- CiPA Update October 2018 October 11, 2018
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) email@example.com
CiPA and Cardiac Safety
The Comprehensive In Vitro Proarrhythmia Assay (CiPA) effort will substantially evolve the preclinical and clinical proarrhythmia assessment of new chemical entities. At its simplest levels, more comprehensive channel-screening efforts could be implemented early in drug discovery using automated patch-clamp techniques, with the resulting data used to assess proarrhythmic risk using in silico APD reconstructions. Such data could be used for candidate selection as well as to guide further testing.
It is encouraging that elements of the CiPA are already being used in early drug discovery (for example, increasing the number of ionic currents being interrogated and using stem cell cardiomyocytes) as well as guiding early medicinal chemistry efforts, refining early hazard identification, and potentially impacting clinical development. Such efforts should reduce the automatic exclusion of IKr-blocking drugs from early drug discovery. It is anticipated that the commercial costs for such services would be substantially reduced as these efforts are implemented.
Academicians, clinicians and regulators who are familiar with clinical QT studies, mechanisms of proarrhythmia, drug safety assessments, and regulatory submissions are working together under the auspices of the CiPA Steering Committee, Cardiac Safety Research Consortium, HESI, FDA, SPS, EMA, Health Canada, Japan NIHS, and PMDA on this effort. For more information and updates, please contact us at firstname.lastname@example.org.