Admission Criteria and Safety Classification for Dietary Supplements Guideline
October 18, 2012 update: During a meeting held on September 18th, 2012, the Dietary Supplement Expert Committee (DS–EC) revised the Admissions Criteria and Safety Classification for Dietary Supplements Guideline (version 1.1) to allow exemptions from comprehensive safety evaluation of articles that have been reviewed by FDA. The (DS–EC) also modified the Admission Criteria clarifying the conditions for equivalency to the materials that have gone through review without questions from the Agency.
April 10, 2009 posting: During a meeting held February 5–6, 2009, the Dietary Supplement Information Expert Committee made a comprehensive review of various aspects of its dietary supplement safety evaluation, including the progress made and challenges experienced with the previous classification system (see “Background” below), recommendations from other organizations and stakeholder comments received. The Expert Committee determined that the previous classification system did not allow sufficient flexibility to appropriately communicate safety concerns. Specifically, the Class 2 designation was considered overly rigid in that it mandated that safety concerns be addressed through a warning statement in the labeling section of the corresponding USP monograph. A simpler and more general system that would allow communication of safety concerns through a variety of mechanisms and channels was considered more appropriate.
Based on its review and discussions, the Expert Committee adopted a revised admission policy and safety classification system for development of USP monographs as follows:
Class A: Admitted into the Compendia
Articles for which the available evidence does not indicate a serious risk to health* or other public health concern that precludes inclusion of a quality monograph into the compendia.
Class B: Not admitted into the Compendia
Articles for which the available evidence indicates a serious risk to health* or other public health concern that precludes inclusion of a quality monograph into the compendia.
*Serious risk to health means that the use of the article could:
(A) result in: (i) death; (ii) a life–threatening experience; (iii) inpatient hospitalization; (iv) a persistent or significant disability or incapacity; or (v) a congenital anomaly or birth defect; or
(B) require, based on reasonable medical judgment, a medical or surgical intervention to prevent an outcome described under subparagraph (A).
The new safety classification system provides clear criteria for admission of a dietary supplement ingredient into the USP–NF, and broadens the Expert Committee's ability to accommodate diverse situations. The revised policy recognizes that even where an article is categorized as Class A there may be specific safety concerns. After conducting the safety reviews for admission classification, the committee may decide to communicate their findings and recommendations through publications in peer–reviewed journals, public communications, Pharmacopeial Forum notices, or other appropriate means.
In essence, the proposed new classification system is intended to preserve the critical safety review function performed by the Expert Committee while allowing the Expert Committee additional flexibility in addressing safety issues, depending on the particular issues involved, the level of available safety data, and other relevant considerations.
As before, and in keeping with USP's "continuous revision" approach, the Expert Committee will monitor the safety information for all dietary ingredients for which USP monographs are developed on an on–going basis for possible safety re-evaluation and re-classification depending on the safety signal.
USP's Dietary Supplements Information Expert Committee adopted in 2002 a safety classification system for dietary supplement ingredients that would be used to determine admission to the USP–NF. The criteria required the Expert Committee to review of safety information from diverse sources for selected dietary ingredients, including but not limited to human data from clinical studies and adverse event reports, animal pharmacological and toxicological data, historical use, regulatory status, and current uses worldwide. After reviewing the safety information cited above, the Expert Committee would recommend that a candidate dietary ingredient be placed into one of the following four safety classes:
Class 1. Articles for which the Committee is unaware of significant safety issues present when the article is used and formulated appropriately that would prohibit a monograph being developed.
Class 1a. Articles for which the Committee is aware of limited human scientific data concerning safety of the article, but is unaware of significant safety issues present when the article is used and formulated appropriately that would prohibit a monograph being developed.
Class 2. Articles for which the Committee is unaware of significant safety issues present when the article is used and formulated appropriately that would prohibit a monograph being developed, provided there is a warning statement in the labeling section.
Class 3. Articles for which the Committee is aware of significant safety issues present that would prohibit a monograph being developed.
Under this classification system, if an article fell within Class 2, a warning statement would be included in the labeling section of the monograph.
Revision of the Admission Criteria and Safety Classification:
From 2002–2008, Expert Committee reviewed and monitored safety profiles for dietary ingredients with USP monographs in accordance with the safety classification system described above. Based on experience and internal discussions, and taking into account other factors like the recent implementation of mandatory requirements for serious adverse events reporting, Expert Committee decided in the fall of 2008 to revisit its safety classification system and review process. The Expert Committee sought stakeholder comments regarding the proposed revisions through a public notice.
- The United States Pharmacopeia and the National Formulary (USP–NF) Development Process: http://www.usp.org/usp-nf/development-process; (Accessed March 04, 2009).
- United States Pharmacopeia New Admission Criteria for Dietary Supplements. (2003) Pharmacopeial Forum. 29:19–21.
- USP Invites Public Comments on its Dietary Supplement Safety Review Process. (2008)