Consistent development of bioprocesses from microliter cultures to the industrial scale

Abstract

Bioprocess development today is slow and expensive compared to chemical process development. A drastic paradigm shift is necessary and possible by the consistent application of engineering strategies that are typically used in the process development phase already in the early product development. Aside from providing a consistent pathway, strategies such as statistical‐based design of experiments, fed‐batch, minibioreactors, new on‐line sensors, process modeling, and control tools in combination with automation of manual steps offer a higher success rate and the opportunity to find the optimum parameters and operation point. This also directly benefits the early phases of biomolecular screening and initial production of small amounts of the target molecule. The paper reviews the bioprocess developmental phases from a business perspective and the available systems and technologies.

Detection of growth rate‐dependent product formation in miniaturized parallel fed‐batch cultivations

“…After an adaptation phase of 3 h, samples for OD 600 and EPG measurement were taken using a liquid handling robot (Hamilton Microlab Star, Hamilton Bonaduz AG, Bonaduz, Switzerland). The OD 600 values were converted to biomass with a predetermined factor of 0.38 and the growth rate and product formation rates were calculated using (2) and (3):…”

“…Selection and evaluation of production strains, however, is mostly done in batch cultures. This may cause problems during industrialization Correspondence: Prof. Dr. Peter Neubauer (peter.neubauer@tu-berlin.de), Chair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, Ackerstraße 76, ACK24, 13355 Berlin, Germany Abbreviations: EPG, endo-polygalacturonase; OD 600 , optical density at 600 nm of production processes [2]. Ideally, the cultivation conditions should remain as similar as possible during scale-up [3].…”

Valorization of Proteins from Co- and By-Products from the Fish and Meat Industry

“…The reason for the challenges is in part due to the process chemistry of scale-up, where differences in mixing, shear rate, and mass and heat transfer causes differences in how the biomass is processed compared to in small-scale processes. In addition, the production of process inhibitors that are effective in large scale and not in small scale can be experienced [54][55]. Another challenge can be the economics of the demonstration phase.…”

Robotic Platform for Parallelized Cultivation and Monitoring of Microbial Growth Parameters in Microwell Plates

“…A consistent strategy has not yet been introduced to industrial bioprocess development. 2 As a result of this, the time to market may vary in industrial biotechnology between 2 and 15 years, 3 resulting in expenses of millions of dollars. In the pharmaceutical industry, regulatory authorities emphasize that the quality of a product should be the result of scientific knowledge (quality by design, QbD) by means of process analytical technology (PAT), among others.…”

“…4 But the commonly used screening systems, such as microwell plates and shake flasks, suffer from a lack of relevant information on the latter process, whereas bench-scale cultivations consume time and money due to the lack of miniaturization and parallelization. 2 Modern cultivation systems such as the BioLector (m2p-labs GmbH, Baesweiler, Germany), bioREACTOR 48 (2mag AG, München, Germany), or Micro-24 MicroReactor (Pall Corporation, Port Washington, WI) combine the latest technology on miniaturization, parallelization, and sensing. Although these systems may be upgraded by a microfluidic control device 5 or by micropumps, 6 enabling fed-batch cultivations at the small scale, sampling, liquid addition, analytics, and data processing still need to be done manually.…”