Thermal stabilization of biologics inside glass vials using light-assisted drying (LAD)

ABSTRACT

Vaccination against infectious diseases stands as one of the most significant advances of modern medicine. It has led to the worldwide elimination of smallpox and prevented millions of deaths annually from diseases such as diphtheria, whooping cough, and measles. However, vaccines are temperature-sensitive biologics, and most must be stored between 2-8 ºC from production to the end user. Temperature excursions above or below this recommended temperature range can decrease the vaccine's potency. However, inadequate access to cold chain storage is one of the leading causes of under-vaccination globally.

New methods are needed to provide thermally stable vaccines that do not require refrigeration. Thermostable vaccines boost global health security by enabling rapid deployment during emergencies and crises. These vaccines can withstand challenging environmental conditions, allowing for effective immunization campaigns in regions with limited or disrupted refrigeration infrastructure. Anhydrous (dry state) preservation in an amorphous trehalose matrix may provide an alternative to cold storage strategies. Our lab has developed a new processing technique called light-assisted drying (LAD) that can form an amorphous preservation matrix stored at ambient temperatures.

Light-assisted drying (LAD) uses near-infrared (1064 nm) laser light to selectively heat water, quickly dehydrating samples and forming an amorphous trehalose preservation matrix for biologics that can be stored at ambient temperatures. This study uses LAD to create preservation matrices inside glass vials used in industry. LAD processed sample volumes of 0.25 and 0.50 mL containing the model protein lysozyme. After LAD processing, samples were stored at 4 ºC or 20 ºC for one month. Thermal histories and transmitted laser power were monitored throughout processing to determine optimal drying times. The trehalose matrix was characterized using polarized light imaging to detect crystallization during storage. Karl Fischer titration was used to measure the water content of samples, and differential scanning calorimetry was used to assess protein structure. LAD-processed samples had low water content (2%), were stable against crystallization, and had unaltered protein structures.