Safety Pharmacology
Services
We are ready to answer your questions and provide guidance.
Safety Pharmacology
Services
We are ready to answer your questions and provide guidance.
Safety Pharmacology
Safety pharmacology examines potentially harmful pharmacodynamic effects on physiological functions, particularly targeting the cardiovascular, respiratory, and central nervous systems. It is typically implemented for small molecule test articles and drugs.
The safety pharmacology core battery studies are conducted as an essential step in an IND program to evaluate the potential for off-target drug effects on major organ systems, as well as the reversibility of any characterized effects prior to human use. When filing an IND application, safety pharmacology studies are a requirement prior to the start of Phase I human clinical trials.
The International Conference on Harmonization (ICH S7A) guidelines for safety pharmacology studies recommend evaluating the impact on the following systems collectively known as the safety pharmacology core battery:
| Central Nervous System (CNS) |
• Functional Observation Battery (FOB) to detect effects on behavior, locomotion, and coordination (including peripheral neuropathy studies in NHPs) • Neurotoxicity assessment |
| Cardiovascular (CV) System |
• Telemeterized dogs: Systolic, diastolic and mean arterial blood pressures, heart rate, electrocardiogram (RR, PR, QRS, QT and QTc intervals) and body temperature monitored continuously • hERG inhibition in vitro assays to evaluate potential for QT interval prolongation |
| Respiratory System | Plethysmography: respiratory rate, tidal volume, and minute volume |
IITRI SOlutions
IITRI has over 20 years of experience providing preclinical studies for safety pharmacology. We provide preclinical insight into various strategies for implementing methodical study plan, based on the type and class of molecule being developed, to minimize risk and reduce costs.
For instance, cardiovascular (CV) studies may be conducted in canine species using surgically implanted telemetry devices for continuous, real-time monitoring of CV parameters. This approach allows for the measurement of heart rate, arterial blood pressure (systolic, diastolic, and mean), body temperature, and ECGs without restraining the animals. However, for certain classes of drugs, it is possible to substitute the cardiovascular study with ECGs instead of using implanted telemetry devices to save time and reduce costs.
Additionally, respiratory function (respiratory rate, tidal volume and minute volume) can also be measured simultaneously along with the cardiovascular measurements using the same telemetry devices or evaluated separately in non-telemetered animals (mice, rats, dogs, and non-human primates), alongside the ECG study, as part of the study program. IITRI’s extensive experience allows us to provide insights into when these substitutions can be made while still meeting regulatory requirements for the FDA and other regulatory agencies.
Additionally, the functional observational battery (commonly referred to as an FOB), is another regulatory requirement for small molecule test articles and drugs that assesses neurological effects. IITRI has more than two decades of experience providing FOBs for IND enabling study programs for FDA and other regulatory agencies in mice, rats, and dogs.