packet 1 - rocca Flashcards
how much time does it take to develop drug
10-15 years
percent of generic drugs used in 2000 vs. 2012
49% 2000
84% in 2012
cost of drug development in 2000 compared to 70s 80s 90s
2000 - 1.2 billion
90s- 800 mil
80s- 318 mil
70s- 140 mil
what are the steps in the research and development process (4 steps)
- drug discovery and pre-clinicals
- clinicals - 3 phases
- FDA review and scale-up manufacturing
- post marketing, monitoring, and research
length of time in each step of the research and drug development process
- drug discovery and pre-clinicals: 3-6
- clinicals: 6-7
- FDA review and scale-up manufacturing: 1/2 - 2 years
- post marketing, monitoring, and research: indefinite
between 2000-2007 what was the industry with the highest expenditures and how much do they spend on a yearly basis
biopharmaceuticals
50 million each year
2 key facts of the pharmaceutical industry
- most research-intense industry
2. as much as 5 times more in research and development relative to sales
NDA
new drug application
FDA
food drug administration
IND
investigation new drug
value of medicine as it pertains to life expectancy: what significant changes have been seen
50-60% of life expectancy increase has been due to meds
cancer- 3 year increase, 83% attributed to new treatment and meds
cardiovascular disease- death rate fell by 33%
hiv/aids- death rate has dropped more than 85%
3 main acts of drug regulation and control
1906 federal food and drug act
1938 federal food, drug, and cosmetic act
1962 kefauver (harris drug amendments)
1906 federal food and drug act
benefit was not regulated
strength, purity, quality
1938 federal food, drug, cosmetic act
increased safety
FDA
NDA
1962 kefauver (harris drug act)
efficacy
IND must be filed
code of federal regulation CFR
codification of general and permanent rules published in the federal register by executive departments and agencies of the federal government
what are the number of titles in the CFR and how is it divided and what does it represent
50 titles
divided into branches - bears name of issuing company
represents areas that are subject to fed regulation
title 21 of the CFR
consists of 8 volumes containing regulation by federal food drug and cosmetic act and other statues administered by FDA
title 21 part 300-314
requires new drugs to be approved by FDA before legally introduced
applies to drug manufactured in US and imported
the FDA will approve NDA only if it demonstrates evidence of:
safety
effectiveness
condensed steps in the development of new product
identify molecular entity
pharmacological activity
small scale lab manufacturing
small scale lab manufacturing assess what 3 things
toxicity
research
preformulation- identify its stability
What are the federal approval requirements no what do they preserve
Adequate manufacturing and control
Processing of drug
Packaging of drug
Preserves: strength, safety, identity, purity, quality
Product goals of drug
Safety Strength Identity Purity Quality
Product is free of unwanted side effects when used appropriately by patient
Safety
product exactly matches the labeling and related documents
identity
product has correct concentration, potency, or therapeutic activity of active ingredient
strength
product is free of contamination
purity
quality
product meets all standards, expectations; performs as claimed
product made consistently
important factor that must be present in order to obtain FDA approval is
CMC chemistry manufacturing control
what happens if you do not have chemistry manufacturing and control
drug is recalled — can be do to contamination, yeast etc
disciplines of drug discoveries and design
chemist biologist/molecular biologist pharmacologist toxicologist staticians physicians, pharmacists pharmaceutical engineers, scientists, etc
a clinical study cannot be conducted without:
optimal dosage form
drug discovery resources
natural
semi-synthetic
synthetic
drug resource examples
vinca rosea - yielded vinblastine and vincristine
pacific yew tree extract - paclitaxel
animal endocrine gland - thyroid extract
urine of pregnant mares - estrogen
many drugs, vitamins, biotechnology and many other substances produced this way:
fermentation
methods of drug discovery (6)
random screens non-random screens molecular modifications mechanism-based drug design molecular graphics pharmcogenomics p
types of non-random screens
bio-assay
disease specific animal models
high throughput screenings
molecular modications
proves efficacy by attaching a functional group
mechanism based drug design
drugs designed to interfere/inhibit a known or suspect pathway of mechanism of a disease process
molecular graphics
the use of computers to represent and manipulate the structure of a drug molecule to fit the simulated molecular structure of the receptor site
pharmacogenetics
refers to the genetics differences which can affect the individual responses to drug, both in terms of therapeutic effect and adverse effects
pharmacology
the study of drugs
genomics
the study of genes and their functions
pharmacology + genomics =
pharmacogenetics: the study of how your genes affect your response to drugs
pharmacogenomics benefits (4)
development of tailored medicine
more accurate method of determining appropriate drug dosages
improvement of drug discovery an approval process
better vaccines
micro-array monitors change in dna sequencing
if so, can be evaluated for pathotoxins T/F
true
what is a sandwich assay used for
to identify infectious agents responsible for illnesses
steps in protein array (sandwich array)
- blood sample placed on array/chip
- multiple Ab assigned to each well
- Ab will bind to specific protein from one organism (represent disease causing agent)
- apply fluorescent Ab (attaches to 2nd site on protein)—forms sandwich — scanned to determine organism present
new drug definition
drug not recognized by experts
qualify as being safe and effective for its use
FDA definition of new drug (5)
new combination of two or more drugs new use for old drug new dosage schedule and regimen new route of admin new dosage form
drug nomenclature - 4 steps
- empirical formula
- systemic name - more descriptive than emperical
- nonproprietary name (generic)- only if drug is promising
- code numbers United States adopted names council (USAN council) - assigns name to nonproprietary names
3 areas that we look at for pre-clinical development
- pharmacology
- drug metabolism
- toxicology
chemical and physical properties of a compound are evaluated to provide an _______ and _______ pharmaceutical products.
effective and stable
pharmaceutics and formulations involves: (chemistry manufacturing control) (3)
in which section of the CFR is it found
physical and chemical properties
initial formulations - clinical trails
pilot plant-scale up - large scale manufacturing
CFR title 21 part 300
pharmaceutical industry accounts for the majority of drug delivery system in global market. drug delivery technology accounts for ___%
10
the total size of pharmaceutical products is ____. drug delivery technology is ___ billion
800 billion
90 billion
____ types of drug delivery will remain the largest drug delivery category while parenteral, inhalation, and implantable system grow the fastest.
oral
investigational new drug
what happens if approved
program by which pharmaceutical companies obtain permission to ship experimental drugs across state lines to clinical investigators before a marketing app has been approved. If cleared by the FDA, the drug candidate will enter phase one of clinical trials
an investigation new drug (IND) is required for a clinical study if it is intended to support a: (4)
new indication
change in route of admin or dosage level
change in approved patient population or population at greater risk
significant change in the promotion of the drug
information gathered by IND (8) #SCRODLE
- SAFETY evaluation -NUMBER of patients
- any CLINICAL data - estimated LENGTH of treatment
- DRUG identification and manufacturing instructions
- detailed OUTLINE of proposed study
- ROUTE of administration
- ENVIRONMENTAL impact statement
multiple areas of drug approval process
preclinical IND phases I, II, III NDA IV
timeline for drug development (include phases and time frames)
PRECLINICAL RESEARCH- discovery and early screening, large scale synthesis, animal testing, takes 5 years
CLINICAL STUDIES: phase I take 1 1/2 year, phase II takes 2 yrs, phase III takes 3 1/2 yrs (total of 7 years)
REVIEW OF FDA - 1 1/2 year
POST MARKETING SURVEILLANCE- ongoing
what occurs in pre-clinical trials
discovery and early screening
large scale synthesis
animal testing
takes 5 years
what occurs in clinical study stage and phases involved
file IND
take 7 years
3 phase:
Phase I - using healthy patient, use small dose, look for absorption response, takes 1 1/5 years
Phase II- recruit sick indv. determine actual dose, called dose response study because dose can be identified, need to make sure you have right formulation before entering phase III, 2 years
Phase III- efficacy study, longest phase bc you need indv with therapeutic need, all data is collected in this phase, takes 3 1/2 years
phase that is called dose response study
phase II
