Lec 15 - Drug Dev Flashcards
what is the dif between pharma and biotech
pharma is drugs from chemicals, biotech is tech based on bio
describe the cycle from drug discovery to evolution of product. where does preclin studied, clinical trial review, submission review, monitoring and intervention, and product removal occur?
drug discovered
pre clin studises not in humans
then health canada approves studying in humans
clinical trials
clinical trial review
drug submission
submission review
licence
post market
knowledge aquisition
monitoring, needed interventions
revaluation
removal if needed
evolution
what are the four phases of drug discovery? what happens in each?
target discovery: finding the targets for the drug
target validation: eliminating the wrong targets
lead generation and refinement: generating molecules
preclinical development: eliminating and dvancing molecules
this all happens in drug discovery! way before any trials and testing!
t/f: all of the drugs make it to the market. why or why not?
false: lots of the drugs get eliminated along the way bc they done pass tests
describe the drug dev funnel
lots during basic research, funneling out from 100 000-25000 to 10-20 in preclin/animal studies
then 5-10 in phase 1
2-5 in phase 2
2 in phase 3
1 in phase 4
typically how long does the drug dev process take? describe what happens at each time point
in total up to 15 years.
3-6 years spend on drug discovery and preclin
6-7 years spent on clinical studies
0.5-2 years spent on regulatory review
afterwards is post marketing review
contrast phase 1, 2, 3, clinical studies
- looking mainly at pk/pd, dosing range, safety
- looking at efficacy, dose, safety
- looking at safety, efficiacy
more volunteers in each category as u go up the phases
why was the covid vaccine timeline so accelerated?
many people working on it at once, review process happened a lot faster
what happens after you determine a vaccines efficacy?
approval, manufacturing, global vaccinations, and future directions
what does the second wave of vaccines do?
improves protection, deals with mutants
what is the drug dev process in the US?
drug discovery, preclinical studies + IND application
clinical development, fda review, post market monitoring
how does canada regulate food and therapeutics (ie: legislation? regulation?)`
food and drug act legislation, and food and drug regulation, and natural health product regulation
what is the role of the health products and food branch?
monitors safety and efficacy of health product, food, and vet drugs
nutrition and food policies
public health response wrt food and nutrition
what is the pharmaceutical drugs directorate> what do they do?
they review safety and efficacy of prescription drugs, clinical trial applications,
what does the patent act state?
manufacturers of a brand name drug have 17 years of patent protection from patent issuing or 20 years from patent filing date
when should preclinical testing happen? what do you examine during this phase?
before clinical trial application for humans. look at structure activity relationship, animal studies, pk, adrs, pregnancy
when does the clinical trial application occur>
after preclin testing and before clinical trials start
describe pathway from drug synthesis to new drug submission
synthestis, preclin testing, cta, clincal traisl (1, 2,3), new drug submission
what happens during phase 1 of clinical trials? what are u measuring? how many people?
drug is admin to health volunteers - small group – with controlled inclusion and exclusion.
measuring pk parameters, some safety by data safety monitoring board.
contrast blinding and double blinding
blinding: patient doesnt know what theyre getting
double bl: patient and doc dont know what theyre getting
when would you not use healthy volunteers for phase 1?
for wnticancer drugs, hiv drugs: you wouldnt want to test on health patients bc these are very potent drugs.
what is the inclusion/exclusion criteria for phase 1?
want people that are going to stay for the whole study and who will have the least adverse effects
what is the main goal of phase 1 clinical trial?
to figure out the pk principles of a drug
when would you bypass phase 1 clinical trial?
when youre patient population is very sick and the drug is such that it would be harmful to a healthy patient
why shouldnt you give all patients the dose at the same time during a clinical trial?
wait some time so you can see if the drug is affecting someone first (2006 paraxel for tgn1412 - leukemia and arthritis drug, 2016 trial in france)
what happens during a phase 2 clinical trial? what is the main goal?
actually testing the drugs in patients, seeing if the drug has therapeutic use, dosing adjustments, and examining safety
what is proof of concept?
seeing if a drug does what it is supposed to from a therapeutic perspective
what happens during phase 3 clinical trial?
thousands of patients, comparisons to stand therapy, controlled inc.ex, expesnsive, can be sep while waiting for notice of compliance
which phase of clinical trial does comparisons?
phase 3
what is notice of compliance?
once the manufacturer receives it and the DIN, they can sell the product in canada: noc tells us that benefits outweigh risks and harms of product
what i a new drug submission? what must it include?
contains scientific info about safety and efficacy and quality of product
preclinr esults
clin results
production details
packaging and labelling
ther value
conditions of use
adrs
when would you have an abbreviated nds?
when youre a generic drug company
what does an abbreviated nds need to have?
infor about packaging, production and labelling
safety and efficacy same as brand name
similar endpoints as brand name
what is a supplemental nds? when would you use it?
when the manufacturer wants to make changes to a product already authorized
what is the drug review process in canada? who does it?
all pharm drugs and devices reviewed and regulated by pharm drugs directorate, health products and food branch, and health canada. they look for safety, efficacy and quality
what happens when a manufacturer receives notice of compliance
they can sell their product
when would a NOC be assigned
when benefits of drugs outweigh the harms
what is NON? what happens?
notice of non compliance: what a failed submission gets, and the manufacterer has to respond appropriately within a period of time
what is a DIN?
drug identification number
do natural products have a DIN?
nope. they are under the natural and non prescription health products branch and have a natural product number
what is the PMPRB? what do they do?
patented medicine prices review board: regualtion of prices of patented medicines to make sure theyre not excessive (how much does it cost for wholesalers? hospitals? pharmacies?) but they cant control how mcuh wholesalers and retails sell for, and cant control generic drug pricing
what happens during pricing review?
patentees have to file price and sales info about the drug twice a year for each form of their drug
what is the special access program? when can it be used?
lets practitioners request access to drugs unavailable for sale in canada
can be used when patients have serious or life threatening conditions on compassionate and emergency basis when conventional therapies are unavilable
what is the CADTH?
the canadian agency for drugs and tech in health
not for profit org that helps healthcare workers make infomred decsiions about best use of drugs and medical devices
what happens during phase 4 clinical trials
post marketing surveillance and safety, read world issues with drug
what are common reason that drugs are withdrawaled
lack of safety, efficacy, therapeutic interest, poor market performance
how is study design related to trials
you can design trials in such a way that they are more efficient at the outset to figure out who the study works for
contrast cohort vs case control designs
cohort looks forward in time: takes a sample of healthy patients, exposes them, sees if they have illness
case control: looks at population, sees if they have the illness, then sees if they were exposed (good for diseases that take a long time to develop)
contrast the placebo and the nocebo effect
placebo: give someone something that looks like what should work and they start feeling better
nocebo: you think you have side effects just because you were exposed
what are natural health products
naturally occuring substances made from plants animals, in tablets, creams, drops, etc
what regulation oversees nhps
the natural and non presciption health products directorate (nnhpd) for regulatory approval
the marketed health products directorate for post market safety
the health products and food branch inspectorate to enforce regulations
what is the nnhpd
the natural and non presciption health products directorate
what is the mhpd
marketed health products directorate
what is the hpmi
health products and food branch inspectorate
what are the regulations for nhps
must be safe to use as overthe counter products for self medication
what falls under nhps
vitamins and minerals, herbal remedies, homeopathy, traditional meds, probiotics, emino acids, essential fas
what does not count as an nhp
biologics, injectables, tobacco, marijuana
what is the npn
the natural product number
what are the characteristics s of authorized nhps
safe and effective, have an npn, have detailed label info, safe and effective when used according to instructions
how do you know if nhps are safe
clinical trial data evidence, published studies, trad sources
contrasting modern vs traditional health claims
modern: studies, animal, in vitro, textbooks, peer reviewed, regulatory authority reports
traditional health claimes: based on knowledge and practice based on theory belief and culture , but has to be shown to be used for two generations
what is the objective of nhp regulations
providing assurance that products are safe effacacious and high quality
what is homeopathy
super dilute products, based that a disease can be cured by a product that results in similar symptoms
how are homeopathic products reviewed
make sure that what they aim to do is referenced somewhere, generally approved on the basis that the products would be low risk
what are nosodes
homeopathic treatment derived from an element of disease or diseased tissue
how are nosodes regulated? what happens to children given nosodes?
should not be used as a vaccine alternative. regulated by health canada. children are at higher risk of getting fatal childhood illnesses.
how do homeopathic products have to be labelled
“this claim is based on traditional homeopathic references and not modern scientific data”
how can a drug be eligible to have DIN-HM
(homeo medicine number) : can only be sold if they meet minimum homeo potency as established by nnhpd
what do product liscencing submissions need to have? site liscening?
this isnt required for products compunded on an individual basis
product: they need to have ingredients, source, potency, non med ingredients, recc use
site: distribution record, procedure for product recall, handling strage and delivery, meet gmp
what is good manufacturing process
proper stands for testing, manufacture, storage, handling, and distribution of nhp
ie product specs, premises, equipment, personnel, sanitation, quality assurance, stability, records..
what are labelling requirements for nhps
product name, liscence number, quanity, ingredients, recc use, route of admin, cautionary statements, storage
what are potential risks for nhps
manufacturing problems, unproven claimes, not enough info, interactions with prescription drugs, unwanted side effects
