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• Pharmacokinetic properties: It must have an acceptable rate of absorption,
  bioavailability, clearance, volume of distribution and plasma half-life to ensure that its
  dosing size and frequency and onset and duration of action meet patient needs.


• Toxicological properties: Ideally it must possess a large therapeutic index, but in some
  forms of therapy, notably with cytotoxic drugs, this is not possible.
  Most candidate drugs in clinical development fail to reach the clinical market for one
  of four reasons – inappropriate pharmacokinetics, lack of efficacy, unacceptable
  toxicology and adverse effects in humans.

18.2 Drug discovery

18.2.1 Drug discovery and development processes

The launching of a new drug onto the clinical market is the culmination of three

distinct processes – drug discovery, drug development and drug marketing. Schemati-

cally the processes can be represented as follows:

Although presented as three linear stages, in practice it is essentially a parallel

activity supporting a ‘learn and confirm’ approach with the ‘proof of concept’ as an

important decision point. The high cost of drug discovery and development, variously

estimated at $500 m to $3 bn, and the long-term nature of drug discovery and

development coupled with the competitive need to get the drug licensed and in clinical

use as quickly as possible, drive the management strategy underlying the discovery

and development processes. To minimise potential development losses there is a

Promotion of drug to

authorities for clinical use

Assessment for

economic value

Clinical

use

Post-marketing

surveillance

Drug marketing – an ongoing process

Candidate

drug

Preclinical

development

‘proof of concept’

decision point

for ‘go’/‘no go’

NDA

application

Clinical development

Phase I Phase II Phase III

Regulatory

approval

New

drug

Drug development – lasts 8–10 years

Therapeutic

concept

Selection

of target

Drug discovery – lasts 2–5 years

Development

and validation

of assay

Screening and

identification of

lead compounds

Lead optimisation and

identification of

candidate drug

718 Drug discovery and development