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In vitro
Drug product
Figure 1: mRNA process development steps
making of a platformable process, similar to what
we have at the moment with mAbs. In that case,
this has arisen from the advantage of having 20+
years of knowledge accumulated in that space,
whereas with mRNA, there is still much to learn. "
Many of the challenges associated with the development
and manufacture of mRNA are reminiscent
of the early days of mAbs, when the industry
struggled to overcome low titer and poor purification
yields, leading to costly and inefficient
commercial manufacturing. A focused effort to
overcome those production challenges resulted
in mAbs becoming the fastest growing class of
biopharmaceutical products.6 A critical factor in
driving mRNA forward is likely to be achieving
consistency in process development of mRNAbased
products. " The processes used for mRNA
today have all been created by independent
developers, each of which applied their own skills
and knowledge, " says Dr. Liddell. " It should be that
the same methods used to make a COVID vaccine
are the same ones used for an influenza vaccine,
which thus requires standardization across a
range of areas. " One of the main challenges in
mRNA process development and scale-up is the
lack of dedicated equipment and consumables fit
for the relatively small volumes and large size of
the mRNA compared to traditional recombinant
proteins. There is also a lack of experience and
knowledge of scaling up mRNA processes as well
as associated perceived regulatory uncertainties.
A Closer Look At mRNA Process
Development Challenges
A more detailed examination of mRNA process
development (Figure 1) uncovers several areas
for improvement across multiple steps.
An integral raw material for mRNA-based
therapies and vaccines is plasmid DNA (pDNA),
which acts as a template for the mRNA. Yet,
pDNA is also used for the production of viral
vector-based therapies-another growing area
of biopharma. This has led to a significant strain
on GMP-quality pDNA supply. CPI has been
fortunate to secure long-standing agreements
with companies that make pDNA, but emerging
companies like GeneLeap Biotech struggle to
get the attention they need in an increasingly
competitive environment. However, Dr. Liddell
highlights a possible solution, " For DNA template
production, there are a number of alternative
cell-free technologies to generating pDNA, such
as rolling circle DNA amplification approaches, | 19


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