And breathe! Outsourcing stability studies for inhalation testing

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Malcolm Saxton, senior consultant for chemistry at Broughton, explores the benefits of outsourcing stability studies for inhalation devices.

Stability studies are a crucial step during the development of inhaled medicines to ensure the product maintains quality, safety, and efficacy for its entire shelf life. However, they can be resource, time, and space intensive, so outsourcing these studies to a trusted partner can streamline the process.

Inhalation therapy is the cornerstone of treatment for many patients with chronic respiratory disease, a global issue affecting around 450 million people worldwide. Due to the benefits of inhalation as a rapid drug delivery method with the potential for reduced side effects, researchers are investigating inhalation therapy for novel applications.

For example, with the advent of novel respiratory diseases, including COVID-19, researchers are considering inhaled biologics, such as monoclonal antibodies, as therapeutic approaches. Inhaled antimicrobial peptides and proteins are also emerging to target multi-drug resistant bacteria.

When bringing inhaled medicines to market, a stability study is an essential body of work required for regulatory submission. Stability studies are designed and conducted according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The ICH offers guidance on the proposed length of the study, storage conditions, and sampling frequency based on the product and its intended shelf life, although some products may require custom conditions.

Stability studies for inhaled medicines 

However, designing a stability study for inhalation devices, such as nebulisers, pressurised metered-dose inhalers (pMDIs), and dry-powder inhalers (DPIs), can be complex, and numerous device-specific factors must be controlled.

For example, it is essential to ensure that particle and droplet size remains consistent as part of the stability study, as particle size can directly impact the rate of dissolution and bioavailability in the lungs, affecting product efficacy.

In addition, the orientation of pMDIs — whether they are stored upright or not — may impact the device's effectiveness. DPIs also have stability study design considerations; they are often packaged in a foil overwrap, for instance, and so the study should include removing the product from the packaging to measure the impact on shelf life, quality, and efficacy against the drug product specifications.

Furthermore, as more large molecule drug products, like biologics, come to market, stability assessments must adapt accordingly. These molecules are more prone to degradation, typically requiring more complex analysis, additional parameters to measure, and/or the need for custom test conditions. Biopharmaceuticals, for example, tend to exhibit more unpredictable degradation pathways than small-molecule APIs and may precipitate during the test due to their concentration and/or low solubility. Study design may be more challenging as a result.

Why outsource?

Pharmaceutical companies typically outsource stability studies due to space, facility, and resource constraints. Stability testing and analysis is a specialist field — if a company does not have in-house experts for method development and validation, particularly when working with a complex drug product, outsourcing may be a good solution.

Some stability study providers will have broader expertise and can give you access to subject matter experts, such as analytical chemists and toxicologists, who can help complete test data analysis, understand deviations, and troubleshoot problems. If the partner is also an expert in extractables and leachables (E&L), studies can be run in parallel, streamlining the route-to-market. In addition, a partner with an in-house regulatory team can help prepare everything needed for submission to the regulatory body.

How can a provider support with documentation?

For stability studies, it is extremely important to document that test conditions were maintained throughout to validate the study. Pharmaceutical businesses, therefore, must ensure their stability study provider offers end-to-end quality-controlled processes for the receipt, management, storage, and disposal of samples. Some providers take this up a level, by offering real-time access to stability data through Laboratory Information Management Systems (LIMS), ensuring compliance with regulatory standards.

With over 450 million patients worldwide suffering from respiratory diseases, the market for inhaled medicines is growing. Regarding stability studies, manufacturers can save time, effort, and resources by outsourcing to a trusted provider. Doing so enables manufacturers the ability to focus on their core competencies.