Inhaled antibodies: Quality and performance considerations

Abstract

The use of antibodies in the treatment of lung diseases is of increasing interest especially as the search for COVID-19 therapies has unfolded. Historically, the use of antibody therapy was based on multiple targets including receptors involved in local hyper-reactivity in asthma, viruses and micro-organisms involved in a variety of pulmonary infectious disease. Generally, protein therapeutics pose challenges with respect to formulation and delivery to retain activity and assure therapy. The specificity of antibodies amplifies the need for attention to molecular integrity not only in formulation but also during aerosol delivery for pulmonary administration. Drug product development can be viewed from considerations of route of administration, dosage form, quality, and performance measures. Nebulizers and dry powder inhalers have been used to deliver protein therapeutics and each has its advantages that should be matched to the needs of the drug and the disease. This review offers insight into quality and performance barriers and the opportunities that arise from meeting them effectively.

Keywords: Aerosols; antibodies; formulation; lungs; stability; therapeutics.

Figure 1.

Diagram depicting the contributing factors from the drug product, conditions and contacts that contribute to the analytical quality and performance measures.

Figure 2.

Environmental and product factors that contribute to the quality and performance of inhaled monoclonal antibodies that are uses to assure efficacy and safety outcomes.

Figure 3.

Images of: (a) Next generation impactor showing collection cups (lower section); (b) assembled Andersen 8-stage non-viable impactor with collection plates (below) that are present on each stage and; (c) two-stage liquid impinger showing glass vessels in which samples are collected.

Figure 4.

Schematic of droplet behavior following aerosol generation in transit through the airways and upon deposition based on their colligative properties and water activity.