Development of a Full Process Train, Single-Use Facility

This article describes best practices for implementing a single-use process train at a bioproduction facility.
Nov 02, 2012

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.

Figure 1: Single-use, upstream production suite with a 200-L bioreactor.
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 first time.

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.

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