Science & Technology: The Current Regulatory Landscape for Cardiac & Cardiovascular Safety Assessments: Part I
Posted 01 January 2011 | By
Cardiac and cardiovascular safety concerns continue to be leading reasons for drug failures during development and marketing, and have led to product withdrawals. Several high-profile marketing withdrawals involved drugs for non-life-threatening diseases. For example, in 1998, terfenadine (Seldane), an antihistamine used for allergies, was removed from the US market following deaths from a form of polymorphic ventricular tachycardia called Torsades de Pointes (TdP)-a French term, which literally translated, means "twisting of the points." In 2000, cisapride (Propulsid), a very effective and successful gastroprokinetic agent marketed by Janssen/Ortho for gastroesophageal reflux disease (GERD), to speed gastric emptying while increasing esophageal sphincter tone, was withdrawn from the market after a warning from the US Food and Drug Administration (FDA) to prescribers regarding the product's propensity to prolong cardiac repolarization. Regulatory concern over drug-induced TdP led to preclinical and clinical draft guidance documents in 2002, which were finalized in 2005 with the publication of the cornerstone International Conference on Harmonisation (ICH) guidelines "S7B"1 and"E14,"2 respectively. E14 is discussed later.