Biomedical Engineering Reference
In-Depth Information
Small Companies
It is well established that no matter how Big Pharma reduces its cost, it can
never compete with smaller companies on the cost of production: with dis-
posable systems, many small companies will be able to offer the quality and
quantity of products that are needed by Big Pharma, which means it would
be prudent for Big Pharma to outsource manufacturing of their biological
APIs. The shift that took place 40 years ago when the manufacturing of
chemical APIs was outsourced is about to take place for biological drugs,
and smaller, efficient companies built using this max-dispo philosophy will
be in high demand.
Unitary Systems
The predictions about the future of biological manufacturing are evolution-
ary, as demand and supply meet and as the awareness of the cost reduc-
tions and need for cost reductions collide. However, the real changes in the
universe of biological manufacturing will come from deconstructing the
locked-in paradigms of manufacturing that continue to survive. The talk
about upstream and downstream stages continues as if they are inextrica-
bly inseparable. A disruptive technology breakthrough will take advantage
of the flexibility of disposable systems and combine upstream and down-
stream stages. A typical process of monoclonal antibody production should
be examined. A cell line is introduced in a flexible bag to grow the culture
and, when it reaches a certain confluence, allows it to express the target
protein, all of which can be done swiftly in a disposable container such
as the Wave Bioreactor or the newly introduced MayaBioReactors (
www.
mayabio.com
)
. The next step is to remove the cells by filtering them through
a 0.22 µm filter, reduce the volume of media to about one-tenth of the vol-
ume, and then load the remaining solution into a column, such as an ion-
exchange column for erythropoietin, for further purification. As long as the
media volumes are tens to hundreds of liters, these steps are manageable,
but when one enters thousand liter systems, the time and cost for these pro-
cess steps become prohibitive. Furthermore, the delays in processing and
the force applied on the target proteins in the solution reduce the yields.
The question arises that if the purpose is to isolate the target protein from
a large mass of culture media, why are components such as cells and fluids
being removed from the media? Why not just pick up the target protein
using a resin or a combination of resins, and drain out the balance of media?
The resin can be a specifically made resin or a mixture of resins for nonspe-
cific binding. Systems to remove resins may include introducing the resin
