As part of an IND application, GLP safety pharmacology studies are required to investigate the potentially undesirable pharmacodynamic effects of a substance on physiological functions in relation to exposure in the therapeutic range and above. For the conduct of these studies, harmonized guideline ICH S7A, entitled Safety Pharmacology Studies for Human Pharmaceuticals, has been adopted by regulatory agencies like the FDA, the European Medicines Agency (EMA), and Health Canada.

What Kind of GLP Safety Pharmacology Studies are Required

The ICH S7A document outlines a core battery of tests that are required to be performed as part of this assessment. These tests are performed in rodent and non-rodent species prior to first-in-human clinical trials. The core battery of safety pharmacology studies includes evaluations of the drug’s effect on:

• The Central Nervous System (CNS);
• The Cardiovascular System; and
• The Respiratory System

CNS Safety Pharmacology Studies

For the Central Nervous System, the safety pharmacology studies assess the drug’s potential to cause behavioral changes, motor activity, coordination, sensory/motor reflex responses, and other neurological effects. Typical a functional observational battery, a modified Irwin test, or other appropriate methodology would be utilized. These studies help identify any potential for the drug to cause adverse CNS-related events in humans. These CNS tests can also potentially be integrated as a separate arm in a pivotal safety toxicology study reducing the number of animals that are required to meet this particular endpoint.

Cardiovascular and Respiratory System Safety Pharmacology Studies

Cardiovascular safety pharmacology studies examine the effects of a drug candidate on the heart and circulatory system. This typically includes In vivo telemetry studies in conscious, freely moving animals to monitor parameters such as heart rate, blood pressure, and electrocardiogram (ECG) waveforms. For the respiratory safety pharmacology parameters such as respiratory rate, tidal volume, and minute volume are measured in conscious, freely moving animals. To maximize efficiency and minimize animal use, at Nucro-Technics the cardiovascular and respiratory system safety pharmacology studies are combined into a single cardiopulmonary safety evaluation design using telemetered animals with digital implants. This combined approach minimizes the number of separate studies required and allows for a more comprehensive evaluation of the drug’s impact on these vital systems. The use of digital implants (as opposed to jacketed animals), improves the accuracy and precision of the data generated.

Why Choose Nucro-Technics for your Safety Pharmacology Needs?

Nucro-Technics brings decades worth of experience in the performance of GLP safety pharmacology studies. We have worked across a wide range of therapeutics indications and can incorporate these endpoints as part of a larger IND-enabling safety toxicology program.