Regulation of Over-the-Counter (OTC) Drugs
August 29, 2016
Regulation of Over-the-Counter (OTC) Drugs
The Food and Drug Administration (FDA) regulates the
The OTC Monograph Process
safety and effectiveness of drug products sold in the United
In 1972, FDA established the OTC Drug Review to
States. FDA’s regulatory authority covers both prescription
evaluate the effectiveness of OTC drug products marketed
and nonprescription (i.e., over-the-counter, or OTC) drugs,
in the United States prior to May 11, 1972. The OTC Drug
among other things.
Review is an ongoing, three-phase public rulemaking
process.
Legislative Background
The Pure Food and Drug Act of 1906 prohibited the
Three-Phase Drug Review
interstate commerce of adulterated and misbranded drugs,
The first phase of the process is advisory panel review.
but it did not provide FDA with the authority to review and
When the OTC Drug Review first began, the FDA
approve products before they enter the market. Thus, drugs
Commissioner convened an advisory panel for each drug
introduced between 1906 and 1938 were considered “pure”
category (e.g., antacids, sleep aids; drug categories are
but with unknown safety and effectiveness. In 1938,
listed at 21 C.F.R. 330.5). The commissioner also published
Congress passed the Federal Food, Drug, and Cosmetic Act
a notice in the Federal Register (FR) calling upon
(FFDCA), which authorized FDA to regulate the safety of
interested persons to submit for review by an advisory
drug products sold in the United States. In 1951, the
panel data and pertinent information for a category of
FFDCA was amended to include a prescription-only
drugs. Each panel was tasked with evaluating the active
category of drugs. While prescription drugs require health
ingredients and existing labeling for a particular class of
practitioner supervision (due to drug toxicity, potential
OTC drug products to determine what should be allowed to
harmful effect, and/or method of use), OTC drugs can be
be classified as generally recognized as safe and effective
used without a prescriber’s authorization, provided that they
(GRASE) for self-diagnosis, self-selection, and self-
have an acceptable safety margin, low potential for misuse
treatment. The advisory panel categorized the active
or abuse, and are adequately labeled so that consumers can
ingredients in each drug category as GRASE, not GRASE,
self-diagnose the condition, self-select the medication, and
or more information needed. The panel then submitted their
self-manage the condition.
recommendations in a report to FDA, which was published
in the FR as an advance notice of proposed rulemaking
Although the FFDCA of 1938 required a manufacturer to
(ANPR) with a 90-day public comment period.
demonstrate that its drug product was safe, the law did not
provide FDA the authority to require premarket evaluation
In the second phase of the OTC Drug Review, FDA
of effectiveness. A safety tragedy with the drug
evaluated the panel recommendations, public comments,
Thalidomide and birth defects in other countries led to
and other available data. The agency published its tentative
public support for stronger drug regulation in the United
conclusions regarding the GRASE status of ingredients in
States. In 1962, the FFDCA was amended to require that a
that therapeutic class in the FR as a tentative final
drug manufacturer demonstrate that its drug is effective, in
monograph (TFM), or proposed rule. If an advisory panel
addition to safe, for its intended use. This standard became
or FDA found no ingredients to be GRASE for a particular
the basis for the new drug application (NDA) process in
use, the agency issued a proposed rule to remove such
place today (see CRS Report R41983, How FDA Approves
ingredients from further consideration and to require
Drugs and Regulates Their Safety and Effectiveness).
approval of an NDA for that drug product. The public was
Because drugs introduced between 1938 and 1962 were
once again provided with a comment period on the TFM.
considered safe but with unknown effectiveness, FDA
formed the Drug Efficacy Implementation Study (DESI),
The third phase of the review—monograph finalization—is
contracting with the National Academy of Science/National
ongoing, and a number of marketed OTC products are not
Research Council (NAS/NRC) to evaluate the effectiveness
yet covered by a final monograph (e.g., some external
of those drugs approved on the basis of safety alone.
analgesic products). In this phase, FDA considers the public
However, the new requirement that a sponsor demonstrate
comments provided in response to a TFM and any new data
the effectiveness of a drug product prior to marketing
the agency receives. FDA then publishes a final monograph
created a dilemma for FDA. It is estimated that in the early
in the FR as a final rule (and later in the Code of
1970s there were over 100,000 OTC drug products, made
Regulations). The monograph functions as a sort of
up of hundreds of different active ingredients, belonging to
“rulebook.” It establishes standards for each therapeutic
26 broad therapeutic drug categories (as determined by
category, addressing acceptable conditions (e.g., active
FDA), which limited the feasibility of an FDA product-by-
ingredients, dosage strength, dosage form, route of
product review of effectiveness data.
administration). The final monographs are published in 21
C.F.R. parts 331-358. Provided that an OTC drug meets the
specifications of the monograph, it is does not have to go
through the FDA premarket approval process. Drug
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Regulation of Over-the-Counter (OTC) Drugs
products that do not meet the conditions of the monograph
Summary of Regulatory Pathways
can apply for approval via the NDA process.
An OTC drug may enter the market via an approved NDA
or abbreviated new drug application (which are product-
Figure 1. OTC Monograph Process
specific) or by conforming to a monograph (which is
ingredient-specific). Both pathways involve a scientific
decision by FDA; however, there are some differences
between the two mechanisms (see Table 1). Note that
NDA-approved prescription drugs can switch to OTC
status. The “Rx-to-OTC switch” is not discussed in this In
Focus.
Table 1. Regulatory Pathways for OTC Drug Products
NDA Process
OTC Monograph
Premarket approval
No premarket approval
Confidential filing
Public, rulemaking process
Drug product-specific
Active ingredient-specific
May require a user fee
No user fees
Potential for marketing
No marketing exclusivity
exclusivity
Source: Figure created by CRS based on FDA’s website,
http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/
Mandated review timelines
No mandated timelines
UCM148055.pdf.
Generally requires clinical
Generally does not require
FDA continues to consult with its advisory committees
studies
clinical studies
(e.g., the Nonprescription Drugs Advisory Committee) on
Reporting requirements
Limited reporting requirements
monograph-related issues.
(serious adverse events only)
Source: FDA, Regulation of Nonprescription Drug Products,
Time and Extent Applications
http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/
The OTC monograph is a living document, as data and
UCM148055.pdf.
clinical understanding are constantly evolving. There are
mechanisms to incorporate a new product or product
Issues for Congress
condition into an existing monograph. A Citizen’s Petition
Although the OTC Drug Review began in the 1970s, many
(CP) or a Time and Extent Application (TEA) may be used
OTC monographs have not yet been finalized. FDA
to request that FDA amend an OTC drug monograph to
estimates that there are approximately 88 simultaneous
incorporate a new product or product condition. The CP
rulemakings in 26 broad therapeutic categories, and
may be used only to include an ingredient that would have
approximately 800 active ingredients for over 1,400
been eligible for inclusion in the original TFM (i.e., the
different therapeutic uses. The Division of Non-Prescription
product must have been marketed in the United States prior
Drug Products within FDA’s Center for Drug Evaluation
to 1972), while the TEA applies to products initially
and Research (CDER) currently has 18 full-time employees
marketed under an approved NDA after the OTC drug
devoted to overseeing the entire OTC market, which is
review began, or those without any U.S. marketing
about the same number of employees it takes to review one
experience (21 C.F.R. 330.14(a)).
novel prescription drug application, according to CDER
Director Janet Woodcock. Moreover, the agency’s
The TEA is a two-step process. The first step is eligibility—
resources have been constrained by activities related to
the interested party must demonstrate that the OTC drug
congressional mandates. On June 10, 2016, FDA held a
has been marketed for a “material time” and to a “material
public meeting to gather stakeholder input on the potential
extent.” “Material time” is defined as marketing for a
development of a user fee program for OTC monograph
minimum of five continuous years in the same country, and
drugs. Such user fees would be used to support FDA review
“material extent” is defined as marketing a sufficient
of the effectiveness and safety of ingredients to be included
quantity as described in FDA regulation at 21 C.F.R.
in a monograph. FDA is currently seeking input regarding
330.14(c). These criteria have to be assessed for each
the types of user fees (e.g., product listing fees, application
specific product. If FDA determines that the drug is eligible
fees) and performance goals that might be appropriate for a
for inclusion in the monograph, the second step is
monograph user fee program.
submission of safety and effectiveness data. FDA publishes
a notice in the FR asking interested parties to submit data
Agata Dabrowska, Analyst in Health Policy
and pertinent information for that drug product. FDA or an
advisory panel then reviews the data using the same safety
IF10463
and effectiveness standards as the OTC Drug Review. FDA
has followed the TEA process to evaluate topical acne
active ingredients, as well as sunscreen active ingredients
prior to the enactment of the Sunscreen Innovation Act.
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Regulation of Over-the-Counter (OTC) Drugs
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