• Marilyn Brown

    A Look at the 3Rs

    The 3Rs proposed by scientists Russell and Burch in the 1950s set the standard for minimizing animal use and maximizing animal well-being in laboratory experimentation.
  • Henry Holzgrefe

    Preclinical QT Assessment Reduces Late-stage Drug Failures

    The clinical effects of drugs on cardiac repolarization and rhythm, particularly the induction of potentially fatal arrhythmias, such as Torsade de Pointes (TdP), have been increasingly documented over the past two decades. These concerns have given rise to specific regulatory measures, such the ICH S7A, S7B and E14 guidance. These, in turn, have given rise ...
  • Robert Kaiser

    “Covering” Cardiovascular Safety in Repeat-Dose Studies

    Jacketed external telemetry (JET) is the latest technology available for collection of continuous electrocardiograms (ECGs) from unrestrained animals. It delivers higher‑quality cardiovascular safety data than predecessor external technologies and has become a premier solution for preclinical research without the use of invasive implantation techniques. After all, Cardiovascular Safety Pharmacology is a logical target as a ...
  • Mark Anderson

    Cardiovascular Safety In Vitro Models

    Many drugs have either been withdrawn from the market or placed on restricted use due to their (or their metabolites) undesirable ‘off-target’ effects on the heart. An increase in the cardiac action potential duration (APD), caused by a drug blocking the hERG (human ether a go-go) ion channel, can be defined by a prolongation of ...
  • Henry Holzgrefe

    Regulatory Perspective of Cardiovascular Risk Assessment

    The harmonization of regulatory guidance for drug development traces its origins to the European Community (EC) in the mid 1980’s. The current governing body of record, known as the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), was formed in 1990 at a joint meeting of regulatory agencies ...
  • Barbara J. Patterson

    Regulatory Anticipation

    When I hear the word anticipation, I can’t help but think of the first line in the song with the same title that Carly Simon made famous in the 1970’s: “We can never know about the days to come.” That is where we are with the long-anticipated modernization of the Food and Drug Administration (FDA) Good ...
  • Marie-Soleil Piche

    Immunology and Risk Assessment

    Historically, advances in immunology have been closely associated with studies of infectious diseases. However, in the past 10 years, immunology has moved from identifying and characterizing individual molecules and cell types to understanding the roles of each, and the regulatory networks that govern interactions between immune cells. This increased understanding has led to the elucidation of ...
  • Christine Copeman

    The Evolution of Toxicology Testing

    For decades, the requirements for determining the toxicological profile of a new chemical entity (NCE) through a safety assessment study were well-defined. But advances in research brought about novel entities, bringing new challenges to toxicology testing. Biopharmaceuticals introduced many of these challenges in the 1980s. Half-lives for these larger molecules were measured in days, not minutes ...
  • Richard Long

    Toxicologic Pathology: Past, Present and Future

    Toxicologic pathology integrates the disciplines of toxicology and pathology . Those who practice in this field identify the effects of test articles (e.g., drugs, chemicals and other therapeutic devices) on research models. The data generated are a critical component of the safety assessment process and can be used to predict responses in humans and other animals ...
  • Joe Cornicelli

    Anti-inflammatory Agents as Therapies for Diabetes

    This month’s series of articles has focused on the worldwide prevalence of obesity and how it increases the risk for metabolic and respiratory diseases. The underpinning across all of these disorders appears to be activation of the immune system. It’s well-established that autoimmunity is important in the development of Type 1 diabetes (T1D) in humans, ...