In Vitro Safety Pharmacology Assays

In Vitro Safety Pharmacology Insights for Early Program Decisions

Understanding potential risks early and advancing the right compounds can be a difficult task. Many early safety assays can be overly sensitive and lack specificity, potentially limiting development pipelines and increasing costs in drug development. To better predict potential risks and reduce unwarranted drug discovery attrition, Charles River recommends an approach that places greater emphasis on the accurate evaluation of potential risks earlier in development. Leveraging our vast ex vivo and in vivo capabilities, we can conduct a comprehensive, integrated assessment of the cardiovascular and central nervous systems.

Dispelling the “Cookie Cutter” Fallacy of Small Molecule IND
View this webinar to discover how to adapt your approach to your IND program’s unique challenges to gain a competitive edge.
Watch the Webinar

GLP offerings, including hERG and action potential duration (ADP) assays, are recommended for candidate selection and IND submissions. Our integrated in vitro and in vivo scientists can interpret your results and design in vivo assays to advance your program further.

• Expertise with whole-cell, inside-out, outside-out, and cell attached patch clamp electrophysiological configurations
• Cardiac assays
  • hERG serum shift assay
  • hERG (Ikr)
  • hCav1.2 (L-type ICa++)
  • hNav1.5 (peak and late INa)
  • ion channel trafficking assay
  • action potential duration (ADP) assays
  • integrated human cardiomyocyte assays (impedance and field potential)
  • cultured cells (e.g., HEK-293) and isolated cardiomyocytes
• Neuronal assays
  • large ion channel portfolio for neurodegeneration and stroke, pain and inflammation, psychiatric disorders, seizure/convulsion
  • acute brain slices, dissociated and/or cultured neurons (from all preclinical animal species)
  • extracellular and intracellular assays

Drug development can be stressful, especially with a lot relying on your compound’s success. We know developmental delays are costly, so our goal is to keep your pipeline moving, removing possible frustrations.

Discuss My Needs

CiPA Initiative

Currently, the proarrhythmic potential of new drugs is determined by evaluating their effects on the hERG ion channel and the in vivo QT interval. However, due to the overly sensitive nature of these assays, it is believed that many potentially valuable therapeutics have been inadvertently prevented from reaching the clinic.

The comprehensive in vitro proarrhythmia assay (CiPA) is a new strategy proposed by expert working groups sponsored by the Cardiac Safety Research Consortium (CSRC), Health and Environmental Sciences Institute (HESI) and Food and Drug Administration (FDA). This proposal shifts the emphasis away from QT prolongation and focuses on predicting torsadogenic hazard through an expansion of the in vitro components of nonclinical safety evaluation.

Our cardiac ion channel panel fulfills the ion channel recommendations as laid out by the ICH_E14-S7B recommendation.

Assess Risk Potential with ChanTest Cardiac Channel Panel

Receive greater insight into potential cardiac risk to make effective decisions in early preclinical development.

Automated or conventional (manual patch clamp) screening and concentration-response (IC50) assays in panels of cardiac ion channels provide a rapid, comprehensive evaluation of multiple ion channel effects (MICE).

• Complements S7B integrated cardiac risk assessment
• Provides mechanistic interpretation
• Predicts proarrhythmia potential
• Fully validated by expert electrophysiologists

ChanTest Cardiac Channel Panel includes: Cav1.2 (ICa,L), Cav3.2 (ICa,T), HCN2, HCN4, hERG (IKr), Kir2.1 (IK1), Kir3.1/3.4 (IK,Ach), Kir6.2/SUR2A (IK,ATP), Kv1.5 (IKur), Kv4.3 (ITO), KvLQT1/minK (IKs), and Nav1.5 (INa).

GLP Ion Channel Assays and Dose Formulation Analysis

Satisfy IND submission requirements and move your program along with GLP ion channel assays. We have expertise in the conventional manual patch clamp configurations used in measurement of the concentration-response relationship in ion channels. Stably expressed in mammalian cells, they provide IC50 values for IND-enabling, cardiac risk evaluation.

GLP hERG (I_Kr)

• Required for IND submissions
• Quantitative assessment of inhibitory potency
• Physiological temperature standard

Additional GLP ion channel assays include Cav1.2 (I_Ca,L), Nav1.5 (I_Na), Kv1.5 (I_Kur), Kv4.3 (I_TO), and KvLQT1/minK (I_Ks).

Concentration verification via chemical analysis of dosing formulations strengthens the accuracy and thoroughness of nonclinical cardiac safety studies. Dose formulation analysis (DFA) is a requirement for GLP studies submitted in an IND dossier.

Dose Formulation Analysis

• Same-day DFA and hERG analysis
• HPLC with UV detection

Get an Early Start on Predicting Risks

Don’t wait too late to uncover potential risks. Our safety pharmacology experts understand the significance of your program, and how critical navigating complex environments is to the success of your development. We support you with the expertise and flexibility necessary to ensure that you succeed in reaching your milestones

Start My Study

Frequently Asked Questions( FAQs) About In Vitro Safety Pharmacology Assays