Q&A: USP on Monographs for Dietary Supplements

The U.S. Pharmacopeial Convention (USP) is a scientific nonprofit organization that establishes standards for the identity, strength, quality and purity of medicines, food ingredients and dietary supplements manufactured, distributed and consumed worldwide through its public monographs. USP monographs for dietary supplements and dietary supplement ingredients are used to guide the testing for the identity and purity by the manufacturers, a requirement under GMPs (good manufacturing practices). These test also ensure quality, safe and effective products. Without using the correct test methods (such as those verified by USP monographs), supplement brands could see their business fail due to FDA action or consumer mistrust.

USP standards are developed and revised by more than 900 volunteer experts, including international participants, who work with USP under strict conflict-of-interest rules with scientists, practitioners, and regulators of many nations to help protect public health worldwide. For a dietary product to carry the USP seal, it must:

·         contain the ingredients listed on the label in the declared potency and amounts,

·         not contain harmful levels of specified contaminants,

·         break down and release into the body within a specified amount of time, and

·         have been made according to FDA cGMPs (current good manufacturing practices) using sanitary and well-controlled procedures.

INSIDER talked to USP's Gabriel Giancaspro, Ph.D., vice president of foods, dietary supplements and herbal medicines about its monographs and the implications they have in the supplement industry.

INSIDER: What is a monograph and how does it apply to the supplement industry?

Gabriel Giancaspro: A monograph is a written standard that establishes public specifications for an article (e.g., drug substance, drug product, excipient, food ingredient, dietary ingredient or dietary supplement). A monograph published in any USP compendium provides: the name of the article; its definition; package, storage, and labeling requirements; and a collection of tests with their acceptance criteria needed to ensure identity, strength, performance, composition, purity and absence of contaminants.

INSIDER: What is the process for determining which tests will be included in each monograph?

Giancaspro: Each ingredient and/or product monograph (tablets, capsules, etc.) has its own testing requirements to assert the identity, strength and purity. The requirements will vary depending on the nature of the ingredient (botanical, vitamin, mineral or non-botanical) and the dosage form (tablets, capsules or liquids). Scientists at USP work with sponsors to determine the appropriate tests for each monograph. Comments from third parties during the public review period may suggest the inclusion or deletion of some tests. For dietary supplements, the process is further explained here.

INSIDER: How do these monographs help to set a standard for dietary supplements?

Giancaspro: Monographs are standards in themselves. Public standards, rather private ones, provide scientists, governments, manufacturers and others a common measure to judge an article’s quality. Without a monograph, the uniformity, consistency and quality of ingredients and products cannot be ensured. The existence of public quality standards in the marketplace is a key element of the safety net that helps maintain and improve public health. Primarily, monographs are used to help control the quality of dietary supplements. USP monographs for dietary supplements and dietary supplement ingredients are used to guide the testing for the identity and purity by the manufacturers.

INSIDER: What are the USP Expert Committees, and how are members chosen?

Giancaspro: USP Expert Committees (EC) are responsible for developing and revising USP standards that comprise its compendia: the USP-NF, Medicines Compendium, Herbal Medicines Compendium, Dietary Supplements Compendium and Food Chemicals Codex. They each focus on a different area of standards for medicines (including chemical medicines, biologic medicines, excipients and compounded preparations), dietary supplements and food ingredients. After publication of the proposed standards for public comment, the ECs review the comments. The standards are adjusted based on the EC’s consideration of the public comments and balloted for adoption by a majority vote. Members are elected every five years. The last cycle of EC members is about to end (2010 to 2015) and applications for the next cycle (2015 to 2020) are open. Here is the application site with the deadlines for applicants.

INSIDER: How long does the comment period last for new monographs, and what options do stakeholders have at this time?

Giancaspro: Any standard (new or revision) is proposed for comment for 90 days. The Pharmacopeial Forum and the FCC Forum are free, online tools where stakeholders can look at any proposed standard and offer feedback. Stakeholders have many opportunities to contribute even before the comment period. Even after a monograph is published, stakeholders have an opportunity to request a revision and provide comments.

INSIDER: Can you provide a case study to explain the monograph process?

Giancaspro: Monographs are usually developed in the same way. An example would be Calcium L‐5‐Methyltetrahydrofolate Tablets. The monograph was initially published for public comments in PF 39(3) May/June 2012, for which the EC received three comments. All of these comments were incorporated in the final version of the monograph as appeared in the First Supplement of USP 37. The comments and the response from the Expert Committee can be found in here.

INSIDER: Is there anything else you’d like to add?

Giancaspro: Stakeholder participation is critical to USP’s activities. They can participate as volunteer experts in our ECs and Expert Panels, as donors of documentation and samples to develop quality standards, as collaborators providing comments to proposed monographs and by requesting monograph revisions. We encourage their participation in the process.