Delivering biologics via inhalation is notoriously complicated. Justin Lacombe, Chief Scientific Officer at Experic, explained that maintaining biological activity during processing and delivery with stability, aggregation, and potency is a major concern. Understanding progress around the inhalation of large molecules will help scientists figure out where inhalation will go in the future.
With biologics becoming more and more popular, the percentage of small molecule drugs versus large molecule ones is expected to undergo a drastic shift. However, only a few inhaled biologic products are commercially available, most notably insulin and dornase alpha. Yet many more are in clinical or academic development.
Within the US government, the Department of Health and Human Services has set up an initiative called Beyond the Needle, which seeks to increase the number of inhaled biological drug products. Lacombe went on to give brief overviews of various inhalation platforms, including nebulisers, pressurised metered dose inhalers, and nasal sprays and powders. His main area of expertise is dry powder inhalers, which require converting from liquids to powder. All of these platforms have specific formulation and stability requirements, and no universal platform for biologics has been established yet.
In comparison to small molecules, characterising biologics requires more advanced and varied analytical techniques like LC-MS, capillary electrophoresis, and dynamic light scattering. Proteins are also prone to aggregation, oxidation, and fragmentation. Lacombe also mentioned that potency is assessed in a different way for biologics due to the high volume of biological activity.
Ensuring delivery dose uniformity, particularly in the case of MDIs and nasal sprays, is difficult because one must consider spray pattern and plume geometry. Furthermore, dry powder inhalation systems, pressurised metered dose inhalation systems, and dry powder nasal systems don't require sterilization, whereas SMIs and nebulizers often necessitate sterilization, which adds an additional step.
Switching gears, Lacombe introduced several manufacturing methods for creating inhalable biologics. For example, spray drying is a scalable option but may denature proteins, and print technology is a technique that Liquidia uses to precisely design particles. Lacombe also commented on methods like thin film freezing, spray drying, and electrostatic spray drying.
Lacombe closed by addressing regulatory uncertainties; he noted that current guidance lacks specificity for biologics delivered via inhalation. He re-emphasised the need for a more defined strategy and platform approach to biologics in inhalation because the field currently lacks the standardisation seen with small molecule therapies.
