29th April 2025 | 10:00am EDT / 7:00am PDT / 3:00pm BST / 4:00pm CEST | Yana Chervona, Drug Safety Team Lead in Drug Safety Research and Development at Pfizer |BOOK FREE SEAT FOR THIS WEBINAR
The pharmaceutical industry acknowledges the potential for compounds to leach at low levels into drug products from manufacturing and packaging systems. Evaluating the stability, quality, and safety of materials used for packaging systems and manufacturing components is an important aspect of the drug development process. If potential leachables exceed established safety thresholds but lack toxicity data, in silico models and the Extractables and Leachables Safety Information Exchange (ELSIE) non-mutagenic parenteral thresholds of toxicological concern (TTCs) may be used to inform the toxicological assessment (ICH M7 (R1), 2017; Chilton et al, 2022; Masuda-Herrera et al. 2021; Masudra-Herrera et al., 2023; Parris et al, 2022; Parris et al, 2023). Conducting repeat dose toxicity studies on low level (µg-ng) leachables contradicts the principles of 3R’s and may be challenging with respect to synthesising material for the study. Alternative methods like ‘read across’—which uses toxicity data from structural analogues to inform the potential toxicity profile —are being explored. However, there’s currently no specific regulatory guidance for this method with respect to leachables. Incorporating surrogate selection recommendations into the developing ICH Q3 E guidance, Assessment and Control of Extractables and Leachables for Pharmaceuticals and Biologics, would provide a harmonised approach to read across assessments.
To support leachable read-across assessments, Pfizer developed an in-house computational tool, JARVIS 2.0 (Just A Read-across Virtual Intelligence System 2.0), based on the EPA ToxValDB (Nelms et al. 2019). Only toxicity values associated with SMILES structure representations were selected, providing a database of 12,549 unique chemicals as potential surrogates. Once the structure of interest is entered, scored and rank ordered based on a combination of structural similarity using chemical fingerprints via Tanimoto coefficient and structural molecular descriptors correlation (Pearson’s) followed by an adjustment for molecular weight discrepancies are a list of surrogate structures is generated. The toxicologist can then evaluate the top ranked surrogates and perform the read across toxicity assessment.
An opportunity to utilize JARVIS arose when a regulatory Information Request was received relating to the implementation of single-use aseptic connectors on the filling line for a sterile injectable product. An extractable study from the connector supplier was available, and a comprehensive toxicological risk assessment by the clinical route of administration (intravenous (IV) infusion) was requested for all leachables with a TDI >5 µg/day. A single leachable, hexamethylene diacrylate CAS 13048-33-4, with a TDI of 14 µg/day lacked toxicological data.
A comprehensive review of general toxicological data for the 5 surrogates identified by JARVIS was performed and it was concluded that there was negligible safety risk for the identified leachable at the TDI. With the acceptance of regulatory response there were no delays to the implementation of the aseptic connectors in the filling line for the drug product. This case study exemplifies, in the absence of toxicity data, a scientifically justified read across assessment is a valuable tool for the toxicological assessment of low-level potential leachables.
Presented by Yana Chervona, Drug Safety Team Lead in Drug Safety Research and Development at Pfizer

Dr. Yana Chervona is a Drug Safety Team Lead in Drug Safety Research and Development at Pfizer, where she is responsible for the development and implementation of nonclinical safety scientific and regulatory strategies across various therapeutic areas, including vaccine, anti-infectives, and inflammation/immunology. She also authors or contributes to toxicological risk assessments, including E&L risk assessments. She has been at Pfizer since 2021. Her educational background includes a BA from Barnard College, an MPH in Molecular Toxicology from Columbia University, and a Ph.D. from New York University, where her research focused on arsenic’s impact on the epigenome.
With extensive expertise in toxicology, Dr. Chervona has had roles in at the Department of Environmental Medicine, NYU, and SafeBridge Consultants, Inc., where she worked from 2013 to 2021 and focused on occupational toxicology, product safety, and risk assessment. Dr. Chervona is a Diplomate of the American Board of Toxicology, and a member of both the American College of Toxicology and Society of Toxicology.
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