GEN-Thermo_Oct22_MakingThePromiseOf - 15

OVERCOMING mRNA PRODUCTION SCALE-UP CHALLENGES
Here are nine considerations for scaling up mRNA
production:
1. Be ready for a change in equipment and
raw materials
When you are new to mRNA and in the discovery
stage, reaction volumes are usually at the microliter
scale and are performed in microtubes with a heat
block. As you move to process development, reaction
volumes will increase to anywhere between 1 mL
and 5 L. Once you hit production scale, you'll then be
working with 10-50 L volumes. This increase to larger
volumes and reactions as you scale up will require a
change in equipment and raw materials, which can
come with significant costs at each stage, in terms of
both investment and the time needed to optimize
new workflows.
You can help ensure a seamless transition to production
scale by designing robust workflows that utilize
equipment and raw materials suitable for every scale.
For example, shake flasks can accommodate over 1L
volumes. When moving to medium-scale process
development, you could consider using a controlled
vessel such as a bioreactor that can be used all the
way to production scale. In addition to introducing
consistency early on in your workflow and avoiding
additional optimization steps, it will allow you to
prove the scalability of your process and even enable
production for early-phase clinical trials. For raw materials,
Thermo Scientific™ TheraPure™ GMP* standard
enzymes and nucleotides are readily available for IVT
reactions, providing an excellent starting point to
enable seamless transition from early-stage mRNA
production to scale-up for commercial manufacture
using GMP-quality materials (Figure 1).
2. Keep a robust workflow: think about the
process as a whole
The change in equipment due to scale-up may
also require a change in protocol. For example, a
* " TheraPure GMP " refers to the quality level of the raw, ancillary, or
starting materials to be used for further manufacturing. TheraPure GMP
products are manufactured in facilities with ISO 9001-certified quality
management systems that operate in accordance with relevant good
manufacturing practice (GMP) principles, as outlined in ICH Q7 or equivalent
guidance documents or standards.
Highthroughput
screening
Manufacturing
Process
development
Figure
1. Scaling up
IVT reactions for mRNA
production.
GENengnews.com | 15
https://www.thermofisher.com/us/en/home.html https://www.genengnews.com
GEN-Thermo_Oct22_MakingThePromiseOf

Table of Contents for the Digital Edition of GEN-Thermo_Oct22_MakingThePromiseOf
