USP is a scientific nonprofit organization that sets public standards for identity, strength, quality and purity of medicines. USP publishes these standards in the United States Pharmacopeia–National Formulary (USP–NF). The quality standards contained in USP–NF monographs apply to any articles that are marketed in the U.S. that are intended or labeled for use as drugs or as ingredients in drugs. The USP Talc monograph contains requirements applicable to talc for pharmaceutical applications.
Enforcement of USP standards is the responsibility of the U.S. Food and Drug Administration (FDA) and other government authorities in the U.S. and elsewhere. USP has no role in enforcement per General Notices 2.30 Legal Recognition.
In response to a 2010 request from Food and Drug Administration (FDA), the current USP Talc monograph is being modernized to ensure that the tests for asbestos have adequate specificity.
The current USP Talc monograph contains a test for Absence of Asbestos that includes three procedures. Analysts are given the option to perform either Procedure 1 or Procedure 2, which consist of infrared spectroscopy (Identification Tests–General 191) and x-ray diffraction [Characterization of Crystalline and Partially Crystalline Solids by X-Ray Powder Diffraction (XRPD) 941], respectively. If either test gives a positive result, then the third procedure, consisting of optical microscopy (Optical Microscopy 776) must be performed to confirm.
The infrared spectroscopy (IR) and x-ray diffraction (XRD) methods, as currently written, can lead to false-negative results, which could allow talc samples with asbestos contamination to pass the Absence of Asbestos test in the USP Talc monograph. Even after applying the current USP microscopy method, the analyst cannot rule out the presence of hazardous fibers in a sample of talc. In addition, the lack of identification procedures in the optical microscopy section of the method could lead to false-positive results. This underscores the need to modernize the current monograph. For further detail, see: Stimuli Article in Pharmacopeial Forum (PF) 40(4) [Jul.–Aug. 2014] Modernization of Asbestos Testing in USP Talc, available at https://www.uspnf.com/pharmacopeial-forum.
USP standards are developed and revised by independent volunteers, organized into Expert Committees (ECs). The 2015-2020 Excipient Monographs 2 EC is the EC responsible for revising the USP Talc monograph. In response to FDA’s request for revision of the USP Talc monograph, USP has formed two Talc Expert Panels. Expert Panels are groups of independent volunteers who provide scientific recommendations to the ECs that approve USP standards.
- The 2011–2015 Talc Expert Panel considered procedures and criteria for recommendation to the USP Excipients EC to update the test for Absence of Asbestos in USP Talc.
- The present day Talc Methods Expert Panel (2015–present) is currently addressing the task of identifying appropriate analytical methods and Reference Standards (RS) for testing Absence of Asbestos in USP Talc. The members of the Expert Panel will develop and optimize Talc analytical methods and develop RS based on knowledge gained from the 2011-2015 Talc Expert Panel.
The Talc Expert Panels have published two Stimuli articles in Pharmacopeial Forum (PF) available at https://www.uspnf.com/pharmacopeial-forum. Both intended to solicit public comment on approaches to modernizing the USP Talc monograph:
- PF 40(4) [Jul.–Aug. 2014] Modernization of Asbestos Testing in USP Talc
- PF 43(4) [Jul.–Aug. 2017] USPC Responses to Comments on Stimuli Article “Modernization of Asbestos Testing in USP Talc”
The Expert Panel consists of volunteer members from entities including talc suppliers, pharmaceutical manufacturers, regulatory and government agencies, academia, and instrument manufacturers. USP has robust conflict of interest management policies and procedures and requires volunteers to disclose issues that represent perceived or actual conflicts of interest.
To maintain independence and neutrality as a public standards-setting organization, it is USP’s policy not to get involved in litigation. USP has no position on the ongoing litigation in this area, and we will continue to advance our scientific efforts to modernize the USP Talc monograph.
USP plans to engage in outreach and consultation with diverse stakeholders. We are planning a possible roundtable meeting, where representatives from industry, regulators, and academia would be invited to discuss proposed modernization approaches prior to publication in Pharmacopeial Forum (PF).
USP also plans to publish another Stimuli article containing the draft proposed revisions to the USP Talc monograph prior to publication in PF. The purpose of this approach would be to solicit early-stage feedback on the proposal.