Key Considerations for Scale-Up and Outsourcing in Biopharma
Whitepaper
Last Updated: May 17, 2024
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Published: May 13, 2024
Credit: Thermo Fisher Scientific
Small and midsize biopharmaceutical firms play a crucial role in driving innovation for novel therapeutics, with biopharmaceuticals constituting a growing proportion of clinical pipeline candidates.
As biopharmaceutical companies scale up manufacturing, many are turning to outsourcing for buffer and process liquid preparation. But before making this decision, organizations must carefully weigh up various factors, including manufacturing space, personnel requirements and analytical capabilities.
This whitepaper explores these considerations, evaluating the benefits of outsourcing and how to determine its cost-effectiveness.
Download this whitepaper to discover how to:
- Optimize scale-up and outsourcing in the biopharmaceutical industry
- Significantly streamline operations and reduce regulatory risk
- Enhance quality control, data management and regulatory compliance
Buffers and process liquids for biopharmaceutical
production: considerations for scale-up and outsourcing
White paper | Process Liquid Preparation Services
Overview
• The global biopharmaceutical
market is rapidly growing, with
small and midsize organizations
outpacing large organizations in
market share growth
• When scaling up manufacturing,
biopharmaceutical organizations
are increasingly opting to
outsource buffer and process
liquid preparation
• Many factors should be
considered before an organization
decides to outsource, including
manufacturing space, personnel
needs, and analytical capabilities
Current trends in
biopharmaceutical manufacturing
Small and midsize biopharmaceutical
organizations are increasingly important
drivers of innovation in the development of
novel therapeutics, and biopharmaceuticals
account for a rapidly growing percentage of
new candidates in the clinical pipeline. The
size of the total global biopharmaceuticals
market in late 2022 was estimated to be
$333.1 billion with a projected increase to $856.1 billion by 2030 [1]. The market share
of small and midsize biopharmaceutical organizations is expected to increase at a
projected compound annual growth rate (CAGR) of about 11% to reach $22 billion
by 2025 [2]. In contrast, the CAGR of the 20 largest biopharmaceutical companies is
projected to be just 5% to reach $24 billion over the same timeframe.
The explosive growth in the number of biopharmaceutical candidates in the clinical
pipeline is due in part to fast-track processes recently implemented by regulatory
agencies in the US and European Union for therapeutics intended to treat serious
conditions and fulfill unmet medical needs [3]. Fast-track designation by the US Food
and Drug Administration (FDA) significantly accelerates timelines for conducting clinical
trials, filing for approval, and gaining authorization for market launch [4]. Fast tracking
has greatly facilitated the introduction of new product classes, like vaccines and cell
culture–based products for cell and gene therapy, into the clinical pipeline.
Bioproduction
In addition to a rapidly growing market share and the introduction
of new product classes, small and midsize biopharmaceutical
organizations can expect to see continued increases in the costs
of development and operations as well as ongoing pressure
to reduce these costs [4]. The biopharmaceutical industry
will also have to contend with inherent uncertainties around
patient selection for clinical trials, dosing, and safety. Other
uncertainties include clinical success, regulatory approval, and
market success.
Another notable trend among biopharmaceutical manufacturers
is outsourcing [5]. Scaling up activities like in-house buffer and
process liquid preparation requires time, personnel, and facility
space that a small or midsize organization may not have or may
not wish to reallocate [6]. Most biopharmaceutical organizations
outsource to some extent, and the wide range of outsourcing
services offered spans the entire process from development
to manufacturing [7]. The decision to outsource should be
considered carefully, as excessive outsourcing can erode
in-house capability over time. However, for example, outsourcing
activities that do not require a high level of expertise can enable
an organization to focus on its core competencies and eliminate
Figure 2. Usage of buffers and process liquids throughout a general biomanufacturing workflow.
the need to expand capacity for low-value tasks. This can make
it easier to scale up operations and help expedite navigation of
lead drugs from clinical trials to market. Outsourcing can also
enable access to more advanced technologies and a diverse
pool of skilled professionals for activities that require specialized
expertise such as production of buffer concentrates.
The importance of buffers and process liquids in
biopharmaceutical manufacturing
Biomanufacturing buffers and process liquids are used to
maintain pH or to stabilize components such as proteins. They
are used as solvents, as diluents, or for cleaning purposes
and provide necessary cofactors for enzymatic activity and
supply nutrients to cells [8]. They are employed throughout
the biomanufacturing workflow from biological sample receipt
to upstream processing, downstream processing, storage of
chromatography resins, and production of final drug products
(Figure 2). Since 10–20 times more buffer may be needed for
downstream purification processing when an upstream process
is scaled up, robust and economical buffer preparation is critical
for avoiding downstream bottlenecks [5].
Factors to consider before outsourcing buffer and
process liquid preparation
While it is not always practical to outsource buffer and process
liquid preparation entirely, outsourcing some portion of it can
have important benefits for an organization depending on its
priorities. An organization that is thinking about outsourcing
should consider the following factors [8]:
• Space in the manufacturing facility—Scaling up in-house
preparation activities may take up a significant amount of
space or impinge upon the use of shared suites, equipment,
or personnel.
• Time and labor required—Additional personnel and
equipment may increase operating costs.
• Potential formulation errors—Deviations and failures
due to formulation errors can be costly and upend
production timelines.
Harvest
Ultrafiltration
and diafiltration
(UF/DF)
Cell
expansion
Polish
chromatography
Media
and buffer
preparation
Viral
inactivation
Capture
chromatography Bulk fill Cell
culture
Viral
filtration
Media and buffer
preparation Production scale-up and harvest
Upstream
Downstream
Process Liquid Preparation Services: Gibco™ buffers and process liquids
(WFI,* NaOH, NaCl, EtOH, buffer library formulations, and custom solutions)
* Water for injection.
2
• Special requirements—Preparation of biomanufacturing
buffers can be highly complex. For example, the use of
concentrated buffer components requires an experienced
operator as well as tanks and other equipment designed to
withstand corrosive materials. Biomanufacturing buffers may
also have special quality requirements like sterility that will
depend on their formulations and the processes for which
they are used (e. g., manufacture of final drug products).
• Quality control (QC) and quality assurance (QA)—An
organization must assess its analytical, QC, and QA
capabilities to determine whether its existing quality system
and capacity are sufficiently robust for in-house current good
manufacturing practice (CGMP) buffer preparation.
• Storage capacity—Buffers that are used for CGMP
processes must be stored in a temperature-controlled
environment with periodic quality testing by trained personnel.
There are clearly many variables to consider before deciding
whether to outsource buffer and process liquid preparation. Cost
may be the most important factor for some organizations, but the
entire biomanufacturing workflow and different buffer preparation
philosophies in the industry should be evaluated to determine
whether outsourcing is the most suitable option [9]. The
evaluation should take into account the number of buffers and
process liquids needed for the entire workflow, their volumes, and
the capabilities of the existing facility, equipment, and personnel.
The cost-effectiveness of outsourcing can also be assessed with
the help of process modeling tools and software.
Benefits of outsourcing
While there is no one-size-fits-all approach to outsourcing, it has
the potential to:
• Streamline buffer and process liquid preparation
• Reduce costs
• Mitigate risk
• Enhance quality control
• Simplify data management and documentation
• Address environmental health and safety concerns
• Minimize storage requirements
• Meet needs for customized packaging or other raw materials
A skilled outsourcing partner should be able to supply buffers
and process liquids of consistent quality at a cost per liter that is
more than offset by savings in capital, labor costs, and the cost
of single-use consumables [8]. Organizations that outsource can
also benefit from quality control enhancements and efficiencies of
scale that would otherwise be unachievable [10].
Evaluating the cost-effectiveness of outsourcing
When constructing a process model using modeling software,
consider the following factors [8,10]:
• Formulation, process design, and material specifications
• Volume, production schedule, and testing requirements
• Existing suite capacity, equipment, and personnel
• Existing analytical, QA, and QC capabilities
• Anticipated changes in buffer types and volumes
• Number of separate facilities in which buffers and process
liquids are used
• Operating cost
Eliminate bottlenecks and improve efficiency
Outsourcing buffer and process liquid preparation can reduce
the number of bottlenecks in the manufacturing workflow. A
reliable outsourcing partner can provide buffers and process
liquids on demand in the quantities needed without disrupting the
production schedule or straining in-house capabilities. Even when
smaller batches are needed for research or cell and gene therapy
applications, outsourcing buffer supply can still have significant
benefits. An organization that outsources buffer and process
liquid preparation can utilize its resources more efficiently, enjoy
assurance of supply, and establish the groundwork for easy
scale-up [10]. The organization can also request a process walk
and lean assessment of its weigh, dispense, and hydration
workflow to identify more opportunities to improve efficiency,
mitigate risk, and reduce costs.
Simplify quality control, data management,
and documentation
A biopharmaceutical organization can greatly simplify its
preproduction workflow by outsourcing raw material sampling,
QA inspections, and QC testing. Quality-related activities often
create production bottlenecks, and smaller organizations
may lack the manpower or expertise needed to scale up QA
inspections and QC testing. Outsourcing quality-related activities
can thus help manufacturers avoid production delays, reduce
the workload for personnel, and mitigate regulatory risk. An
outsourcing partner who can manage quality testing, quality data,
and the documentation needed to satisfy regulatory requirements
can also make the CGMP transition easier by facilitating the
traceability of CGMP raw materials and buffers and generating
certificates of analysis [8]. A skilled outsourcing partner may
even be able to help set specifications for custom buffers and
buffer components.
3
For Research Use or Further Manufacturing. Not for diagnostic use or direct administration into humans or animals. © 2024
Thermo Fisher Scientific Inc. All rights reserved. All trademarks are the property of Thermo Fisher Scientific and its subsidiaries unless
otherwise specified. COL28298 0424
Learn more at thermofisher.com/gibcoprocessliquids
Address environmental health and safety concerns
Some biopharmaceutical facilities are not equipped for handling
certain hazardous materials, such as caustic chemicals and
flammable organic solvents. Outsourcing buffer and process
liquid preparation can reduce environmental health and safety
(EH&S) risk, since the outsourcing partner does all of the
weighing, dispensing, and hydrating.
Minimize storage requirements and
customize packaging
A biopharmaceutical organization with an automated
bioprocessing facility can benefit in several ways by outsourcing
to a vendor that can supply buffer concentrates and concentrates
of individual buffer components for in-line dilution. When final
buffers are needed, the concentrates are diluted with WFI in
automated dilution skids and monitored in-line. One advantage of
using concentrates instead of traditional 1X batch solutions is that
it reduces the need for material handling and dispensing. Other
advantages include the widespread commercial availability of
individual buffer components as concentrated stocks and the fact
that concentrates require less storage space than traditional 1X
solutions. Concentrates provide high flexibility in dilution as users
can adjust the final concentration depending on specific process
conditions. In the end, they support environmental sustainability
goals due to a reduced impact through transportation and
storage, and reduced waste. Some premier vendors offer custom
packaging for direct connection to hydration processes, and they
may be able to package single or multiple buffer components as
dry powders in specified quantities.
Conclusion
Preparing bioprocessing buffers and process liquids at
manufacturing scale is time-consuming and labor-intensive. It
also requires devoted facility space and storage capacity, an
assurance of supply, and traceability with quality documentation.
When a small or midsize biopharmaceutical organization wants
to scale up its processes, it may find that it lacks the space and
production capacity to prepare buffers and process liquids at
manufacturing scale. It may also be difficult for an organization
that lacks a robust quality system to achieve or maintain
CGMP-level regulatory compliance.
An outsourcing partner
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