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<p>Therapeutic antibody dosing regimens are often constrained by formulation and administration factors that limit flexibility in dose and schedule. Subcutaneous (SC) delivery offers advantages over intravenous (IV) administration—such as improved convenience and potentially more favorable pharmacokinetic (PK) profiles—but is typically restricted by injection volume, requiring lower doses and more frequent dosing. Recombinant human hyaluronidase PH20 (rHuPH20) enables rapid administration of high-dose, high-volume therapeutics, thereby expanding the feasible SC delivery landscape. Despite these advances, biopharmaceutical development teams often lack tools to quantify the strategic impact of SC-enabling technologies and interpret PK simulations in a decision-ready format. This work introduces Operating Space Maps, a visual PK simulation framework that organizes multiple dosing scenarios into an intuitive landscape of dose–frequency options. Using rHuPH20 as a case study, a two-compartment PK model is applied to simulate representative antibody regimens for two illustrative scenarios: converting IV regimens to SC with rHuPH20 and extending SC dosing intervals beyond standard limits with rHuPH20. For example, relative to a 1000 mg IV benchmark regimen, a 1400 mg SC dose with rHuPH20 maintains equivalent average exposure while reducing C<sub>max</sub> by approximately 50%. The methodology is broadly applicable to other SC-enabling technologies for which sufficient foundational data exist to parameterize the model. By making trade-offs between C<sub>min</sub>, C<sub>avg</sub>, and C<sub>max</sub> explicit and integrating SC delivery constraints, Operating Space Maps enable cross-functional development teams to evaluate regimen feasibility, optimize target product profiles, and guide strategic decisions early in development.</p>

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Optimizing Subcutaneous Antibody Dosing Regimens Through Operating Space Maps: rHuPH20 Case Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月29日

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  • Ryan P. Nolan,
  • Harish Chintakuntla

摘要

Therapeutic antibody dosing regimens are often constrained by formulation and administration factors that limit flexibility in dose and schedule. Subcutaneous (SC) delivery offers advantages over intravenous (IV) administration—such as improved convenience and potentially more favorable pharmacokinetic (PK) profiles—but is typically restricted by injection volume, requiring lower doses and more frequent dosing. Recombinant human hyaluronidase PH20 (rHuPH20) enables rapid administration of high-dose, high-volume therapeutics, thereby expanding the feasible SC delivery landscape. Despite these advances, biopharmaceutical development teams often lack tools to quantify the strategic impact of SC-enabling technologies and interpret PK simulations in a decision-ready format. This work introduces Operating Space Maps, a visual PK simulation framework that organizes multiple dosing scenarios into an intuitive landscape of dose–frequency options. Using rHuPH20 as a case study, a two-compartment PK model is applied to simulate representative antibody regimens for two illustrative scenarios: converting IV regimens to SC with rHuPH20 and extending SC dosing intervals beyond standard limits with rHuPH20. For example, relative to a 1000 mg IV benchmark regimen, a 1400 mg SC dose with rHuPH20 maintains equivalent average exposure while reducing Cmax by approximately 50%. The methodology is broadly applicable to other SC-enabling technologies for which sufficient foundational data exist to parameterize the model. By making trade-offs between Cmin, Cavg, and Cmax explicit and integrating SC delivery constraints, Operating Space Maps enable cross-functional development teams to evaluate regimen feasibility, optimize target product profiles, and guide strategic decisions early in development.