The purification procedures for the two recombinant products were similar, in that both processes used an anion exchange resin
followed by the hydroxyapatite column purification steps. However, the previous process used Amersham Pharmacia Biotech's
Source 30Q resin, and linear gradients were used to elute the product. In the new process the Q-Sepharose Fast Flow resin
was used, and step-wise elutions were used for ease in scale-up and manufacturing. The process described above makes a consistent
product at acceptable yields for the current stage of development. IDRI is producing nearly 200,000 doses per lot of vaccine
based on the highest dose level currently envisioned. This level is satisfactory for the amounts needed to conduct current
clinical trials, but scale-up of the process to the 300-liter scale is already ongoing. Assuming no loss in unit production,
this scale would deliver 2,000,000 doses per lot and could enable large-scale clinical trials of the vaccine even without
further process improvements.
An additional encouraging fact is the stability of the lyophilized protein. When performing trials or vaccinations in field
settings where a cold chain cannot be guaranteed, stability of the product is crucial to successful deployment of the trial
and the final product. This lyophilized vaccine product has been shown to be stable for more than three years.
IDRI has developed a process to manufacture a new recombinant protein product for the treatment and prophylaxis of leishmaniasis.
This candidate vaccine consisting of Leish-110f formulated in MPL-SE will be tested in a spectrum of diseases caused by the
various Leishmania species. A robust, scalable procedure will allow rapid progress in bringing this vaccine to patients and will be a step in
the fight against leishmaniasis.
THOMAS S. VEDVICK, PHD, is director of process sciences, 206.330.2530, email@example.com
LAUREN CARTER is a research associate, GARNER MOULTON is a senior research associate, YASUYUKI GOTO, PHD, is a scientist, SYLVIE BERTHOLET, PHD, is a senior scientist, STEVEN G. REED, PHD, is founder and head of research and development, and DARRICK CARTER, PHD, is director of formulations, all at at the Infectious Disease Research Institute, Seattle, WA. Dr. Carter is also the vice
president of research and development at Dharma Therapeutics, Seattle, WA.
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