LOOKING UNDER THE HOOD
The AutovaxID instrument consists of two components: the control unit and an enclosed, disposable bioreactor (cultureware).
The disposable component is completely enclosed in a plexiglass housing that slides into, and snaps in place within the instrument.
The series of photographs in Figure 2 demonstrates the ease of use of the AutovaxID. Initially, a completely enclosed, disposable
culture module is removed from its packaging (middle left) and placed in the control unit (upper left). Next, the culture
parameters are programmed into the instrument (upper right), followed by bar code scan (middle right) for materials tracking
and data capture. Following this, cells are introduced into the bioreactor and the automated culture process is initiated
(lower right). For the duration of the culture, clarified supernatant is continuously collected and stored in the refrigeration
compartment of the AutovaxID (lower middle) until the run is terminated, or product is ready for further processing. With
conventional hollow fiber instruments, technicians must first prepare the cultureware for installation into the instrument.
This may include loading peristaltic pumps, aseptically inserting an autoclaved pH probe, and manually opening and closing
clamps to facilitate a preinoculation fill and flush procedure. The entire preparative process may take several hours and
is prone to mistake by an inexperienced technician. All these manual operations have been eliminated with the AutovaxID. Technicians
need only snap the cultureware into the device and connect a media feed source. Following an automated fill and flush procedure,
inoculation and secondary pH calibration, the instrument's process control then allows for unattended operation for the duration
of the culture.
The disposable cultureware for the AutovaxID contains all disposable fluid or product-contact components, including the bioreactor
and associated tubing, pH probe, cycling and harvest bags, and a gas exchange cartridge to oxygenate and provide feedback
control of pH in these densely packed cultures. Note that although the AutovaxID is described as a "closed" system, users
must still introduce cells and change media bags, which is normal for any cell culture device.
The AutovaxID control unit contains a built-in computer, touch screen display, and built-in solid-state refrigerator. The
entire system can be monitored and controlled remotely via a web browser. The software was designed to maintain process parameter
setpoints for pH, lactic acid, and temperature, and also to monitor pump speeds and calculate media volumes. When media reach
a critical low point, for example less than five liters, the technician is alerted to replace or add a new container.
Biomanufacturing has benefited for 20 years from hollow fiber bioreactors, whose principal advantages are their disposability
and ability to support a large cell population within a very small space. Hollow fiber bioreactor devices are also continuous,
densely-packed cultures that facilitate product harvest at high concentrations. This, combined with online product filtration
in the AutovaxID, greatly facilitates or eliminates the first step in the product purification process. In hollow fiber bioreactor
systems, it is common to harvest protein continuously at concentrations of several milligrams per milliliter, as opposed to
micrograms per milliliter in conventional batch processes. As an added benefit, hollow fiber bioreactors conserve costly,
high molecular weight growth factors or serum-based additives by retaining these expensive reagents on the same side of the
membrane as the cells.
The AutovaxID was specifically designed for use in multiproduct facilities that must manufacture large numbers of patient-specific,
cell-based therapies simultaneously and in a relatively compact space. In designing the AutovaxID to include such features
as product segregation capability, automation, and software security we believe that we have addressed the key regulatory
requirements relating to production of personalized biologics by the instrument.
THE FUTURE OF PATIENT-DERIVED PERSONALIZED THERAPIES
The challenges for developing a bioreactor that addresses the manufacturing needs of personalized therapeutics are daunting.
Any application involving the expansion of specialty or patient-specific cells will be extremely labor-intensive and expensive
using traditional cell culture methods. As medical science struggles with the regulatory issues and labor burden of expanding
cells in culture for personalized treatments, we believe that the AutovaxID platform technology is the only way to cost effectively
manufacture and market these products.
AutovaxID has shown its value and versatility for producing patient-specific secreted proteins for therapeutic use, at a cost
that makes potentially life-saving therapies accessible to patients with many serious illnesses. While we expect to continue
to serve this important area of personalized medicine, we also expect that many new and promising treatments will arise from
cell-based therapies. Biovest is currently exploring ways to optimize the AutovaxID for applications which involve recovery
of whole cells grown in the AutovaxID for therapeutic use. At present, our challenge is to develop a process that allows for
cost-effective growth and efficient recovery of unique or specialized cell types, including stem cells.
Biovest and its parent company, Accentia Biopharmaceuticals, are committed to the continued development and improvement of
the AutovaxID instrument for the production of therapeutic materials. Both companies believe that within the next several
years it will become a key enabling technology for the emerging field of cell and cell-derived therapeutics.
Mark Hirschel, PhD, is chief scientific officer at Biovest International, Inc., Minneapolis, MN, 800.325.111 ext.206, firstname.lastname@example.org