Drugs & Medication

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 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 human. 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 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.

See also

• Drug design
• Drug discovery
• Pharmaceutical company

External links

• Drug Development Technology Projects, companies and industry news
• International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
• Food and Drug Administration (FDA)
• Good Clinical Practices (GCP)
• Good Review Practices (GRP)
• Innovation and Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products (FDA)
• Belmont report - 18 April 1979
• IND Rewrite Regulations (FDA Title 21 CFR Parts 312, 314, 511, and 514)
• CDER Drug and Biologic Approval Reports
• Pharmaceutical Research and Manufacturers of America (PhRMA)
• European Federation for Pharmaceutical Sciences (EUFEPS)
• Innovative Medicines Initiative (IMI - EU)
• European Medicines Agency (EMEA)
• Pharmaceuticals and Medical Devices Agency (PMDA)
• Council for International Organizations Of Medical Sciences (CIOMS)
• Priority Medicines for Europe and the World Project "A Public Health Approach to Innovation" (WHO)
• WHO Model List of Essential Medicines
• Clinical Data Interchange Standards Consortium (CDISC)
• World Medical Assocation (WMA)
• Nuremberg Code - ethical code
• Declaration of Geneva - ethical code
• Declaration of Helsinki - ethical code
• Tufts Center for the Study of Drug Development
• Institute for Regulatory Science
• Association of Clinical Research Professionals (ACRP)