Frequently Asked Questions on
the Regulatory Process of
Over-the-Counter (OTC) Drugs
is an Over-the-Counter (OTC) Drug Product?
An OTC drug
product is a drug product marketed for use by the consumer without
the intervention of a health care professional in
order to obtain the product. Two post-1938 regulatory pathways exist
for the legal marketing of such products:
compliance with an OTC drug monograph
the authority of an approved product-specific new drug application
(NDA), or an abbreviated new drug application (ANDA)
is a prescription drug product?
drug product is a drug product approved for marketing that can only
be obtained with a prescription from an appropriate health care
is the OTC drug review?
The OTC drug
review was established to evaluate the safety and effectiveness of
OTC drug products marketed in the United States before May 11, 1972.
It is a three-phase public rulemaking process (each phase requiring
a Federal Register publication) resulting in the
establishment of standards (monographs or non-monographs) for an OTC
therapeutic drug category.
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is the first phase of the OTC drug review?
The first phase
was accomplished by advisory review panels. The panels were charged
with reviewing the ingredients in nonprescription drug products to
determine whether these ingredients could be generally recognized as
safe and effective for use in self-treatment. They were also charged
with reviewing claims and recommending appropriate labeling,
including therapeutic indications, dosage instructions, and warnings
about side effects and preventing misuse.
According to the
terms of the review, the panels classified ingredients in three
categories as follows:
Category I: generally recognized as
safe and effective for the claimed therapeutic indication;
Category II: not generally recognized
as safe and effective or unacceptable indications;
Category III: insufficient data
available to permit final classification
5. What is
the second phase of the OTC drug review?
The second phase
of the OTC drug review was the agency’s review of ingredients in
each class of drugs, based on the panel’s findings, on public
comment, and on new data that may have become available. The agency,
in turn, publishes its conclusions in the Federal Register in
the form of a tentative final monograph. After publication of the
tentative final monograph, a period of time is allotted for
objections to the agency’s proposal or for requests to be submitted
for a hearing before the Commissioner of FDA.
is the third phase of the OTC drug review?
The publication of
final regulations in the form of drug monographs is the third and
last phase of the review process. The monographs establish
conditions under which certain OTC drug products are generally
recognized as safe and effective.
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Drug Product Applications
is a human drug application?
term human drug application means an application for:
approval of a new drug submitted under
section 505(b)(1) of the
Federal Food, Drug, and Cosmetic Act
approval of a new drug submitted
under section 505(b)(2) of the FD&C Act
approval of an abbreviated new
drug application under section 505(j) of the FD&C Act
licensure of certain biological
products under section 351 of the Public Health Service Act
What is a 505(b)(1)
A 505(b)(1) application is an
application that contains full reports of investigations of safety
the applicant relied on for approval were conducted by, or for the
applicant, or the applicant has obtained a right of reference or use
for the investigations.
What is a 505(b)(2)
application is one described under section 505(b)(2) of the FD&C Act as
an application for which one or more of the investigations relied
upon by the applicant for approval "were not conducted by or for the
applicant and for which the applicant has not obtained a right of
reference or use from the person by or for whom the investigations
were conducted" (21 U.S.C. 355(b)(2)). This provision permits FDA to
rely on a previous finding of safety and effectiveness that led to
approval of an NDA or on data not developed by the applicant such as
applications are submitted under section 505(b) of the Act and are
therefore subject to the same statutory provisions that govern
505(b)(1) applications that require among other things, "full
reports" of safety and effectiveness.
10. What is an
Abbreviated New Drug Application (505)(j)?
An abbreviated new
drug application is described under section 505(j) of the Act as an
application that contains information to show that the proposed
product is identical in active ingredient, dosage form, strength,
route of administration, labeling, quality, performance
characteristics and intended use, among other things to a previously
approved application (the reference listed drug (RLD)). ANDAs do not
contain clinical studies as required in NDAs but are required to
contain information establishing bioequivalence to the RLD. In
general, the bioequivalence determination allows the ANDA to rely on
the agency’s finding of safety and efficacy for the RLD.
11. What is a supplement to an
Federal Food, Drug, and Cosmetic Act says, “The term
supplement means a request to the Secretary to approve a change
in a human drug application which has been approved.” Each
indication or claim is considered a separate change for which a
separate supplement should be submitted. This policy allows FDA to
approve each indication or claim when it is ready for approval
rather than delaying approval until the last of a group of
indications or claims is ready to be approved.
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OTC Drug Product Monographs
12. What is an OTC monograph?
OTC monographs represent regulatory standards for the marketing of
non-prescription drug products not covered by new drug applications.
These standards provide the marketing conditions for some OTC drug
products including the active ingredients, labeling, and other
13. Is pre-clearance necessary if
the standards of the OTC monograph are met?
Marketing pre-clearance of OTC drug products by the FDA is not
required if the standards of the applicable monograph are met.
Additional requirements for the marketing of human drug products may
be found in Title 21 of the Code of Federal Regulations
14. Are there other options for marketing an OTC drug products
besides on OTC monograph?
A 505(b)(1) application, a 505(b)2 application, or an abbreviated
new drug application can be submitted.
What is the appropriate process to request amendment or repeal of
conditions covered by exiting proposed or final OTC monographs?
NDA can be used to request approval of an OTC drug that deviates in
any respect from a monograph that has become final (see
However, a citizen petition (see
21 CFR 10.30) is another means to request an amendment or repeal
of conditions covered by an existing proposed or final OTC drug
monograph. In order for FDA to act on the petition, accompanying data
general safety and effectiveness
(or lack thereof). An advantage of submitting a citizen petition is
that a Prescription Drug User Fee Act (PDUFA) fee is not required as with a NDA. But the NDA process
does provide confidentiality during the review, an established
review timeframe (as provided under PDUFA), and a period of potential marketing exclusivity upon
approval, if certain conditions are met.
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What is prescription to OTC
OTC switch refers to over-the-counter marketing of a product that was once a
prescription drug product for the same indication, strength, dose,
duration of use, dosage form, population, and route of
17. How is a
prescription to OTC switch accomplished?
supplement should be submitted to an approved NDA for a prescription
product if the sponsor plans to switch the drug product covered
under the NDA to OTC marketing status in its entirety without a
change in the previously approved dosage form or route of
administration. An NDA 505(b)(1) should be submitted if the sponsor
is proposing to convert some but not all of the approved
prescription indications to OTC marketing status. An original NDA
(505)(b)(1) or 505(b)(2) needs to be submitted if the sponsor plans
to market either a new product OTC whose active substance,
indication, or dosage form has never previously been marketed OTC.
Time and Extent Application
18. What is
the purpose of a time and extent application?
The purpose of a Time and Extent
Application (TEA) is to request that applicable conditions be
considered for inclusion in the OTC monograph system (21
CFR 330.14). Submission of a TEA is only the first step of a
two-step process to demonstrate eligibility of the condition for the
OTC monograph review process. A TEA should only be submitted for
conditions that the applicant believes have been marketed
to “a material extent” and “for a material time” as follows:
If FDA believes that material time
and extent has been demonstrated through the TEA, the condition is
then declared eligible for the monograph review. The second step of
the process, requiring demonstration of general safety and
What is a "condition" for an OTC drug product?
Condition refers to an active ingredient or botanical drug substance
(or combination of both), dosage form, dosage strength, or route of
administration marketed for a specific over-the-counter use. This includes
conditions regulated as cosmetic products or dietary supplements in
a foreign country(ies) that would be regulated as OTC drugs in the
20. Where can I find additional
information on the time and extent application?
The final regulations (21CFR
330.14) for criteria and procedures for a Time and Extent
Application (TEA) were published in the Federal Register on January
23, 2002. A copy of the final rule can be obtained at:
draft guidance for industry for TEA applications is also available:
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Standardizing the OTC Labeling
What is standardizing OTC labeling?
In the Federal
Register of March 17, 1999, FDA published a final regulation (21
CFR 201.66), establishing standardized content and format for
the labeling of OTC drug products.
labeling for OTC drug products is intended to make it easier for
consumers to read and understand OTC drug products safely and
effectively. The labeling regulations in
21 CFR 201.66 cover all
OTC drug and drug-cosmetic products, whether marketed under a
505(b)(1) application, a 505(b)(2) application, abbreviated new drug
application ,or an OTC drug monograph.
22. What is professional labeling?
Some OTC monographs contain
professional labeling that provides specific information to health
professionals for uses not included in OTC drug labeling.
monographs contain professional labeling?
drug monographs with professional
labeling include those in the following drug categories:
- Topical Antifungal
- Cough and cold
- Internal analgesics
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24. Where can I find additional
information about OTC drug products?
should I contact if I still have questions about OTC drug products?
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Date created: April 5, 2004