The FDA’s action is being taken to address a safety issue associated with the need to reformulate drug products that contain carbomers manufactured with benzene. The goal is to expedite and provide a clear and less burdensome path than might otherwise be required under the applicable Scale Up and Post Approval Changes (SUPAC) guidances for the specific dosage form, for manufacturers to reformulate these products to reduce the exposure of patients to the risks associated with high levels of benzene. The guidance includes “recommendations to applicants and manufacturers on what tests should be performed and what documentation should be submitted or available to support the reformulation of drug products that use carbomers manufactured with benzene.”

The FDA says, “[C]ertain United States Pharmacopeia (USP) carbomer monographs currently allow for unacceptable levels of benzene, which raises safety concerns. The FDA has requested that the USP omit (or remove) these monographs, and applicants and manufacturers may need to reformulate their drug products to avoid use of these carbomers.”

“The Agency is implementing this guidance without prior public comment because it has determined that prior public participation is not feasible or appropriate (§ 10.115(g)(2) and (3)). The FDA made this determination because benzene is a known human carcinogen, and the Agency seeks to facilitate the transition away from using carbomers manufactured with high levels of benzene.”

The guidance explains that “[W]hen switching to non-benzene-containing grades of carbomers, applicants and manufacturers should consider the following information [contained in the guidance] regarding chemistry, manufacturing, and controls; in vitro release or dissolution testing; and in vivo bioequivalence documentation.”

The guidance document details the quality expectations that might qualify for a reduced regulatory burden and identifies appropriate supplemental filing types and additional data that might be required, depending on the impact of the quality considerations that apply to the reformulated product.

The final guidance can be found here.