(This article is sponsored by The Boston Group)
Target Identification, Target Validation, Lead Identification and Lead
Optimization have been completed, the drug development goes through
various preclinical and clinical studies.
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
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.
the preclinical development of a drug, laboratory tests document the
effect of the investigational drug in cells in the test tube (in vitro)
living organisms (in vivo).
Chemical Manufacturing Controls (CMC)/Pharmaceutics
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.
testing determines effects of the candidate drug on the body.
Toxicology studies are conducted to ensure that any risks to humans are
Investigational New Drug (IND) Applications
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.
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.
Phase I Clinical Studies
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
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
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)
(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
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
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.
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.