APR January/February 2022 - 40

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MANUFACTURING
»
Large Molecules, Small Batches: Understanding the
Sterile Fill-Finish Needs of Pharma's Emerging Market
Alex Garner
Director of Formulation and Clinical Trial Manufacturing
Element
Frank Manella
Consultant
Element
It may seem counterintuitive, but the often-reported shortage of large
batch CDMOs and the resulting backlogs in production actually may hit
small batch manufacturing companies the hardest. The competition
for available sterile fill large batch slots means companies requiring
less capacity may unfortunately slip through the cracks in the process.
And yet, advanced and personalized therapeutics (like cell and
gene therapies) generally use large molecules and are produced
in small batches. That's where the market seems to be headed. The
ideal solution, therefore, would be for these smaller companies to
partner with a CDMO specializing in small batch manufacturing when
producing large molecule drug product therapeutics. In time, it's
likely that more such CDMOs will come online as the advanced and
personalized therapeutics market matures.
When finding the right partner, it's important to fully understand the
ins and outs of sterile fill, to be able to match the CDMO's capabilities
with the pharma manufacturer's needs. Together the organizations
can arrive at a strategy to develop formulations for clinical trials at
smaller scales.
There are several aspects to consider when understanding sterile fill
and finish:
* The fundamentals of a sterile fill and types of products that need
sterile fill
* Manual processes versus automation
* Challenges associated with sterile fill for large molecule
formulations
* Considerations when partnering with a sterile fill lab
Let's take a look at each of these considerations more closely.
Sterile Fill Fundamentals
All FDA-approved drug products must comply with Current Good
Manufacturing Processes to ensure they are safe, pure, effective, and
fit for intended use. To meet these requirements, drugs that cannot
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| January/February 2022
Khanh Ngo Courtney, PhD
Sr. Director of Biologics
Element
contain preservatives must be produced in a sterile fill lab, which
packages and labels these drugs under strict aseptic conditions.
Sterile fill and finish is essential to prevent infections in patients
caused by contaminated drug products. But as previously indicated,
most large-scale sterile fill labs are currently operating at capacity to
produce COVID-19 vaccines as well as various COVID-19 treatments,
and that poses a challenge to small-batch manufacturers looking to
develop a new drug on a small scale for early-stage clinical studies.
Pharmaceutical products are susceptible to many types of
contamination, particularly when filling vials, cartridges, and
syringes. Complicating matters, an increasingly greater number
of products on clinic shelves now actually carry a heightened risk
of contamination, because they cannot contain preservatives.
This increases the demand on biomanufacturers to have a sterile
environment for their fill-finish process.
Aseptic processing is particularly important for otic, ophthalmic,
and topical products. For example, topical products that cannot
contain preservatives must use sterile fill, to prevent bacterial
growth that may reduce the effectiveness of the product or shorten
its shelf life. Therefore, the FDA requires that drug manufacturers
ensure their fill and finish process for certain drug formulations, use
aseptic techniques.
At its core, the fill-finish process requires the sterilization of the drug
product, container, and closure. The sterilized products are then
moved to a cleanroom to be combined (in most cases, using some
type of self-contained equipment).
Understandably, aseptic manufacturing and sterile fill finish for
biologics and conventional drugs is a complicated process demanding
highly specialized capabilities. This extends not only to having
purpose-built facilities, equipment and processes, but also to welltrained
and experienced teams that can execute the meticulous plans
involved in the process.
Decontamination practices are of utmost importance. The drug
products, filling components and other cleanrooms must be

APR January/February 2022

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