USP is in the process of updating its compendial monographs and FDA applauds this change, which will help improve the standards
companies follow when making drug products. In fact, the agency, along with the Consumer Healthcare Products Association (CHPA),
is working closely with USP on the pharmacopeial convention's monograph modernization project, which began in 2010. The aim
is to update key USP compendial monographs (to clarify, these are different from FDA's OTC monographs) to incorporate modern
analytical methods and technologies.
The most significant gaps reside in USP monographs that have relatively nonspecific identification and/or assay procedures
and in monographs lacking procedures for impurities and degradants, says Karen Russo, vice-president for small molecules at
USP. In addition to these gaps, methods for certain procedures are outdated (e.g., packed column gas-chromatography and wet-chemistry
techniques) and need updating.
Furthermore, USP notes that only about 25% of the monographs targeted for revision are OTC-related. Although, says USP, it's
important to note that the same product or active pharmaceutical ingredient can be used in OTC and prescription form based
on the dose or other FDA criteria.
Behind the Counter
In February 2011, the standard-setting body said it would be focusing on a few specific OTC monographs based on an FDA request.
The agency asked USP to make a priority the monographs for acetaminophen and diphenhydramine (as well as copovidone, crospovidone,
povidone, and talc) based on potential health concerns with these drugs (4).
"Acetaminophen- and diphenhydramine-containing drug products are two of the highest-volume selling OTC monograph drugs," explains
FDA's Kubaska. "There are known impurities in both of these drugs that represent known (acetaminophen) and theoretical (diphenhydramine)
concerns with respect to toxicity. So, the extent of exposure (using sales volume as a surrogate) and toxicity concerns played
key roles in the selection of these drugs...."
Adds Russo, "The challenge with diphenhydramine and acetaminophen are the many drug products, particularly those combined
with other drugs, and the variety of dosage forms, such as tablets and oral liquids. For example, there are more than 25 acetaminophen-containing
dosage form monographs in the USP–NF representing primarily OTC drugs."
Another challenge to the project overall, says Russo, is finding the replacement procedures for those monographs that need
revision. "We encourage manufacturers to submit their procedures to USP so that the monograph can be revised to incorporate
the new procedure(s).... USP is ... using its own laboratory resources to the extent possible to develop and validate procedures
to serve as the basis for the monograph revisions; however, we are not able to accomplish this on our own." In addition, says
Russo, USP has to find procedures that can accommodate all manufacturers of a given drug substance or drug product.
There is no set deadline for completing the monograph project, according to USP, although a general target is to finish before
the 2010–2015 convention cycle ends. USP is hosting an OTC workshop in September 2011 to discuss with industry and FDA some
of these compendial issues. (For more details on the monograph modernization project, see the Inside USP column
in this issue "Monograph Makeover Requires Industry Input".)