Cell and Gene Therapies: Challenges in Designing Extractables and Leachables Studies and Conducting Safety Assessments

Arroyo, Adeyma; Booij, Petra; Woldemariam, Getachew; Bruen, Uma; Creasey, Jason; Stanard, Brad; Parris, Patricia; Nagao, Lee; Bielinski, Mary Kate

doi:10.1016/j.xphs.2023.12.024

Cited by 1 publication

(1 citation statement)

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“…USP 〈1043〉 (United States Pharmacopoeia) provides a tiered approach for risk assessment of ancillary material selection, which prefers highly qualified materials for manufacturing AT products 8 . Currently, there is a general lack of data on compatibility of materials with cells and products from advanced therapy medicinal products (ATMP) manufacturing 10 .…”

Section: Introductionmentioning

confidence: 99%

Assessing biologic/toxicologic effects of extractables from plastic contact materials for advanced therapy manufacturing using cell painting assay and cytotoxicity screening

Pahl,

Hauk

et al. 2024

Sci Rep

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Plastic components are essential in the pharmaceutical industry, encompassing container closure systems, laboratory handling equipment, and single-use systems. As part of their material qualification process, studies on interactions between plastic contact materials and process solutions or drug products are conducted. The assessment of single-use systems includes their potential impact on patient safety, product quality, and process performance. This is particularly crucial in cell and gene therapy applications since interactions with the plastic contact material may result in an adverse effect on the isolated therapeutic human cells. We utilized the cell painting assay (CPA), a non-targeted method, for profiling the morphological characteristics of U2OS human osteosarcoma cells in contact with chemicals related to plastic contact materials. Specifically, we conducted a comprehensive analysis of 45 common plastic extractables, and two extracts from single-use systems. Results of the CPA are compared with a standard cytotoxicity assay, an osteogenesis differentiation assay, and in silico toxicity predictions. The findings of this feasibility study demonstrate that the device extracts and most of the tested compounds do not evoke any measurable biological changes on the cells (induction ≤ 5%) among the 579 cell features measured at concentrations ≤ 50 µM. CPA can serve as an important assay to reveal unique information not accessible through quantitative structure–activity relationship analysis and vice versa. The results highlight the need for a combination of in vitro and in silico methods in a comprehensive assessment of single-use equipment utilized in advanced therapy medicinal products manufacturing.

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Section: Introductionmentioning

confidence: 99%