The Bio-Process Systems Alliance (BPSA) is an organization of equipment suppliers, service providers, and users in the biopharmaceutical industry whose shared mission is to facilitate implementation of single-use technologies in biomanufacturing processes. A key focus of BPSA's core activities is to educate users and develop guides that help safeguard the quality of drugs and therapies produced with single-use process technologies.

As an extension of its technical guides and white papers, BPSA realized the importance of developing a white paper that provides a high-level understanding of single-use systems to an audience of manufacturing decision-makers within end-user organizations. For an overview of what is contained here, please see the “Implementation” box on the next page.

Section One: Perspectives on the “New” Pharma Market

Single-use systems (SUS) are gaining wide use and acceptance in the biotechnology and pharmaceutical markets. As our first publication to address the topic from this perspective, we anticipate that this initial publication will be an evolving document that BPSA will address with future papers and more detail as the needs of the market evolve.

Why have SUS generated so much interest in the biotech and pharmaceutical markets? Fundamentally, the commercialization of new drugs and therapies occurs at only a fraction of a percent for every project that is initiated from an initial DNA molecule. Because the odds of a project going from concept to full commercialization are small, a need has been created in the market to test as many concepts as possible with the least amount of cost given the current market conditions in capital expenditures. No one wants to spend hundreds of millions of dollars on a facility that may never produce a commercial product. The business model based on discovering the next blockbuster drug is evolving toward a more personalized approach because it is becoming clearer every day that one pill will not cure all patients.

It is not often that we get to witness the beginning of a real paradigm shift, but preferences for SUS over traditional glass and stainless steel systems are unfolding. Stainless steel systems will not be completely replaced by single-use systems, but the benefits of single-use create many options to enable this transition, including the following:

• There is a need for greater flexibility, speed, and safety in development and production of drugs and biotherapies. As medical approaches become more personalized, a reduction in the “one pill fits all” mentality is already taking hold.

• Increased review criteria by the US Food and Drug Administration (FDA) are already reducing drug approvals.

• Less capital is available for research and development activities.

• Blockbuster drugs are a rarity now, and no one can afford the inefficiencies in discovery with high capital costs. Patent expiration and emergence of biosimilars also continue to be factors behind exploration of single-use benefits (1).

• The paradigm shift is also contributing to an increased recognition of single-use activities; for example, BPSA, which had a 3% recognition rate in 2005, now has a 31% recognition rate, and that continues to grow (2).

• Partnerships are increasing in number with contract manufacturers to fix or reduce costs.

• Legacy products, systems, and processes won't be changed, but new applications are available for adoption. Validation costs are high, as are revalidation costs–an important factor in the decision to design or redesign a process.

IMPLEMENTATION ROADMAP
This white paper outlines the current status of SUS implementation in the biopharmaceutical industry.
Introduction
Section One: Perspectives on the “New” Pharma Market
Section Two: What Is Single-Use?

• History

• Benefits of using polymers in SUS

• Benefits of SUS

• SUS parts and components

• SUS applications

• Designing SUS for your operations

• Making the business case

• Addressing the concerns of change and risk — business continuity

• The “make or buy” SUS decision

• Identifying vendors for SUS

Section Two: What Is Single-Use?

As we look into the future of single-use technology and realize the benefits these components, devices, and systems can offer, understanding the past is critical. How did we get to the point of single-use implementation today, and what is the history behind these polymers and plastics and their benefits? When we understand where we often see single-use polymers used, what the key components are, and how they are traditionally supplied, we can make better sense of what the pathway forward looks like. This will also provide us with capabilities for bringing about faster solutions to currently incurable diseases.

History of Polymers in Biomedical Applications: Over the past few years, flexible polyvinyl chloride (PVC) bags have for the most part replaced the use of glass bottles for storing blood and its components. Blood bags enable greater sterility than glass in both the separation of blood components and the safer transfusion of components. With single-use blood bags, companies reduced contamination and the costs of washing, sterilization, and overall manufacturing. That led to increasingly wider use of blood-component therapies than of whole blood use, thus enabling more effective use of scarce donor blood.

As such PVC bags became more of a standard in the medical device marketplace for IV and intravenous blood/plasma applications, a natural evolution of this “new” technology spread into parallel markets. Individuals found new areas in which they could implement these systems—as storage containers for buffers, cell culture media, and cell harvesting, for example. SUS started to gain a greater acceptance, increasing the diversity of products manufactured with them and of redesigned processes based on shorter, multiproduct runs.

Benefits of Using Polymeric SUS: If we look at the benefits of polymeric materials over stainless steel, we find the following:

• Polymeric components used in container systems are comparable in strength, yet lighter and more cost effective than stainless steel (3).

• Using polymeric components in biopharmaceutical processes brings distinct advantages over stainless steel by reducing the risk of corrosion and long-term degradation of malleable parts.

• These materials also are chemically resistant (compatible with most acids and bases) and biologically inert for use with most biopharmaceutical products.

• The smaller footprint, greater flexibility in design, and lower costs—therefore, the ability to start up a facility at a fraction of the traditional cost anywhere in the world—also have contributed to the acceptance of polymers for these applications.

Furthermore, the United States Pharmacopeia (USP) Class VI-grade plastics are an ideal replacement for stainless steel, other types of metal tubing, and even glass for weight reduction, comparable strength/mass, chemical resistance, hardness, and low levels of extractables.

Benefits of SUS: Understanding that polymers can be comparable to stainless steel in the biopharmaceutical industry provides product solutions for improving operating costs, speeding validation cycle times, reducing contamination, and improving product yield. When we take a deeper look at the benefits single-use products and systems can offer, they can be broken down into four broad categories:

Cost Effectiveness and Economic Advantages: They reduce capital expenditures and facility footprints.

Safety and Quality: They reduce cross contamination, product loss, and cleaning validation while improving sterility assurance.

Operating Efficiencies: They reduce labor costs, facilitating implementation through faster batch turn-around and product changeover, improving process flexibility and speed to market.

Sustainability: They reduce use of water, utilities, and chemicals.

Vendor Availability: Sufficient, qualified vendors exist to supply and service SUS.

Section 5, “Economic Advantages of SUS,” covers the benefits of SUS in more extensive detail.

SUS Parts and Components: With the advantages SUS can offer, availability of single-use components continues to increase. Today's SUS can contain one, all, or a few of the following products: tubing, filters, filtration in general, bags, fittings, sterile connections, sensors for monitoring pH, O₂, CO₂, pressure, temperature, and many other containers such as bottles, carboys, flasks, and centrifuge tubes. As the needs and requirements from FDA and other governing bodies grow stronger, the need to monitor process conditions also gets stronger, therefore setting up needs for more unique single-use products each day.

SUS Applications: Just as the number of available components has increased for SUS over the years, the areas in which such products are used have also increased. SUS have found their way into the biopharmaceutical market with buffer storage, media storage, and cell harvesting. Today, we see these same products used in manufacturing operations upstream (single-use bioreactors/fermentation and media preparation) as well as downstream (direct filtration, purification, formulation, and final fill). Moving forward, the same products are now being specified into new areas such as chromatography, mixing, seed train, and tangential filtration.

SUS can offer significant benefits in direct manufacturing and contract manufacturing operations and toward debottlenecking processing challenges. Adapting and implementing innovative single-use technologies will help make our industry more competitive in the new global economy.