(This article is sponsored by The Boston Group)

Once Target Identification, Target Validation, Lead Identification and Lead Optimization have been completed, the drug development goes through various preclinical and clinical studies.

Preclinical Studies:
In the preclinical stage of drug development an investigational drug must be tested extensively in the laboratory to ensure that it will be safe to administer to humans. Testing at this stage can take from 1 to 5 years and must provide information about the pharmaceutical composition of the drug, its safety, how the drug will be formulated and manufactured, and how it will be administered to the first human subjects.

Results of all testing must be provided -- to the Food and Drug Administration (FDA) in the U.S. and/or other appropriate regulatory agencies -- in order to obtain permission to begin clinical testing in humans. Regulatory agencies review the specific tests and documentation that are required to proceed to the next stage of development.

Preclinical technology
During the preclinical development of a drug, laboratory tests document the effect of the investigational drug in cells in the test tube (in vitro) and in
living organisms (in vivo).

Chemical Manufacturing Controls (CMC)/Pharmaceutics
The results of preclinical testing are used by experts in pharmaceutical methods to determine how to best formulate the drug for its intended clinical use. For example, a drug that is intended to act on the sinuses may be formulated as a time-release capsule or as a nasal spray. Regulatory agencies require testing that documents the characteristics -- chemical composition, purity, quality and potency -- of the drug’s active ingredient and of the formulated drug.

Pharmacology/Toxicology
Pharmacological testing determines effects of the candidate drug on the body. Toxicology studies are conducted to ensure that any risks to humans are identified.

Investigational New Drug (IND) Applications
IND is an example of requests submitted to appropriate regulatory authorities for permission to conduct investigational research.  In addition to obtaining permission from appropriate regulatory authorities, an institutional or independent review board (IRB) or ethical advisory board must approve the protocol for testing as well as the informed consent documents that volunteers sign prior to participating in a clinical study.

Clinical testing is usually described as consisting of Phase I, Phase II and Phase III clinical studies. In each successive phase increasing numbers of patients are tested.
 
Clinical Studies:

Phase I Clinical Studies
Phase I studies are designed to verify safety and tolerability of the candidate drug in humans and typically take 6 to 9 months. These are the first studies conducted in humans. A small number of subjects, usually from 20 to 100 healthy volunteers, take the investigational drug for short periods of time. Testing includes observation and careful documentation of how the drug acts in the body -- how it is absorbed, distributed, metabolized and excreted.

Phase II Clinical Studies
Phase II studies are designed to determine effectiveness and further study the safety of the candidate drug in humans. Depending upon the type of investigational drug and the condition it treats this phase of development generally takes from 6 months up to 3 years. Testing is conducted with up to several hundred patients suffering from the condition the investigational drug is designed to treat. This testing determines safety and effectiveness of the drug in treating the condition and establishes the minimum and maximum effective dose.

Phase III Clinical Studies
Phase III studies provide expanded testing of effectiveness and safety of an investigational drug, usually in randomized and blinded clinical trials. Depending upon the type of drug candidate and the condition it treats this phase of development usually requires one to four years of testing. In Phase III, safety and efficacy testing is conducted with several hundred to thousands of volunteer patients suffering from the condition the investigational drug treats.

New Drug Application (NDA)/Marketing Authorization Application (MAA)
NDAs (in the U.S.) and MAAs (in the U.K.) are examples of applications to market a new drug. Such applications document safety and efficacy of the investigational drug and contain all the information collected during the drug development process. At the conclusion of successful preclinical and clinical testing, this series of documents is submitted to the Food and Drug Administration (FDA) in the U.S. or to the applicable regulatory authorities in other countries. The application must present substantial evidence that the drug will have the effect it is represented to have when people use it or under the conditions for which it is prescribed, recommended or suggested in the labeling. Obtaining approval to market a new drug frequently takes between 6 months and 2 years.

Phase IIIb/IV Studies
Phase IIIb trials, which often begin before approval, may supplement or complete earlier trials by providing additional safety data or they may test the approved drug for additional conditions for which it may prove useful. Phase IV studies expand testing of a proven drug to broader patient populations and compare the long-term effectiveness and/or cost of the drug to other marketed drugs available to treat the same condition.

Post-Marketing Studies
Post-marketing studies test a marketed drug in new age groups or patient types. Some studies focus on previously unknown side effects or related risk factors. As with all stages of drug development testing, the purpose is to ensure the safety and effectiveness of marketed drugs.

This is the reason why discovering and bringing one new drug to the public typically cost a pharmaceutical or biotechnology company nearly $900 million and takes an averagge of 8 to 10 years.

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