Pharmacy Perspectives - Winter 2012 - 14

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Technology advances changing vaccine delivery.
New technology produces stable vaccines that can withstand long temperature variations. In effect, the thermostabilization technology could potentially revolutionize the vaccine industry.

Professor of Pharmaceutical Biotechnology at the Skaggs School of Pharmacy and Pharmaceutical Sciences John Carpenter (PhD), together with Theodore W. Randolph, PhD, professor of pharmaceutical biotechnology at the University of Colorado Boulder, conducted preclinical studies of Soligenix, Inc.’s proprietary vaccine thermostabilization technology. The results prove that Soligenix is able to produce stable vaccine formulations using adjuvants, protein immunogens, and other components that ordinarily would not withstand long temperature variations exceeding customary refrigerated storage conditions. Dr. Randolph stated, “Early indications from the ongoing stability evaluation of the ricin vaccine stored at elevated temperatures are very encouraging for a protein immunogen that is otherwise so inherently unstable.” These studies were conducted with Soligenix’s aluminum-adjuvant ricin toxin vaccine, RiVax(TM), made under precise lyophilization conditions using excipients that aid in maintaining native protein structure of the ricin A chain, the immunogenic compound of the vaccine. When RiVax(TM) was kept at 40 degrees C for over one month, all of the animals vaccinated with the lyophilized RiVax(TM) vaccine developed potent and high titer neutralizing antibod-

ies. In contrast, animals that were vaccinated with the liquid RiVax(TM) vaccine kept at 40 degrees C did not develop neutralizing antibodies and were not protected against ricin exposure. The ricin A chain is extremely sensitive to temperature and rapidly loses the ability to induce neutralizing antibodies when exposed to temperatures higher than 8 degrees C. “We are very excited about these results, as the achievement of extended stability under elevated temperature represents a significant step forward in vaccine technology,” stated Robert N. Brey, PhD, Chief Scientific Officer of Soligenix. “These studies successfully establish the proof of concept that our vaccine thermostabilization technology works and now allows for the potential to apply this technology to other conventional vaccines that require refrigeration. Cold chain requirements add considerable cost to the production and storage of current conventional vaccines. Further, lack of long-term stability is a significant problem in vaccines for use in emergency situations and especially for vaccines used in the developing world where the cold storage chain is difficult to maintain. We believe that this technology has the potential to add value to many existing and developing vaccines.” The removal of water from pharmaceutical preparations by lyophilization is often used to confer extended shelf life to therapeutic protein products, but vaccines often lose potency during lyophilization, especially if they are formulated with aluminum salt adjuvants that are commonly used in vaccines. Therefore, most aluminumadjuvanted vaccines must be refrigerated or frozen because of the sensitivity of vaccine components to room temperature or higher. Soligenix has been developing its thermostabilization technology under a license agreement from the University of Colorado that was initiated to support the technology development efforts funded by a $9.4 million grant from the National Institute of Allergy and Infectious Diseases (NIAID). The license agreement has an expanded scope for thermostable vaccines

Castor beans are processed throughout the world to make castor oil. Ricin is part of the waste “mash” produced when castor oil is made.

for biodefense as well as all potential vaccine indications. The novel technology involves the use of several unique process and formulation steps that fix sensitive vaccine ingredients in the correct, native configuration. For biodefense indications, the company is using the stabilization technology to advance RiVax(TM), its subunit vaccine against ricin toxin, as well as its DNI rPA anthrax subunit vaccine. The underlying technology has been developed by Drs. Amber Clausi, John Carpenter and Theodore Randolph at the University of Colorado. The World Health Organization (WHO) reports that 50% of all global vaccine doses are wasted because vaccines are not kept within required temperature ranges. Aluminum-adjuvanted vaccines usually need to be maintained between 2-8 degrees C and often even brief excursions from this temperature range (especially those which result in freezing) necessitate the destruction of the product or the initiation of costly long-term stability programs. The savings realized from the elimination of cold chain costs and related product losses would significantly increase the profitability of vaccine products. Elimination of the cold chain would also enhance the utility of these vaccines for emerging markets and for other applications requiring, but lacking, reliable cold chain capabilities. For vaccines that are intended for long-term stockpiling, such as for use in biodefense or in pandemic situations, the utilization of Soligenix’s thermostability technology has the potential to facilitate storage and distribution of strategic national stockpile vaccines in emergency settings. It may also enable preparation of otherwise difficult multivalent (protective against multiple pathogens) formulations.

We believe that this technology has the potential to add value to many existing and developing vaccines.”
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CU Skaggs School of Pharmacy and Pharmaceutical Sciences

Pharmacy Perspectives - Winter 2012

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