Service Area

Impurity Assessments

Qualification of impurities in drug substances and drug products is essential for approval of a new drug, formulation, or drug manufacturing process.  Gradient provides our clients with extensive expertise in assessing the potential patient risks of drug impurities.  Our team includes board-certified toxicologists, health scientists, and chemists who provide our clients with fit-for-purpose assessments that address the toxicological evaluation of drug impurities.  We are skilled in assessing data-poor chemicals and chemical classes through well-developed in silico and read-across methodologies.  Beyond small molecule impurities, Gradient also supports the qualification of large molecule biological impurities, such as nucleic acids, host cell residuals, and cell media components.

  • Permitted daily exposure (PDE) monographs
  • ICH methodology (Q3A, Q3B, Q3C, Q3D, M7)
  • Biologic residuals and impurities
  • In silico predictions and expert review
  • Screening assessments
  • Dermal assessments


Chang, RY; Mohar, I; Lewandowski, T. 2020. “Risk assessment of 1,1,1-trifluoroethane (HFA-143a) as a potential impurity in HFA-134a in metered dose inhaler products.” Toxicologist 174(1):295. Abstract 2236. Prepared for presentation to the Society of Toxicology (SOT) 59th Annual Meeting & ToxExpo, Anaheim, CA, March 15-19.

Cohen, JM; Liu, W; Jordi, M. 2019. “Safety Evaluation of High Potency Mutagenic Impurities: A Timely Case Study.” Poster #P511. Presented at the American College of Toxicology (ACT) 40th Annual Meeting, Phoenix, AZ, November 17-20.

Mohar, I; Lewandowski, T. 2021. “Toxicology-Based Exposure Limits for Residual HEK-293T Cell DNA and Protein.” Int. J. Epidemiol. 41(1). doi: 10.1177/10915818211061894. Abstract P506. Presented at the American College of Toxicology (ACT) 42nd Annual Meeting 2021, Virtual, November 10-19.

Mohar, I; Lewandowski, T. 2020. “Risk evaluation of residual recombinant lentiviral vector Capsid Protein p24.” Mol. Ther. 28(4(Suppl. 1)):383. doi: 10.1016/j.ymthe.2020.04.019. Abstract 875. Presented at the American Society of Gene & Cell Therapy (ASGCT) 23rd Annual Meeting, Virtual, May 12-15.

Sample Projects

Drug Product ICH M7 Qualification with Expert Review

For a pharmaceutical company, Gradient conducted ICH M7 qualification with expert review of the starting materials, reaction intermediates, impurities, and degradants of a drug product.  Our client used our assessment to prioritize manufacturing improvements and justify drug specification.

Toxicological Risk Evaluation of Viral Vector Residuals

Gradient conducted human health hazard and risk assessments for potential impurities, including plasmid DNA, viral DNA, and host cell line residuals, in a viral vector cancer treatment for a biopharmaceutical company.  We provided our client with detailed monographs on each impurity, including a comprehensive review of issues and regulations, toxicology and clinical data, and, when possible, an exposure limit for the impurity.

Toxicological Risk Assessments on Leachable Compounds from a Dermal Drug Container

For a pharmaceutical testing laboratory, Gradient derived a permitted daily exposure (PDE) and tolerable contact level (TCL) for several impurities in a dermally administered drug product in accordance with ICH methodology.  Gradient relied on publicly available scientific literature and in silico tools to derive the PDEs and TCLs, which the drug manufacturer used to support and justify the manufacturing specification of the drug product.

Toxicological Risk Assessment of Drug Container Label

For a pharmaceutical company, Gradient conducted a toxicological risk assessment of chemicals identified as migrating from a printed ink label of an over-the-counter ocular drug product.  We provided the client with a report that was used to evaluate the safety of the label.

Toxicological Evaluation of Residual DNA in Dermal Xenograft Device

Gradient performed a safety assessment for residual DNA identified in a dermal xenograft prepared from axolotl skin.  Our client used our summary to respond to a deficiency raised by the US FDA.

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