Drug development

Drug development or preclinical development is defined in many pharmaceutical companies as the process of taking a new chemical lead through the stages necessary to allow it to be tested in human clinical trials, although a broader definition would encompass the entire process of drug discovery and clinical testing of novel drug candidates.

New chemical entitity (NCE) development
New chemical entities (NCEs) are compounds which emerge from the process of drug discovery. These will have promising activity against a particular biological target thought to be important in disease, however little will be known about the safety, toxicity, pharmacokinetics and metabolism of this NCE in humans. It is the function of drug development to assess all of these parameters prior to human clinical trials. A further major objective of drug development is to make a recommendation of the dose and schedule to be used the first time an NCE is used in a human clinical trial ("first-in-man", FIM).

In addition, drug development is required to establish the physicochemical properties of the NCE: its chemical makeup, stability, solubility. The process by which the chemical is made will be optimized so that from being made at the bench on a milligram scale by a synthetic chemist, it can be manufactured on the kilogram and then on the ton scale. It will be further examined for its suitability to be made into capsules, tablets, aeresol, intramuscular injectable, subcuteneous injectable, or intravenous formulations. Together these processes are known in preclinical development as CMC: Chemistry, Manufacturing and Control.

Many aspects of drug development are focused on satisfying the regulatory requirements of drug licensing authorities. These generally constitute a number of tests designed to determine the major toxicities of a novel compound prior to first use in man. It is a legal requirement that an assessment of major organ toxicity be performed (effects on the heart and lungs, brain, kidney, liver and digestive system), as well as effects on other parts of the body that might be affected by the drug (e.g. the skin if the new drug is to be delivered through the skin). While, increasingly, these tests can be made using in vitro methods (e.g. with isolated cells), many tests can only be made by using experimental animals, since it is only in an intact organism that the complex interplay of metabolism and drug exposure on toxicity can be examined.

The process of drug development does not stop once an NCE begins human clinical trials. In addition to the tests required to move a novel drug into the clinic for the first time it is also important to ensure that long-term or chronic toxicities are determined, as well as effects on systems not previously monitored (fertility, reproduction, immune system, etc). The compound will also be tested for its ability to cause cancer (carcinogenicity testing).

If a compound emerges from these tests with an acceptable toxicity and safety profile, and it can further be demonstrated to have the desired effect in clinical trials, then it can be submitted for marketing approval in the various countries where it will be sold. In the US, this process is called a New Drug Application or NDA. Most NCEs, however, will fail during drug development, either because they have some unacceptable toxicity, or because they simply do not work in clinical trials.

As this drug discovery process becomes more expensive it is becoming important to look at new ways to bring forward NCEs. One approach to improve efficiency is to recognize that there are many steps requiring different levels of experimentation. The early phase of drug discovery actually has components of real innovation, components of experimentation and components that involve set routines. This model of Innovation, Experimentation, and Commoditization ensures that new ways to do work are adopted continually. This model also allows the discipline to use appropriate internal and external resources for the right work.

Cost
Studies published in 2003 report an average pre-tax cost of approximately $800 million to bring a new drug (i.e. a drug with a New Chemical Entity) to market.

A study published in 2006 estimates that costs vary from around 500 million to 2,000 million dollars depending on the therapy or the developing firm.

These figures relate only to new, innovative drugs (drugs with a New Chemical Entity BCE, also called New Active Substance NAS). Each year, worldwide, only about 26 such drugs enter the market (2005: 26, 2004: 24, 2003: 26, 2002: 28). The development cost of the thousands of other drugs are much smaller. The $800 million quoted include the cost of all drug development which did not result in a new drug. It also includes some 400 million $ of opportunity costs.

The consumer advocacy group Public Citizen suggests on its web site that the actual cost is under $200 million, about 29% of which is spent on FDA-required clinical trials.