Biomedical Engineering Reference
In-Depth Information
lies in the interactions in the final dosage forms. A notable incidence was the
reporting of pure red cell aplasia (PRCA) in using erythropoietin and, while
many causes were brought to attention, one was the interaction between the
rubber stopper and the newly formulated drug containing a new surfactant
that might have extracted some extractables from the rubber stopper.
The fear of leachables, the strong presence of a well-established stainless
steel industry, and a user industry in no rush to learn how to reduce the cost
of production slowed down the implementation of plastic containers, more
particularly of the disposable containers in drug manufacturing.
First came the changes in practice as the industry began using dispos-
able filters, flexible containers, membranes, sampling devices, and now
there has been a wave of disposable bioreactors to address the most criti-
cal barriers in biological drugs manufacturing. The stainless steel indus-
try remains robust today, thanks to the reluctance or perhaps the inability
of Big Pharma to junk their dinosaurs and give in to the “disruptive”
technology for upstream manufacturing that first appeared as the famous
Wave bioreactor that utilized a rocking platform and a 2D flexible bag in
1998. (In this way, the industry owes much to Vijay Singh, the inventor of
Wave technology.)
Disposable bioreactors have since evolved beyond the wave-based design
and have been adopted both for research purposes and Good Manufacturing
Procedures (GMP) production. Other disposable technologies, such as
disposable filters, flexible containers, membranes, sampling devices, and
chromatography columns, have also made a significant headway in being
accepted as the standard of manufacturing.
The final decade of the 20th century was good for the biotechnology indus-
try, which raised billions in the public market, and a rush for new regulatory
filings was soon on; however, many of these companies did not have in-house
expertise to manufacture these molecules and that caused a mushrooming
of contract research organizations (CROs) and contract manufacturing orga-
nizations (CMOs) that were ready to fill the gap. It became relatively easy
to secure clinical test supplies without having to construct a recombinant
manufacturing facility: this eased the financial pressure as well as made up
for the dearth of qualified individuals in this newly found science of manu-
facturing. However, CROs and CMOs could not afford the capacity of large
stainless steel technology since they would not know which product they
would be handling the next day: disposable became very popular (because
they required so little capital investment) among the CRO/CMO groups as
well as research organizations, even though their need for regulatory com-
pliance was less.
The improved efficiency of being able to switch over to different products
and manufacturing methods pushed the equipment supplier industry to
make some quick innovations. The list of disposable items expanded very
quickly, and we can readily classify them in three categories.
