Vendor Notes: The Biovest AutovaxID: Enabling the Promise of Personalized Medicine

Jul 01, 2007

ABSTRACT

The AutovaxID is a self-contained, completely enclosed, fully automated hollow fiber bioreactor that permits rapid, efficient scale up of patient-derived cells. It is based on hollow fiber bioreactor technology and is an ideal system for high-density cell culture and the production of monoclonal antibodies or other therapeutic proteins.



With the era of personalized medicine upon us, developers of novel, patient-derived cell- and vaccine-based therapies face two enormous challenges: generating safe products under good manufacturing practices (GMP), and delivering these new treatments at reasonable cost.

Platform technologies can standardize and streamline manufacturing operations for personalized treatments. Influenza vaccine, for example, is developed and manufactured rapidly through well-known platform techniques involving egg-based virus culture. For treatments derived from a patient's own cells, an ideal cell culture platform approach should be:
  • Compact, to minimize the size of manufacturing facilities (especially for treating diseases with large patient populations)
  • Rapid, to permit treatment of acute conditions
  • Composed of disposable elements for all product contact components, to maximize speed and manufacturing flexibility
  • Closed and self-contained to improve regulatory compliance.
  • Automated, to enhance productivity and reduce operator induced errors

In 2001, Biovest International began investigating options for manufacturing patient-derived therapies in a compact, production-worthy cell culture device that required significantly less human interaction than traditional stainless steel or multiple flask-based cell cultures.

The design was driven by ongoing development of a vaccine against non-Hodgkin's lymphoma, which is currently in Phase 3 testing at several sites in the United States and Russia. The challenge was to develop a scalable, commercializable platform technology, or an instrument that could run in parallel with multiple other devices. Moreover, this production methodology needed to be suitable for production in a cGMP facility in which multiple, patient-derived products are manufactured simultaneously.

Biovest scientists recognized early on that no such personalized biologic could be commercialized without a significant reduction in process complexity compared with conventional cell culture. Biovest believed that regulatory agencies would support a device that could eliminate cross-contamination and minimize operator errors.

NECESSITY, THE MOTHER OF INVENTION

In the mid-1980s, through its predecessor company, Cellex Biosciences, Biovest was the first vendor to offer commercial-scale hollow fiber bioreactor systems. These bioreactor systems included Acusyst Technology (mini-Maximizer, Maximize, Xcell, and Xcellerator), which provided hollow fiber technology suitable for research to commercial scale.

In 1999, the National Cancer Institute granted an award to Biovest to evaluate patient-specific cell line–derived antibodies to treat follicular lymphoma, and subsequently became the commercial sponsor of this cancer vaccine. As part of this cooperative research and development agreement (CRADA), Biovest began designing a novel production device that could be used in a multiproduct facility to facilitate the manufacture of patient-specific products as per US Food and Drug Administration GMP guidelines.

Development of the device was slow until Accentia Biopharmaceuticals became a majority shareholder of Biovest. Accentia recognized the value in emerging personalized medicines and believed this patient-specific treatment showed tremendous promise in improving and enhancing the quality of life. After acquiring Biovest and its scientific assets in June 2003, Accentia immediately invested in the lymphoma vaccine (BiovaxID) and the platform technology (AutovaxID) required for ultimate commercialization. BiovaxID, which confers immunity against non-Hodgkin's lymphoma, is currently in Phase 3 clinical trials.

As our personalized lymphoma vaccine product(s) progressed through clinical testing, the deficiencies of conventional cell culture manufacturing became evident, promoting a complete rethinking of the production process. It became clear that the process ideally required a device that could offer sample containment or segregation, high-throughput, a small-footprint, and the ability to concurrently manufacture thousands of patient-specific products in one facility. Based on this premise, the AutovaxID emerged after several years of development effort that combined cell culture, engineering, electrical, and mechanical expertise.

The AutovaxID is a self-contained, completely enclosed, fully automated hollow fiber bioreactor that permits rapid, efficient scale up of patient-derived cells. Because it is based on hollow fiber bioreactor technology, the AutovaxID device is an ideal system for high-density cell culture and production of monoclonal antibodies or other therapeutic proteins. A commercial version of the AutovaxID became available in October 2006.