Reformulating drug products that contain carbomers manufactured with benzene: guidance for industry
- Collection:
- Health Policy and Services Research
- Contributor(s):
- Center for Drug Evaluation and Research (U.S.), issuing body.
- Publication:
- Silver Spring, MD : Center for Drug Evaluation and Research, December 2023
- Language(s):
- English
- Format:
- Text
- Subject(s):
- Benzene Drug Compounding Drug Industry Government Regulation Legislation, Drug Pharmaceutical Preparations United States
- Genre(s):
- Guideline Technical Report
- Abstract:
- The purpose of this guidance is to provide recommendations for applicants and manufacturers on what tests should be performed and what documentation should be submitted or available to FDA to support the reformulation of drug products that use carbomers manufactured with benzene. Certain United States Pharmacopeia (USP) carbomer monographs currently allow for unacceptable levels of benzene, which raises safety concerns. FDA has requested that the USP omit (or remove) these monographs, and applicants and manufacturers may need to reformulate their drug products to avoid using these carbomers. This guidance provides recommendations for testing and documentation related to reformulation, taking into consideration the various routes of administration and dosage forms of affected drug products. For application holders, this guidance also recommends appropriate submission types to notify the Agency of such changes. The recommendations in this guidance are consistent with the International Council for Harmonisation (ICH) guidance for industry Q3C Impurities: Residual Solvents (December 1997) and the companion ICH guidance for industry Q3C - Tables and List (August 2018) (2018 ICH Q3C guidance), as well as applicable scale-up and post-approval changes (SUPAC) guidances. The recommendations in this guidance apply to drug products subject to both new drug applications (NDAs) and abbreviated new drug applications (ANDAs) (hereafter application products), as well as other marketed drugs, including nonprescription drugs without an approved application governed by the provisions of section 505G of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355h) (i.e., OTC monograph drugs). This guidance applies to topically applied liquid and semisolid dosage forms (e.g., creams, gels, lotions, ointments), immediate-release solid oral dosage forms, modified-release solid oral dosage forms, and oral suspensions. This guidance does not address toxicological considerations related to the unavoidable use of benzene in drug products, drug substances, or inactive ingredients. FDA is implementing this guidance without prior public comment because the Agency has determined that prior public participation is not feasible or appropriate (see 21 CFR 10.115(g)(2) and (g)(3)). FDA made this determination because benzene is a known human carcinogen. By providing recommendations on how applicants and manufacturers can reformulate certain drug products, the Agency seeks to facilitate the transition away from using carbomers manufactured with high levels of benzene. Publishing this guidance without prior public comment addresses the immediate public health need to expedite the discontinuation of the use of these carbomers and provides a less burdensome risk-based approach to applicant submissions, relative to existing guidances on SUPAC. In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
- Copyright:
- The National Library of Medicine believes this item to be in the public domain. (More information)
- Extent:
- 1 online resource (1 PDF file (10 pages))
- NLM Unique ID:
- 9918751182306676 (See catalog record)
- Permanent Link:
- http://resource.nlm.nih.gov/9918751182306676