Lecture 10 - The regulatory framwork Flashcards
give an overview of the drug development process
Step 1: Discovery and Development
Step 2: Preclinical Research
Step 3: Clinical Development
Step 4: Regulator (MHRA) review
Step 5: Post market surveillance – yellow card
Describe step 1 of the drug development process
Drug discovery is how new medicines are discovered.
Since human DNA was sequenced, reverse pharmacology has found remedies to existing diseases through testing.
drug discovery involves screening hits, medicinal chemistry, and optimization of hits to reduce potential drug side effects (increasing affinity and selectivity). Efficacy or potency, metabolic stability (half-life), and oral bioavailability are also improved in this step of the drug development process.
outline the target identification nd validation in drug discovery
Target identification finds a gene or protein (therapeutic agent) that plays a significant role in disease and when identified, therapeutic characteristics are recorded.
Targets are efficacious, safe, usable as drugs, and capable of meeting clinical and commercial requirements.
Research uses disease association, bioactive molecules, cell-based models, protein interactions, signalling pathways analysis, and functional analysis of genes to validate targets, or in vitro genetic manipulation, antibodies, and chemical genomics.
describe the hit discovery process, assay development and screening and high throughput screening in drug discovery
Hit Discovery Process
Following target validation, compound screening assays are developed.
Assay Development & Screening
Assays are test systems that evaluate the effects of the new drug candidate at the cellular, molecular, and biochemical levels.
High Throughput Screening (HTS)
uses robotics, data processing/control software, liquid handling devices, and sensitive detectors to rapidly conduct millions of pharmacological, chemical, and genetic tests.
what happens in the hit to lead process?
In the Hit to Lead process, small molecule hits from an HTS are evaluated and optimized in a limited way into lead compounds. These compounds then move on to the lead optimization process.
what happens in the lead optimisation process?
In the lead optimization process, the lead compounds discovered in the hit to lead process are synthesized and modified to improve potency and reduce side effects.
Lead optimization conducts experimental testing using animal efficacy models and ADMET tools, designing the drug candidate.
what are active pharmaceutical ingredients?
Active pharmaceutical ingredients (APIs) are biologically active ingredients in a drug candidate that produce effects.
All drugs are made up of the API or APIs and excipients.
(Excipients are inactive substances that deliver the drug into the human system.).
The drug discovery process ends when one lead compound is found for a drug candidate, and the process of drug development starts.
describe step 2 pre-clinical trials
Once a lead compound is found, drug development begins with preclinical research to determine the efficacy and safety of the drug.
For this we identify the following about the drug:
1. Absorption, distribution, metabolization, and excretion information (ADME)
2. Potential benefits and mechanisms of action
3. Best dosage, and administration route
4. Side effects/adverse events
5. Effects on gender, race, or ethnicity groups
6. Interaction with other treatments
7. Effectiveness compared to similar drugs
reclinical trials test the new drug on non-human subjects for efficacy, toxicity, and pharmacokinetic (PK) information. These trials are conducted by scientists in vitro and in vivo with unrestricted dosages.
In vivo, preclinical research examples are the development of new drugs using mice, rat, and dog models.
In vitro is research conducted in a laboratory.
Ex vivo uses animal cells or tissues from a non-living animal
Formulation Optimization & Improving Bioavailability
Formulation optimisation is ongoing throughout pre-clinical and clinical stages.
The correct formulation is needed to support
drugs are delivered to the right place, at the right time, and in the right concentration.
Formulation strategies can be used to e.g.
Improve low solubility issues
Improved targeting
Protect the drug
Meet the needs of the route of administration
describe stage I in step 3 clinical development
The first step in testing a new drug is to determine the safety of single doses in a small number of healthy volunteers. This stage helps researchers understand some aspects of how it works and establishes the likely dose required.
describe phase 2 in step 3 clinical development
If the treatment proves to be safe, studies begin to determine the effectiveness of the drug in people with the condition to be treated. These studies may last several months or years and involve larger numbers of people, perhaps one or two hundred.
The study may be:
controlled - the drug is compared with the standard treatment or placebo (dummy treatment)
double-blind - neither the investigators nor the participants know which treatment they are receiving
randomised - participants will be randomly allocated to receive active treatment or placebo.
describe phase 3 in step 3 clinical development
If a drug shows effectiveness, a larger study is conducted in hundreds of people. These clinical trials take place at different locations (multi-centre) and across several countries and may last several years
These studies allow us to more accurately assess the potential of the new drug in a wider range of people and compare it to existing treatments
step 4 licensing; what is the MHR and its role
If the MHRA is satisfied that the new medicine is effective, safe and meets manufacturing quality standards, a marketing authorisation or licence will be issued.
The Medicines and Healthcare products Regulatory Agency (MHRA) is the executive Agency of the Department of Health and Social Care that acts on behalf of the Ministers to protect and promote public health and patient safety, by ensuring that medicines and medical devices meet appropriate standards of safety, quality and efficacy.
The Medicines and Healthcare products Regulatory Agency regulates medicines, medical devices and blood components for transfusion in the UK.
what is information and data reviewed by MHRA?
Data on Quality, Safety and Efficacy
This includes
Drug substance information (name, structure, general properties, how it is manufactured, characterisation, and stability)
Drug Product information (components and excipients, manufacturing process, control processes, sterility and stability)
descried step 5 post market surveillance
Once the newly-licensed medicine is in general use, it will be carefully monitored for safety.
All medicines have a patient information leaflet (PIL), which gives instructions on how the medicine should be used, and on its side effects.
Rare side effects, for example those occurring in 1 in 10,000 people may only become apparent once a medicine is in general use
