Programma van Single Use Technologies in biopharmaceutical manufacturing

John Rook, Bioprocess Development Expert, Meatable (www.meatable.com)

In Biopharmaceutical production, new innovative technologies are implemented over years.  One of the main advances in the industry is the use of disposables. Starting about ~20 years ago with simple solutions (like blood bags), single use technology has developed significantly the last 5-10 years.

These days single use technologies are reliable and a true alternative for stainless steel. Single Use manufacturing is omnipresent and just about every bioprocess technology has a single use format. Fully single use production platforms and even fully single use facilities are now a serious option.

Being part of teams that implemented several innovations from fully flexible SU platforms to cGMP facilities with SU capabilities, I will show considerations in the choice for a fully disposable process from a CDMO perspective and the applicability of the learnings to Bioprocesses in other fields. 

Guy de Roo, Principal Scientist, Synthon Biopharmaceuticals B.V.

Antibody–drug conjugates (ADCs) are biopharmaceuticals consisting of a monoclonal antibody linked with a highly potent cytotoxic drug. The purpose of the antibody is primarily to target the drug to receptors on tumor cells and secure internalization while the function of the cytotoxic drug is to kill the targeted tumor cells.

A major focus during the manufacturing of ADCs is protecting a product from contaminants in the environment of a production facility but also the protection of employees within that environment from exposure to what can be very hazardous substances. While the use of glass or stainless-steel systems may effectively protect operators, significant equipment decontamination and cleaning validation is required. As an alternative, single –use technologies offer specific benefits but also come with challenges. 

The approach and challenges to handle safely both antibodies and high potency molecules (ADC, cytotoxic linker drug) will be presented.

Gerben Zijlstra, Global Technology Consultant, Intensified and Continuous Biomanufacturing, Sartorius Stedim Biotech

Single Use technologies, from storage bags, tubing and filter assemblies, complex bioreactors, up to complete Single Use production lines, have been quickly and widely adopted in early stage Biomanufacturing and especially in CDMO’s where they add value through their flexibility and ease of changeover.

More recently single use technologies are also being implemented for commercial manufacturing, this however poses a whole new range of challenges and demands to single use systems and suppliers, such as assurance of biocompatibility, bag integrity and assurance of supply.

Another aspect is that despite their low costs, rapid deployment and flexibility, the current Fed Batch based Single Use production lines are limited by their output, typically 500 kg/year for a 6 x 2000 L facility at 3 g/L Fed Batch titer. This also limits their usefulness for commercial product supply. Process intensification can solve this limitation. In this presentation several upstream process intensification examples are shown, using commercially available platform tools, including cell line, media, process development tools and commercial scale single use bioreactors and manufacturing tools.

With these intensified (including continuous) approaches, Single Use facilities have become a viable option for (multi-product) commercial manufacturing.