Chemistry Reference
In-Depth Information
with which new generic drug products need to be compared to show that they are
bioequivalent, thus avoiding the possibility of signi
cant variations among generic drugs
and their brand name counterpart.
Approval for market authorization for the generic drugs is obtained upon successful
review and approval of an
Abbreviated New Drug Application
(ANDA)
filed with the
FDA. Under the FD&C Act, a drug is considered
if it is made by a different
manufacturer, uses different excipients or inactive ingredients, is used for a different
purpose, or undergoes any substantial change.
4
Generic drug applications are called
“
“
new
”
because the sponsors are generally not required to include preclinical
(animal) and clinical (human) data to establish safety and effectiveness. Instead, they are
required to scienti
abbreviated
”
cally demonstrate that the generic drug is bioequivalent (i.e.,
performs in the same manner) to the innovator drug product. Bioequivalence may be
demonstrated by comparing the rate of absorption, or bioavailability, of the generic drug
with that of the innovator drug in 24
36 healthy volunteers [2]. An ANDA sponsor must
refer to the RLD in its application when seeking approval to market a generic equivalent
in the country. The ANDA review process focuses on the review of the chemistry,
bioequivalence and microbiology data, labeling information, and inspection of the
sponsor
-
s manufacturing facilities. Upon approval, the generic drugs are considered
to be therapeutically equivalent to the innovators product.
Over-the-counter
(OTC) drugs are developed and marketed under the OTC Mono-
graph process or through the already described NDA process. Each OTC drug mono-
graph is a kind of
'
covering acceptable ingredients, doses, formulations,
labeling, and, in some cases, testing parameters. Although preapproval by FDA for drugs
marketed under a drug monograph is not required, many companies seek assurance that
the product they intend to market under the drug monograph complies with the
regulations. FDA continually updates the OTC drug monographs to add new ingredients
and labeling as needed. Products conforming to an OTC monograph may be marketed
without FDA preapproval.
5
For products not con
“
recipe topic
”
rming to OTC drug monograph, an
approved NDA or ANDA is required before they could be marketed in the United States.
A sponsor may also use the NDA process to introduce these products into the OTC
marketplace. For example, OTC drug products previously available only by prescription
are
to OTC status is approved
via the NDA process. OTC drugs marketed overseas can be introduced into the U.S.
market via a monograph under a Time and Extent Application (TEA) as described in
21 CFR 330.14.
Since all possible side effects of a drug cannot be identi
first approved through the NDA process and their
“
switch
”
ed or anticipated during the
clinical trials, FDAmaintains a system of postmarketing surveillance and risk assessment
programs to identify adverse events that did not appear during the drug approval
process [3]. FDA monitors adverse events such as adverse reactions and poisoning.
The Agency uses this information to take preventive actions such as updating the
drug labeling and, on rare occasions, to reevaluate the approval or marketing decision.
4
Title 21, Code of Federal Regulations, Part 310. New Drugs, 2012 ed.
5
Title 21, Code of Federal Regulations, Part 330. Over the-Counter (OTC) Human Drugs Which Are Generally
Recognized as Safe and Effective and Not Misbranded, 2012 ed.
