Large Animal Inhalation Facility Up and Running

The addition of two large animal inhalation suites has broadened IITRI capabilities to offer efficacy and safety studies of new pharmaceuticals administered via inhalation. The large animal inhalation capability complements IITRI's experience in rodent inhalation studies. IITRI's large animal facility was completed in the Fall of 2005, and is a component of a $20 million facility expansion project.

	The new large animal inhalation suites have broadened IITRI's inhalation research capabilities

Prior to approving agents for entry into Phase I clinical trials, the Food and Drug Administration (FDA) normally requires toxicity data from both rodent and non-rodent species. Until 2005, Sponsors seeking expert inhalation services often utilized IITRI scientists for toxicity studies in rodents, but were forced to seek other sites for large animal studies. The new facility allows IITRI to offer inhalation toxicology capabilities in both small and large animal models in a single location. According to Narayanan Rajendran, Ph.D., Vice-President and Manager of the IITRI Inhalation Toxicology Division, "most of IITRI's sponsors seek both small and large animal pre-clinical toxicology services. From the perspectives of both project management and cost-effectiveness, they often prefer that the studies are performed at a single location." IITRI has now become an even more attractive "one-stop shop" to pharmaceutical companies desiring to conduct pre-clinical studies to meet FDA requirements.

Prior to approving a drug for clinical trials, the FDA and other regulatory agencies also require a core battery of safety pharmacology studies in which the effects of a test article on the functions of the central nervous system, cardiovascular system and respiratory system are evaluated (ICH S7A Guideline on Safety Pharmacology Studies for Human Pharmaceuticals). IITRI now offers GLP-compliant safety pharmacology testing that includes cardiovascular studies in conscious, unrestrained naïve or non-naïve non-rodents, using the Data Science International (DSI) Ponemah telemetry systems for hemodynamic evaluation (blood pressure, left ventricular pressure, heart rate, electrocardiogram (QT/QTc) and body temperature). IITRI also performs respiratory function evaluations in canine models using pneumotachograph and Buxco BioSystem XA software (respiratory rate, tidal and minute volumes and other derived parameters).

Inhalation toxicology studies with large animals require intensive labor, often lasting 10 to 12 hours a day. While core competencies for inhalation toxicology were already available in-house, inhalation technicians received special training in large animal handling, as cooperation of the animals is crucial in these studies. The foremost concern is that the animals are comfortable during the exposure. An acclimation period of approximately three weeks, in which the animals are handled by technicians to establish a rapport, usually precedes the exposure in order to ensure the animals breathe normally with the exposure.

	Matt Pytynia, B.S., Lab Biologist II, working in the new facility

Several GLP-compliant studies have been completed since the initial validation studies of the new facility were finalized. As the large animal facilities are increasingly utilized, Dr. Rajendran anticipates requests for primate studies.

Without question, IITRI has the capability to provide the necessary pre-clinical toxicology and safety pharmacology studies required before a drug administered via inhalation goes into the clinic. Asserting that the IITRI Inhalation Toxicology Division has "unmatched expertise in aerosol science and test atmosphere generation", Dr. Rajendran looks forward to the new facilities expanding IITRI's horizons in inhalation research.