Industry-Sponsored Symposia

07:15 - 08:15 | Tuesday, September 12

Frontage Laboratories

Metabolites in Safety Testing (MIST): What, Why, and How

Philip Tiller, Distinguished Scientist, DMPK, Frontage Laboratories

The goal is to have attendees understand why and how to address the FDA MIST guidance.

Learning Objectives

  1. Understand the origins of MIST

  2. Understand the risks involved in not addressing MIST in a timely manner

  3. Understand when the optimal time is to address the MIST guidance

  4. Understand how to address the MIST guidance in an appropriate manner

Target Audience: All who are involved in early clinical development of small molecule drugs

Regulatory agencies have provided recommendations on when and how to identify and characterize drug metabolites to ensure their non-clinical toxicity has been adequately evaluated. The studies conducted to comply with these recommendations are often referred to as metabolites in safety testing or MIST. This presentation will review the origins of these recommendations and the specific requirements that need to be considered in designing studies to address the regulatory expectations.

We will discuss an approach that integrates a series of in-vitro and in-vivo assays that in combination demonstrate due diligence in meeting MIST regulatory expectations.

07:15 - 08:15 | Tuesday, September 12

Eurofins Discovery

Evaluating P-gp and BCRP Drug-Drug Interaction Assessment - New Approaches with CRISPRTM Knock-Out/ Knock-In Cell Lines for Applications in Drug Discovery

Shantanu Roychowdhury, ADME-Tox Business Leader, Eurofins Discovery

Screening for drug-drug interactions involving transporters remains an important focus for regulatory agencies and sponsors alike. Several in vitro models have become industry standard systems providing useful data for assessing drug transporter interactions. However, as with all in vitro models, there are limitations to consider with these models. Participants will learn how current in vitro models can be improved with genetic engineering tools to create models that are more physiologically relevant.

Learning Objectives

  1. Learn about benefits and limitations of in vitro models for evaluating transporter-mediated drug interactions

  2. Learn how genetically engineered tools can be utilized to improve existing in vitro models

  3. Learn how the creation of low efflux MDCK cells and Knock-out and Knock-in MDCK cells provides superior models for assessing transporter interactions.

  4. Ask our expert speakers questions and benefit from their knowledge and guidance

Target Audience: DMPK/ADME scientists in Pharmaceutical and Biotechnology companies, Laboratory Leads, Regulatory Scientists

The role of P-glycoprotein (P-gp) and breast cancer related protein (BCRP) is well known in Drug-Drug Interactions. Evaluation of whether an investigational drug is a substrate or inhibitor of transporters is a regulatory requirement. The United States Food and Drug Administration (FDA) Guidance on Drug-Drug Interactions states that if drugs are highly soluble and highly permeable, the drug must be evaluated for interactions with P-gp and BCRP. Cell-line models (such as Caco-2 or MDCKII) or Artificial Membrane (such as PAMPA) models are used for evaluation of permeability. Caco-2 or MDCKII can be further extended to evaluate if an investigational drug is a substrate or inhibitor of P-gp or BCRP through determination of efflux ratios and subsequent reduction in efflux ratio. However, there are shortfalls of both Caco-2 and MDCKII cell lines that may not allow for full characterization of investigational new drugs. For example, Caco-2 expresses a wide variety of transporters that may not be able to be specifically probed and inhibited for determination of efflux. MDCKII cells also exhibit endogenous expression of canine versions of human transporters which share significant sequence similarity.

In this symposia, we will present some new offerings for evaluation of P-gp and BCRP drug interactions with cell lines developed with CRISPRTM technology. The symposia will highlight development, generation and characterization of both Knock-out and Knock-in MDCKII cell lines, as well as evaluation of reference pharmacology for use in Drug Discovery and Regulatory Applications.

07:15 - 08:15 | Wednesday, September 13

BioIVT

Highlights of the In Vitro Sections of the Draft ICH Drug Interaction Studies M12 Guideline and Comparison With Current Guidance

Dr. Brian Ogilvie, Vice President, Scientific Consulting, BioIVT

This symposium is intended to provide perspectives on the impact that the ICH M12 guideline will have on the in vitro DDI studies required for drug development.

Learning Objectives

  1. Facilitate understanding of the in vitro DDI study needs to meet the draft ICH M12 guidelines

  2. Provide examples of the comments provided to the ICH and how they may impact the final guideline

  3. Discuss what changes to drug development programs may be needed now to plan for the finalization of the guideline in 2024

Target Audience: Researchers engaged in the design and implementation of ADME, DMPK, and DDI programs with an interest in developing the data needed for successful regulatory submissions.

In June 2022, the ICH released the first draft of its harmonized Drug Interaction Studies Guideline (M12). The guideline is the result of several meetings of the Expert Working Group since 2018 with the goal of harmonizing member regulatory agencies’ guidelines to create a single guideline that will be used across all member countries. After a review period, the guideline will be adopted in early 2024.

This presentation will offer perspectives on the differences between current in vitro drug-drug interaction guidance from the relevant US FDA, EMA and PMDA guidance documents, and how to plan drug development strategies to meet the ICH M12 guideline.

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