Chemistry Reference
In-Depth Information
the acute toxicity of the drug in at least two species of animals. If novel excipient is used
to prepare the drug product, then the information on the pharmacological and toxico-
logical pro
les of the novel excipient is also included. Any previous experience with the
drug in humans, for example, from another country whose population is relevant to the
U.S. population, is also included as part of the information provided in this section.
Manufacturing Information
section includes information, pertaining to the composition,
manufacturer, stability, and controls (used for manufacturing the drug substance and the
drug product), that would ensure that the sponsor can adequately produce and supply
consistent batches of the drug.
Clinical Protocols and Investigator Information
section
includes detailed protocols for proposed clinical studies to assess whether the initial-
phase trials will expose subjects to unnecessary risks. This section also includes
information on the quali
cations of clinical investigators, that is, professionals (generally
physicians) who oversee the administration of the experimental compound, to allow an
assessment of their quali
lling their clinical trial duties and commitments to
obtain informed consent from the research subjects, to obtain review of the study by
an institutional review board (IRB), and to adhere to the investigational new drug
regulations.
Clinical trials are performed to evaluate the safety and effectiveness of an IND in
treating, preventing, or diagnosing a speci
cation in ful
c disease or condition. The most important
consideration in these trials is the safety of the human subjects. Hence, the FDA carefully
monitors the design and conduct of these clinical trials to ensure that subjects in these
trials are not exposed to unnecessary risks. The sponsors are therefore required to ensure
the identity, quality, purity, and strength of the IND during the clinical trials and submit
this information to the FDA. A sponsor must wait 30 days from the date of submitting an
IND application before starting a clinical trial. This allows FDA to review the prospective
study. If FDA
finds problem(s) with the study, it may order a clinical hold to delay the
start of the clinical trials. In some cases, FDA interrupts a clinical trial if problems are
found during the study.
Clinical trials of an IND are generally divided into three phases, which are generally
conducted sequentially.
Phase 1
is the initial introduction of the IND into human
subjects. The subjects in these studies are generally healthy volunteers, although they
may also be conducted in patients. The total number of subjects and patients included in
phase 1 studies varies with the drug, numbering anywhere from 20 to 80 subjects. The
studies in this phase are designed to determine the metabolism and pharmacological
actions of the drug in humans, the side effects associated with increasing doses, and, if
possible, to gain early evidence on effectiveness. These studies also evaluate drug
metabolism, structure
activity relationships, and mechanism of action in humans, as well
as explore the use of the IND in biological phenomena or disease processes. The
information on the drug
-
s pharmacokinetics and pharmacological effects collected in
phase 1 clinical trials is used to design well-controlled, scienti
'
cally valid, phase 2
studies.
Phase 2
includes the early controlled clinical studies conducted in a relatively
small number of patients, generally no more than several hundred subjects. The studies in
this phase are designed to obtain preliminary data on the effectiveness of the drug for a
particular indication or indications in patients with the disease or condition under study.
These studies also help determine the common short-term side effects and risks
