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PharmTech.com Trends in Manufacturing eBook May 2024 Pharmaceutical Technology ® 39 Qualit y can be considered in terms of its ability to reduce or mitigate the effect of the extractables and can be used to mitigate the risk by 1 level. Clinical use can be con- sidered as a mitigation factor for non-parenteral dosage forms clubbed with their daily dose volume and the du- ration of the clinical use. If the sum of mitigation factors that apply is 0, then there is no adjustment in the char- acterization level. If the sum of mitigation factors that apply is 1, then the characterization level established by other dimensions is reduced by one level of testing (example level B testing is reduced to level A testing). If the sum of mitigation factors that apply is 2, then char- acterization level A is applicable in all circumstances. The next example looks at the risk evaluation pro- cess in a step-by-step manner for the risk assessment of the sterilizing grade filter used as a part of a single-use assembly (Mobius, Merck) in the manufacturing pro- cess of remdesivir injection. Figure 1 shows a representative schematic of the sin- gle-use assembly used in the fill/finish of a biophar- maceutical drug product in this case study (3). In this example, the assembly has a polyvinylidene f luoride filter (Durapore, Merck) along with silicon tubing and connectors as the product contact parts. The assembly is sterilized by gamma irradiation. Remdesivir for injection, 100 mg/vial, is a preserva- tive-free, white to off-white or yellow lyophilized solid. The concentrate for solution for infusion contains 100 mg remdesivir that is to be reconstituted with 19 mL of sterile water for injection and diluted into intravenous (IV) infusion f luids prior to IV administration. Rem- desivir injection is produced by aseptic filtration. The process steps include dissolution of betadex sulfobu- tyl ether sodium in water for injection, pH adjustment and dissolution of remdesivir, dilution with sufficient quantity of water for injection, pH adjustment (pH 3.0 to 4.0), bioburden reduction via filtration, sterile filtra- tion, vial filling, stopper insertion, lyophilization, and capping. The product before lyophilization contains remdesivir 5 mg/mL, betadex sulfobutyl ether sodium FIGURE 1. Single-use assembly used in fill/finish of injectables manufacturing. FIGURE IS COURTESY OF THE AUTHORS