Skip to main content
SpringerLink
Log in

Comprehensive In Vitro Proarrhythmia Assay (CiPA) Update from a Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA Meeting

  • Regulatory Science: Meeting Report
  • Published:
Therapeutic Innovation & Regulatory Science Aims and scope Submit manuscript

Abstract

A Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA-sponsored Think Tank Meeting was convened in Washington, DC, on May 21, 2018, to bring together scientists, clinicians, and regulators from multiple geographic regions to evaluate progress to date in the Comprehensive In Vitro Proarrhythmia Assay (CiPA) Initiative, a new paradigm to evaluate proarrhythmic risk. Study reports from the 4 different components of the CiPA paradigm (ionic current studies, in silico modeling to generate a Torsade Metric Score, human induced pluripotent stem cell—derived ventricular cardiomyocytes, and clinical ECG assessments including J-Tpeakc) were presented and discussed. This paper provides a high-level summary of the CiPA data presented at the meeting.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Sager PT, Gintant G, Turner JR, Pettit S, Stockbridge N. Rechanneling the cardiac proarrhythmia safety paradigm: a meeting report from the Cardiac Safety Research Consortium. Am Heart J. 2014;167:292–300.

    Article  Google Scholar 

  2. CiPA Update Workshop: an CSRC-HESI-SPS-FDA Meeting. http://www.cardiac-safety.org/think-tanks-meetings/2014-meetings/cipa-update-workshop-csrc-hesi-sps-fda-meeting/. Published December 2014. Accessed June 29, 2018.

  3. CSRS/FDA Workshop: the proarrhythmic assessment of new chemical entities (with a focus on Phase I ECGs). April 2016. http://www.cardiac-safety.org/2016/04/csrcfda-workshop-the-proarrhythmic-assessment-of-new-chemical-entities/. Accessed June 29, 2018.

  4. CSRC. Critical discussion: future of the assessment of drug-induced arrhythmias and the Comprehensive in Vitro Proarrhythmia Assay (CiPA). http://www.cardiac-safety.org/2016/12/critical-discussion-future-of-the-assessment-of-drug-induced-arrhythmias-and-the-comprehensive-in-vitro-proarrhythmia-assay-cipa/. Published December 2016. Accessed June 29, 2018.

  5. FDA. Pharmaceutical Science and Clinical Pharmacology Advisory Committee Meeting, March 2017. https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AdvisoryCommitteeforPharmaceuticalScienceandClinicalPharmacology/ucm535520.htm. Accessed June 29, 2018.

  6. de Ponti F. Pharmacological and regulatory aspects of QT prolongation. In: Vaz JR, Klabunde T, eds. Antitargets: Prediction and Prevention of Drug Side Effects. Weinheim, Germany: Wiley-VCH, 2008:55–88.

    Google Scholar 

  7. Fermini B, Hancox JC, Abi-Gerges N, et al. A new perspective in the field of cardiac safety testing through the Comprehensive In Vitro Proarrhythmia Assay Paradigm. J Biomol Screen. 2016;21:1–11.

    Article  CAS  Google Scholar 

  8. Vicente J, Zusterzeel R, Johannesen L, et al. Mechanistic model-informed proarrhythmic risk assessment of drugs: review of the “CiPA” Initiative and design of a prospective clinical validation study. Clin Pharmacol Ther. 2018;103:54–66.

    Article  CAS  Google Scholar 

  9. O’Hara T, Virag L, Varro A, Rudy Y. Simulation of the undiseased human cardiac ventricular action potential: model formulation and experimental validation. PLoS Comput Biol. 2011;7: e1002061.

    Article  Google Scholar 

  10. Li Z, Dutta S, Sheng J, et al. Improving the in silico assessment of proarrhythmia risk by combining hERG (human ether-à-go-go-related gene) channel-drug binding kinetics and multichannel pharmacology. Circ Arrhythm Electrophysiol. 2017;10:e004628.

    CAS  PubMed  Google Scholar 

  11. Dutta S, Chang KC, Beattie KA, et al. Optimization of an in silico cardiac cell model for proarrhythmia risk assessment. Front Physiol. 2017;8:616.

    Article  Google Scholar 

  12. Chang KC, Dutta S, Mirams GR, et al. Uncertainty quantification reveals the importance of data variability and experimental design considerations for in silico proarrhythmia risk assessment. Front Physiol. 2017;8:917.

    Article  Google Scholar 

  13. Blinova K, Stohlman J, Vicente J, et al. Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias. Toxicol Sci. 2017;155:234–247.

    Article  CAS  Google Scholar 

  14. Ando H, Yoshinaga T, Yamamoto W, et al. A new paradigm for drug-induced torsadogenic risk assessment using human iPS cell-derived cardiomyocytes. J Pharmacol Toxicol Methods. 2017;84:111–127.

    Article  CAS  Google Scholar 

  15. Millard D, Dang Q, Shi H, et al. Cross-site reliability of human induced pluripotent stem-cell derived cardiomyocyte based safety assays using microelectrode arrays: results from a blinded CiPA pilot study. Toxicol Sci. 2018;164(2):550–562.

    Article  CAS  Google Scholar 

  16. Johannesen L, Vicente J, Gray RA, et al. Improving the assessment of heart toxicity for all new drugs through translational regulatory science. Clin Pharmacol Ther. 2014;95:501–508.

    Article  CAS  Google Scholar 

  17. Johannesen L, Vicente J, Mason JW, et al. Differentiating drug-induced multichannel block on the electrocardiogram: randomized study of dofetilide, quinidine, ranolazine, and verapamil. Clin Pharmacol Ther. 2014;96:549–558.

    Article  CAS  Google Scholar 

  18. Johannesen L, Vicente J, Mason JW, et al. Late sodium current block for drug-induced long QT syndrome: results from a prospective clinical trial. Clin Pharmacol Ther. 2016;99:214–223.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Applied Regulatory Science, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA

    David G. Strauss MD, PhD (Director)

  2. AbbVie, Chicago, IL, USA

    Gary Gintant PhD

  3. US Food and Drug Administration, Silver Spring, MD, USA

    Zhihua Li PhD, Wendy Wu PhD, Ksenia Blinova PhD & Jose Vicente PhD

  4. DRT Strategies, Inc, Arlington, VA, USA

    J. Rick Turner PhD, DSc

  5. Stanford University, Palo Alto, CA, USA

    Philip T. Sager MD

Authors
  1. David G. Strauss MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gary Gintant PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhihua Li PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wendy Wu PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ksenia Blinova PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jose Vicente PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Rick Turner PhD, DSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Philip T. Sager MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David G. Strauss MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Strauss, D.G., Gintant, G., Li, Z. et al. Comprehensive In Vitro Proarrhythmia Assay (CiPA) Update from a Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA Meeting. Ther Innov Regul Sci 53, 519–525 (2019). https://doi.org/10.1177/2168479018795117

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/2168479018795117

Keywords

Search

Navigation