USP–NF contains more than 4,500 individual quality standards. These all require updating over time, but keeping pace with
OTC monograph medicines is particularly challenging, given that manufacturers may introduce new dosage forms, new combinations,
and new colors and flavors to meet consumer preferences without submitting an application to FDA and/or providing information
and materials to assure an up-to-date USP monograph. There are 37 individual quality monographs for acetaminophen alone in
the USP–NF, for example. How to approach updates comprehensively given the sheer volume of monographs is a key question. OTC
formulations themselves pose challenges when considering new approaches to standards-setting, particularly those involving
products with multiple active ingredients (e.g., cough and cold products) as well as inactive ingredients. USP faces fundamental
challenges to modernizing OTC monographs that are best addressed through industry involvement, especially in obtaining updated
procedures from manufacturers. The pace of modernization is directly linked to the availability of procedures with allied
For the most part, USP modifies a drug substance monograph based on information and materials submitted from a pharmaceutical
manufacturer. But manufacturers may have little incentive to do this, particularly for old OTC drug substance monographs made
by multiple manufacturers. Increasingly though, USP is finding that it can create such monographs in its own laboratories.
If this approach is allied to current practices, USP believes that the process might be accelerated to update the several
hundred OTC drug substances used in OTC monograph products.
Responding to the challenge posed by the large number of continually changing monograph dosage forms, USP is seeking new approaches
as well. Some of these may include increased reliance on USP general chapters. Many of these general chapters speak across
a broad grouping of OTC medicinal products. When this is the case, a general chapter consolidating assay and impurity procedures
for acetaminophen products, for instance, would be more efficient than updating 37 individual monographs. Furthermore, such
a general chapter would give manufacturers more flexibility to create new OTC monograph medicines—so long as they adhered
to the overall stipulations of the general chapter. One central consideration is just how broad the general chapter can be.
For pseudoephedrine, as an example, there could be a class general chapter for pseudoephedrine products; at a broader level,
for oral nasal decongestants; at a broader level still, for cough, cold, allergy, bronchodilator, and anti-asthmatic products;
and at the broadest level, for all products with an oral route of administration. How broad the general chapter could go while
still retaining the important value that a public standard provides must be determined—the necessary intersection of flexibility,
specific quality attributes, and the enforceability of USP standards. Beyond this "granularity" issue lies the practical need
for regulatory enforceability. For a class general chapter, USP might promote industry compliance and FDA enforcement through
a "pointer" in USP–NF's General Notices that alludes to the general chapter without a monograph—except perhaps for its name.
USP hopes to engage regulators and industry through various public forums to consider this opportunity.
The Three-legged Stool
Underscoring these activities is the critical need for a partnership. At a high level, this is occurring through USP's work
not only with FDA but also with the Consumer Healthcare Products Association (CHPA). As noted earlier, a key form of participation
is manufacturer donation of procedures. As all will be required to comply once a standard becomes official, the donating manufacturer
will have the opportunity to have the public standard based on its in-house standard. To assure broad acceptability, other
manufacturers should review and comment on USP proposals for new or revised monographs in the Pharmacopeial Forum. Working
together, FDA, USP, and CHPA have engaged in a dynamic collaboration to create a win-win for all—and particularly the consumer
of OTC monograph medicines.
Roger L. Williams, MD, is the Chief Executive Officer of the U.S. Pharmacopeial Convention