Drug Development Flashcards
Pros of natural sources
More structural diversity and novelty
Can interact with proteins and other biological molecules
More complex in structure = allows for more selective binding to targets
Cons of natural sources
More time consuming
Expensive
Less sustainable
May be hard to obtain the active ingredient
The chemical compound may work differently than expected once isolated
Pros of synthetic drug sources
Less time consuming
Less costly
May be more sustainable
Cons of synthetic drug sources
Fewer therapeutic effects
Unacceptable side effect profile from off-target effects
Less likely to be novel
More likely to develop resistance
Relies on computer modelling databases to screen
Desirable characteristics of an anticancer drug
Potent = to use low doses
Specific = minimise off-target effects
Cross BBB if that is where the tumour is = lipid soluble and water soluble (logP of 1.5-2.7) + low Mr + low hydrogen bond potential
Target all stages of cell cycle = especially if the cancer is slow-growing
Novel
GASHAN PP
How to increase the solubility of a drug?
Salt formation
Hydrogen bonding sites
Change formulation (granules)
Strategies to shorten the clinical development of a drug?
Drug repurposing
Biosimilar drugs
Fast track
Breakthrough therapy
Accelerated approval
Priority review
Drug repurposing
Reformulating
Reusing
New indication
New dose?
Biosimilar drugs
Very similar in structure to drugs that have already been approved
They may not need to conduct as robust safety and efficacy trials if the data collected from preclinical studies correlates to the data from the approved drug
Fast track
Communication between the drug sponsor and regulatory authority before submission of a New Drug Application (avoids issues that could delay the review and approval)
Breakthrough therapy
Review data early with the regulatory agency
Accelerated approval
Request an approval based on study results that are a sign of how well the drug may benefit patients.
Priority review
The regulatory agency will review the application within 6 months instead of within 10 months
Which regulatory agency authorises licenses in the UK?
MHRA
Which regulatory agency authorises licenses in the EU?
EMA
Which regulatory agency authorises licenses in the USA?
FDA
Why do drugs go through a review process before they receive a license?
Ensures they are safe, effective and benefits outweigh side effects
What does the MHRA specifically look at when reviewing clinical trial data?
Safety and quality standards of medicines, medical equipment and blood products
Safety and supply chain for meds
Promoting international standards to ensure biological medicines are effective and safe
Educating public and healthcare professionals about risks and benefits of meds
Supporting research and development that benefit public health
Influencing UK, EU and international regulations so they protect public health
What happens if the drug is proven to be safe and effective?
Can be manufactured, labelled, and distributed
How can the approval process be improved?
Meetings with the pharmaceutical companies / drug sponsor / regulatory authority early to ensure the clinical trial has been developed in the best possible way
Working with drug regulatory agencies to streamline approval of drugs approved in other countries.
The international conference of harmonisation (ICH) = makes sure the details required for drug approval are similar between countries
Provide incentives for sponsors to develop new drugs that treat rare diseases (Orphan Drug Act)
Issues in the development of anticancer drugs
Lack of suitable tests
Difficulty of conducting early clinical trials
Difficult to predict which chemical will be effective against a certain class of cancer
Expensive and lengthy trials
Issues in the development of anticancer drugs
Lack of suitable laboratory tests to detect small but important repsonses
Difficult to predict which chemical will be effective against a certain class of cancer
Expensive and lengthy trials
New drugs can only be tested against advanced and usually heavily pre-treated diseases = unlikely to show a dramatic response
Preclinical trials must be carried out in both rodents and one other species
Drug effects in animal models aren’t accurate as you have to induce the cancer so may not replicate key aspects of human malignancies
Issues with identifying a cancer target in anticancer drug design
Understanding the role of the target in the pathogenesis of disease
Target overexpression
Single nucleotide polymorphisms in genes responsible for drug metabolism = complicated drug PK
