Today’s show discussed biosimilar development from a clinical pharmacology perspective. I describe what biosimilar products are and the necessary comparisons to the reference product. I review requirements for PK similarity, PD similarity, immunogenicity, and safety. I also touch on the idea of interchangeability between the biosimilar and reference products. Links discussed in the show: FDA Guidance on Clinical Pharmacology Data to support Biosimilarity (May 2016) FDA Guidance on Demonstrating Interchangeability (May 2019) FDA Q&A on Biosimilarity and Interchangeability (Sep 2023) You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show discussed approaches for modeling absorption profiles. I discussed the rationale behind modeling absorption and then described some common models. These included first-order absorption, zero-order absorption, transit compartments, distributed delay, Weibull, and zero/first order absorption. I also provided my recommendations on how to model absorption. Links discussed in the show: Distributed delay modeling in PK and PD Modeling biphasic formulation of methylphenidate You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show was an overview of Aplos Analytics and the development story for Aplos NCA. Please consider participating in the Early Access Program. Use the link below to learn more about Aplos NCA. Links discussed in the show: Aplos Analytics website Aplos Analytics Contact Us Page You can connect with me on LinkedIn and send me a messageSend me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show is about hepatic impairment clinical studies. I cover the rationale behind evaluating hepatic impairment, common study designs, and key factors in the analysis and interpretation of the study results. I also share a huge announcement about Aplos NCA, a cloud-based solution for calculating NCA PK parameters. Use the link below to learn more about Aplos NCA. Links discussed in the show: FDA guidance EMA guideline Aplos Analytics website You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC

Today’s episode was about Project Optimus, the FDA initiative to improve dose selection and optimization for oncology products. Julie Bullock was a guest on this episode and shared her expertise as a former oncology clinical pharmacology reviewer at the FDA and as a current consultant in the pharmaceutical industry. Links discussed in the show: Project Optimus FDA List of FDA guidances and publications for Project Optimus May 2022 FDA-ASCO workshop: Getting the Dose Right: Optimizing Dose Selection Strategies in Oncology Sept 2023 Second Annual FDA ASCO WORKSHOP on Getting the Dosage Right (this one focused on combinations) Feb 2024 FDA/AACR Public Workshop: Optimizing Dosages for Oncology Drugs You can connect with Julie on LinkedIn You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s show is about TMDD or target-mediated drug disposition models. I review the scientific and physiologic basis for TMDD models, how to review data and determine if a TMDD model is needed. I review the various modeling approaches along with my recommendations for specific TMDD models. I hope this information helps you understand how to recognize TMDD behaviors and the options for modeling that data. Links discussed in the show: A tutorial on target-mediated drug disposition (TMDD) models Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Today’s episode is about communication for scientists. I believe that improvements in communication skills can have a greater impact on your career and work than technical skills. Michael Piperno, an expert in communication and leadership skills joins me to discuss communication challenges and solutions for clinical pharmacologists and pharmacometricians. Links discussed in the show: You can connect with Michael On his websiteOn LinkedInOn his blogOn his podcastSubscribe to Michael’s newsletterView upcoming leadership and communication workshops You can connect with me You can connect with me on ⁠LinkedIn and send me a message⁠⁠Send me a message⁠⁠Sign up for my newsletter⁠ Copyright Teuscher Solutions LLC All Rights Reserved

Today’s episode is about cell therapies, including CAR T-cell theraphy for cancer. I give an overview of cell therapy and the challenges of clinical pharmacology in this new area of research. Links discussed in the show: CAR T-cell Therapy Image You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Happy New Year! Today’s episode is all about allometric scaling in pharmacokinetic and pharmacodynamics. In particular, I’ll discuss how to use it for scaling from adults to pediatrics and for selection of first in human doses. Links discussed in the show: Boxenbaum manuscript FDA guidance on First in Human doses You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This is the last podcast for 2023. Thank you for listening throughout the year! In today’s episode I talk about computer system validation for pharmacometrics. I review my experience with validation in multiple companies over 20 years and discuss what auditors and FDA inspectors want to see. Links discussed in the show: Computer system validation guidance for medical devices Computer systems used in clinical trials Computer system assurance guidance for medical devices EMA guidance on computer systems and electronic data in clinical trials You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In today’s episode I cover 4 different modeling approaches: QSP, PBPK, PopPK, and PKPD. All of these are methods for analyzing data to predict either drug concentrations, or a response variable. But each method is developed in a different way and has different assumptions and limitations. Links discussed in the show: You can connect with me on LinkedIn and send me a messageSend me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In today’s episode I discuss BLQ handing for both non-compartmental and modeling analysis approaches. I discuss how BLQ samples are defined, methods for analyzing them, and situations when you should use different analysis approaches. Links discussed in the show: FDA guidance on bioanalytical method validation ICH M10 guidance on bioanalytical method validationHandling data below the limit of quantitation in mixed effects models Ways to fit a PK model with some data below the quantification limit You can connect with me on LinkedIn and send me a message Send me a messageSign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In today’s episode I covered the different types of drug interactions, followed by features of clinical drug evaluation studies recommended in the guidance. Then I will review recommendations for both stand-alone clinical drug interaction studies, as well as nested drug interaction studies. I’ll finish with recommended approaches for interpreting drug interaction study results and expressing that information in drug labeling. Links discussed in the show: Prevalence and factors associated with polypharmacy: a systematic review and meta-analysis by Delara et al. FDA guidance on clinical drug interactions FDA guidance on in vitro drug interactions FDA guidance on therapeutic protein drug interactions EMA guideline on drug interactions You can connect with me on LinkedIn and send me a message Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

In today’s episode I discuss the evaluation of pharmacokinetics in patients with impaired renal function. I include information from both the US FDA and EMA guidance documents linked below. I discuss the determination of when a dedicated renal impairment study is needed, characteristics of the study design and how to analyze and interpret the results. Links discussed in the show: • FDA guidance on PK in patients with impaired renal function • EMA guidance on Evaluation of PK in patients with decreased renal function • You can connect with me on LinkedIn and send me a message. • Send me a message • Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode is a discussion on model evaluation and selection. I discussed diagnostic plots using predictions and residuals. I covered approaches for model selection and factors to consider. The focus of this episode is on models that predict continuous endpoints like drug concentration, biomarkers, or other continuous endpoints. Several figures are mentioned in the podcast and links to those images can be found below. Links discussed in the show: Figure 1: Observed vs Predicted for single-subject model (example of a good model fit). Figure generated using ggplot in R. Figure 2: Observed vs Predicted for single-subject model (example of a poor model fit) using logarithmic scales. Figure generated using ggplot in R. Figure 3: Observed vs Population and Individual Predicted for population model. Figures generated using ggCertara package in R. Figure 4: Weighted residuals versus time, time after dose, and population prediction for population model. Figures generated using ggCertara package in R. You can connect with me on LinkedIn and send me a message Do you need help with model selection? Send me a message Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode is a discussion of the FDA guidance “Exposure-Response Relationships”. The relationship between drug exposure and response is critical to any determination of the safety and effectiveness of a drug product. In this episode I discuss the regulatory applications of exposure-response, the exposure-response relationships over time, the design of studies to collection exposure-response information, and modeling exposure-response relationships. Links discussed in the show: • FDA guidance “Exposure-Response Relationships” • ICH E4 guideline “Dose-Response Information” • You can connect with me on LinkedIn and send me a message • Send me a message • Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode I talk about finding a job in Clinical Pharmacology or Pharmacometrics. I share a few thoughts from my experience followed by an interview with TJ Elder, the president of STEM Sourcing Recruiting and Staffing. TJ shares his insights and best practices on securing a new job in Clinical Pharmacology or Pharmacometrics. Links discussed in the show: • Connect with TJ Elder on LinkedIn • You can connect with me on LinkedIn and send me a message • Send me a message • Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

This episode is a discussion of the FDA and ICH guidance E14 titled “Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs”. I start with background on the reason for these evaluations, then move to an overview of the key evaluations needed. I then discuss in some detail the thorough QT study and the concentration QT analysis. Then I provide some parting thoughts from my experiences with these analyses. Links discussed in the show: • ICH E14 Guidance (FDA website) • Scientific white paper on concentration – QTc modeling by Garnett et. al • Correction to publication • You can connect with me on LinkedIn and send me a message () • Send me a message • Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Thank you to everyone who sent me feedback on this podcast. This episode is based on a suggestion from Kushal and Parmesh. In this episode, I discuss a general clinical pharmacology pediatric extrapolation plan. I describe the basics of the plan that is commonly proposed to regulatory bodies. I discuss specific technical approaches for extrapolation of adult pharmacokinetic data to pediatric patients and the extrapolation of adult exposure-response or pharmacodynamic data to pediatrics. And I conclude with a discussion of how to use physiologic-based pharmacokinetic models for pediatric extrapolation. Links discussed in the show: • Baby arms over head video • PBPK Models in Pediatric Development • You can connect with me on LinkedIn and send me a message • Send me a message • Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved

Thank you to everyone who sent me feedback on this podcast. This episode is based on a suggestion from Drew. In this episode, I discuss bioequivalence studies and generic drug development. I will refer to guidance documents from both the European Medicines Agency or EMA and the US Food and Drug Administration or FDA. First, I will start with a discussion of the definition of bioequivalence or BE. Then I will discuss the statistical basis for bioequivalence and how you can leverage that for study design. And I will end with some unique challenges related to bioequivalence. Throughout, I will give practical suggestions based on my experiences in the past with BE studies. Links discussed in the show: • EMA guidance on bioequivalence • FDA guidance on statistical approaches to bioequivalence (December 2022) • FDA statistical approaches to BE (January 2001) • FDA guidance on BE studies (2022) • FDA product-specific guidances on BE • Lecture from Helmut Schütz on finding intra-subject variability (or CV%) for power calculations • PowerTOST R Package • You can connect with me on LinkedIn and send me a message • Send me a message • Sign up for my newsletter Copyright Teuscher Solutions LLC All Rights Reserved