SBIR-STTR Award

Assuring the success of mass campaigns against bioterrorist or naturally occurring pathogens requires that vaccines, therapeutics, and other products are stored and ready for immediate use at the time the threat to public health is perceived. Storage is a major contributor to the cost of administration under these circumstances and a requirement to keep the active product refrigerated can increase the cost by a factor of three, or more. It is also generally accepted that single dose delivery systems provide additional benefits in terms of disease transmission and microbial contamination. These and other issues are resolved by Immunoject, a new platform device with application to the parenteral delivery of the many pharmaceutical products that may now be formulated as rapidly dissolving powders. The unit-dose auto-reconstitution device is compact, relatively flat, and presents an economically attractive storage profile. It consists of an integrally sealed aseptic film pouch with two compartments separated by a frangible membrane, together with an administration device made from molded plastic parts. One compartment of the pouch is sized to hold a pre-determined volume of water for injection while the other compartment houses a dose of pharmaceutical compound formulated as a rapidly dissolving and thermally stable powder. In four user-friendly steps, a healthcare worker applies thumb pressure to the water compartment which, in turn, causes the active powder to dissolve and then to be administered through a needle to the patient. The overarching goal of this project is to accelerate Immunoject on its path to commercialization by demonstrating that the device will maintain its functionality and the thermal stability of thimerosal-free hepatitis-B vaccine stored within its powder compartment. This will be achieved by achieving three specific aims. The first of these formulates the vaccine as rapidly dissolving nano- and micro-scale powders and completes assays to verify that the HBsAg antigen remains bonded to the alum adjuvant, and that the powders retain the vaccine's original potency. The second aim assures that the powders have adsorbed no statistically significant moisture in 48 hours and tests the functionality and performance of the Immunoject. And finally, the third aim assesses the stability of powders and filled Immunoject devices at temperatures from -20 ¿C through 65 ¿C with storage periods from one week through twelve months.

Public Health Relevance:
This project seeks to accelerate Immunoject, a new unit-dose, auto-reconstitution device for parenteral delivery, on its path to commercialization. The new device will significantly reduce the costs of storing and administering a prophylactic or therapeutic dose to subjects of a mass public health campaign provoked by the transmission of a bioterrorist or naturally occurring pathogen. Key to Immunoject's potential is the innovative formulation of active ingredients as thermally stable and rapidly dissolving dry powders.

Thesaurus Terms:
Atgn; Adjuvant; Alum Adjuvant; Antigens; Assay; Australia Antigen; Bioassay; Biologic Assays; Biological Assay; Devices; Dose; Drug Formulations; Equilibrium; Excipients; Film; Formulation; Formulations, Drug; Fungi, Filamentous; Goals; Hbv Vaccine; Hbsag; Hbsag (Hepatitis B Surface Antigen); Health Campaign; Health Care Providers; Health Personnel; Healthcare Providers; Healthcare Worker; Hepatitis B Surface Antigens; Hepatitis B Vaccines; Hepatitis B Virus Vaccine; Hour; Housing; Hydrogen Oxide; Injection Of Therapeutic Agent; Injections; Membrane; Mercurate(1-), Ethyl(2-Mercaptobenzoato(2-)-O,S)-, Sodium; Mercurothiolate; Molds; Needles; Patients; Performance; Permeability; Pharmaceutical Agent; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Plastics; Powder Dose Form; Powders; Pressure; Pressure- Physical Agent; Process; Public Health; Rewards; Risk; System; System, Loinc Axis 4; Technology; Temperature; Testing; Therapeutic; Thimerosal; Thiomersal; Thiomersalate; Thumb; Thumb Structure; Time; Transmission; Vaccines; Water; Alum; Aluminum Sulfate; Balance; Balance Function; Commercialization; Communicable Disease Transmission; Cost; Disease Transmission; Health Care Personnel; Health Care Worker; Health Provider; Healthcare Personnel; Hepatitis Associated Antigen; Immunogen; Infectious Disease Transmission; Innovate; Innovation; Innovative; Medical Personnel; Membrane Structure; Microbial; Nano; Pathogen; Pressure; Prophylactic; Public Health Medicine (Field); Public Health Relevance; Reconstitute; Reconstitution; Seal; Success; Therapeutic Vaccine; Transmission Process; Treatment Provider; User-Friendl

The overarching goal of this project is to move a new, dry powder formulation of Hepatitis-B vaccine on its path to commercialization. In the Phase I SBIR we tested in vitro three Hep-B dry powder formulations of commercially available Shanvac-B and demonstrated powder stability and immunogenicity at temperatures ranging from -20 ?C through 65 oC. At these temperature extremes the currently marketed liquid Hepatis B vaccine is inactivated as the HBsAg antigen separates from the alum adjuvant. Our studies also showed that the dry micro-scale powders dissolved very rapidly, suggesting their utility in single dose auto-reconstitution devices aimed at parenteral administration. These results have far-reaching implications in regard to vaccine storage, transport and administration, especially in developing countries where limited refrigeration and electric power and high ambient temperatures restrict the useful life and potency of liquid vaccines. In the proposed Phase II SBIR study, we will choose the"optimum"formulation from the three that we developed earlier and pair this powder with a single dose auto-reconstitution device being developed by Becton Dickinson (BD). The drug- device combination will be used to assess potency in a mouse model compared to a control group of animals that will be administered Shanvac-B by needle and syringe. Potency will be assessed from ELISA analysis of animal sera. . The outcome of the Phase II work will be judged based on the potency of the Hep-B dry powder formulation and the functionality and performance of the BD device as compared with the potency of the needle and syringe administration.

Public Health Relevance:
This project seeks to accelerate a new Hepatitis-B vaccine formulation on its path to commercialization. A commercially available thimerosal-free liquid vaccine, Shanvac-B, was formulated as a dry, rapidly dissolving micro-powder with stability over an 18-month period at temperatures ranging from -20 oC through 65 oC. When considered in the context of combining Aktiv-Dry's vaccine powders with single dose auto-reconstitution devices, these results have far-reaching implications in regard to vaccine storage, transport and administration, especially in developing countries where limited refrigeration and electric power and high ambient temperatures restrict the useful life and potency of liquid vaccines.