Transporters of Emerging Importance in Drug Development: Beyond the Guidance Documents

Aired:  16 May 2019

Presenter: Brian Ogilvie, Ph.D., Sekisui XenoTech Vice President of Scientific Consulting

In October, 2017, the US FDA revised and split its 2012 draft guidance for industry on in vitro drug-drug interaction (DDI) studies, into one document for in vitro DDI studies, and another for clinical DDI studies. For investigation of the transporter inhibition or substrate potential of drug candidates, the FDA updated the prior in vitro list (i.e., P-gp, BCRP, OATP1B1 & 3, OAT1 & 3, and OCT2) to include MATE1 and MATE2-K. Notably absent from this list was OCT1, which is a highly polymorphic hepatic uptake transporter, included in the European Medicines Agency (EMA) Final DDI Guideline from 2013.

In 2018 the International Transporter Consortium published a paper recommending prospective evaluation of OCT1. Other transporters covered by the ITC, including OATP2B1 and OAT2, along with the evidence for their emerging importance will also be highlighted. Finally, consideration of other transporters important for drug distribution during atypical routes of administration will be discussed (e.g., nasal and ophthalmic).

Key concepts discussed in this webinar will include:
  • 2017 FDA guidance update
  • In vitro transporter additions and eliminations in updated guidance
  • OCT1 evaluation in FDA versus EMA official documents
  • Impacts of polymorphisms
  • 2018 ITC paper discussing OCT1
  • Other important transporters covered by ITC paper
  • Extended Clearance Classification System (ECCS) prediction of rate-determining step in Absorption, Distribution, Clearance & Elimination (ADCE)
  • Atypical routes of administration

In Vitro Induction Studies: Elements of Design and Important Considerations in Data Analysis

Aired:  24 April 2019

Presenter: Joanna Barbara, Ph.D., Vice President of Scientific Operations at Sekisui XenoTech

When evaluating drug-drug interaction (DDI) risk of an investigational drug, a battery of studies is needed to investigate victim/perpetrator potential. One of these comprises evaluation of the potential of a new therapy to induce drug-metabolizing enzymes, which can impact clearance of concomitantly administered drugs. The team at Sekisui XenoTech has built a reputation of dedicating high quality resources and specialists to conduct such studies with scientific rigor.

In this webinar, Dr. Joanna Barbara will address frequently asked questions from sponsors seeking induction studies and elaborate on some recommendations we give to achieve successful regulatory submission. Points of discussions will include an overview of enzyme induction studies and critical considerations in design, from determination of supporting data to conclusive interpretation.

Key concepts discussed in this webinar will include:
  • Standard study considerations
  • FDA guidance requirements
  • Required endpoints for IND submission
  • 3A induction and associated challenges
  • Next-step recommendations

In Vitro Evaluation of Immunomodulating Drugs as Perpetrators of Drug Interactions

Aired:  20 February 2019

Presenter: Dr. Maciej Czerwinski, Sekisui XenoTech Director of Consulting

On October 15th, 2018, Sekisui XenoTech presented on "In Vitro Direct and Cytokine-Mediated Effects of Therapeutic Peptides and other Biologics on CYP Enzymes" at the Peptide ADME Discussion Group Workshop in Gothenburg, Sweden. Following subsequent requests for a follow-up webinar, Dr. Czerwinski will be presenting on the following subjects...

Key concepts discussed in this webinar will include: