bit of everything Flashcards
PoP
Proof of Principle
PoC
Proof of Concept
PoP/PoC
study i wich we go for a new target; new kind of approach; try to show that hitting that target results in the resolution of the problem and the efficacy you are looking for
Therapeutic gain
difference between percentage of people free of pain with the drug and with placebo (30% is typical for placebo)
RoI
return on investment
NDA
New drug application
RCT
radomized controlled trial
SoC
Standard of Care
IVRS
Interactive voice response system
eCTA
exploratory Clinical Trial Application
RCT
randomized control trial
QSP
Quantitative System Pharmacology
IND
Investigational new drug
NDA
nw drug application
BLA
biologics licence application
GCP
good clinical practice
GMP
good manufacturing practice
NITAG
National immunization technnical advisory group
Adverse event
Any untoward medical occurrence in a subject to whom a medicinal product is administered and which does not necessarily have a causal relationship with this treatment
eg. Headache, acute myocardial infarction, arthritis,…
adverse reaction
A response to a medicinal product which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the restoration, correction or modification of physiological function
blooc clot after vaccine
Serious adverse event, SAE
= any untoward medical occurrence that at any dose: so it is considered serious if the outcome are:
results in death,
is life-threatening,
requires hospitalisation or prolongation of existing hospitalisation,
results in persistent or significant disability or incapacity, or
is a congenital anomaly or birth defect.
Unexpected adverse reaction
an adverse reaction, the nature or severity of which is not consistent with the information on the experiment, and, when a clinical trial is concerned, with the applicable product information
(e.g. investigator’s brochure for an unauthorised investigational product or the patient leaflet joined to the summary of product characteristics for an authorised product)
eg. Stomach ache following pain killers
Suspected unexpected serious adverse reaction, SUSAR
A serious adverse reaction, the nature, severity or outcome of which is not consistent with the reference safety information
Eg. psychosis/delirium in anti-epileptic medication
Clinical event of interest
= very specific adverse reactions that can be expected within a clinical trial and can be serious
Eg. thrombolytics → bleeding
Eg. Drug-Induced Liver Injury (DILI)
Eg. Vaccines potential immune-mediated disorders
pharmacolvigilance is
all processes concerning vigilance and evaluation of side effects (ADR) of the drug for FAMPH
since and activities concerning the follow-up, evaluation, understanding, and prevalence of side effects of other drug-related problem, ADE occurring with a drug WHO
causality assesment
evaluation of the likelihood that a particular treatment is the cause of an observed adverse event and is essential to be done and reported to the sponsor, regulatory agencies and safety monitoring committees.
two important questions
usually multi causal complex interaction environment drug patient
9 stuff help
time
pharmacological prop
known assoc
underlying di
concomitant med
dechallenge
rechallenge
dose effect
localisation fo the AR
MRP
mutual recognised procedure
SAWP
scientific advice working party
MAA
Marketing authorisation application
CHMP
Committee for Medicinal Products for Human Use
CMA
conditional marketing authorisation
CRA
clinical research associate
INN
international nonproprietary name
CCM
cold chain management
guaranteeing the adequate storage of drugs even if they are kept at special temperatures to ain’t an efficient use
alarm
RECIP-E
paperless prescribing tools that allow patient to get presecribed medicinal product at the pharmacy by giving their national ID card.
CPOE
computerized physician order entry system
CRM
commission for reimbursement of medicine
MIDD
model informed drug development
RACE
rapid assesment of compound exposure
give a single dose of interest to animals orally and parenterally
PAMPA
parallel artificial membrane permeation assay
reservoir system
enteral controlled released system
API is in the core and is coated with a polymer coating (insoluble, slow release, pH dependent table etc. Once swallowed, water and gastric fluid start to penetrate through the coating, the API get dissolved and diffuse through the coating through the dosage form
matric system
enteral controllled release
they are either hydrophilic - polymer in which the API is embedded and start to dissolve very slowly. The gel gets dissolved in the function of the time size of the dosage form
buccal tablet
they work based on the adhesion to the mouth via cross-linked polyacrylic acid. the tablet stick to the mounts and with water the material start to form a gel and the API is slowly released in the mount. VEry efficient
suspension what is needed to keep nit in suspension
it need wetting agents such as surfactant to ensure contact between liquid and solid phase and visocisty increasing agent to prevent and reduce seimentation as well as pay attention to the size of the particle of the API
cream and ointment difference
ointment does not contain water, only the API some lipid and the surfactant
cream need an emulsifier to keep the water in
TTS
transdermal therapeutic systems
stick to you skin and the API get delivered through the ski at constant rate
it is done through a rate controlling polymeric (itself regulate and act as a controlling device) membrane at the bottom and underneat an adbhesive layer. at the top there is athe reservoir with a suspension that dispense the API
microparticle based on biodegradable system
can be given SC or IM - those polymer degrade very shwoly with the API degradation over a few week
there are microcrystal of poorly soluble drug
you can make an ester of these APIs to make the solubility even lower and put it into an injectable system that will dissolve at a steady rate in the muscle over a period of three months
passive targeting for nanosized drug delivery systems
mononuclear phagocyte system
local physiological conditions
enhanced permeability and retention effect EPR
mononuclear phagocyte system
MPS
iv injection, the particulates are cleared by the macrophage from liver and spleen. Once there is macrophage uptake, the drug carrier will be transported to the lysosome and the drug is released upon the breakdown of the carrier
ex are treatment of macrophage intracellular microbial
local physiological conditions
facilitate the release of the active drug from its carrier system at the specific site using the local pH or presence of a specific enzyme within a target organ
ex is increase alkaline phosphatase increase at tumour level site
enhanced permeability and retention EPR effect
integrity of the endothelial barier at the site of inflammation or tumours is often disrupted by the presence of endothelial fenestration that can be quite large
macromolecular compounds such as albumin and other polymer-conjugated drugs beyond certain sizes (above 40 kDa) can progressively accumulate in the tumor vascularized area
active targeting
is when you use targeting groups to bind to specific receptor
targeting via folate receptor
antibodies
lectin-glycoprotein targeting
targeting via folate receptor
these receptor are upregulate in many human cancer and high density of these receptor appears to increase as the stage of cancer progresses
antibodies
as drug to target a range of cells
they can be use to conjugate a drug or carrier system and target specific location
lectin-glycoprotein targeting
can be used to target invading pathogens as lecting are overexperessed on the surface of many tumour cells
nanosized drug delivery
soluble system include monoclonal antibodies and polymeric carrier (eg xyotax, treatment of non-small cell lung cancer and ovarian)
particulate systems (the drug is physically or chemically associated to the carrier, they have a high drug loading and protected against degradation include liposomes (mRNA), polymeric micelles (both passive via EPR and active eg folate), dendrimers and polymeric nanoparticles
requirement for a good efficient drug-targeting system
no non-specific interaction
no toxicity
retaining the drug during the trans to the target
bust be able to access and be retained at the target
drug must be delivered from its delivery system
DSMB role
ensure that the decision is very clear upfront and everything is well decided, and safe.
independent and not blinded
ensure that everything is conducted according to the preset standard.
asses the adverse event provided by the investigator
EVMPD
EudraVigilance Medicinal Product Dictionary: Central European database, registration of product, documenting ADR and evaluation of clinical relevance of ADR
ASR
Annual Safety Report: a list of all SAE and an evaluation on the safety of the participant
HCP
healthcare professional
MAH
market authorisation holders
RMP
risk management plan
PASS
post authorisation safety study
PIMS
Pharmaceutical Information Management System
FAMHP
The FAMHP plays an essential role in the protection of public health with the following mission:
“Ensuring, from development to use, the quality, safety and efficacy of human and veterinary health product
a public institution under the control of the Minister of Social Affairs and Public Health, is the Belgian national competent and control authority for the regulation of medicinal products and medical devices.
The FAMHP supervises the quality, safety and efficacy of medicines for human or animal use and also has responsibilities for medical devices and blood, tissues and cells. It is also responsible for the EU procedures under the decentralised procedure, the mutual recognition procedure and referrals, and for participation in the centralised procedure.
act as the rapporteur co rapporteur for new MA to theEMA
conditional marketing authorisation
CMA
you get this for meds that have less comprehensive data still but that touls immediately benefit society and the benefit outweigh the risks
all the requirement should be met
positive benefit risk analysis
comprehensive data will be provided
ubnmet medical needs
benefit immediately
CSR
clinical study report
PRIME
scheme for priority medicine under development not yet authorised in the EU
it is done to dvp support for the dvp of medicine that target an unmet medical need
based on interaction and early dialogue with the company to optimise the development of these medicines. OI also give early and proactive support and help to improve clinical trial design
it really ims to stimulate research by providing incentive
RMP
risk management plan it is part of the pharmacovigilance activities that is designed to identify, characterise, prevent an minimise risk relating to medicinal product such as the effectiveness of the interventions, risk reduction approach etc
what does the HTA involve
Therapeutic value - aded value of the (efficacy effectiveness etc
price and level of reimbursement
importance in clinical practice
budgetary impact (ability to pay)
ratio cost/ therapeutic value(willingness to pay)
HTA
multidisciplinary process that uses explicit methods to determine the value of the health technology at different point in its lice cycle
the purpose to inform decision making in order to promote an equitable efficient and high quality health system
MEA
managed entry agreement
it is between the manufacturer and payer that will enable early access to HT which is still associated with significatn uncertainties (clinical or budgetary)
CRM
commission for reimubrsement medicine
IHSI
international horizon scanning initiative
it scans the future tendencies to inform on budgetary and health care budget management
it informs decision-makers on emerging new pharmaceuticals for reimbursement decisions and policy development on issues that are relevant
it allows a better player file with the pharmaceutical industry
potential early dialogue
Beneluxa initative
it is done to ensure sustainable access to drug and have a bigger ôwer in front of the company
1) information exchange
2IHSI
3) HTA
4) Pricing and reimbursement including joint negotiations
in case of succesfull joint assesment and negotiation
a decision on reimbursement is made simultaneously but separately in the participating countries
THIS REQUIRES A JOINT HTA
LASA
look alike and soud alike
PIL
patient information leaflet
PARIS
prescription and authorisation requesting information system
P&T
Pharmacy and therapeutic commitee
selection criteria
have to be filled by the company
award criteria
have to be filled by the product
BCFI
Belgian centre for pharmacotherapie information
CU
compassionate use
innovative period
include non clinical part but also clinical part, basically investing money and this is until you get EMA approval
monopoly period
aproval and comericalisation until the end of the exclusivity
you get the ROI
it depends on the price setting and the length of the period
competitive
happend afer the LOE and this decline is determine by police makers such as reimbursement policy or substation policy
the need to prove similarity etc
biosimilar
A biological medicinal product, or biological, is a medicinal product whose active substance is made by a living organism.
A biosimilar is a biological medicinal product that contains a version of the active substance of an original biological medicinal product (reference medicinal product) already authorised in the European Economic Area
class 1
Class 1: medicinal products with a significant therapeutic improvement compared with existing alternatives.
IEC
independent ethic comitee
PASS
post authorisation safety study
PIP
pediatric investigation plan
protocol containing all the key elements
which are needed to describe the future pediatric programme of a compound aiming for a MA. If they develop such a PIP they get an extension of the patent for 6 months, so when they perform the studies in an early phase also in children.
API
active pharmaceutical ingredient
PSUR
periodic safety update report
MBDD
model based drug development
MIDD
model informed drug development
umbrella term for Both separate and integrated application of QSP, PBPK, Empirical & semi- mechanistic PK & PK/PD, dose/exposure-response and disease progression
approaches.
they try to maximise and connect the information gathered to fit the purpose such as population extrapolation or clinical trial design etc
it is based on learning confirming cycle
Model-Informed Drug Development (MIDD), sometimes referred to as Model-Based Drug Development (MBDD), is a process whereby key program decisions are supported by mathematical models and simulations that predict the likelihood of success for the drug.
By using mathematical and statistical methods, one is able to build models of drug concentrations (pharmacokinetic) and/or drug responses (pharmacodynamic) over a time course.
Such models allow one to understand how various dosing choices (e.g., dose amount, frequency, and duration) can affect drug concentrations while also demonstrating the relationship between drug concentration and the desired or undesired pharmacodynamic responses.
In addition, these models help to characterize the PK/PD variability of drugs and assist in understanding the clinically relevant factors contributing to variability.
MID3
model informed drug discovery and devlopment
Face validitiy
quality aspect refering to the degree of similarity between what the model appears to show or measure and what it claims to show
predictive validity
qulity aspect refering the the ability to correctly@ identify the efficacy and safety of a putative therapeutic
construct validity
quality aspect referring to the degree of similarity between the mechanism underlying the pathophysiology present in the model and the human situation
bindinding assay
relates to the affinity of a compound for a R
thermodynamic solubility
highest concentraiton o the solute which is in equilibrium with the most table solid form of the solute
kinetic solubility
dissolve the compound in a organic solvent, add drop in water until there is a precipitate and no longue possible to dissolve
dissolution rate
the rate at which a compound dissolv very important for the bioavailability
can use FASSIF or fessif
medium will depends on the purpose
FASSIF
fasting state stimultation intestinal fluid
ionisation behaviour
determine the pKa pKb via various technique such as potentiometric titration
knowing this allows you to change the pH a bit to increase solubility
for example you can transform in into a salt
ionisation behaviour
determine the pKa pKb via various technique such as potentiometric titration
knowing this allows you to change the pH a bit to increase solubility
for example you can transform in into a saltpa
partition coef
log P log D determine lipophilic or hydrophilic behaviour and help to see the absorption potential
solid state prop
API crystaline or amorphous?
morphous very unstable no melting transition liquid like solid
knowing this is important to get the most stable form
stability
in solid state - ingluence of heat, lightn water etc
stability in solution - heat, pH etcoxifising you want to challenge the stability here
try compatibility with excipient here too
antibodies are eliminated via
catabolic processes such as reticuloendthelial system
antibodies are abosrbed via
SC or IM or IV instead of oral,
convection or lymphatic uptake
reimbursement is decided by
Minister of Social Affairs, following a recommendation by the Medicines Reimbursement Committee, which forms part of the National Institute for Health and Disability Insurance (NIHDI)
correlate of protection
specific immune marker that is associated with proteintion afinst an infection
EMA
support innovations by checking project management, coordination, admministration but no technical expertise. Main responsibility is protection ad promotion of public and animal health
publish guideline
plays a role in simulation innovation and research
medical department
r and d
regulatory
acess
commercialisaiton
empirical statistical models
are descirptive models and not predictive. They rely on data as source of knowledge but has no assumptions
pharmacometrics
it is kind of in the middle of empirism and rationalism
it is more pragmatic but still data driven. it is part of clinical development and can interpolate
it basically gives a bruge between observation and understnading
learning and confirming by taking into account variability but still not too lmulch assumption
systems pharmacology/PBPK
is based on system biology and pharmaco dynamic kinetic. It is based on a lot of assumptions and is knowledge drive.
it can be used for extrapolation between populations
usually used in preclinical, for dose selection etc
physiologically base pharmacokinetic
