A perfect pair: continuous processing and single-use systems

Global Technology Partner, NNE

Morten Munk

Global Technology Partner, NNE

Morten Munk has 30 years of experience within the biopharmaceutical industry and has wide experience from pharma projects in Asia, South America, USA and Europe.

Munk is actively involved in international industry organisations such as ISPE and PDA. Furthermore, he is appointed as member of scientific committees for various international conferences, as well as a member of the CMC Biologics Technical Advisory Committee, PDA Biotechnology Advisory Board and Advisory Board for Master studies at Copenhagen University on Industrial Drug Development and Regulatory Affairs.

Munk holds a degree in chemical engineering from the Technical University of Denmark. In 2001, he co-founded CMC Biologics A/S and held a position as vice president for business development at the company before joining NNE in 2015. Prior to this, he was principal scientist at Novo Nordisk, responsible for the chemistry, manufacturing and control development part of several projects, including development of the slow acting insulin analogue, Levemir®.

When technologies join forces, facility design reaps the benefits. The combination of single-use technology and continuous bio-processing is changing the industry’s approach to facility design for the better.

While there are many strategies to enable flexible manufacturing, single-use systems (SUS) pervade as a key source of flexibility. Utilised in nearly all new products in early clinical trials, we now see an increase in the use of SUS in commercial pharma manufacturing.

This trend is fueling the fast development of a broad range of SUS components in a wide range of industrial applications, which support quality requirements such as robustness, reproducibility and reliable supply. Moreover, on the leachables question, which is a major concern regarding the use of SUS, the industry is continually developing improved products and other solutions, which reduce this concern to a manageable and acceptable level.

Although higher quality requirements have also increased the price of SUS, a combination with continuous bioprocessing (CBP) might well be the solution to increase the value of SUS in biopharmaceutical manufacturing to an even higher level. In fact, the combination of SUS and CBP offers a number of synergetic advantages, including the possibility to utilise the SUS components in a more cost-effective way.

The combination of the possibility for supporting closed operations with the high frequency of introductions of new single-use solutions designed for continuous processing has inspired a paradigm shift in biopharmaceutical facility design.

Morten Munk, Global Technology Partner

1. Fit for flexibility

In general, CBP systems require a large number of valves and low dead volumes in the piping, which offers both flexibility and robustness in operation. SUS enhances this by allowing the construction of an integrated and pre-assembled single-use tubing and valve set. This can also be optimised for a specific CBP set-up. For example, should the set-up change, new valves or tubing sets can be constructed to fit the purpose, offering even more flexibility to accommodate future innovation in the process design.

2. Limited clean-up

The generally more complex nature of continuous bioprocessing systems also heightens the challenge of ensuring all vessels, piping and valves are cleaned sufficiently. The addition of SUS reduces these cleaning challenges, as all components can be discharged upon completion of a CBP campaign.

3. Reduced requirements

The combination of CBP and SUS offers the ability to manufacture in closed systems, which reduces room classification requirements. While chromatographic columns have been the Achilles heel of operating in a fully closed system, the CBP approach requires smaller columns, so pre-packed disposable columns can be fully taken advantage of.

4. Less resin, less costs

Not only that, but pre-packed disposable columns and CBP complement one another. Since CBP requires considerably smaller column sizes, where each column is used for many runs in each CBP campaign, the amount of column resin used is much closer to its full potential. This is rarely the case when chromatography steps are performed in batch mode. This combination results in less resin cost per gram of produced product and less capital bound in resin. Additionally, the smaller column size makes the chromatography systems easier and faster to set up, which also supports the cost effectiveness and flexibility.

5. A leaner footprint

The requirement for both smaller column sizes and a smaller CBP system reduces the clean room footprint requirements. In general, single-use setups are smaller in size in relation to bioreactors, columns and filters, which positively influences investments and running costs. One example is how introduction of pre-packed columns offers a possible elimination of a cleanroom for the open handling associated with column packing as well as the area needed for transportation, cleaning and storage of larger columns.

6. Get more out of your components

CBP provide the opportunity to use single-use components for a longer period of time. An SUS component can only be used for one batch in batch mode, whereas in CBP mode, an SUS component might be used for a full campaign – up to 50 days or more. This extended use of the of the SUS components might also have quality advantages, as the leachables originating from the SUS components might be diluted into large volumes.

7. Reduction of number of SUS items (components)

Last but not least, as CBP reduces the requirements for storage of buffers and products intermediates, both the size and the number of SUS components needed for those operations are substantially reduced.

A paradigm shift in facility design

The combination of supporting closed operations with the high frequency of new SUS solutions designed for CBP has inspired a paradigm shift in biopharmaceutical facility design. In fact, the introduction of single-use and continuous technologies has a significant impact on facility design by offering a smaller footprint and substantially lower cleaning requirements. This results in a considerable reduction of water and energy consumption and other utility requirements.

In addition, SUS decouples equipment from the building, removing the need for complex distribution matrices which pose a risk for operational failures and cross-contamination. Furthermore, this generates valuable flexibility through easier introduction of new technologies.

The industry is indeed transforming, although the trajectory of continuous bioprocessing’s acceptance in the conservative biopharmaceutical industry is slow. But one thing is for certain – continuous bioprocessing, coupled with single-use technology, can fulfil the wishes of regulatory authorities to introduce emerging technologies for the benefit of patients, based on increasing the supply of high quality products at an affordable price.