About CIPA

About CiPA

The objective of the CIPA initiative is to facilitate the adoption of a new paradigm for assessment of clinical potential of TdP that is not measured exclusively by potency of hERG block and not at all by QT prolongation. The new CIPA paradigm will be driven by a suite of mechanistically based in vitro assays coupled to in silico reconstructions of cellular cardiac electrophysiologic activity, with verification of completeness through comparison of predicted and observed responses in human-derived cardiac myocytes. To the extent that the ongoing validation program is successful, we envision petitioning for corresponding changes to regulatory requirements for proarrhythmia assessment and these might include eliminating or waiving the need for the TQT.

What it isProposal to evaluate proarrhythmic risk based on mechanistic electrophysiologic understanding of proarrhythmia with two primary components:

  1. In vitro drug effects, multiple cardiac channels + In Silico reconstruction of cardiac action potential
  2. Confirmation using human stem-cell derived cardiomyocytes

What it is Not: CIPA will not replace need for careful clinical assessment of electrophysiologic effects in phase 1 ECG safety studies .

View more about CiPA here.

CiPA Work Streams

CIPA1

Ion Channel

Develop voltage clamp protocols for core set of cardiac ion channel types.

In Silico

Develop consensus in silico model to reconstruct electrophysiologic activity within a heart cell.

Myocyte

Investigate capabilities of human stem-cell derived cardiomyocyte assays to confirm findings of in vitro and in silico assays.

Regulatory

Plot course to revise ICH guidelines and provide input to the compounds selected to validate and test CIPA.

CiPA Steering Team

The Steering Team acts as liaisons between the work streams and the organizations and stakeholders and meets to discuss project milestones. The Steering Team is composed of members from the following organizations:

FDA, HESI, CSRC, SPS, EMA, Health Canada, Japan NIHS, PMDA

Timelines

Each CiPA work stream has set project milestones and timelines. See the full details here.

CiPA Disclaimer

While there are many additional partners involved with CIPA, the Steering Team has a new statement about use of the CIPA logo, name or endorsement by the Steering Team. Read the document here.