Drug design and development

Question 1

Briefly describe the drug development process

Answer 1

Discovery research 
Pre-clinical development 
Clinical development - Phase I, II, III
Regulatory review - phase IV 
Post marketing development

Question 2

What does phase 1 assess?

Answer 2

Safety

Question 3

What does phase 2 assess?

Answer 3

Efficacy

Question 4

What does phase 3 ssess?

Answer 4

Safety and efficacy in a >50% larger cohort

Question 5

What do the medicines and healthcare regulatory authority (MHRA) do?

Answer 5

Inspection
Enforcement
Authorisation
Vigilance

Question 6

Describe the pre clinical phase

Answer 6

Choose disease
Choose a drug target (High-throughput screening)
Identify a bioassay
Find a lead compound
Isolation, purification, structural determination

Question 7

What is a clinical study?

Answer 7

An investigation in humans which is intended to discover or verify the clinical, pharmacological and/or other effect of one or more therapeutic interventions.

Question 8

What is the aim of a clinical study?

Answer 8

ascertain the safety and/or efficacy of the medicinal product or intervention.

Question 9

List some regulations of clinical trials

Answer 9

Nuremburg code (1947)
Declaration of Helsinki (1964)
Directive 65/65/EEC1 (1965)
ICH GCP (1996)

EU Clinical Trials Directive 2001/20/EC (EUCTD)
UK Clinical Trials Regulations 2004
The Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019

Question 10

Describe the EU Clinical Trials Directive 2001/20/EC (EUCTD)

Answer 10

Framework which sets out how a clinical trial investigating the safety or efficacy of a medicinal product in humans must be conducted

Provides greater protection to participants

Ensures quality of conduct

Harmonise regulation and conduct of clinical trials in Europe

Question 11

Describe the UK clinical trials regulation 2004

Answer 11

Establishment of ethics committees

Sponsor

Clinical studies require authorisation by the MHRA

IMPs must be manufactured to GMP

MHRA may carry out statutory inspections

Question 12

What happened as a result of the new EU regulation of clinical trials in 2014?

Answer 12

The number of applications to carry out clinical trials in the EU fell by 25%

costs increased significantly

delays for launching a clinical trial rose by 90%

Question 13

What were the benefits of the new EU regulations of clinical trials in 2014?

Answer 13

streamlining the procedures

introduce a lighter regulatory regime

simplify reporting requirements

recognise that a trial can be led by more than one organisation, by formally introducing the concept of ‘co-sponsorship’

Question 14

Who is a healthy volunteer?

Answer 14

“an individual who is not known to suffer any significant illness relevant to the proposed study, who should be within the ordinary range of body measurements such as weight, whose mental state is such that she/he is able to understand and give valid consent to the study”

Question 15

Why use healthy volunteers?

Answer 15

Scientific

Practical

Regulatory requirements

Question 16

Describe the ethical considerations

Answer 16

Conscious or subconscious pressures on both the investigator and the volunteer

Motives and incentive

• Interest
• Financial
• Promotion
• Job security

Question 17

What does the health research authority do?

Answer 17

The HRA protects and promotes the interests of patients and the public in health and social care research.

Question 18

What are the roles of ethics comittees

Answer 18

Study is scientifically sound

Protocol

Consent form

Method of recruitment

Pharmacological studies

Question 19

Describe consent and volunteer responsibility

Answer 19

Concept of informed consent and a valid consent

Disclosure of medical history

Comply with the protocol

Report of side effects

Right to withdraw from the study

Declare injury or illness as the result of taking part in the study

Question 20

List some special groups

Answer 20

Women
Children
The elderly
Mentally handicapped
Prisoners
Students
Junior colleagues

Question 21

How are healthy volunteers used in pharmacology

Answer 21

Pharmacokinetics

Pharmacodynamics

Method of administration

Measuring effect, physiological response (eg. changes in BP, pulse, blood flow, etc), plasma and/or urine levels

Question 22

How are drugs promoted?

Answer 22

Drug ‘reps’

Sponsored attendance at industry-organised events or medical conferences

Journals/Publications

Direct advertising

Question 23

What is a new molecular entity

Answer 23

Active ingredient that has never been marketed

Question 24

Describe evergreening

Answer 24

Also known as life-cycle management of a drug

Revenue maintained way beyond the patent life

Drug properties in Europe eligible for patenting in 1980s - Primary uses, processes & intermediates, simple formulations

Drug properties in Europe eligible for patenting in 1990s – Packaging, dosing range, regimen & route, purification of the active ingredient, change of indication

Question 25

Describe me too drugs

Answer 25

Modified mimics of existing medications

Drugs has it’s origins in another

New agent in a class with established efficacy

Has resulted in - 11 ACE inhibitors, 11 ARBs, 7 Calcium channel blockers, 6 Statins

Good or bad?

Question 26

What are biological medicines?

Answer 26

derived from living cells or organisms and consist of large, highly complex molecular entities which may be difficult to characterise.

Question 27

What are biosimilar medicines?

Answer 27

biological medicines that are developed to be highly similar and clinically equivalent to an existing biological medicine. A biosimilar contains a version of an active substance of an already approved biological medicine, which is referred to as the ‘reference medicine’ or ‘originator medicine’.