2022 AAPS PharmSci 360

One of the pivotal milestones of early drug development is obtaining approval for an investigational new drug application (IND). A proposed first-in-human (FIH) study design is required for every IND application, of which a robust FIH dose rationale is a critical component. Physiologically-based pharmacokinetic (PBPK) modeling is a methodology based upon in-depth mechanistic understanding of the biological and pharmacologic phenomena which determine in vivo PK in animals and humans. Consequently, PBPK models are well-posed to make robust predictions of in vivo PK exposures, even when based on the limited data available during the initial stages of drug development. As such, PBPK approaches are being increasingly employed to strengthen the FIH dose rationale. Other applications of PBPK in early development include guiding early formulation development and facilitating lead candidate selection. This eChalk Talk will focus on how PBPK modeling can be applied during early drug development with a particular focus on optimal FIH candidate and dose selection, thereby enhancing the odds of a successful IND and subsequent clinical development.

Have you been interested in a career as a pharmaceutical consultant but didn’t know how to get started? Maybe you’ve got questions on whether you’re experienced enough to be considered seriously by hiring managers? Or you’re currently in a position in academia, industry, or a regulatory agency, and want to make a transition to consulting but don’t know when the best time is? Perhaps you’re wondering if consulting can provide a stable career path? If you’re asking yourself any of these questions, then this is the career development session for you!

Location: Career Center

Location: 151 AB

Physiologically Based Pharmacokinetic (PBPK) models can be used to virtually assess the formulation's bioequivalence (VBE). These applications cover a wide range of oral, dermal, inhalation as well as long-acting injectable formulations. Such capabilities present opportunities and challenges in informing, optimising and saving many unnecessary BE studies. In addition, it allows expanding BE studies beyond healthy populations within a patient-centric paradigm. To enable PBPK modeling for regulatory decision-making, models should be sufficiently qualified and verified for the intended purpose. In this session, the state of the arts in using PBPK models for VBE studies, requirements, and case studies are presented.

Bracketing is an often overlooked approach to not only justify a dose regimen, but to also put into context exposure differences for specific populations and extrinsic factors. Case studies of MIDD approaches and how they can be applied to these scenarios will be discussed and the benefits of bracketing to the overall development program both pre and post approval will be outlined.

The attrition rate of drug programs in early-stage development is high, with two-thirds of preclinical programs failing to move successfully to Phase 1. How do we better inform translational R&D decisions to de-risk investments and help increase probability of success? Physiologically-based pharmacokinetic (PBPK) modeling and simulation is a regulatory-adopted, versatile tool in drug development that helps answer a myriad of “what if” questions without clinical testing. Join this session to learn how to use Simcyp Discovery Simulator for first-in-human dose prediction.

Take your taste buds on tour of Boston’s most iconic flavors—without leaving the conference! Stop by the Certara booth from 2:30 pm – 3:30 pm to experience some of the most delicious clam chowders Boston has to offer.

Location: 151 AB

Location: 151 AB

There should no longer be any question as to the value and myriad benefits of PBPK in drug discovery and development. With the publication of two new ICH and one new FDA guidance documents this past week that incorporate its use, we can affirm that global regulators are bullish on the use of PBPK in an ever-increasing type of use cases. In 2018, a chart was published by the US FDA (with a similar one from EMA) that used a green/amber/red light approach to communicating their openness to using PBPK for regulatory approval. Since that time, there have been many areas and use cases for which the regulators have upgraded that approach (amber to green for example), as documented in new drug approvals and published papers. Additionally, the acceptance and encouragement has expanded across the drug development continuum, with increased use cases in discovery, translation to FIH, across all clinical trials, and for post-marketing label expansion.

The concept of “Virtual Bioequivalence” (V-BE) is built on the back of combination physiologically-based (PBPK) modelling, integration of results from in vitro tests on drug product, use of pre-existing data on systems and drug. The subject is growing out of its infancy as multiple applications are now reported in the literature. Passing the BE criteria involves showing similarity in systemic exposure (pharmacokinetic profile - PK) following the administration of the test and reference products. However, indicating equivalence for average profile is not adequate and the degree of population variability around the average, by means of 90% confidence interval (CI), needs to be within certain range of the reference product (typically 80-125%). The presentation aims to demonstrate the differences between various strategies that help to capture the CI around the PK profile during conduct of VBE studies. The study highlights the propagating physiological within-subject variability (WSV) to PK profiles and how these might be different for test and reference products.

Join us from 12:00 pm – 1:30 pm to learn how you can streamline your PK/PD analyses while enjoying a complimentary lunch. Our experts will introduce the newly launched Phoenix WinNonlin® Hosted, share Phoenix WinNonlin® tips and tricks, and reveal the exciting new features from the latest PK Submit release.

Location: 152

Location: 152