Module #1 - Biopharm Industry Flashcards
4 main types of pharmaceutical companies
ethical
generic
biotech
contract research organizations
characteristics of ethical companies (3)
research heavy
discover new molecular entities
very large
characteristics of generic companies (5)
research limited
focused on manufacturing and breaking/adapting patents
don’t discover new molecular entities
large to medium sized
market products no longer protected by patents
characteristics of biotech companies (4)
exploit academic discoveries
smaller
specialty products
research intensive
characteristics of contract research organizations (4)
provide specialty services for pharmaceutical companies (ex. testing, manufacturing, clinical trials, etc.)
small to medium sized
low risk because they don’t have to worry about drug failing
hired by big companies
what is the drug product database?
health Canada
contains data on over 47000 products
what are molecular entities (drugs) (4)
active ingredient in drug products
pure ingredient
small molecule or biologic
produce the effects of the product
what are drug products (2)
materials that contain a molecular entity
formulation of a drug
how many molecular entities approved each year? how many of those are small molecules?
40 entitites
30 small molecules
are small molecules or biologic molecules more common? trends?
small molecules more common
but trend for biologic molecules due to newer technologies
what are the five major phases of drug development?
discovery
development
clinical trails
FDA approval
market
describe the discovery phase of drug development (time, goals, and end product)
1-3 years
start with an idea + discover a new molecular entity (drug candidate)
end product = drug candidate
describe the development phase of drug development (time, goals, and end product)
1-2 years
turn drug candidate into a potentially sellable product
end product = investigational new drug
describe the clinical trial phase of drug development (time, goals, and end product)
1-5 years
test investigational new drug for safety, establish safe dosing limits, test for efficacy, test for rare side effects, etc.
end product = new drug application
describe the FDA approval phase of drug development (time, goals, and end product)
6 months to 1.5 years
review data from clinical trials, make sure benefits outweigh risks
end product = market approval
describe the market phase of drug development (time, goals, and end product)
unlimited time
make money, continue safety testing (rare side effects could occur because bigger test group)
end product = $$$
what is a drug candidate? (6)
molecular entity that could potentially be a drug
identified in the discovery process
structure kept secret
no approval necessary to discover this
lots of synthesis/testing and gene expression/protein isolation
used to create investigational new drug
what is an investigational new drug (4)
the product that results from the drug candidate
is an application made to the FDA to enter clinical trials
includes data: pharmacology + toxicity data from animal studies, and manufacturing info
includes plan on how clinical trials on humans will take place
what is a new drug application (3)
application made to FDA to enter the market during the clinical trials
includes full data: efficacy, safety, dosing, labelling, results of clinical trials + animal experiments, manufacturing methods etc.
application must show that benefits outweigh risks
what is an abbreviated new drug application
an application made to the FDA by generic drug companies to allow generic drug to enter market
must show that product does same thing as name brand product
shows drug identity, formulation, route of administration, dosing, performance, etc.
what are the 3 main steps of project initiation (3) (not official step)
market analysis
competitive assessment
research analysis
what is involved in market analysis stage of project initiation (3)
assess number/nature of customers (able to pay? lots of people?)
assess nature of disease (chronic? life threatening?)
focus groups take place + literature is observed to see if product will sell
why do drug companies prefer chronic conditions?
because long-term, not just one and done - more money can be made
what is involved in the competitive assessment stage of project initiation (3)
patent literature observed to see what competition is like and what other companies are doing
want to be one of first 3 drugs on the market
why do you want to be one of first three drugs on the market?
1st = first thing the doctor starts to prescribe (becomes favourite)
2nd = makes less money because doctors prefer the first drug
3rd = same as second basically
what is involved in the research analysis stage of project initiation (4)
observe literature to see what is already known
determine if possible to make product
see if disease is understood and can be solved
see if you have tools necessary to carry out research
what is proof of principle?
another experiment that shows that the idea is possible
what are drug testing methods?
ways to test whether drug is sticking to the target, measuring properties of drug, etc.
what are animal models
creating or exaggerating a disease state in animals
what is the first step in the discovery process? what is this? (2)
coming up with a lead
some sort of molecular entity with a beneficial property
characteristics of a good lead (5)
does the fewest amount of things (to avoid side effects)
drug-like properties
chemical structure that is easily modified
not covered by any patents
proven biological activity
what are the five methods of lead identification from most to least used
high throughput screening
rational drug design
natural products
combinatorial chemistry
de novo design
what is involved in high throughput screening methods? (4)
thousands of compounds tested to see if any benefits using biological assays
tested one at a time at same dose
generate hits
hits are sorted out using hit to lead, and then retesting hits (to remove PAINS) so that structure can be confirmed
what is involved in hit to lead? (2nd step of high throughput screening)
removes false positives
why are most hits false in high throughput screening? (4)
impurity
decomposition
compound reactivity (could be a detergent, redox reaction, or strong elec/nu)
could interfere with the assay
are most hits real or false?
false - about 99%
what are PAINS in high throughput screening (4)
promiscuous bioactive components
show up positive with virtually any biological test (show up as hit)
redox activity, strong acid/base, detergents, strong nuc/elec, lipophilic, photo reactive, etc.
how are PAINS dealt with in HTS
are flagged since it is more expensive to remove them
what are common patterns of drugs developed through high throughput screening? (3)
aromatic rings
lots of nitrogen
no chiral enters (most are achiral)
what is extracted from natural product lead identification (2)
chemicals/small molecules extracted from living things
are secondary metabolites - chemicals not directly required for the life of the thing they are apart of (produced by organism for secondary purpose)
what is involved in natural product lead identification (3)
collect large amount of organism
isolate and purify collected materials to determine molecule showing activity
determine structure and confirm activity
limitations to natural product lead identification (3)
stuck with what nature gives you (supply + demand hard)
time consuming + expensive
difficult to perform SAR/modifications because complex chemical structures
what is involved in rational drug design? (4)
utilizes knowledge of chemical reactions + metabolism to design drugs
uses known enzymes, inhibitors, ligands, receptors, existing drugs, etc.
could also be modification method
start with known information, and use to advantage to design drug
patterns of molecules from natural products (5)
lots of oxygen
big structures
lots of stereochemistry
lots of cyclic parts
lots of stereocenters
patterns of molecules from rational drug design? (3)
lots of cyclic
lots of O and OH
has stereochemistry
what is involved in combinatorial chemistry? (3)
similar to HTS - difference is that a bunch of compounds are mixed together and tested (instead of being tested separately)
mixture testing to generate hits
only one drug has been discovered using this methods
what is involved in denovo design?
uses a computer software to design a lead from scratch
what are the two main methods of lead optimization?
SAR and SPR
what is SAR (5)
structure activity relationships
new structure designed based on lead structure
molecule then tested
test results used to determine relationship between change in structure and change in activity
occurs using one compound at a time
what is SPR (3)
structure property relationships
optimizes several properties simultaneously (instead of one like SAR)
optimizes: potency, selectivity, solubility, lipophilicity, chemical stability, acid-base behaviour, toxicity, metabolism, and ease of synthesis
what is the hardest part of medicinal chemistry
getting drugs into the body
difficult because the human body is designed to protect from chemicals in environment
what is the purpose of a patent
developed to make sure that drug candidate and other possible future drugs in class are protected
requirements for a patent
novelty: something made/discovered for first time
utility: must be able to be used for some purpose
non-obvious
what can be patented?
processes, machines, manufactured product, composition of matter, chemicals
what cannot be patented?
laws of nature, physical phenomenon, abstract ideas, and algorithms
what are the two main types of safety testing
in vitro (step 1) and in vivo (step 2)
what is involved with in vitro safety testing (6)
can be done if product capable of being mass-produced
use lots of biochemical assays
goal is a clean profile (under 300 positive results)
cheapest option
look for deal-breakers like carcinogens, or organ interference
done before animal testing
what is involved with in vivo safety tests (3)
performed after in vitro
requires smallest and fewest animals possible (so less drug used, and less money spent)
requires to species, at least one being a primate
why is animal testing necessary
complexity of a living thing cannot be simulated, therefore must be done
what are excipients
non medicinal ingredients
taken from food industry
mixed with active ingredient to form final product
what are the 8 types of excipients?
stabilizers
preservatives
fillers
disintegrants
binders
flavours
colours
lubricants
what are stabilizers? (3)
acid/base
protect product from chemical degradation due to oxygen
drug turned into salt
what are preservatives?
prevent bacteria/mold from forming
what are fillers?
ensure consistent dosing
drug is diluted into filter to make standard solution for easy measurement
what are disintegrants?
blow drug apart in the stomach so it can dissolve easier
what are binders?
hold the ingredients together in the stomach
what are flavours?
bitter flavours used as safety mechanism to prevent people from consuming
what are lubricants?
good for manufacturing so pills don’t stick to machinery
what are colours
used to distinguish between drugs
what is the nuremberg code for research on humans (8)
participation is voluntary
informed consent
prior animal studies must be performed
benefits outweigh risks
qualified scientists used
least suffering possible
experiments stopped if becomes dangerous
used for clinical trials to prevent unecessesary/unethical experiments
what are the three main purposes of clinical trials
safety efficacy and dose range finding
what is the most expensive stage of drug production and why? (4)
clinical trials
60-70% of the cost
doctors more expensive than biochemists
high failure
what is dose-range finding
finding right dose to put into people
what are double blind studies (3)
standard for clinical trials
drug group and placebo group
both the groups and doctors administering are unaware of groups
what is involved in the first stage of clinical trials? (goals, # patients, type of patients, time, drug failure rate)
safety + finding safe max dose
under 100 people
healthy volunteers
under 1 year
30% fail
what is involved in the second stage of clinical trials? (goals, # patients, type of patients, time, drug failure rate)
safety + finding effective dosing + efficacy
200-300 people
patients
about 1 year
70% fai
what is involved in the third stage of clinical trials (goals, # patients, type of patients, time, drug failure rate)
safety, efficacy, rare side effects
thousands
patients
about 1 year
70% failure rate
what are orphan drugs
pharmaceutical agents for rare conditions
given funding and slack in clinical trials
when were the first regulations for drugs created? why? (3)
1908
done so consumers would know what they were buying
focused on labelling only/listing ingredients
describe events that led to creation of FDA (4)
formation of sulfanilamide poisoned children because contained toxic ingredient (company hadn’t done any safety testing + drug was sold without instructions)
FDA introduced safety testing in humans/animals
directions on label and safety testing became required
FDA started inspecting companies
four key requirements for animal testing
two species minimum
one must be primate
take blood samples to show drug is bioavailable
must use dose that is relevant to future human use
how does the FDA and health Canada operate? (6)
safety testing done by companies
full data given to FDA/health canada
data checked to make sure testing done properly
marketing of drugs approved
companies required to continue monitoring on market and report difficulties to FDA
FDA continues to inspect over time
why is it important that government does not perform safety testing (2)
costs of testing drugs paid by consumer instead of taxpayer
forcing companies to spend their own money ensures companies will only test things they think will make it on the market
what are the pros of regulation in drug industry (4)
ensures safe products
ensures products work
provides consumer protection
controls access
what are the cons of regulation in drug industry (3)
increases costs
increases taxes
limits access
