Inhalables & OINDP Testing: Particle Size, Dose & Regulatory Guide
Aerospace corrosion testing per MIL-STD-810 evaluating alloy and coating protection performanceWhat Are OINDPs?
Orally Inhaled and Nasal Drug Products (OINDPs) include metered-dose inhalers (MDIs), dry powder inhalers (DPIs), nasal sprays, and nebulisers—delivery systems that administer pharmaceutical compounds directly to the respiratory tract. OINDPs are used in the treatment of asthma, COPD, allergic rhinitis, and other respiratory conditions, and are among the most complex drug-device combination products regulated by the FDA.
The materials used to construct OINDP devices—polymers, elastomers, metals, adhesives, and lubricants—directly contact or interact with the drug formulation. Material testing is therefore a critical component of device development, regulatory submission, and manufacturing quality assurance.
Why Material Testing Is Critical for OINDPs
Extractables and Leachables (E&L) Testing
This is the most significant material-related concern for OINDPs. Extractables are chemical compounds that can be released from device materials under exaggerated laboratory conditions. Leachables are compounds that actually migrate into the drug product under normal storage and use conditions.
Leachable compounds may:
- Be toxic or irritating to the respiratory tract
- Chemically degrade the active pharmaceutical ingredient (API)
- Alter the aerosol performance characteristics of the device
E&L testing for OINDPs follows the PQRI (Product Quality Research Institute) guidance document, which defines a safety concern threshold (SCT) of 0.15 µg/day for non-volatile leachables.
Regulatory Framework
The FDA requires E&L characterisation for all OINDP container closure systems as part of the 505(b)(1) and 505(b)(2) NDA pathways, as well as abbreviated NDA (ANDA) submissions. ICH Q3E provides additional guidance on E&L assessment.
Key Material Testing Categories for OINDPs
Elastomer and Polymer Component Testing
Elastomeric valve seals, gaskets, and actuator tips are critical leachable sources. Testing includes:
- Exhaustive solvent extraction (GC-MS, LC-MS/MS, IC, ICP-MS)
- Identification and quantification of all extractables above the analytical evaluation threshold (AET)
- Physical testing: hardness (Shore A), tensile properties, compression set, dimensional verification
Canister and Container Testing
Aluminium MDI canisters are tested for:
- Internal coating integrity (brine test, EIS)
- Corrosion resistance
- Coating adhesion (cross-cut test)
- Dimensional compliance
Actuator and Mouthpiece Polymer Testing
Polypropylene and polyethene actuators are evaluated for extractables using aggressive solvents (methanol, acetonitrile, water) and elevated temperature extraction conditions.
Aerosol Performance and Drug Delivery Consistency
Material properties directly affect dose uniformity and aerodynamic particle size distribution (APSD). Valve performance, actuator geometry, and formulation-material compatibility must be validated.
Analytical Techniques Used
Technique | Application |
GC-MS | Volatile and semi-volatile organics |
LC-MS/MS | Non-volatile organics, API degradants |
ICP-MS | Elemental impurities |
IC | Ionic species (acetate, formate) |
NMR | Structural elucidation of unknowns |
TOC | Total organic carbon in extracts |
Conclusion
OINDPs represent a highly complex class of drug-device combination products where material performance directly impacts drug safety, efficacy, and regulatory compliance. Rigorous material testing—especially extractables and leachables evaluation—is essential to ensure that device components do not introduce harmful contaminants or alter drug performance. By integrating comprehensive analytical characterisation with strict regulatory adherence, manufacturers can deliver safe, effective, and reliable inhalation and nasal drug products.
Why Choose Infinita Lab for OINDP Material Testing?
Infinita Lab offers comprehensive material testing services for OINDPs and drug-device combination products, including full extractables and leachables programs, elastomer characterisation, and regulatory support. Our network of accredited pharmaceutical testing laboratories operates under current Good Manufacturing Practice (cGMP) standards.
Looking for a trusted partner to achieve your research goals? Schedule a meeting with us, send us a request, or call us at (888) 878-3090 to learn more about our services and how we can support you. Request a Quote
Frequently Asked Questions (FAQs)
What is the difference between extractables and leachables in OINDP testing? Extractables are all compounds that can be released from device materials under harsh laboratory extraction conditions (elevated temperature, aggressive solvents). Leachables are the subset of extractables that actually migrate into the drug product under real storage and use conditions. Leachables are the primary safety and efficacy concern.
What is the analytical evaluation threshold (AET) in OINDP E&L testing? The AET is the minimum concentration at which a leachable must be identified and quantified to meet the safety concern threshold (SCT). For OINDPs, the PQRI SCT of 0.15 µg/day corresponds to an AET calculated from the expected daily inhaled dose.
When in the product development process should E&L testing begin? E&L testing should begin early in development, during materials qualification. Early extractables screening guides material selection and formulation development before costly clinical batches are committed to a specific device configuration.
Do dry powder inhalers (DPIs) require E&L testing? Yes. Although DPIs do not contain propellants (which are aggressive solvents for MDI E&L), the drug powder and formulation excipients are in intimate contact with device materials throughout shelf life. E&L testing is required for all OINDP types.
Which materials are commonly tested in OINDPs? Polymers, elastomers, metals (like aluminium canisters), adhesives, coatings, and lubricants used in device components.
