BioPharm: With regard to equipment, there is a trend right now towards disposable, or single-use, bioreactors when performing an upstream
process. In your experience, why is the industry changing this preference for material?
Nelligan: There are two aspects of this trend. One must keep in mind that biotechnology is a relatively new industry. We are approximately
10 years old, and technology is changing very quickly. The productivity of the cells has increased enormously over the past
10 years. With newer strains, the amount of drug substance has increased 10-fold compared with before. This increased productivity
is leading to smaller and smaller manufacturing plants.
Ten years ago, production was taking place in 10,000-L vessels, and nowadays, it is taking place in 1000-L vessels or less.
At this smaller scale, there is now the possibility of moving to a disposable plant. A 1000-L vessel is equivalent to a cubic
meter, so new disposable vessels can literally sit on a laboratory countertop. Cells can therefore be cultured in disposable
bags rather than in large stainless-steel bioreactors, which was norm a decade ago.
When using disposables, however, there are concerns regarding extractables in the plastic bags which can be transferred to
the product. This problem does not occur in a stainless-steel environment, which is more robust. Plastics can also be quite
friable. Disposable bags are limited in size because they cannot hold off pressure.
Despite these disadvantages, these bags are becoming the norm in industry. Although disposables are more expensive than perhaps
the industry would like, companies are willing to pay the extra cost because the bags also come pre-validated and presterilized,
which saves time and resources on commissioning and validation. As a result, plants can be established more quickly; a modern
plant can be designed and up and running within three months when using disposable technology, rather than the two to three
years that it may take when building a stainless-steel plant.
WHAT'S TO COME
BioPharm: Looking ahead 10 or 20 years, what do you think will be the standard bioreactor of choice—a disposable, a stainless-steel,
or perhaps a hybrid model?
Nelligan: We are already seeing hybrid models—partial disposable and partial stainless steel. People are gaining more confidence with
disposable systems and favor the advantages they offer. For example, the first to market with a new product usually gets the
lions share. If you have a new product that you want to get on the market quickly, the way to go is the disposable route.
The October issue of BioPharm International will feature a primer on downstream processing with Nelligan. The full interview
with Nelligan on upstream processing can be listened to as a podcast on
Ian Nelligan is the Technical and Training Director at the National Institute for Bioprocessing Research and Training (NIBRT) in Dublin.
Listen to the interview as a podcast on our Drug Development Basic Training web page.