass = 25-30%
In which phase of clinical trials do we start to think about information that must be put in the package insert? (ie: pharmacology, dose, etc)
phase 2 – package insert is finalized in phase 3
Which phase of clinical trials is the easiest to pass
phase 1
When will the drug’s sponsor file an IND
only after….
-the preclinical studies demonstrate adequate safety
-the new agent shows promise as a useful drug
In phase 1, the 20-100 subjects are usually…
healthy patients. but in some cases they may have the disease
In which phase do we start using patients as subjects and not healthy individuals
phase 2
When do we like to use crossovers in clinical trials
when our test subjects are different (ie: different ages) to avoid getting false results
Explain the difference between a single crossover with/without an intervening baseline
single crossover without baseline —- 2 different groups exist. (ie: 1 group is in theyr 20s one is in their 50s) to avoid results being false due to natural comorbidities, the 2 groups are given consecutive alternative treatments.
for example.. for 1 month group A will receive the current standard of care and at the same time treatment B will get the new drug being tested. After 30 days, the groups will immediately swap treatments if there is no baseline
for a single crossover WITH a baseline, it is the same concept except there is a “baseline” (waiting) period for the previous drug to completely leave the body before switching treatments to avoid errors
what is an extra period crossover
in an extra period crossover, group A is given the current treatment and group B is given the tested treatment. After a certain period of time, they swap treatments immediately. (no baseline)
This second treatment is repeated for another se period (whatever it may be.. 30 days etc) to confirm results
Name the 4 components of the dose regimen
-form
-route of administration
-dose
-time and conditions of administration
Name some factors affecting the dose of a drug
-age
-pharmacogenetics
-body weight
-BSA (body surface area)
-sex
-pathologic state (ie: renal impairment)
-tolerance
-concomitant drug therapy (2 drugs given @ same time)
-time and conditions of administration
-dosage form and route of administration
