Inhalation

A: We conduct control from four dimensions including equipment, particles, flow rate and environment to ensure system stability: 1. Equipment calibration and maintenance: Regularly calibrate nebulizers and dry powder generators, clean and replace worn parts in a timely manner. Use anti-static materials to reduce drug deposition on the wall and ensure consistent aerosol generation. 2. Particle size control: Select appropriate equipment according to test requirements, adjust nebulization air pressure and dispersion force. Adopt a particle size analyzer to monitor particle distribution in real time and keep particle size within the target range. 3. Flow rate control: Use flow meters to precisely control gas flow rate. Optimize the concentration and viscosity of test solutions to avoid pipeline blockage or excessive dilution, and prevent flow rate fluctuation from affecting aerosol uniformity. 4. Environmental condition control: Stabilize laboratory temperature, humidity and airflow to reduce external interference and keep consistent conditions throughout the test. The above measures can greatly improve the reliability of aerosol systems and ensure reproducible test data.

A: Different animal species have respective advantages and disadvantages. Model selection depends on test purposes, formulations and filing requirements. Species differences will directly affect the extrapolation of test data to humans. 1. Rodents (mice, rats) o Advantages: Low cost and easy to raise, suitable for large-scale screening. High respiratory rate (150-200 breaths per minute for mice, 80-100 breaths per minute for rats), ideal for acute exposure tests. Abundant gene-edited models, sufficient historical data and simple operation. o Limitations: Complicated nasal structure leads to predominant nasopharyngeal deposition, with lung deposition rate lower than 10% (20%-30% in humans). Rodents are obligate nasal breathers without voluntary oral breathing, which may underestimate the effect of orally inhaled drugs and limit data extrapolation. 2. Dogs (Beagle dogs) o Advantages: Breathing pattern is similar to humans with voluntary oronasal breathing. Lung deposition rate is 15%-25%, close to human level. Large body size facilitates repeated sampling and pulmonary function tests. o Limitations: Species-specific reactions exist; they are more sensitive to irritant gases such as ozone than humans. 3. Non-human primates o Advantages: Airway structure and alveolar morphology are highly similar to humans, providing the best data extrapolation to human beings. o Limitations: High feeding and testing costs, mainly used for the evaluation of macromolecular biologics and high-end innovative drugs. 4. Guinea pigs o Advantages: They have spontaneous airway hyperresponsiveness, serving as the preferred model for asthma pharmacodynamic tests and inhalation irritation & allergy tests.

A: The test cycle varies by study type, animal species and test duration. Aerosol characteristic evaluation and in vitro screening tests take about 2 to 4 weeks. Short-term inhalation toxicity tests and single/multiple-dose pharmacokinetic tests on rodents take about 1 to 3 months. Long-term inhalation toxicity tests and complete sets of pharmacodynamic studies on rodents take about 4 to 8 months. Inhalation tests using large animals such as dogs and non-human primates generally last 6 to 10 months. We can customize expedited test plans, split test phases and deliver interim data according to clients’ R&D schedules and filing deadlines to shorten project cycles as much as possible.

A: The test design differences of the three mainstream formulations mainly lie in aerosol generation mode, particle size control and delivery device adaptation: 1. Inhalation Solution (IS): Nebulizers are used to generate droplets. We focus on controlling drug concentration, viscosity and nebulization air pressure, and pay attention to droplet size distribution and solution stability. It is applicable to intratracheal nebulization and oronasal inhalation. 2. Metered Dose Inhaler (MDI): Aerosols are generated by propellants. We strictly calibrate valve spray dose and spray pattern, and mainly monitor instantaneous aerosol concentration and particle size. Oronasal inhalation is the main administration route. 3. Dry Powder Inhaler (DPI): Dry powder dispersers are adopted for administration. Powder agglomeration is a common problem, so we need to optimize dispersion force and air flow rate, and monitor dry powder dispersion effect in real time. It is not suitable for whole-body exposure administration. We customize test plans according to formulation characteristics to ensure accurate dosing and consistent exposure conditions.

A: Troubleshoot and solve problems step by step from simple to complex: 1. Basic inspection: Check pipelines and connectors for air leakage, and fasten sealing parts in time. Clean residual drugs in nebulization chambers and delivery pipelines to avoid impacts on aerosol status. 2. Material optimization: Adjust the humidity of dry powder properly to reduce static electricity and agglomeration. Optimize the concentration and viscosity of inhalation solutions to prevent solute precipitation. 3. Parameter adjustment: Fine-tune nebulization air pressure, dispersion air flow and delivery flow rate to match material properties. Increase dispersion intensity properly if particles are oversized. 4. Environment adjustment: Control laboratory temperature and humidity. High humidity will cause powder moisture absorption and agglomeration, while low humidity easily generates static electricity. Keep environmental parameters stable all the time.

A: All our operations strictly follow GLP principles and international guidelines issued by OECD, FDA, EMA and other authorities. Our laboratory and multiple inhalation test projects have passed on-site inspections by overseas regulatory agencies for many times. All raw data, test records and reports have complete and traceable audit trails. Our evaluation reports can be directly used for regulatory filings in China, the United States, the European Union and other regions worldwide. We have rich practical experience in dual filing of inhaled drugs for China and the US, and can assist clients with overseas document preparation and regulatory inquiries throughout the whole process.