Inhalation product testing is a critical element of the development of orally inhaled drug products as it is important to fully understand the drug product characteristics.
Specialist inhalation product analysis and testing techniques, performed under controlled conditions and in line with established and robust methods, are essential to characterise the drug product. Critical quality attributes can be established and from these, the performance of the formulation together with a specific device can be assessed. This testing is required throughout the development cycle from testing early stage candidate formulations, to device screening, to formal stability studies and finally through to commercial batch release.
There are various guidance documents from the CDER (FDA) and the EMEA that outline the testing that is required as part of your Chemistry Manufacturing and Controls (CMC) package. These are in place to ensure continuing drug product quality and performance characteristics when developing both novel inhaled drug products and also abbreviated drug applications for generic products. The documents provide guidance on the specific analytical tests and the appropriate body of analytical test data required. This information is then used to confirm release specifications for both clinical batches and commercial batches, as well as inform the Summary of Product Characteristics (SmPC) and finally the Patient Information Leaflet (PIL). Testing should be performed all the way through development (in line with a QbD approach) and detailed specifications should be established before any clinical work.
Our strengths are with method development & validation, product performance testing, impurities content, physicochemical characterisation. We routinely conduct accelerated and real time stability studies to support clinical and commercial batch shelf life, as well as early stage formulation feasibility.
- Aerodynamic Particle Size Distribution:
By measuring the drug particle size distribution, we are able to approximate how much drug is delivered and where it will deposit in the lung. Working to pharmacopeia methods we determine aerodynamic particle size distribution (APSD) by cascade impaction methods. Two instruments that are commonly used to characterise the APSD include the Anderson Cascade Impactor (ACI) and the Next Generation Impactor (NGI). The APSD is a critical quality attribute in the development and testing of inhaled and nasal products.
- Delivered Dose Testing
It is necessary to characterise the dose delivered. The delivered dose should be consistent with the label claim, have low batch to batch variation and must be stable through-life (for example, for a multi-unit dose product, it is necessary to confirm that actuation 1 is the same as actuation 100).Our scientists are knowledgeable in the testing regimes required for success. We deploy the most suitable apparatus for pMDI, DPI, soft mist or nebuliser products using robust methodology conducted in a controlled environment for testing to achieve accurate and reliable data.
- Particle and Droplet Sizing
Particle or droplet size testing by laser diffraction provides a rapid screening tool and can provide valuable performance data which is particularly useful in early stage formulation development. However, this method does not discriminate between multiple components in a formulation and so must be used alongside aerodynamic cascade impaction tests later in development, unless the product is a solution
- Powder and particle characterisation
Our physical characterisation experts employ powder rheology testing (Freeman FT4), particle sizing (Malvern Mastersizer) (and morphology / shape analysis (Malvern Morphologi G3-ID) to map and characterize powder and suspension formulation characteristics. In addition, we can determine physical properties such as solubility, size, density, and crystallinity of the drug substance or excipients which can help you to minimise potential issues on stability.
- Finished product characterisation
As per the CMC guidance of inhaled products, a range of product characterization studies are required to be performed that assess the robustness of the device and formulation across various in-use situations. Nanopharm has a wealth of experience in generating appropriate protocols and performing these studies, including; in-use studies, temperature cycling, photostability, priming / re-priming, stability storage, dropping / shaking, tail-off profile and flow rate studies.