Chemistry Reference
In-Depth Information
12.2 APPROVAL PROCESS IN THE UNITED STATES
Drug development is a multistep and multidisciplinary process involving discovery,
development, Food and Drug Administration (FDA) review and approval, and post-
approval, postmarketing safety surveillance to ensure continued safety and ef
cacy of
the drug. The drug discovery process involves screening of a large number of novel
compounds for pharmacological activity, followed by acute toxicity studies in animals of
the promising compounds. For the new molecular entities that show promising phar-
macological activity, the next logical step is to determine diagnostic and/or therapeutic
potential in humans. The Federal Food, Drug, and Cosmetic Act (FD&C Act) considers
these new molecular entities as new drugs that are subjected to speci
c requirements
before they can be legally tested in human subjects.
1
The FDA is the agency of the U.S.
government that is responsible for enforcing the provision of this FD&C Act. Drugs
intended for human use are evaluated by FDA
s Center for Drug Evaluation and
Research (CDER) to ensure that they are safe and effective for their proposed use.
Drugs that are approved by the FDA are said to be
'
“
safe and effective when used as
directed.
”
All drugs have side effects and no drug is absolutely safe.
“
Safe
”
in this sense
means that the bene
ts of the drug appear to outweigh the known risks.
All new molecular entities undergo rigorous scrutiny by the FDA before they are
approved for human use. Investigational new drug (IND) application is the vehicle that
allows a sponsor to perform clinical trials in human subjects and also provides, to the
sponsor, technical exemption for interstate shipment of the IND, without an approved
market authorization.
2
IND submission is regulated by 21 CFR Part 312. There are three
types of IND applications. An
Investigator IND
is submitted by a physician who both
initiates and conducts an investigation and under whose immediate direction the
investigational drug is administered or dispensed. A physician might submit a research
IND to propose study on an unapproved drug, or on an approved product for a new
indication or in a new patient population. An
Emergency Use IND
allows the FDA to
authorize use of an experimental drug in an emergency situation that does not allow time
for submission of an IND in accordance with 21CFR, Section 312.23 or Section 312.34.
It is also used for patients who do not meet the criteria of an existing study protocol, or if
an approved study protocol does not exist. A
Treatment IND
is submitted for exper-
imental drugs showing preliminary evidence of drug ef
cacy for treating serious or
immediately life-threatening conditions, or if no comparable alternative drug or therapy
is available to treat that stage of the disease in the intended patient population. An
immediately life-threatening disease is de
ned as a stage of a disease in which there is a
reasonable likelihood of death occurring within a few months or in which premature
death is likely without early treatment.
An IND application must contain information on three broad areas [1]:
Animal
Pharmacology and Toxicology Studies
section includes all pertinent preclinical data that
would permit an assessment as to whether the product is reasonably safe for initial testing
in human subjects, including information on the pharmacological pro
le of the drug and
1
Title 21, United States Code, Chapter 9: Federal Food, Drug, and Cosmetic Act, 2012 ed.
2
Title 21, Code of Federal Regulations, Part 312. Investigational New Drug Application, 2012 ed.
