Editorial: Single‐use technology in biopharmaceutical manufacturing

Single-use technology is based on single-use systems whose product contacting parts are only used once. They are made from FDA-approved plastics and exist either as injection-molded versions or flexible bag systems. Typically, these single-use systems, which have their origin in medicine (blood bags) and food techniques (packaging), are already gamma- or beta-sterilized, which means that there is no need for sterilization and time-consuming cleaning procedures. Moreover, today's single-use systems are obtainable for all stages of biopharmaceutical production processes (upstreaming, downstreaming, filling), can be more rapidly brought into operation, and allow safer as well as more flexible production than their glass or stainless-steel counterparts. They are well established in the development and production of pre- and clinical samples of therapeutic antibodies and vaccines, above all where mammalian and insect cells are grown up to middle volume range. The availability of scalable instrumented single-use bioreactors and the increasing knowledge about their bioengineering characteristics have made an important contribution to this development 1. Single-use systems are obtainable for all stages of biopharmaceutical production processes. Current activities of manufacturers and users of single-use technology focus on the main limitation of single-use systems: the possible secretion of leachables and extractables (plastic additives that can migrate into the product), and their identification 2-4. Here, patient safety has the top priority. In addition, efforts are being made to achieve a further increase in process efficiency (for example by coupling single-use bioreactors with external cross-flow filtration systems) 5. Furthermore, the suitability of existing single-use systems is being investigated for production processes with human primary cells (e.g. stem cells) and microorganisms (bacteria, yeasts) 6, 7. This Special issue in Engineering in Life Sciences is introduced by a review by Langer und Rader 8, in which the authors deduce development trends for single-use systems by analyzing the pharma market of the past 10 years. Both predict an ongoing growth for single-use systems, whereby upstream processing is assumed to be the fastest growing segment. In a second Review Pralong et al. 9 prove that single-use systems are advantageous for the rapid realization of vaccine productions up to biosafety level 3. Two research articles comparing product expressions in stirred and wave-mixed single-use bioreactors 10, 11 and three Research Articles describing the scaling-up of stirred single-use bioreactors 12-14 follow. Minow et al. 12, 13 and Schirmaier et al. 14 show the significance of bioreactor engineering data and scale-up factors for efficient antibody and stem cell production at pilot and industrial scale. Engineering data (power input per volume, mixing time, volumetric mass transfer coefficient, Newton number) of single-use bioreactors are also presented in the technical report about the BIOSTAT CultiBag STR-series (50–2000 L), provided by Dreher et al. 15. The possibility of using the Sauter diameter in order to predict shear stress in single-use pumps 16 and a method for clarifying and concentrating a cytomegalovirus-like particle with single-use cross-flow technology 17 are discussed for the first time in further technical reports. Cross-flow filtration is also applied by Blaschczok et al. 18, who exchange the growth medium with the production medium and induce a model protein expression in a biphasic mammalian cell-based production process performed in a single-use stirred bioreactor at pilot scale. In the final short article, Hess and Dudziak 19 summarize best practices for successful implementation of single-use technology and their qualification. The increasing knowledge about their bioengineering characteristics has contributed to the increased usability of single-use bioreactors. We are very grateful for the work and support of all the authors who made this Special issue possible. The contributions are the result of oral and poster presentations given at Biotech 2013 (on single-use technology in biopharmaceutical manufacturing) in Wädenswil. This international conference was organized by the Zurich University of Applied Sciences in co-operation with NTN Swiss Biotech and DECHEMA. Prof. Regine Eibl Prof. Dieter Eibl Guest Editors, Engineering in Life Sciences