Drug Development

Question 1

Pros of natural sources

Answer 1

More structural diversity and novelty

Can interact with proteins and other biological molecules

More complex in structure = allows for more selective binding to targets

Question 2

Cons of natural sources

Answer 2

More time consuming

Expensive

Less sustainable

May be hard to obtain the active ingredient

The chemical compound may work differently than expected once isolated

Question 3

Pros of synthetic drug sources

Answer 3

Less time consuming

Less costly

May be more sustainable

Question 4

Cons of synthetic drug sources

Answer 4

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

Question 5

Desirable characteristics of an anticancer drug

Answer 5

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

Question 6

How to increase the solubility of a drug?

Answer 6

Salt formation

Hydrogen bonding sites

Change formulation (granules)

Question 7

Strategies to shorten the clinical development of a drug?

Answer 7

Drug repurposing

Biosimilar drugs

Fast track

Breakthrough therapy

Accelerated approval

Priority review

Question 8

Drug repurposing

Answer 8

Reformulating

Reusing

New indication

New dose?

Question 9

Biosimilar drugs

Answer 9

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

Question 10

Fast track

Answer 10

Communication between the drug sponsor and regulatory authority before submission of a New Drug Application (avoids issues that could delay the review and approval)

Question 11

Breakthrough therapy

Answer 11

Review data early with the regulatory agency

Question 12

Accelerated approval

Answer 12

Request an approval based on study results that are a sign of how well the drug may benefit patients.

Question 13

Priority review

Answer 13

The regulatory agency will review the application within 6 months instead of within 10 months

Question 14

Which regulatory agency authorises licenses in the UK?

Answer 14

MHRA

Question 15

Which regulatory agency authorises licenses in the EU?

Answer 15

EMA

Question 16

Which regulatory agency authorises licenses in the USA?

Answer 16

FDA

Question 17

Why do drugs go through a review process before they receive a license?

Answer 17

Ensures they are safe, effective and benefits outweigh side effects

Question 18

What does the MHRA specifically look at when reviewing clinical trial data?

Answer 18

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

Question 19

What happens if the drug is proven to be safe and effective?

Answer 19

Can be manufactured, labelled, and distributed

Question 20

How can the approval process be improved?

Answer 20

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)

Question 21

Issues in the development of anticancer drugs

Answer 21

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

Question 22

Issues in the development of anticancer drugs

Answer 22

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

Question 23

Issues with identifying a cancer target in anticancer drug design

Answer 23

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