CiPA Update December 2018

Dear CiPA Community,
Welcome to the CiPA Quarterly Update!

We are happy to share news from the recent ICH face-to-face meeting held in November 2018. The ICH S7B/E14 Q&A concept paper and work plan have been approved! The ICH Assembly endorsed the establishment of an Implementation Working Group (IWG) to begin the process of developing a Q&A document. This IWG will build on work done by the former E14/S7B Discussion Group (DG) including work on the CiPA initiative.

The purpose of the IWG will be to provide guidance around the proposed nonclinical assays (in vitro, in silico, and in vivo). The current plan calls for a two-staged Q&A approach starting with S7B and then E14 guidance with the goal to have this be a more efficient process. Read more online including the concept paper and work plan:

E14/S7B Questions & Answers: Clinical and non-Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential

Concept Paper

Work Plan

Recent Publications:

  • Vicente J, Zusterzeel R, Johannesen L, Ochoa-Jimenez R, Mason JW, Sanabria C, Kemp S, Sager PT, Patel V, Matta MK, Liu J, Florian J, Garnett C, Stockbridge N, Strauss DG. (2018.) Assessment of Multi-Ion Channel Block in a Phase-1 Randomized Study Design: Results of the CiPA Phase 1 ECG Biomarker Validation Study. Clin Pharmacol Ther. 2018 Nov 17. doi: 10.1002/cpt.1303.
  • Li Z., Ridder B. J., Han X., Wu W. W., Sheng J., Tran P. N., Wu M., Randolph A., Johnstone R. H., Mirams G. R., Kuryshev Y., Kramer J., Wu C., Crumb W. J., Strauss,
    D. G. (2018). Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative. Clinical Pharmacology and Therapuetics. Available online August 27, 2018. doi:10.1002/cpt.1184
  • Blinova K., Dang Q., Millard D., Smith G., Pierson J., Liang G., Brock M., Lu H.R., Kraushaar U., Zeng H., Shi H., Zhang X., Sawada K., Osada T., Kanda Y., Sekino Y., Pang L., Feaster T.K., Kettenhofen R., Stockbridge N., Strauss D.G., Gintant G. (2018). (2018). International Multisite Study of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment. Cell Reports. Available online September 25, 2018. https://doi.org/10.1016/j.celrep.2018.08.079.

If you’re interested in finding past Quarterly Updates, they are available online.

Regards,


____________________________
Jennifer Pierson, MPH
Senior Scientific Program Manager
Health and Environmental Sciences Institute (HESI)
jpierson@hesiglobal.org

CiPA Update October 2018


Dear CiPA Community,
Welcome to the CiPA Quarterly Update!

Recent publications from the CiPA workstreams are listed below. Visit the CiPA website to see all publications: http://cipaproject.org/publications/:

  • Strauss D.G., Gintant G, Li Z, Wu W, Blinova K, Vicente J, Turner J.R., Sager P.T. (2018). Comprehensive In Vitro Proarrhythmia Assay (CiPA) Update from a Cardiac Safety Research Consortium / Health and Environmental Sciences Institute / FDA Meeting. Therapeutic Innovation & Regulatory Science. First Published August 29, 2018. doi.org/10.1177/2168479018795117
  • Li Z., Ridder B. J., Han X., Wu W. W., Sheng J., Tran P. N., Wu M., Randolph A., Johnstone R. H., Mirams G. R., Kuryshev Y., Kramer J., Wu C., Crumb W. J., Strauss, D. G. (2018). Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative. Clinical Pharmacology and Therapuetics. Available online August 27, 2018. doi:10.1002/cpt.1184
  • Blinova K., Dang Q., Millard D., Smith G., Pierson J., Liang G., Brock M., Lu H.R., Kraushaar U., Zeng H., Shi H., Zhang X., Sawada K., Osada T., Kanda Y., Sekino Y., Pang L., Feaster T.K., Kettenhofen R., Stockbridge N., Strauss D.G., Gintant G. (2018). (2018). International Multisite Study of Human Induced Pluripotent Stem Cell Derived Cardiomyocytes for Drug Proarrhythmic Potential Assessment. Cell Reports. Available online September 25, 2018. https://doi.org/10.1016/j.celrep.2018.08.079.

Open Data Formatting:
A subteam including volunteers from industry and FDA is currently working on an open data format specification for manual and automated patch clamp data. The open format will be manufacturer independent and will meet CiPA in vitro and in silico needs. The format will be also eCTD compliant.

Best Practices Papers:
The CiPA Work Streams continue to make progress on additional manuscripts including one from each group that will detail some of the discussions and recommendations that came out of the recent May 2018 CiPA Meeting. These publications will cover topics such as quality standards necessary for regulatory submissions to best practices and recommendations. The hope is to help provide some further clarity around expectations around the differences in early drug development screening tools and data that will be submitted as part of a regulatory submission package.

If you’re interested in finding past Quarterly Updates, they are available online: http://cipaproject.org/latest-news/.

Jennifer Pierson, MPH
Senior Scientific Program Manager
Health and Environmental Sciences Institute (HESI) jpierson@hesiglobal.org

CiPA Update September 2018

Dear CiPA Community,

On behalf of the CiPA Steering Team, I would like to share some exciting updates.

We are pleased to share materials from the recent May CiPA Update meeting, “The Future of the Assessment of Drug-Induced Arrhythmias and CiPA.” Presentations and a meeting synopsis are now available on the CiPA and CSRC websites. Feel free to share these links with your colleagues!

In addition to the meeting materials, the recommended cardiac ion channel protocols are now available on the CiPA website: http://cipaproject.org/data-resources/. Protocols included are for hERG, CaV1.2 and NaV1.5. As more data is generated, the protocols may evolve and updates will be posted to the website. Should you have any questions, feel free to contact me.

Finally, the Myocyte Pilot Study MEA results were recently published in Toxicological Sciences and are available online ahead of print: http://cipaproject.org/publications/. The study following these results, “Assessment of an In Silico Mechanistic Model for Proarrhythmia Risk Prediction Under the CiPA Initiative,” has been accepted for publication in the open access journal Cell Reports, and an update on the CiPA initiative is now available in Journal for Clinical Studies.

Look forward to regular, quarterly communications or check the CiPA website for more updates soon!

Jennifer Pierson, MPH
Senior Scientific Program Manager
Health and Environmental Sciences Institute (HESI) jpierson@hesiglobal.org