Review Themed Issue: Antibody–Drug Conjugates
Integration of bioanalytical measurements using PK–PD modeling and simulation: implications for antibody–drug conjugate development
Recent technological advances have enabled precise quantitation of various bioanalytical measurements pertaining to antibody–drug conjugates (ADCs). However, availability of bioanalytical data alone cannot guarantee the provision of correct go/no-go decisions at different stages of ADC development. Integration and comprehension of all the available data at each stage of ADC development is necessary to make a well informed and objective decision about moving the ADC forward to the clinic. In this manuscript, we have reviewed the application of PK–PD modeling and simulation for quantitative integration of diverse bioanalytical data available from different stages of ADC development. We have also elaborated on how similar bioanalytical data can be characterized using different models to gain distinct insights into ADC development.
Bioanalytical measurements are backbone of all the quantitative approaches employed dur- ing drug development. Therefore, bioanalyti- cal scientists work really hard to make sure they deliver good quality bioanalytical mea- surements that are both precise and accurate. The job of bioanalytical scientists becomes especially challenging when dealing with heterogeneous modalities like antibody–drug conjugates (ADCs), which can yield multiple analytes in a biological system, depending on the permutation and combination of catab- olism (for antibody) and metabolism (for druglinker) [1,2]. Nonetheless, technological advances and relentless efforts of bioanalyti- cal scientists have now enabled us to precisely quantify various bioanalytical measurements pertaining to ADCs. However, many times the bioanalytical scientists do not know why the ‘customer’ has asked for
the measure-
ment of a specific set of data, and what do the ‘customer’ do with the high-quality data bioanalytical scientists provided to them. It is especially important for the bioanalytical scientists to know how their data is employed to guide the ADC development efforts and how it is utilized to infer certain properties about the ADC being developed. Hence, in
10.4155/BIO.15.85 © 2015 Future Science Ltd
this manuscript we have attempted to shed some light on this process. We have consid- ered PK–PD modeling and simulation (M&S) scientists, along with the scientists from clinical pharmacology and other phar- macometric disciplines, as the main ‘cus- tomers’ of the bioanalytical scientists who are
involved in quantitatively integrating
their data. Thus, in this manuscript, we have reviewed how PK–PD M&S is employed for quantitatively integrating diverse bioanalyti- cal data available at different stages of ADC development. Of note, this review is mainly written for bioanalytical scientists, the read- ers who are interested in rigorous discussion on the modeling and simulation aspects of this subject matter are referred to reference [3].
Integration of PK data The discipline of PK deals with how a bio- logical system handles drug molecules like ADCs. In order to support the understand- ing of ADC PK and quantitative character- ization of the ADME (absorption, distribu- tion, metabolism and elimination) properties of an ADC, bioanalytical scientists are usu- ally requested to provide the concentration versus time profiles of various ADC analytes
Bioanalysis (2015) 7(13), 1633–1648 ISSN 1757-6180 Antari Khot1 , Sharad Sharma1
& Dhaval K Shah*,1 1
Department of Pharmaceutical Sciences,
455 Kapoor Hall, School of Pharmacy & Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214, USA *Author for correspondence: Tel.: +1 716 645 4819
dshah4@buffalo.edu
part of
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