The Adjuvant Patch: A Universal Dose Sparing Approach for Pandemic and Conventional Vaccines - Preclinical and clinical trials have demonstrated proof-of-concept for the LT-IS patch. - BioPharm
Figure 7. Real time and accelerated stability of a single lot of LT IS patches. Patches were stored at 2–8, 25, and 40 °C
and assessed periodically for LT content (by SE-HPLC, top panel) and potency (by Y-1 cell assay, bottom panel).
The nitrogen-purged foil pouches containing the dry LT patches were placed under real-time (2–8 °C) and accelerated conditions
(25 °C and 40 °C) in controlled temperature chambers. Figure 7 shows the stability of a representative 50 μg/dose lot manufactured
under GMP conditions. The biological potency, as measured by the Y-1 adrenal cell assay,16 showed the LT patch meeting the specification of >3.6 log, μg-1 for all test points, i.e., 22 months for 2–8 °C, six months for 25 °C and one month for 40 °C. The LT content, as measured
by SE-HPLC, met the 75% of label claim specification for all test time points for patch products stored at 2–8 °C (up to 22
months) and at 25°C (up to nine months, the endpoint of accelerated testing). At the higher temperature of 40 °C, the LT content
met specification after one month of storage; however, LT loss was significant thereafter. The moisture content of this lot
throughout the stability studies remained at about 6%. Based on up-to-date stability data, there has been no significant trend
of LT patch deterioration at 2–8 °C; thus, the LT patch appears to be a good candidate for stockpiling for a future pandemic
situation.
Temperature Excursion Studies
Thermal cycling studies were performed according to the 1998 FDA draft guideline and 2003 ICH Guidance for Industry for stability
testing of packaged drug products17–20 in order to gain insight into the tolerance of dry LT patches to temperature excursions that may be encountered during shipping
and distribution. Based on the specific product storage temperature, the product is cycled from low to high temperatures for
several days, and the exposure is repeated over three cycles. Since we were interested in refrigerated and possibly room temperature
distribution, the dry LT patches were exposed to thermal cycling conditions designed for refrigerated and room temperature
stable products as outlined in Figure 8. For the thermal cycling studies, we used 50 μg LT patches (GMP lot) stored at 2–8
°C for approximately 6 months. For each thermal cycle, three patches were used and the average LT content reported.
