1. White Paper
Supplier-Integrated Support of Biopharmaceutical
Raw Material Systems Promotes Operational
Excellence and Risk Mitigation
Abstract
The biopharmaceutical industry is increasingly The challenge for biopharmaceutical manufacturers
engaged with concerns about operational excellence, to become more efficient and safe is daunting,
safety and risk mitigation. These issues have considering the large number of raw materials required
historically affected large-scale pharmaceutical for production and the complexities of cell culture
manufacturing but now are gaining prominence systems. However, this challenge can be overcome
throughout biological production scale-up and if manufacturers partner with knowledgeable and
process transfer. SAFC Biosciences® provides experienced suppliers early in process development.
biopharmaceutical clients with supply chain solutions
through novel applications of vendor-partnered The Challenge
capabilities. This paper presents strategic approaches Unlike small-molecule pharmaceutical for which a
to biopharmaceutical process optimization through chemical reaction remains relatively constant through
supplier integration that maximize revenue, reduce production scale-up, bench-top biopharmaceutical
costs and support reproducibility of production experiments are not necessarily linear to large-scale
processes. It also describes how vendor-partnered manufacture because the processes are much more
solutions deliver leaner and safer processes for raw complex. Biopharmaceutical processes require
material handling. stepwise technology transfers, often with unique
processing steps, in order to ensure that the same
Introduction product is produced at large scale as at small
The biopharmaceutical industry is experiencing a new scale. This stepwise process makes developing
paradigm in which risk mitigation and operational biopharmaceutical processes expensive and
excellence are prevalent trends. It is no longer enough time-consuming and highlights the need for producers
to develop and produce a blockbuster drug candidate; to investigate integrated supply chain solutions early in
it is now critical to effectively manage costs, in-process the development process to ensure cost-effective,
quality, operational safety and supply chain security. safe, and reproducible systems.
No longer is it important to just develop and Recent industry conferences have presented many
produce a blockbuster drug candidate. examples of the impact of increased costs from
biopharmaceutical technology transfer and added
production system complexities. These presentations
To help manage the complexity, SAFC Biosciences
have shown that raw material costs are now less
offers strategic supply chain solutions that assure
of a concern than the overall operational costs for
batch quality and consistency during manufacture,
determining and applying process steps.
support complex regulatory compliance and reduce
shipping delays, so you stay on time to market and
maximize financial results.
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2. Unchecked variability in technology transfer and The impact on the manufacturing routine of adding
production make it difficult to effectively manage multiple components to the production system is not
production resources. Assume, for example, that a completely understood until the entire operational
10,000 L production tank is worth about $10 process is reviewed. This full process includes initial
million in drug product. +/- 10% due to raw receipt and preparation of raw materials, quality control
material or process variability translates testing and charging components for manufacture.
into +/- $1 million in final product.
Each step pictured on the following page details the
If capacity and resource constraints limit cell Total Cost of Ownership (TCO) for each raw material
culture and purification runs by 10% a year, a incorporated into the production process, including:
potential of $50 million in loss revenue is at risk
• Logistics, sourcing and documentation
and/or may lead to increased production costs from
• Inbound receiving steps
outsourcing production to a contract manufacturer.
• Unit sampling
• QC testing
• How can resources be maximized?
• Inventory and tracking
• How can secure supplies of raw
• Media hydration and clean-up time
materials be maintained?
• How can suppliers be better integrated
into overall processes?
Adding to the challenge of complex biopharmaceutical
systems is the desire for manufacturing facilities to be
more flexible. The reality is that more clinical projects
are filling the pipeline but fewer on-site resources are
available to maximize production output.
Below is an example of the complexity that faces
biopharmaceutical production engineers. Steps
required for production in mammalian-based system
can include several feed additions that require time
point-specific supplementation:
The Integrated Supplier Approach
In a February 2006 BioProcess International article,
“Managing a Biopharmaceutical Supply Chain,” Allen
Jacques, Senior Director of BioPharma Supply Chain at
Wyeth, points out the differences and complexities
between classical pharmaceutical production systems
and present day biopharmaceutical systems. His point
is illustrated in the following image (see next page) that
compares molecule sizes of the rheumatoid arthritis
biopharmaceutical, ENBREL, to the legacy small
molecule drug Ibuprofen.
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3. ENBREL Creative supply chain solutions are best achieved
when potential suppliers are integrated early-on into
manufacturing processes. For many organizations, this
means during process development At this point,
suppliers and manufacturers can become intimately
connected in a focused approach to long-term process
and resource optimization. This interconnected focus
approach allows biopharmaceutical manufacturers
This statement holds true for all to backwards-integrate with suppliers, positively
elements of supply chain and influencing the direction and effectiveness of
manufacturing. Creativity is supplier-partner solutions.
required to remove constraints
currently inhibiting process Understanding the following process scenario is
optimization and open opportunities required before actively pursuing and integrating
for cost savings, enhanced suppliers into your production processes:
reproducibility of production
• Map your entire process from development through
processes, and greater safety.
theoretical production scale
• Identify the points where suppliers currently touch
your process
“It is easy to focus on such differences
• Identify areas on the map that currently
in our industry as reasons why classical
cause constraints
supply chain principles do not apply. I
• Begin scenario planning to identify the most likely,
suggest they are applicable; they just need
and worst, operation cases that may affect your
to be applied with a measure of creativity.”
process efficiency and safety
Allen Jacques, Wyeth
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4. Identify Proven Results
1. How much drug product will be required for A biopharmaceutical manufacturer for whom SAFC
clinical trials? Biosciences is a primary supplier of critical raw
2. How much drug product will be required for market materials requested that we work to develop a solution
commercialization? to an operational challenge they posed:
3. How robust and effective is your current process in
Challenge
meeting production goals?
• Enhance logistic
4. What is your production capacity?
operations capacity
5. What additional process development steps may be
- Drum dumping
required to reach your production goals?
process not
6. What is the outlook for your Bill of Materials (BOM)?
optimized
7. How will additional raw material requirements
- Dispensing 3,500 kg
and processing steps affect your Total Cost
- 7,000 repetitions
of Ownership?
Process Diagram presented by
Sartorius Stedim Biotech
Once you understand the various scenarios that may
impact your commercialization process, you can begin
identifying those suppliers best positioned to enhance
your production and operational goals. Use the
following criteria:
1. What are your BOM needs?
2. Which suppliers provide the majority of your
BOM needs?
3. What are your operational constraints regarding
raw material supply and production utilization? Solution
4. Which suppliers are focused on the industrial cell • New filling regime and supplier-managed net
culture market and can provide custom solutions weighing
for your application? - Removed two non-value steps
5. Which suppliers have risk mitigation practices
similar to your own? Powder Filling Machine
6. Which suppliers can integrate with other suppliers Servo Driven Auger Filler
to provide the optimal solution? • Programmable
Logic Control
Scale Feedback
• Multiple Tooling Sets
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5. Benefits
• Reduced ergonomic safety risks and non-core To learn more about examples of how SAFC
labor hours Biosciences has integrated with manufacturers to
- Reduced customer dispensing steps by 50%; enhance production efficiency, supply chain security
reduced handling exposure and operational safety, visit www.safcbiosciences.
- Reduced wasted labor hours from 80 to less than com and click on Case Studies & White Papers in the
20 a week
Technical Library in the Overview section.
Recognizing the value of
To learn more about application-specific solutions
this supplier-integrated
to enhance your process efficiency, visit
relationship, the
customer asked how www.safcbiosciences.com.
SAFC Biosciences
Written by Mason Williams, Product Manager, SAFC; edited by
could further improve Brad Riesenberger, Sigma-Aldrich Corporate Communications
manufacturing efficiency
and supply chain
security. This launched a
new collaborative effort
About SAFC Biosciences: SAFC Biosciences is a leading
in which:
provider of cell culture materials and development services for
• Raw material risk mitigation steps have been upstream and downstream processes in the biopharmaceutical
defined for each raw material in the media industry. Providing an integrated services package in
formulation mammalian cell culture media development, along with
analytical and regulatory support, SAFC Biosciences employs
• A three-phase dry powder media transfer approach
a wealth of industry experience and scientific know-how to
has been recommended, consisting of: deliver reliable, consistent solutions that accelerate customer
Phase 1: A powder transfer bag system to ensure success – from development through to commercialization. The
powder delivery and safety in a timely manner unit has a 35-year history as a manufacturing partner providing
Phase 2: A drum dumper process that relieves leading biopharmaceutical companies with the broadest range
manual addition steps of highly customized products and services possible.
Phase 3: Design and application of a flexible bulk
About SAFC: SAFC is the custom manufacturing and services
intermediate contaminant unit to provide as few as
group within Sigma- Aldrich that focuses on high-purity
one media addition steps, reducing QC sampling
inorganics for high technology applications, cell culture
requirements and personnel handling steps. Note:
products and services for biopharmaceutical manufacturing,
Final phase requires capability development and
biochemical production and the manufacturing of complex,
continual collaborationIdentify
multi-step organic synthesis of APIs and key intermediates.
SAFC has manufacturing facilities around the world dedicated
SAFC Biosciences Integrated Supplier Approach
to providing manufacturing services for companies requiring
SAFC Biosciences offers the world’s broadest
a reliable partner to produce their custom manufactured
range of products, services and capabilities for the
materials. SAFC has four focus areas – SAFC Pharma® , SAFC
biopharmaceutical industry. SAFC Biosciences partners Supply Solutions® , SAFC Biosciences® , and SAFC Hitech® –
with other suppliers, including Sartorius Stedim Biotech, and had annual sales of $624 million in 2008. SAFC is one
Vivalis and Novozymes, to provide integrated solutions of the world’s 10 largest fine chemical businesses. For more
that impart unmatched value to the industry. information about SAFC, visit www.safcglobal.com.
United States Europe Asia Pacific
SAFC Biosciences, Inc. SAFC Biosciences Ltd. SAFC Biosciences Pty. Ltd.
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