How long has your company been involved with disposable bioprocess equipment?
Dr. Jenkins: We currently operate 100 L process development and 200 L stainless steel cGMP trains, but are expanding our capabilities for more lines and a larger scale.
We have used Wave bioreactors (GE Healthcare Life Sciences) for seven years for non-cGMP production and for five years as part of our cGMP bioreactor trains in scale-up vessels. During our expansion planning, over a year ago, we undertook a thorough evaluation of single-use bioreactor systems.
After evaluating several units and integrators, we decided to work with Thermo Fisher/Hyclone SUBs using Finesse Solutions as the integrator. Today we have one unit onsite, and decided to build our new facility with multiple SUB trains and no stainless steel vessels.
Catalent’s biotech facility uses disposable technology throughout our Phase I/II mammalian cell culture operations. We use Wave reactors and SUBs to produce recombinant proteins, as well as pallet tanks and other “bag” technologies throughout our purification processes. We do not work with nonmammalian systems, primarily because we have a gene insertion technology (GPEx®) to engineer mammalian cells to express biopharmaceuticals.
Matthews: We have not yet begun production, but our company intends to be truly end-to-end disposable. Major disposable unit ops include mammalian (CHO) seed train, inoculation train, production bioreactor, depth filter, buffer and media dissolution, chromatography, TFF formulation, and freezing of bulk drug substance.
Munk: We have gradually increased the use of single-use equipment over the last eight years, with a very steep increase over the last four years. The main applications are buffer and product storage, filters, SUBs, buffer mixing, membrane processes, sampling, and development activities. We try to apply single-use for as many applications as possible, from the seed train to final fill of the API for both microbial and mammalian projects. The only exceptions are microbial fermentations, harvest of microbial products, and limited single-use for chromatography.
Dr. Runser: Our large-scale cell culture facility for recombinant protein production, located in Huningue, France, started using disposable equipment in 2005 when it began operations.
The Huningue plant is fully GMP compliant. Its main disposable solutions include bags for media and buffer storage, and fully disposable filter systems incorporating disposable connectors and tubing. We use disposable bags for intermediate storage of product and for final storage of the drug substance.
Dr. Schlatter: We have been using disposable bioprocess equipment for more than 10 years, since 2007 for cell culture. The equipment we use consists of Wave bioreactors, media and buffer bags of up to 1,000 L, shake flasks, harvest filters, filter capsules for downstream processing, the ATMI media formulation system, 100 L/500 L SUBs, and bags for intermediate and bulk drug substance storage (up to 1,000 L). We employ disposable process equipment for mammalian cell culture, and downstream processing up to fill and finish.
VonEsch: Our company began using disposable technologies for mammalian upstream and downstream processing in 2006. In 2009, with the footprint of our sterile filling process under way, we began exploring the possibilities of bringing these technologies further down the line to our sterile fill-finish production.
Dr. Witcher: Disposables have been used for cell culture inoculum development for many years. The use of disposables for large-volume cell culture systems is increasing. Many companies are exploring using disposable bioreactors up to the 1,000 liter scale, although skepticism remains regarding volumes above 500 liters.
Disposables are most attractive for operations that require a small number of low- to medium-volume lots, such as clinical manufacturing, or very high-yield commercial processes such as some vaccine manufacturing.