Scale‐Down Model Development in ambr systems: An Industrial Perspective

Abstract

High‐Throughput (HT) technologies such as miniature bioreactors (MBRs) are increasingly employed within the biopharmaceutical manufacturing industry. Traditionally, these technologies have been utilized for discrete screening approaches during pre‐clinical development (e.g., cell line selection and process optimization). However, increasing interest is focused towards their use during late clinical phase process characterization studies as a scale‐down model (SDM) of the cGMP manufacturing process. In this review, the authors describe a systematic approach toward SDM development in one of the most widely adopted MBRs, the ambr 15 and 250 mL (Sartorius Stedim Biotech) systems. Recent efforts have shown promise in qualifying ambr systems as SDMs to support more efficient, robust and safe biomanufacturing processes. The authors suggest that combinatorial improvements in process understanding (matching of mass transfer and cellular stress between scales through computational fluid dynamics and in vitro analysis), experimental design (advanced risk assessment and statistical design of experiments), and data analysis (combining uni‐ and multi‐variate techniques) will ultimately yield ambr SDMs applicable for future regulatory submissions.

Developing a new class of engineered live bacterial therapeutics to treat human diseases

“…For the purposes of fermentation process development, bench scale bioreactors allow for accurate measurement and control of pH, dissolved oxygen, temperature, as well as the automated addition of nutrients and chemical inducers during cell growth. In recent years, automated parallel bioreactor systems have accelerated fermentation process development by combining smaller volumes and higher throughput to enable greater iteration than traditional benchtop bioreactors [84][85][86] .…”

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

“…A mini-chemostat (MC) system (16 reactors with 40 ml working volume) was developed to characterize yeast physiology, and it was shown that the MC system provided the same environmental conditions as the DASGIP R parallel bioreactor system (Eppendorf) (Bergenholm et al, 2019). In a recent review, a systematic approach toward scale-down model (SDM) development in ambr 15 systems was described, and it was suggested that ambr SDMs are suitable for future regulatory submissions (Sandner et al, 2018). In a study by Vit et al (2019), the efficiency of a microfluidic cell cultivation device and its applicability for rapid screening of multiple parameters was also established.…”

Development of Novel Bioreactor Control Systems Based on Smart Sensors and Actuators

“…Parallel miniature bioreactors with small working volumes (also called microbioreactor systems) are an important alternative to the traditional batch cultivation apparatuses for use in bioprocess development and scale-up/scale-down investigation. Many important studies offer a detailed discussion of this topic, and many commercialized products (e.g., DASGIP from Eppendorf, AMBR from Sartorius Stedim Biotech) are also available in the market (Faust et al, 2014;Hemmerich et al, 2018a;Bjork and Joensson, 2019;Sandner et al, 2019;Znidarsic-Plazl, 2019). Process monitoring and control of miniature bioreactors are more complicated than single-bioreactor control, but investigations have shown encouraging results.…”