Medical Design Briefs - February 2022 - 11

the chemicals used to sanitize pharmaceutical
processing systems, usually at extreme
temperatures. This necessitates stringent
sterilization regimes potentially involving
harsh chemicals and steam, resulting in
considerable energy consumption to
bring systems up to the extreme temperatures
required for effective sterilization.
The second type is partly disposable systems.
These utilize some parts of the processing
system more than once, depending
on the therapeutic produced. Reused parts
undergo cleaning and sterilization regimes
like those used in stainless-steel systems,
and maintenance is required as reusable
elements deteriorate over time. Both stainless-steel
systems and the reusable parts of
disposable systems have the inherent risk
of contamination, even with validated
cleaning and sterilization programs.
Single-use systems, the third type of biopharmaceutical
processing system, are de -
signed for use for the duration of the production
process of a single batch of therapeutics
and then discarded. The rise in the
adoption of single-use technologies is
proving to reduce product crosscon
tamination risks by eliminating the
need for cleaning between batches. Manu -
factured in a cleanroom, double bagged
and then sterilized by gamma, EtO, or xray
sterilization methods, these systems
ensure a sterile system for every batch, as
well as being highly efficient and cost
effective.
According to a study conducted by
Single Use Support GmbH, single-use systems
lower operating costs by offering 46
percent water and energy reductions, a 35
percent more favorable CO2 footprint due
to lower facility emissions, and a 40 percent
lower initial investment cost. They allow
pharmaceutical manufacturers to push
products to market faster by increasing
throughput and making scalability easier.
The Shift to Single-Use Systems
Single-use bioprocessing systems have
gained significant traction due to the
rapid adoption of disposable technology
by pharmaceutical manufacturers. According
to Allied Market Research, the
value of the global single-use bioprocessing
market was $2,800 million in 2016, and
the projection is for it to reach $9,342 million
by 2023; at a CAGR of 18.7 percent
over the period.
The technology is primarily applied in
the manufacture of biologics both in the
upstream, including bioreactors (see the
sidebar, " Customer Collaboration
Engineered Solutions " ), media preparaMedical
Design Briefs, February 2022
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tion, buffer preparation, and downstream
processes of manufacturing, including
fluid path transfer for filtration, chromatography,
viral clearance, and other
steps. Common therapeutics produced
with these methods include monoclonal
antibodies, mRNA vaccines, and other
pharmaceutical components on a commercial
scale. However, there are challenges
in developing these systems relating
to gaining regulatory approval of component
materials, navigating the nuances of
material compatibility with process fluids,
and maintaining the supply chain. For
these reasons, suppliers must provide
assurance that their products deploy operational
best practices and are certifiably
and regulatorily safe.
A Brief Overview of
Biopharmaceutical Drugs
Biopharmaceuticals include a wide range
of products, such as vaccines, therapeutic
proteins, blood and blood components, and
tissues. In contrast to small molecule
chemically synthesized drugs, which have a
well-defined structure, biopharmaceuticals
derive from living materials (human, animal,
microorganism, or plant) and are much
larger and more complex in structure.
Because biopharmaceuticals work with
the immune system and do not contain
chemical-based drugs, there is a rapidly
expanding acceptance of biopharmaceuticals
to treat a range of diseases, and the
market is growing quickly. In addition, an
increasing aging population in Western
countries, rising costs of healthcare globally,
widespread presence of chronic ailments,
technological advancements, and
manufacturing and contamination factors
are all driving the rise in biopharmaceutical
market demand.
The biopharmaceutical method of making
drugs is an especially high-profile topic due
to the global COVID-19 pandemic and the
use of the mRNA vaccine, which is made
using the biopharmaceutical process.
Value of Quality and Material
Expertise
When utilizing a stainless-steel system,
after biopharmaceutical manufacturers
produce a batch of drugs, they must clean
and sterilize all the equipment to prevent
cross-contamination and ready the equipment
for the next batch. This can be a
costly and time-consuming process, and
the risk for contamination remains.
In single-use systems, all process parts,
including hoses, bags, and seals, are disposed
of, and replaced with a new set, so
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ToC
the system is quickly back up and running.
This saves time and money, involves less
risk of contamination, and generates
greater throughput. An experienced supply
partner can provide manufacturers
with all the data that supports the quality
of the component materials and parts
requirements. This may include production
of parts in a cleanroom and independent
laboratory testing.
There are two main bodies of regulation
impacting components used in singleuse
systems: material biocompatibility and
leachables and extractables. Biocompati -
bility looks at the material used in the component
and whether there are any harmful
reactions or long-term bodily effects
caused by chemicals. Biocompatibility testing
requirements fall within USP 87, USP
88, and ISO 10993 depending on the
application, while extractable and leachable
tests run on the finished products
used in single-use systems. These requirements
fall within USP 665 or the
BioPhorum Operations Group (BPOG)
Extractable and Leachable protocol.
The BioPhorum Group is an industry
group leading the development of new
best practice guides for single-use systems.
This is stimulating the development of
standards and guides by other organizations,
such as ASTM-BPE, PDA, and ISPE.
BPSA guides cover irradiation and sterilization
validation, determination of ex -
tractables and leachables, and disposal of
single-use systems.
Extractables and Leachables
To select processing materials that avoid
risk, it is important to understand the
chemical nature of extractables and leachables.
Extractables are compounds emitted
from a packaging component, delivery system,
or manufacturing surface during
aggressive testing. Leachables are compounds
that migrate into the drug over
time from contact with the system componentry
and manufacturing surfaces.
An interaction of extractables or leachables
with drugs or other media can be
harmful to individuals and have possible
long-term effects on the human body.
Thorough testing ensures that products are
suitable for high-risk applications, such as
drug-delivery devices, combination products,
and long-term implants. For example,
extensive tests conducted by Trelleborg
experts determine the extraction levels of
substances under different conditions.
Results show that Trelleborg's tubing and
hoses meet the highest standards and
demonstrate outstanding purity levels.
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Medical Design Briefs - February 2022

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