Drug Safety in preclinical studies

The development of new medicines is a long and expensive process. Despite growing efforts in R&D over the last decades, the attrition rate due to safety (especially cardiac toxicity) remains a major challenge for the pharmaceutical industry. Hence, safety assessment is of crucial importance during preclinical drug evaluation, and is particularly vital for upholding the integrity of the study and regulatory compliance.

Safety pharmacology studies are defined as those studies that investigate the potential undesirable pharmacodynamic effects of a substance on physiological functions, in relation to exposure in the therapeutic range and above” (source ICH S7A).

Biotrial-preclinical-Drug-Safety

When you work with Biotrial, you are partnering with a global CRO with a team of preclinical experts holding extensive experience in drug safety and working in state-of-the-art laboratory facilities to deliver high quality data and reports.

Biotrial-preclinical-Eeg-Signals

Early Safety De-risking

Early safety de-risking is a process of conducting non-GLP safety studies early in the drug development process to reduce the risks, time delays, and costs of advancing basic research compounds. This approach can help to identify potential safety concerns early on so that they can be addressed before moving into more expensive and time-consuming GLP studies.

Biotrial offers a variety of early safety de-risking services and solutions, including:

  • Anesthetized and telemetered studies: anesthetized and fitted with telemetry devices to monitor their heart rate, blood pressure, and other physiological parameters, this study allows for the early detection of potential cardiac toxicity, as well as other safety concerns.
  • Rapid screening format for early detection of QT prolongation and other CV issues: This format uses a high-throughput approach to screen for potential QT prolongation and other cardiovascular safety concerns. This can help to identify potential problems early on, so that they can be addressed before moving into clinical trials.

By conducting early safety de-risking studies, Biotrial can help to improve the safety of new drugs and reduce the risk of costly failures in clinical trials.

 

The core battery of safety pharmacology studies is a set of tests that are conducted to investigate the potential effects of a drug on the central nervous, cardiovascular, and respiratory systems and anticipate future effects in patient trials. These systems are considered to be the most vital for life, and therefore, any potential adverse effects on these systems could have serious consequences. The core battery of safety pharmacology studies typically includes the following tests:

Central nervous system (CNS) studies

CNS studies are important in the safety assessment of new drugs because the brain and spinal cord are vital organ systems that control many important functions, such as movement, cognition, and behavior. CNS studies can help to identify potential adverse effects of drugs on the CNS, such as sedation, motor impairment, and cognitive dysfunction. These studies can also help to determine the safe dose range of a drug for the CNS.

By conducting CNS studies, Biotrial can help to ensure the safety of new drugs for the CNS. This is an important part of the drug development process, as it helps to protect patients from potential harm and protects the validity of a clients project.

  • Irwin Test / Functional Observational Battery
  • Rodents and large animals
  • Can be adapted according to your in-house protocol
Biotrial-preclinical-Follow-Up-Cardiovascular

Cardiovascular system (CVS) studies

CVS studies are important in the safety assessment of new drugs because the heart and blood vessels are vital organ systems that are essential for circulation and blood flow. CVS studies can help to identify potential adverse effects of drugs on the cardiovascular system, such as QT prolongation, arrhythmias, and heart failure. These studies can also help to determine the safe dose range of a drug for the cardiovascular system.

Biotrial offers a comprehensive range of CVS studies, including ECG, telemetry, and blood pressure measurements. These studies are conducted in rodents and large animals, such as dogs and monkeys.

  • Anesthetized and conscious models.
  • Rodents and large animals
  • Multi-frequency telemetry recording in group-housed animals
  • High quality ECG in chronically-instrumented animals
  • QT evaluation / Arrhythmias detection, according to ICH S7B

Respiratory system (RS)

Respiratory system (RS) studies are important in the safety assessment of new drugs because the lungs are a vital organ system that is essential for breathing and gas exchange. RS studies can help to identify potential adverse effects of drugs on the respiratory system, such as respiratory depression, bronchoconstriction, and pulmonary edema. These studies can also help to determine the safe dose range of a drug for the respiratory system.

  • Whole-body plethysmography in mouse, rat and guinea pig (IV route of administration possible)

Specific tests that are performed may vary depending on the drug and the species being studied.

Safety Pharmacology Studies: Follow-up and Supplemental Studies

Safety concerns may arise from core battery studies, clinical trials, other experimental in vitro or in vivo studies or from literature reports. If such potential adverse effects raise concern for human safety, these should be explored.

  1. Supplemental Studies to evaluate potential adverse pharmacodynamic effects on organ systems not addressed by the core battery:
    • renal/urinary system (diuresis, electrolytes excretion, creatinine clearance, renal injury biomarkers)
    • Gastrointestinal System (GI motility, gastric emptying)
  2. Follow-up studies to provide additional knowledge or greater depth of understanding on vital functions:
    • CNS (abuse liability, memory performance, seizure liability, change in sleep)
    • cardiovascular (cardiac output, ventricular contractility, vascular resistances, troponin)
    • Respiratory (pulmonary arterial pressure, airway resistance, blood gas analysis)
Biotrial preclinical Follow Up Cardiovascular 1
Biotrial preclinical Eeg Signal
Biotrial preclinical Follow Up Cns Brain
Biotrial preclinical Follow Up Respiratory

Resources

EEG Hypnos Poster
The Tilt test in non-human primate using manual restraint
Renal Biomarkers Poster
Guinea-Pig Telemetry Poster

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