By Denise DeTommaso, Marketing Manager, Biodisposables – SAFC Biosciences

Introduction/Overview

As little as three years ago disposables were often seen as the preserve of the bio contract manufacturer – a useful item in the “flexibility” toolbox. Today, the market in disposables and single-use systems in cell culture applications is approximately $120-130 million, and expanding at approximately 20%-30% annually. (Note: These figures exclude filters, housing and downstream purification components.)

And while there are significant challenges – not least in the regulatory context – “plug-in, use and dispose” systems and associated technologies are rapidly heading into the industry mainstream.

Use of disposables started to gain appeal in the late ‘90s, when the fashionable wisdom was that both cell culture and fermentation-based production routes would be constrained by a lack of stainless steel.

In that climate, contract manufacturers were quick to recognize the potential of disposables to drive up all-important plant productivity via better processing and yields. Reduced contamination risk and significant capital expenditure savings over “steel on the ground” also appealed to the bottom line. Since then, the industry’s perceived threat of under capacity has more than receded and disposables have come a long way from being regarded as a few useful components.

Today, we are seeing the adoption of “disposable-based manufacturing” for a whole range of operations, from ultra low volume, patient-specific production to adoption for integrated large-scale upstream and downstream processes.

Time, cost and speed-to-market are all challenges in which disposables increasingly figure as part of industry’s reply.

Products and Applications

Although plastic bags won’t be replacing stainless steel anytime soon, the era of the integrated disposable manufacturing system is certainly on the long-range radar.

Disposable products and applications aren’t exactly new. Filter cartridges – the most common example – have been around for years and the next favorite, media bags and reagent bags, tubing and connection accessories are also familiar to the process. What is most recent and most exciting has roots in the widening range of applications and use of complete, pre-sterilized, preassembled disposable “packages” of modular components – including filters, bags, tubing, connectors and rigging – that are integrated into complete manufacturing assemblies.

Elements of this complete package already have three main applications. The first is in STORAGE, with systems used to hold growth media, buffers, reagents, bulk harvest fluid and intermediate and/or final products. In the BLEND & FORMULATION “mode” disposables facilitate reconstitution of dehydrated media at its point-of-use, but with lower storage space demands than those required for liquid media. Areas of promise in terms of future development include the REACTOR application, ranging from scale-up to product conversion, and incorporating capabilities for mixing, stirring and temperature control, new connectors and connection options, and alternate contact surface that further minimize adherence, leachables and extractables.

The Advantages

As we will see later, the apparent advantages of single-use, high-flexibility systems do have their offsets – however they remain impressive. Single-use systems may, in some cases, offer cost savings over traditional stainless steel-based production of up to 40%, derived from a combination of factors.

Aside from the advantages of volume throughput and productivity over production in conventional “fixed” assets, a big driver favoring disposables is the decreased cost and low risk of cross-contamination, with the complete elimination of cleaning and cleaning validation cost.

These combine with lower capital cost than (less flexible) stainless steel, multi-use equipment – and the savings inherent in cleaning time, water consumption and consequential environmental burden. More intensive use of lab space can appeal to smaller companies, while plastic components give greater visibility to production steps.

Trends

All these advantages are persuasive enough to drive some key trends in the use of disposable systems. Associated with a move towards complete systems is the increasing size of fully developed systems, with high levels of functionality and integration.

As system capacity limits increase, larger and larger tubes are required to cope with higher flow rates. To accommodate a wide range of mixing requirements, custom design, rather than “standardization” is increasingly notable. Bigger and more complex systems have also brought an attendant increase in the number of supplier joint ventures and collaborations in provided packaged solutions.

Single-use systems are also innovation-friendly, with notable examples being in the context of membrane chromatography, depth filtration and the development of bioreactors.

Key Challenges

While disposables and single-use systems carry much good news, significant challenges remain and could conceivably influence the rate of their continuing future growth.

One set of key issues concerns testing, validation and “fit” into the increasingly sensitive regulatory arena. Thus far, two key documents include a May 1999 FDA guidance document: “Container-closure Systems for Packaging Human Drugs and Biologics” and the EMEA’s more recent: “Guidelines on Plastic Primary Packaging Materials”.

Such considerations relate especially to leaching, extractables and compatibilities – and the clear need to favor animal-free components. Another typical consideration – where single use systems are (for example) used in downstream processing and final formulation – will be where container protein interactions may include protein adsorption onto container surfaces by hydrophobic and electrostatic interactions.

To a degree, these are issues of customer confidence as related to the “risk” in adopting new ways of working, and the comparative lack of “real world data” to support the business case of moving to “single use” technology.

While a huge range of standardized disposable components are available, 90% of customers are looking for a process-specific set-up. This means that almost all individual requirements must be subject to specific testing and validation. Compliance sensitivities also beg questions over the risk of changing from tried and proven routines with multi-use, stainless steel processes.

In turn, this creates the imperative of close partnership between suppliers and customers, with suppliers having a major responsibility in terms of information and customer education, especially where disposables are being introduced into existing process and production operations.

Creation of the BPSA

The “knowledge and standards” scenario has been the main driver for creation by the US Society of the Plastic Industry (SPI) of the Bio Process Systems Alliance (BPSA), which had its debut in late March at the 2006 INTERPHEX show in New York.

An alliance of 26 leading providers of single-use process components and systems to the biopharma industry, the BPSA has been established as an umbrella organization to represent the sector. The BPSA will provide a unified voice on the benefits of single-use manufacturing, and give timely visibility to the advance of disposals in biomanufacturing.

Its primary objectives are to grow the market by facilitating adoption of single-use components and systems; establish guidelines and standards for their use and disposal, and to educate and inform customers, regulators and other key organizations on their benefits.

Disposables – the business case

Currently, the relative lack of comparative financial data (notably ROI- Return On Investment) alongside stainless steel for this still young technology sector can make a “business case” in its favor complicated to produce – even though its operational advantages are often clear.

But growing interest in the potential and use of complete disposable systems suggests it will be only a matter of time before the traditional trust in “fixed assets” is balanced by new understandings and customer confidence – and a changed regulatory climate. The disposables industry must play a full part in the re-assurances needed as part of that transition, and creation of the BPSA is a significant step down this road.

Plastic disposables and integrated single-use systems are unlikely to fully replace stainless steel as the volume leader in biomanufacturing anytime soon, but volumes are increasingly not the key issue for the industry. As biomanufacturing output over the next few years swings ever further towards lower volumes of more complex, more targeted medicines, their clear operational and cost advantages will secure a prominent role for single-use systems.