The Role of the Food and Drug Administration in Drug Development: On the Subject of Proarrhythmia Risk

Abstract

The Food and Drug Administration (FDA) is responsible for the regulation of the pharmaceutical industry in the interest of protecting public health. The aim of this review was to outline the evolution and current role of the FDA in the development and approval of new drugs. Additionally, we describe current assessments of proarrhythmia risk to illustrate recent FDA initiatives intended to harness information technology to modernize the regulatory process. In order to identify the literature required to produce this review, search tools such as PubMed and Google Scholar were used to locate relevant web pages and articles. The job of the FDA is not only to ensure that high standards for drug efficacy and safety are applied to products available to American consumers and patients but also to balance the lengthy, costly process of maintaining these standards against the pressure to provide access to effective treatments earlier and without surplus expenditures. In order to provide expedited access to the newest effective therapies for critically ill patients in the safest way possible, the FDA has developed several accelerated pathways to fast-track drug approval. Through partnerships with industry and academic institutions, research is being conducted into how information technology can be integrated into the drug development process to improve its cost-effectiveness.

Update on ICH E14/S7B Cardiac Safety Regulations: The Expanded Role of Preclinical Assays and the “Double‐Negative” Scenario

“…A number of excellent reviews concerning proarrhythmic risk have been published whose focus was to describe the individual preclinical assays, clinical studies, and analysis schemes involved in assessing a compound's effect on ventricular repolarization. 1 , 2 , 3 , 4 As the science and technology in the field of cardiac safety have evolved, so has the regulatory landscape. As such, the purpose of this review is to highlight the principal regulatory changes from the IWG publication and FDA webinar regarding the expanded role of concentration response analysis (CRA) and preclinical assays designed to evaluate the proarrhythmic potential of compounds when a substitute for a thorough QT study (TQT) study is sought or when a dedicated TQT study is not feasible.…”

Multifunctional in vitro, in silico and DFT analyses on antimicrobial BagremycinA biosynthesized by Micromonospora chokoriensis CR3 from Hieracium canadense

“…BagA was also screened for potential cardiotoxicity by Pred-hERG, as the FDA mandates that every biomolecule undergo hERG safety testing prior to being employed as a drug candidate since blocking of the hERG protein channel has been linked to fatal cardiac arrhythmias 111 . The Pred-hERG classified BagA as non-cardiotoxic with a 60% prediction probability, as given in Table 5 .…”

A Review of the Potential of Poly-(lactide-co-glycolide) Nanoparticles as a Delivery System for an Active Antimycobacterial Compound, 7-Methyljuglone

“…By initiating communication with regulatory agencies early in the development process, researchers can better understand the expectations of regulatory authorities. Researchers can also obtain guidance on study design and ensure that preclinical data align with regulatory requirements, streamlining the transition to clinical trials [ 108 ]. Researchers need to work closely with regulatory agencies to address the specific regulatory challenges associated with PLGA nanoparticle-based drug delivery systems.…”