生物等效研究与生物豁免的几点考虑

Points-to-consider: bioequivalence studies vs. biowaivers

Bioequivalence is a critical tool that links the results of clinical studies to the pharmaceutical products that have undergone various manufacture changes. Although in vivo BE studies are still regarded as the "gold standard" for evaluating the therapeutic equivalence of pharmaceutically equivalent drug products, in vitro testing as a sufficiently reliable surrogate for an in vivo BE study (biowaiver) has been increasingly accepted by regulatory agencies for some drug products. The guidances and regulations on biowaivers for oral solid dosage forms have facilitated the application of the biowaiving approach in formulation development for a new drug product, line extensions, a generic drug product development and post-approval changes both for innovator and generic drug products. Although biowaivers have demonstrated to reduce the drug development time and cost, the regional regulatory differences in the current requirements for biowaivers may complicate the decision to take the biowaiver approach. Time to file a biowaiver request to obtain a formal approval from the agency may be too long to risk project timelines, especially in the late stages of development. Since Japan does not accept the BCS based biowaiver, a decision to use the approach in the US and EU may present future issues for registration in Japan. The agreed BE strategy with one agency may not always work with another authority, which may result in a BE study for a region and a biowaiver request from another. When biowaivers are being considered as part of registration strategy, the different regulatory requirements for biowaivers, the time and expense of conducting in vivo BE studies versus the application for biowaiver and the overall impact on product development costs and timeline must be carefully considered and balanced.

Bioequivalence is a critical tool that links the results of clinical studies to the pharmaceutical products that have undergone various manufacture changes. Although in vivo BE studies are still regarded as the ＂gold standard＂ for evaluating the therapeutic equivalence of pharmaceutically equivalent drug products, in vitro testing as a sufficiently reliable surrogate for an in vivo BE study （biowaiver） has been increasingly accepted by regulatory agencies for some drug products. The guidances and regulations on biowaivers for oral solid dosage forms have facilitated the application of the biowaiving approach in formulation development for a new drug product, line extensions, a generic drug product development and post-approval changes both for innovator and generic drug products. Although biowaivers have demonstrated to reduce the drug development time and cost, the regional regulatory differences in the current requirements for biowaivers may complicate the decision to take the biowaiver approach. Time to file a biowaiver request to obtain a formal approval from the agency may be too long to risk project timelines, especially in the late stages of development. Since Japan does not accept the BCS based biowaiver, a decision to use the approach in the US and EU may present future issues for registration in Japan. The agreed BE strategy with one agency may not always work with another authority, which may result in a BE study for a region and a biowaiver request from another.