FDA Investigates Benzene Contamination in Drugs Urges Manufacturers to Take Action

The Food and Drug Administration (FDA) has initiated an investigation into the cause of benzene contamination in certain drugs, raising concerns about potential health risks associated with the presence of this carcinogenic compound. Benzene contamination has prompted recalls of certain hand sanitizers and aerosol drug products and prompted the FDA to issue warnings to drug manufacturers regarding the dangers posed by benzene in drug components.

Benzene:

Benzene, a known human carcinogen, has been linked to leukemia and other blood disorders. Contamination can occur from inactive ingredients such as carbomers (thickening agents) or isobutane (a spray propellant), as well as other drug components derived from hydrocarbons. More than 60% of FDA-approved small molecule drugs contain at least one benzene ring motif. These include acetylsalicylic acid (Aspirin), acetaminophen (Tylenol), and ibuprofen (Advil) which are all painkillers sold over the counter. It is used primarily as a solvent in the chemical and pharmaceutical industries, as a starting material, and as an intermediate in the synthesis of numerous chemicals.

Action taken:

In light of these findings, the FDA emphasizes the need for drug manufacturers to establish scientifically sound specifications and testing procedures to ensure that both active and inactive ingredients, as well as finished drug products, meet appropriate quality standards. This includes rigorous testing of raw materials and finished product batches prior to release, to ensure conformity to specified criteria for identity, strength, quality, and purity.

Manufacturers are encouraged to use risk assessments to identify potential sources of contamination and implement appropriate risk mitigation measures. Specifically, the FDA has worked with manufacturers to conduct risk assessments focusing on ingredients derived from hydrocarbons or manufactured with benzene or other related compounds. Additionally, the FDA recognizes the potential for benzene formation from interactions between certain ingredients, such as sodium benzoate and antioxidants, which requires thorough testing throughout the shelf life of a drug product.

The International Conference on Harmonization (ICH) Q3C Impurities: Residual Solvents guidance and its companion document Q3C Tables and List provide guidance on limited cases where the presence of benzene may be tolerated. 

To address concerns regarding benzene contamination, drug manufacturers are advised to conduct testing and not release any product batch containing benzene levels above 2 parts per million (ppm). Manufacturers that identify batches that exceed this threshold must immediately initiate a recall and communicate with the FDA for further guidance.

Furthermore, manufacturers are urged to provide the FDA with comprehensive test results and information concerning the potential sources of benzene contamination to facilitate ongoing investigations.