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USFDA : CMC Guidance Reformulating Drug Products That Contain Carbomers & Potency Assurance for Cellular & Gene Therapy Products

The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research and Center for Biologics Evaluation and Research released guidance "Reformulating Drug Products That Contain Carbomers Manufactured With Benzene" and "Potency Assurance for Cellular and Gene Therapy Products" on 27th and 28th December 2023 respectively.



Carbomers are a group of polymers composed of acrylic acid. They are widely used as inactive ingredients in drug products as fillers, emulsifiers, gelling agents, and binding agents. There are carbomers currently used as inactive ingredients that are manufactured using benzene as a polymerization solvent. Benzene is a known human carcinogen.


Currently, certain United States Pharmacopeia (USP) carbomer monographs contain unacceptable amounts of benzene, which raises safety concerns. FDA has requested that these monographs be omitted (or removed), and manufacturers and applicants may have to change their formulas so that these carbomers are not used.


Applicants and manufacturers can use this guidance to determine what tests should be performed and what documentation should be provided to FDA as support for reformulations of drug products made with carbomers containing benzene.


As part of this guidance, recommendations are made for testing and documentation related to reformulation, taking into account the different routes and dosage forms of affected drugs. For application holders, this guidance also recommends how to notify the Agency of such changes in the appropriate form.


Developing assays that measure the potency of CGT products can be challenging. A potency assurance strategy is a multifaceted approach that reduces risks to the potency of a product through manufacturing process design, manufacturing process control, material control, in-process testing, and potency lot release assays.


In a potency assurance strategy, the product is ensured to achieve the intended therapeutic effects in every lot it is released.


The guidance provides recommendations for developing a science- and risk-based strategy for ensuring the potency of human cellular therapy or gene therapy products.


The recommendations in this guidance regarding the selection and design of potency assays are necessarily general due to the wide variety of CGT products and the product-specific nature of potency assays.


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