Our goal is to develop a vaccine that is stable at ambient conditions, and to incorporate the vaccine into an effective dosage presentation that can facilitate storage, distribution, and mass vaccination campaigns. The current pharmaceutical manufacturing processes that are able to stabilize vaccines are generally expensive to implement in developing countries and the dosage forms (mainly glass vials, prefilled syringes) are generally not cost effective for large scale storage, transportation, and distribution associated with mass vaccination campaigns. We propose the development of quick dissolving oral thin films as a technology solution. This dosage form offers a remarkable array of advantages for vaccine applications including compact size and weight (~<1/100th of size and weight of typical vaccine package) that is highly transportable, and is simple to use, thus enhancing patient compliance. Furthermore, there is no reconstitution step ensuring dosage accuracy, and there is a well-established manufacturing process (e.g. ListermintTM breath freshener strips). To achieve an optimal technology solution, we propose to incorporate a pharmaceutical stabilization formulation which does not require complex pharmaceutical drying processes to achieve room temperature stability, which at the same time is compatible with existing thin film manufacturing processes. Preliminary data indicate that Aridis has developed a thin film formulation and manufacturing process that successfully encased a thermally labile live virus vaccine with complete preservation of activity and storage stability at high temperature (45o C). We combined our liquid vaccine stabilization technology (21) and plasticized glass stabilization technology (10,22,23) to demonstrate an OTF (oral thin film) formulation that successfully encased live rotavirus vaccine with complete preservation of vaccine potency and stability at 45?C improved from several days to several months (see preliminary data). We have chosen rotavirus vaccine as a case study not only to demonstrate the effectiveness of the OTF formulation in stabilizing a thermally labile, complex live vaccine, but also because it is an important vaccine that has already demonstrated the potential to significantly reduce mortality (~500,000 annual deaths) due to rotavirus infection in children worldwide (26). Successful demonstration of the proposed studies will advance this technology into formal biopharmaceutical product development and will provide proof-of- concept data that can be applicable to other oral vaccines and biologics. The primary goal of this project is to develop stable formulations of rotavirus vaccine that do not require cold storage (i.e., stable at room temperature and above) with dosage forms that are suitable for oral delivery. Our hypothesis is that this vaccine can be physically stabilized with the appropriate formulation selection and using a simple 'one-pot' method without the need for pharmaceutical drying. Preliminary data has shown that formulations can be developed that stabilize several rotavirus serotypes at high temperatures for a month or more. The proposed work scope is designed to further optimize the lead formulation, extend the demonstration to a quadrivalent mixture of strains in a single film, and determine the biodistribution of the vaccine and in vivo immunogenicity in vaccinated mice. Finally process development will be initiated at pilot plant scale. This technology will not only simplify vaccine storage, distribution and administration, but also provide cost savings to the vaccine distributor and the physician or clinic administering the vaccine.
We are developing a room temperature stable vaccine formulation in the form a quick dissolving thin film strip that can conveniently deliver vaccines t the oral cavity. We applied advanced formulation stabilization technology to demonstrate that a complex live vaccine such as rotavirus vaccine can be fabricated into oral thin films and stabilized for high temperature exposure. This technology is applicable to a wide range of biologics, including vaccines, proteins, antibodies.
