On the analysis end, it is new equipment, like DNA sequencers that have become far more efficient and sophisticated. They
can analyze multiple samples simultaneously. In the future, we'll be able to increase what we're doing today, logarithmically
with computers, and with equipment using microcapillaries. We can now process a thousand samples in the amount of time that
one sample took in the past.
What are some of the manufacturing developments that have led to personalized therapies?
After we receive a biopsy sample, sequence the DNA, and determine the relevant sequence for the patient's antibody, we generate
a plasmid that is integrated into a virus specific for insect cells. The use of this viral and insect cell system has been
a big breakthrough. We use insect cells—Fall Armyworm (Spodoptera frugiperda) and Cabbage Looper (Trichoplusia ni)—with a
baculovirus vector. The virus replicates within the insect cells and they produce antibodies with a glycosylation pattern
that we believe is best suited for eliciting the immune response we are seeking. In fact, we can generate and harvest a cell
culture in a fraction of the time it would take using mammalian cells.
So, how long will it take you to develop a therapeutic for a cancer patient?
Our proprietary production system allows for manufacturing a patient's FavId and returning it to the patient's physician in
eight weeks. Mammalian cell production systems require 4–6 months.
Does the manufacture of patient-specific therapies require unique facilities and regulatory considerations?
Safety is always the number one concern, and with insect cells, there is a slightly lower risk of viral contamination for
humans compared with mammalian cells.
One of the biggest measures we can take to ensure safety is segregating patient-specific lots. There are different approaches
to this. One is through facility design.
We have already completed the construction of a commercial facility. The biggest regulatory concern is segregating the lots
of patients' antibodies. We have a dedicated area for the final production phases of each lot, and will be processing and
releasing up to 80 lots per week. In any given day, we could have more than 500 lots at various stages of production in the
facility. Those are staggering numbers.
The other measure is establishing a dedicated tracking number and bar code for the biopsy sample when it comes through the
door, and then following it all the way to the final vial shipped out to the patient.
Another major consideration is scale. We have essentially the same stages as other typical recombinant protein biotech companies:
cell culture, purification, formulation and filling, but at a very small scale. We are only making enough vials for one patient.
How do you scale up?
You have to scale up horizontally, not vertically. We have multiples of small pieces of equipment: dozens of laminar air flow
hoods and purification skids.
Do you use disposables?
Our entire process uses disposable technology. There are virtually no cleaning validation issues, to avoid the possibility
of cross-contamination. The disposable industry has evolved to the point where lots of equipment is available that is presterilized
and single-use, and that eliminates validation concerns for cleaning and sterilizing.
What type of testing will be done?
We sequence the patient's DNA at the beginning of the process, and verify it at the end, to make sure the sequence matches
what came in. Otherwise, the testing is fairly typical for protein products.
The benefit of patient-specific therapy is doing everything at small scale. When you get to process validation, you can validate
at actual commercial scale. In general, the biotech industry has to use scale-down models to validate the process.