The biopharmaceutical industry continues to face enormous pressure to accelerate time to market, improve productivity and
efficiency, and reduce costs. To address these challenges, drug developers are actively evaluating and leveraging single-use
products and systems. The move to single-use solutions, either alone or in conjunction with stainless steel, is likely to
continue growing to address these imperatives.
To date, many discussions on the topic of single-use system implementation have been theoretical in nature rather than describing
actual examples of implementation and the rationale guiding the decision-making process. This article provides insights into
how a single-use process train was developed at EMD Millipore's Advanced Bioproduction Facility in Martillac, France, how
templated processes are being leveraged, and offers some best practices when considering a single-use process train.
The Advanced Bioproduction Facility has been designed as a single-use facility for the manufacture of biopharmaceuticals (see
Figure 1). Owned by Serono since 1994, the facility became part of Merck KGaA in 2007, and was transferred to EMD Millipore
in 2012. The 37,000-square-foot site, which has been inspected by FDA and Agence Francaise de Securite Sanitaire des Produits
Sante (AFSSAPS), can provide support across different stages of production of a therapeutic protein, including clone selection,
cell banking, upstream and downstream process development, GMP production, formulation, and fill-finish.
The facility is used to provide biodevelopment and clinical-supply services for biopharmaceutical companies globally. The
combination of single-use technology with template processes make it possible to go from clone selection to GMP product in
twelve months, whereas the typical timeframe is on the order of 15 to 18 months or longer for a company doing this for the
Figure 1: Single-use, upstream production suite with a 200-L bioreactor.
Adoption of single-use technology is growing, especially in the area of small-scale or clinical-scale production. The drivers
for this adoption are numerous and include:
- Reduction/elimination of cleaning and cleaning validation costs
- Elimination of carryover
- Reduction in turnaround time between batches/campaigns
- Ease of duplication of manufacturing suites in multiple locations
- Increased flexibility.
From EMD Millipore's perspective, the industry is actively considering what its standard single-use platforms are, particularly
around bioreactor systems. Many customers are evaluating or have evaluated use of single-use bioreactors for both feed train
and in the GMP environment at least for production of preclinical material. Gaps in the downstream area are now being filled
though single-use chromatography systems that are as efficient, as easy to use, and as flexible as traditional systems.
Adding to the interest in single-use systems is the ability for systems and technologies to handle larger batch sizes. Until
recently, single-use systems did not have capacity to handle a one kilogram batch of protein, but the newer systems, in particular
tangential flow filtration (TFF) and chromatography, offer the necessary capacity.