Advanced Preclinical Inhalation Studies: Technical Capabilities And Expertise At Prisys Biotech

While traditionally focused on respiratory diseases like asthma and COPD, the inhalation route is increasingly explored for systemic delivery targeting cardiovascular, cerebrovascular, endocrine, pain, and other neurological conditions. This expanding therapeutic landscape underscores the need for rigorous and specialized preclinical evaluation. Preclinical inhalation studies are essential for comprehensively assessing drug candidates, involving evaluation of drug substance characteristics, aerosol generation performance, pharmacokinetics (PK), toxicology, aerosol stability, and detailed safety assessment before clinical trials commence.

Unlike conventional oral or intravenous administration where doses can be precisely prepared beforehand, inhalation delivery involves dynamic aerosol generation. Key technical considerations include:

• Aerosol Concentration Monitoring: The concentration of the generated aerosol can fluctuate during administration. Therefore, real-time or frequent monitoring of aerosol concentration throughout the exposure period is critical. This data is essential for accurately calculating the actual delivered dose to the animals, ensuring the reliability and reproducibility of PK and toxicology data.
• Particle Size Distribution (PSD) Characterization: The aerodynamic particle size of the aerosol is a crucial determinant of deposition within the respiratory tract. For effective delivery to the deep lung (alveolar region), aerosols typically need to be generated with a specific Mass Median Aerodynamic Diameter (MMAD), often targeted within the 1 to 4 micrometer range. Particles significantly larger or smaller may deposit prematurely in the upper airways or be exhaled, respectively. Accurate measurement of MMAD and Geometric Standard Deviation (GSD) during studies confirms appropriate aerosol generation for the intended target site.

Prisys Biotech has established a comprehensive suite of technologies and expertise to address the complexities of preclinical inhalation drug development, particularly in large animal models. Our capabilities ensure robust data generation for regulatory submissions.

Specialized Inhalation Administration Systems:

We offer various administration routes tailored to specific research needs and compound characteristics:

• Oro-nasal / Nose-Only Exposure Systems: We possess significant experience with systems designed for both powder and liquid formulations, enabling controlled exposure in species like dogs and non-human primates (NHPs).
• Intratracheal (IT) Administration: Direct delivery to the trachea via instillation (liquid bolus or microspray) or atomization/nebulization of liquids or dry powders.
• Intranasal (IN) Delivery: Includes administration via nasal drops or specialized spray devices, also relevant for exploring potential nose-to-brain delivery pathways.

Species Expertise:

Our primary focus includes key large animal species relevant for translational research:

• Beagle Dogs
• Non-Human Primates (Cynomolgus and/or Rhesus Macaques)

Species selection is critical, especially for biologics and novel chemical entities, and Prisys Biotech assists clients in determining the most appropriate model based on scientific rationale.

Comprehensive Study Support & Monitoring:

Successful inhalation studies require meticulous execution and monitoring:

• Method Development: Prior to study initiation, we conduct preliminary work to optimize aerosol generation conditions and confirm achievable concentrations and particle size distributions for the specific test article and formulation.
• In-Study Monitoring: During exposures, we implement rigorous monitoring schedules for aerosol concentration and particle size distribution. Environmental parameters like temperature, humidity, and oxygen/carbon dioxide levels are continuously monitored within exposure chambers.
• Animal Monitoring: Real-time observation of animals during exposure and detailed clinical observations post-dose are standard procedures.
• Downstream Assessments: Following exposures, we conduct comprehensive evaluations including pharmacokinetics, pharmacodynamics (efficacy), safety pharmacology, and toxicology assessments, incorporating gross necropsy and detailed histopathological evaluation, with particular focus on the entire respiratory tract.

Proven Track Record:

Prisys Biotech has successfully supported multiple clients in completing complex efficacy and safety studies utilizing our large animal oro-nasal inhalation exposure systems and other specialized inhalation techniques.

Conclusion

Preclinical evaluation of inhaled therapeutics demands specialized infrastructure, technical expertise, and rigorous adherence to validated procedures. Prisys Biotech provides an integrated platform encompassing diverse administration techniques, critical in-study aerosol characterization, expertise in relevant large animal models, and comprehensive downstream analysis. We are equipped to partner with pharmaceutical and biotechnology companies to navigate the technical challenges of inhalation drug development and advance promising candidates towards clinical success.