Over-the-counter medicines (OTCs) occupy an important place in healthcare delivery. Often self-administered, they may be used
by consumers without a prescription. A few OTCs begin as prescription medicines approved by FDA. If FDA later approves, the
manufacturer may switch to OTC status. Most OTC products, however, were in widespread use prior to the modern regulatory era
and were deemed "generally recognized as safe/effective" by FDA, starting and staying as OTCs, using the FDA monograph system
as a basis for marketing. Yet, like all drugs, they rely on quality monographs in the official compendia of the United States
Pharmacopeia–National Formulary (USP–NF), published by the US Pharmacopeial Convention. These OTCs do not require FDA approval
and thus may adapt more quickly to market demands for new dosage forms, combinations, and colors and flavors.
Roger L. Williams
Both OTCs and prescription drugs are subject to the same modern challenges of a globalized industry, including supply chain
management/security and the need for rigorous quality control, as active ingredients and finished products increasingly are
manufactured outside the US. Both types of medications also are subject to the same consumer expectations for specified efficacy,
safety, and quality. This is a point made by Dr. Janet Woodcock, director of FDA's Center for Drug Evaluation and Research
(CDER), at a USP workshop on OTC quality held in September. Dr. Woodcock noted that while the FDA OTC monograph system has
served all parties well for decades, a serious quality problem could be "catastrophic," not only for consumers but for the
system itself. Patient harm is rare and we need to keep it that way, Dr. Woodcock noted.
Drug quality is protected through interwoven, critically important safety nets: a strong regulatory body; ethical manufacturers;
and the existence of, and adherence to, private and public standards that help assure the identity, strength, quality, and
purity of medicines and their ingredients. Public standards in USP–NF are legally recognized under the Food, Drug, and Cosmetics
Act, and manufacturers are required to adhere to them. USP is not an enforcing body—it only creates the standards—but FDA
is, and may enforce USP's quality standards. Additionally, USP–NF standards are closely connected in law with GMP standards
The challenge for FDA, USP, and OTC manufacturers—and for consumers—is that standards can get out of date, and this may be
particularly true for OTC products where the offerings continually change. This is also true of the approximately 240 drug
substances that may be used in OTC monograph products, most of which are older ingredients made by multiple manufacturers.
And it can be true as well for prescription medicines that are more closely regulated.
At the September USP workshop, Dr. Scott Furness, director of the Division of Nonprescription Regulation Development at FDA,
explained the agency's concerns in more detail, noting that because FDA OTC monograph drugs undergo no pre-market approval,
no individual assessment of quality is performed for those drug products also having a USP monograph. Manufacturers assess
quality through conformance to the monographs in USP–NF—making the USP monograph even more critical. Furness emphasized that
OTC monograph drug products cannot afford to lag behind the quality regulatory standards required for prescription drugs.
He also said that one cannot have a safe product that is not also a quality product—the two "go hand in hand." Furness indicated
that this is not just a "theoretical concern;" FDA has found OTC products with high levels of impurities that would not be
acceptable in a prescription drug.
Together, FDA, USP, and industry are working to modernize USP's monograph standards. There are many benefits here, including:
strengthening public standards, increasing consistency of monographs, moving from non-specific to specific procedures, and
helping to guard against economically motivated adulteration. Practical benefits for industry include removing non-value-added
tests and requirements for hard-to-find, outdated equipment. Because USP standards are used by all manufacturers marketing
products in the US, they create a level playing field for the ultimate protection of the consumer.
Under an FDA Modernization Task Force formed in 2010, FDA is assisting USP in prioritizing standards for modernization, using
a scientific and risk-based approach. This effort is coupled with USP's own criteria for when a monograph needs updating.
In 2011, FDA provided USP with an initial list of OTC priorities, focusing first on acetaminophen and diphenhydramine, as
well as a number of inactive ingredients. Acetaminophen drug products rise in concern because of widespread use and lack of
control of an impurity (p-aminophenol) potentially damaging to kidneys. FDA later provided USP with a second group of drug
substances, some of which are used in OTC monograph products. USP has begun work on updating these standards, along with many
others previously identified by USP.