FDA Bioequivalence Standards

Yu, Lawrence X.; Li, Bing V.

doi:10.1007/978-1-4939-1252-0

Cited by 15 publications

(1 citation statement)

References 294 publications

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“…The easiest way of in vitro - in vivo extrapolation is to compare toxicity at in vivo relevant concentration ranges. An accepted procedure is the quantitative comparison based on the plasma peak concentration (Cmax; C max ) or the area under the curve (AUC) of a test compound ( Yu and Li, 2014 ) ( Figure 1IV ; Figure 1III ); named “direct Physiologically-Based-Pharmacokinetic (PBPK) based extrapolation’’ from now on. This procedure often fails because: 1) In vitro , concentrations of test compounds in the culture medium are either relatively constant during the exposure period or decrease only slowly, due to the much larger volume of culture medium compared to the cell fraction.…”

Section: Introductionmentioning

confidence: 99%

In vitro to in vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmacodynamic models and a multiscale spatial-temporal liver twin

Dichamp

Cellière

Ghallab

et al. 2023

Front. Bioeng. Biotechnol.

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In vitro to in vivo extrapolation represents a critical challenge in toxicology. In this paper we explore extrapolation strategies for acetaminophen (APAP) based on mechanistic models, comparing classical (CL) homogeneous compartment pharmacodynamic (PD) models and a spatial-temporal (ST), multiscale digital twin model resolving liver microarchitecture at cellular resolution. The models integrate consensus detoxification reactions in each individual hepatocyte. We study the consequences of the two model types on the extrapolation and show in which cases these models perform better than the classical extrapolation strategy that is based either on the maximal drug concentration (Cmax) or the area under the pharmacokinetic curve (AUC) of the drug blood concentration. We find that an CL-model based on a well-mixed blood compartment is sufficient to correctly predict the in vivo toxicity from in vitro data. However, the ST-model that integrates more experimental information requires a change of at least one parameter to obtain the same prediction, indicating that spatial compartmentalization may indeed be an important factor.

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Section: Introductionmentioning

confidence: 99%

In vitro to in vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmacodynamic models and a multiscale spatial-temporal liver twin

Dichamp

Cellière

Ghallab

et al. 2023

Front. Bioeng. Biotechnol.

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Assessing the ratio of means as a causal estimand in clinical endpoint bioequivalence studies in the presence of intercurrent events

Lou

Jones

Sun

2019

Statistics in Medicine

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In clinical endpoint bioequivalence studies, the observed per‐protocol (PP) population (compliers and completers in general) is usually used in the primary analysis for equivalence assessment. However, intercurrent events, ie, missingness and noncompliance, are not properly handled. The resulting estimand is not causal. Previously, we proposed the first causal framework to assess equivalence in the presence of missing data and noncompliance. We proposed a causal survivor average causal effect (SACE) estimand for the difference of means (DOM). In equivalence assessment, DOM is not as widely used as the ratio of means (ROM). However, no existing formula links the observed PP estimand to the SACE estimand for ROM as exists for DOM. Herein, we propose a similar causal framework for ROM using the principal stratification approach, one of the strategies recommended by the International Conference on Harmonisation (ICH) E9 R1 addendum. We quantify the bias of the observed ROM PP estimand for the SACE estimand, which provides a basis to identify three conditions under which the two estimands are equal. We propose a sensitivity analysis method to evaluate the robustness of the current PP estimator to estimate the SACE estimand. We extend Fieller's confidence interval for the SACE estimand using ROM, which can be applied to many settings. Simulation demonstrates that the PP estimator is biased in either directions and may inflate type 1 error and/or change power when the three identified conditions are violated. Our work can be applied to comparative clinical biosimilar studies.

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Determination of prazosin in pharmaceutical samples by flow injection analysis with multiple-pulse amperometric detection using boron-doped diamond electrode

Guedes

Alecrim

Oliveira

et al. 2015

J Solid State Electrochem

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FDA Bioequivalence Standards

Cited by 15 publications

References 294 publications

In vitro to in vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmacodynamic models and a multiscale spatial-temporal liver twin

In vitro to in vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmacodynamic models and a multiscale spatial-temporal liver twin

Assessing the ratio of means as a causal estimand in clinical endpoint bioequivalence studies in the presence of intercurrent events

Determination of prazosin in pharmaceutical samples by flow injection analysis with multiple-pulse amperometric detection using boron-doped diamond electrode

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