Chapter 2: New Drug Development and Approval Process Flashcards
requires a new drug to be approved by the Food and Drug Administration before it may be legally introduced in the interstate commerce
the federal Food, Drug, and Cosmetic Act
initiated to define physical and chemical properties of the agent
preformulation studies
follow to develop the initial features of the proposed pharmaceutical product or dosage form
formulation studies
the federal Food, Drug, and Cosmetic Act is regulated by
Title 21 of the US Code of Federal Regulations
factors that triggered drug development
cumulative body of scientific and biomedical information generated worldwide,
combined efforts of those participating in drug discovery and development
pharmaceutical industry in the US grew rapidly during
World War II
discovered by Alexander Fleming in England
penicillin
penicillin became commercially available
1944
date of discovery of penicillin
1929
date of end of World War 2
1945
ways of producing new drugs
variety of natural sources,
synthesis in the laboratory,
creation through biotechnology
served as reservoir of potential new drugs
plant materials
major contributions to modern drug therapy may be attributed to
conversion of botanic folklore remedies into modern wonder drugs
a tranquilizer and hypotensive agent
reserpine
reserpine is isolated from
Rauwolfia serpentina
also known as periwinkle
Vinca rosea
original indication of vinca rosea
treatment of diabetis mellitus
after screening of pharmacological activities, V. rosea exhibited ____ capabilities
anti-tumor
materials of V. rosea for treating tumors
vinblastine,
vincristine
used in the treatment of ovarian cancer
paclitaxel (Taxol)
paclitaxel is isolated from
Pacific Yew Tree
also known as mexican yams
Dioscorea
rich in the chemical steroid structure from which cortisone and estrogen are derived
Dioscorea
hormonal substances such as thyroid extract, insulin, and pituitary hormone are derived from
endocrine glands of cattle, sheep, and swine
rich source of estrogen
urine of pregnant mares
pioneered work for smallpox vaccine in 1796
Edward Jenner
prepared in cultures of renal monkey tissue
poliomyelitis vaccine
prepared from fluids of chick embryo
mumps and influenza vaccine
prepared from duck embryo
rubella (German measles) vaccine
prepared from skin of bovine calves inoculated with vaccinia virus
smallpox vaccine
two basic technologies that drive the genetic field of drug development
recombinant DNA,
monoclonal antibody production
common characteristics of rDNA and mAb production
ability to manipulate and produce proteins,
ability to influence the cell’s ability to produce proteins
characteristics of rDNA technology
more fundamental of two techniques,
potential to produce any protein,
allows gene-splicing (transplant of genetic material from higher species into lowly bacterium)
more fundamental of two techniques
recombinant DNA technology
has the potential to produce any protein
recombinant DNA technology
allows gene-splicing
recombinant DNA technology
transplant of genetic material from higher species into lowly bacterium
gene-splicing
human insulin
recombinant DNA technology
human growth hormone
recombinant DNA technology
hepatitis B vaccine
recombinant DNA technology
epoetin alfa
recombinant DNA technology
interferon
recombinant DNA technology
characteristics of mAb production
conducted entirely within the cells of higher animals,
exploits ability of cells with the potential to produce a desired antibody,
stimulates an unending stream of pure antibody production
conducted entirely within the cells of higher animals
monoclonal antibody production
exploits ability of cells with the potential to produce a desired antibody
monoclonal antibody production
stimulates an unending stream of pure antibody production
monoclonal antibody production
used in home pregnancy testing hormones
monoclonal antibody production
lupus erythematosus
belilumab
Hodgkin lymphoma
brentuximab
colorectal cancer
cetuximab
multiple sclerosis
natalizumab
macular degeneration
ranibizumab
rheumatoid arthritis
tocilizumab
used to prevent, treat, cure, diagnose, or mitigate human disorders caused by genetic disorders
human gene therapy
first human gene therapy
treatment of (ADA) adenosine deaminase deficiency
produces specifically desired effect,
be administered by the most desired route (generally orally) at minimal dosage,
dosing frequency has optimal onset and duration of activity,
exhibit no side effects,
no residual effect
goal drug
involves testing of large numbers of synthetic organic compounds or substance of natural origin for biologic activity
random or untargeted screening
maybe used initially to detect an unknown activity of the test compound or substance or to identify the most promising compounds to be studied
random screens
used to detect and evaluate biological activity
bioassays
used to differentiate the effect and potency of the test agent
bioassays
initial bioassays maybe performed in ___
in vitro (cell cultures)
subsequent bioassays maybe performed in
in vivo (animals)
chemical alteration of a known and previously characterized organic compound (lead compound) for the purpose of enhancing its usefulness as a drug
molecular modification
means enhancing its specificity for a paticular body site, increasing its potency, improving its rate and extent of absorption, modifying to advantage its time course in the body, reducing its toxicity, or changing its physical or chemical properties to provide desired features
molecular modification
molecular modification to design a drug that interferes specifically with the known or suspected biochemical pathway or mechanism of a disease process
mechanism-based drug design
use of computer graphics to represent and manipulate the structure of drug molecule to fit the similated molecular structure of the receptor site
molecular graphics
prototype chemical compound that has a fundamental desired biologic or pharmacologic activity
lead compound
requires metabolic transformation after administration to produce the desired pharmacologically active compound
prodrug
conversion of an inactive prodrug to an active compound occurs primarily through
enzymatic biochemical cleavage
example of prodrug
enalapril maleate
enalapril is bioactivayed by hydrolysis to ___
enalaprilat
criteria of prodrug
solubility,
absorption,
biostability,
prolonged release
active ingredient that has never before been marketed in the US in any form
new molecular entity
A combination of two or more old drugs or a change in the usual proportions of drugs un an established combination product is considered the same if the change introduces a question of safety or efficacy.
false
generally formidable that it soon is replaced in scientific communication by a shortened name
systematic name
chemical’s nonproprietary (or generic name)
shortened name
serves numerous and varied purposes, its principal function being to identify the substance to which it applies by means of designation
nonproprietary name
nonproprietary name are issued only for ____ agents
single
science concerned with drugs, their sources, appearance, chemistry, actions and uses
pharmacology
subareas of pharmacology
pharmacodynamics,
pharmacokinetics,
clinical pharmacology
study of biochemical and physiologic effects of drugs and their mechanisms of actions
pharmacodynamics
deals with absorption, distribution, metabolish or biotransformation and excretion
pharmacokinetics
also known as metabolism
biotransformation
applies pharmacologic principles to the study of effects and actions of drug in humans
clinical pharmacology
when the receptors are saturated, the effects of the specific interaction are ___
maximized
today’s emphasis of drug development
identifying the cause and process of a disease and then designing molecules capable of interfering with that process
the quantity of drug molecules available for interaction is related to
the capacity of the specific receptor site
has worked toward harmonization or bringing together the regulatory requirements with the long-range goal of establishing a uniform set of standarfs for drug registration within geographic areas
International Conference on Harmonization
required to report to FDA each adverse drug experience that is both serious or unexpected
drug’s sponsor
day limit for reporting of adverse effects
15 day
summary of all of the preclinical and clinical studies conducted over the period from drug discovery through product devolepment
labeling
following summary information in the package insert
description of the product, clinical pharmacology, indications and usage, contraindications, precautions, adverse reactions, drug abuse and dependence, overdosage, dosage and administration, how supplied
decides whether to allow sponsor to market the drug or not
FDA
180 day period of receipt of an application
review clock
types of letters FDA uses to respond to a drug’s sponsor
approval,
complete response
drug has met agency standards and can be marketed in the US
approval
review period for a drug is complete and the application is not yet ready for approval
complete response
purpose of NDA
to gain permission to market drug product
disease or condition that affects fewer than 200,000 people in the US
orphan disease
amount of drug that will produce the desired effect in most adult patients
drug’s adult dose, or
starting dose
determined during clinical investigation and is based largely on a drug’s inherent duration of action, its pharmacokinetic profile, and characteristics of the dosage form
dosage regimen
amount administered to protect patient from contracting the illness
prophylactic dose
administered to a patient after exposure or contraction to illness
therapeutic dose
doses of vaccines expressed in
units of activity
units of activity are derived from
bioassays
minimum concentration that can be expected to produce the drug’s desired effects in a patient
minimum effective concentration (MEC)
second level of serum concentration
minimum toxic concentration
expected to produce dose-related toxic effects in the average individual
minimum toxic concentration
amount that will produce desired intensity of the effect in 50% of the individuals tested
median effective dose
relationship between desired and undesired effects of drug is expressed as
therapeutic index
ratio between a drug’s median toxic dose and median effective dose
therapeutic index
formula for therapeutic index
TD50/ED50
negates desirable effects of drug
minimum toxic concentration
ability to endure influence of a drug during continued use
drug tolerance
