Greg Hileman, Ph.D., Sr. Director and Principle Regulatory Scientist of Cato Research
The International Conference on Harmonization (ICH) last updated its guidance “THE CLINICAL EVALUATION OF QT/QTC INTERVAL PROLONGATION AND PROARRHYTHMIC POTENTIAL FOR NON-ANTIARRHYTHMIC DRUGS (ICH E14 (R3)) in 2005. This month, FDA published the most recent ICH updated list of questions and answers (ICH E14 Q&As ()) related to ICH E14, effectively making it an FDA guidance. R3 included an updated question on the use of concentration-response modeling in lieu of point estimate and confidence interval calculation at Cmax. Important considerations when using modeling include the possibility of pooling data across multiple studies to explore a wider range of exposures than a single thorough QT prolongation study could explore while maintaining a focus on ECG quality and managing trial heterogeneity. If data are available to estimate QT effects at sufficiently high multiples of clinically relevant exposures, a separate positive control may not be required. As always, the focus of the analysis is to exclude a change of 10 ms or more (upper limit of the 90% confidence interval) at relevant concentrations. Significant savings with valid concentration-response modeling may result from predicting results at regimens not studied. A sponsor may be able to avoid certain intrinsic (enzyme induction or inhibition) and extrinsic (DDI) studies by predicting QTc effects. High quality models may aid in deciding inclusion/exclusion criteria or in predicting dose adjustments needed in phase 3 and 4 studies where such factors are encountered.
”ICH guideline E14: the clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (R3) – questions and answers”
By Michelle Villasmil, Ph.D., RAC (US), Regulatory Scientist at Cato Research
FDA draft and final guidances released from CDER, CBER, and CDRH and Manual of Policies and Procedures (MAPPs) of interest released from CDER in June 2017 are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.
By Amelie Rodrigue-Way, Ph.D., RAC (CAN), Associate Director, Regulatory Strategy
What’s New in:
Therapeutic Products Directorate:
Biologics and Genetic Therapies Directorate:
Medical Devices: https://www.canada.ca/en/health-canada/services/drugs-health-products/medical-devices/what-new.html
Natural and Non-prescription Health Products Directorate: https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/what-new.html
Health Canada New Guidance Documents (Drugs and Biologics)
Updates from Health Canada (Drugs and Biologics)
Santé Canada: Quoi de neuf?
Par Amélie Rodrigue-Way, Ph.D., RAC (CAN), Directrice associée, Stratégie réglementaire
Quoi de neuf :
Direction des produits thérapeutiques
Direction des produits biologiques et thérapies génétiques:
Instruments médicaux: https://www.canada.ca/fr/sante-canada/services/medicaments-produits-sante/instruments-medicaux/quoi-neuf.html
Direction des produits de santé naturels et sans ordonnance:
Nouvelles lignes directrices de Santé Canada (Médicaments et Produits biologiques)
Mises à jour de Santé Canada (Médicaments et Produits biologiques)
By Sheila Plant, Ph.D., R.A.C., Assistant Director, Regulatory Strategy, US at Cato Research
One revised draft FDA guidance, released from CBER, and two MAPPs, released from CDER, in May 2017, are posted. In addition, upcoming advisory committee meetings to be held in June and July are listed below with links to more information.
By Joanne McNelis, Ph.D., Clinical Strategy Scientist at Cato Research
FDA draft and final guidances, released from CDER, CBER, and CDRH, and Manual of Policies and Procedures (MAPPs) of interest, released from CDER in March and April are posted. In addition, upcoming advisory committee meetings are listed below with links to more information.