Single-use technology left its mark, but where is it heading?

Global Technology Partner, NNE

Niels Guldager

Global Technology Partner, NNE

Niels Guldager is an expert within bioprocess and technology. 

He is currently engaged in single-use technology community work for the industry organisations PDA and ISPE and is also a member of PDA’s task force for Gene and Cell Based Therapies. Guldager holds the Certified Pharmaceutical Industry Professional™ certification from ISPE.

Guldager has a Master’s degree in Chemical Engineering from the Technical University of Denmark. He started his career at Novo Nordisk as a production engineer, responsible for upstream production of recombinant human insulin. In this role, he also facilitated production of clinical batches and manufacturing technology transfer for next generation products. Later, he moved on to downstream manufacturing.

 

Guldager heads NNE's biopharmaceuticals design group, where his focus is on process and technology in front-end project activities, capturing customer strategy and requirements and transforming these inputs into a well-defined process and facility design scope.

Pharma manufacturing facilities have long embraced single-use technology. Now the technology is pushing new boundaries and supporting new processes, making strides in fill-finish and continuous processes.

Single-use in fill and finish

Fill-finish operations are seeing a marked increase in uptake of single-use technology. The single-use applications range from individual formulation bags and process filters to filling pumps and needles and entire filling assemblies. Driven by the need for fast change-over and set-up as well as cross-contamination prevention, fill finish facilities are testing several applications of single-use technology today.

Manufacturers are playing with combinations of single-use technology amid the current regulatory focus on barrier and isolator technology. Companies are testing the application of ready-to-use components such as primary product containers, stoppers, caps (not associated with wash or sterilisation) as well as strategic use of robotics. All of these new approaches represent a potential platform shift in efficient fill-finish operations.

Driven by the need for fast change-over and set-up as well as cross-contamination prevention, fill finish facilities are testing several applications of single-use technology today."

Niels Guldager, Global Technology Partner

 The 2,000L bioreactor

Single-use does not necessarily mean small batches. Biotech facilities based on single-use technology are zeroing in on the 2,000L bioreactor as the inflection point for a standard single-use technology process scale. Some companies also combine several 2000 L bioreactors to create a larger, effective volume and one supplier also offers 4000L bioreactors with the same objective.

In fact, associated upstream and downstream process equipment is being developed right now to match the 2,000L scale bioreactor. Innovators are making strides in bag systems for media and buffer preparation and hold. They are also targeting bottleneck steps in harvest and clarification. And chromatography steps working with prepacked formats and/or in multi column or continuous process mode promise even stronger process intensification.

The net effect is an industry landscape that allows customers to install a 2,000L process in full single-use technology and thereby realise the advantages of agility, flexibility and cash flow.

Scaling out, not up

Drug substance facilities that utilise single-use technology and have capacities of various combinations of 2,000L volume bioreactors are one answer to fluctuations in process yields and market demand. These facilities don’t follow the typical scale-up strategy – instead, they scale out by adding more of the same proven volume capacity in lieu of increasing process equipment volume.

The strategy provides fast and simple responses to, for example, low-yield process by combining two or more of the 2,000L bioreactors or the need to rapidly increase capacity by adding additional 2,000L bioreactors and sidestep need for scale-up studies and validation. To date, combinations of up to 12 x 2,000L and 14 x 2,000L are cited in the industry.

Continuous processes

The low batch frequency and high productivity of continuous processes compensate for the two traditional disadvantages of single-use technology: variable costs and scale limitations. Several drug manufacturers and suppliers have announced continuous process initiatives in the field of monoclonal antibodies (mAbs). 

Design drivers include plant throughput optimisation and plant footprint reductions and may involve switching over to new production platforms and comparability studies. Companies without a history of fed batch products – and therefore the need to maintain a fed batch manufacturing network – may be the first to fully embrace continuous processes. On the other hand, several elements of continuous processes may be used on process intensification of fed batch processes, so the overall picture is of throughput optimisation and depends on product volume projections.

The low batch frequency and high productivity of continuous processes compensate for the two traditional disadvantages of single-use technology: variable costs and scale limitations."

Niels Guldager, Global Technology Partner

Supplier platforms

On the supply side of operations, single-use technology has seen considerable consolidation over the last few years. The emerging landscape is dominated by perhaps five major suppliers. These suppliers are close to full-range process offerings with platforms supported by parallel offerings in, for example, materials, facility concepts, laboratory equipment, automation, process development and even financing. These major suppliers are supplemented by an ecosystem of smaller suppliers with some focusing on individual single-use components. A disruptive supplier coming out of traditional low-cost manufacturing locations like China or India has yet come enter the stage.

When asking what’s new in single-use technology, one might feel overwhelmed with replies. Movement in the field is varied, interdisciplinary and often still in infancy. However, the common denominator of single-use trends is the agility and flexibility they integrate in pharma manufacturing facilities.