"In our study, we evaluated biomanufacturers' current usage of single-use/disposable systems. Disposable filter cartridges were the most commonly listed disposable items, noted by 94% of our respondents (equal to last year's usage data). On the whole, however, the survey responses suggest that almost every kind of disposable has penetrated the market broadly (Figure 1). Fully 61% of our respondents reported using at least one disposable bioreactor, and 74% reported using buffer containers, and 56% were using a disposable mixing system. Even for filled media bags, acceptance in at least some part of the production network was reported by 59% of those we surveyed (from 48% in 2005)."
"This year, decision makers' objections to disposables declined both in 'quantity' and importance. For example, we asked respondents about their most important reasons for not increasing their use of disposables (Figure 2). Factors such as how regulatory agencies would treat leachables and extractables issues have consistently been near the top of the list. However, in this year's study, the number of respondents citing regulatory worries as a primary concern for restricting their adoption of disposables fell to 10.4%, down from 16.6% last year. In addition, in previous years lack of disposable equipment that meets process requirements, and breakage of bags and loss of material were major concerns. This year, these issues were no longer primary concerns to respondents," notes Langer.
Figure 1. Current use of disposables: Most biopharmaceutical manufacturers surveyed rely on
Equipment vendors certainly see promising prospects. For instance, Shire Human Genetic Therapies, Wayne, Pa., announced in March a $250-million investment in a new production facility in Lexington, Mass. When completed next spring the plant, which reportedly will be the largest manufacturing site for disposable biotechnology equipment in the U.S., will make vessels and tank liners.
The mid-March Interphex trade show in New York City also testified to the vibrancy of the disposables market; more single-use solutions were on display than ever before. It also provided the setting for a forum sponsored by the BioProcess Systems Alliance (BPSA), a business unit of the Society of the Plastics Industry, Washington, D.C. The group, which has 38 member companies, used the forum to discuss the inherent benefits of single-use bioprocessing for the end-user.
"Reduction of risk, ease of use, reduced validation requirements, better process economics, faster campaign turnaround times and disposability are benefits inherent in the adoption of single-use processing as compared to traditional capital-intensive systems," noted Ken Ott, BPSA executive director.
Ott particularly emphasized the importance of last year's decision by BPSA to begin accepting end-users of single-use systems into its membership ranks. Already companies such as Bristol-Myers Squibb, Dow Corning and Lonza have joined.
"The addition of end-users into the BPSA organization is ongoing, with the objective of establishing a safe harbor business-oriented information exchange opportunity between users and suppliers of single-use systems and components. Such a forum is intended to assist end users in navigating the steps to implementation of plastics-based manufacturing and to share best practices to optimize costs, validation, deployment, disposability and testing," he explained.
Meanwhile, Millipore, Billerica, Mass., was among several vendors using Interphex to launch single-use systems. The company describes its new Mobius FlexReady Solutions, which handle clarification, media and buffer preparation, tangential flow filtration and virus filtration (Figure 3), as significant because they allow manufacturers to readily convert to single-use technologies.
It all comes down to the systems engineering involved: ensuring that solutions are easy to assemble, install, operate and change-out, and have the modularity/configurability the market demands, notes Paul Chapman, vice president of downstream processing. "We are bringing the Mobius FlexReady Solutions to market because our customers want more operational flexibility — varied batch sizes, faster process times, more efficiency."
Figure 2. Barriers to disposables: Existing investments in durable assets pose
"We went from preliminary design concepts to launch in nine months. This is unheard of in our industry or any other industry for that matter," boasts Chapman. During development Millipore worked with several unnamed biotech companies.
Millipore's experiences in the last year echo findings of BioPlan's survey that almost every kind of disposable has broad market penetration now. Overall the disposables business is one of the company's fastest growing areas.
Overall, speed remains the key challenge in the disposables market. "Our customers and Millipore are like-minded. They need to bring more molecules to market faster and we develop the technologies that enable them and the industry to gain efficiencies by producing smaller batches in faster process times," he concludes.
ATMI LifeSciences, Minneapolis, Minn., used Interphex to launch the next generation of its Nucleo bioreactor. The new unit brings together the expertise of single-use-mixing expert Pierre Guerin, Mauze, France, and ATMI's know-how in ultra-clean films. The scalable Nucleo bioreactor reportedly minimizes stresses on anchorage-dependent cultures while achieving new levels in high-density cell line growth.
Colder Products, St. Paul, Minn., demonstrated its HFC39 quick-disconnect couplings that are specifically designed to prevent external organisms from entering through the connector into the flow path during disconnection. The plastic components are polysulfone and the seals are platinum-cured silicone.
"Biopharmaceutical manufacturers have been using HFC39 connections for years, proving the product's reliability," says John Boehm, business unit manager, bioprocessing. "Now we have validated its aseptic disconnect capability, giving bioprocessors the confidence to use the HFC39 in their most critical applications."
Figure 3. Pre-assembled hardware:
Meanwhile, Pall Life Sciences, East Hills, N.Y., unveiled a flexible single-use depth-filter capsule system for demanding pre-filtration and clarification processes (Figure 4). The Stax system integrates as a pre-filtration step — for example after a disposable bioreactor — and makes it easier to develop a complete single-use process.
"The Stax high-performance depth filter system has engendered a considerable amount of interest because of the flexibility of the system. Because capsules are available in three different surface-area configurations, which can be mixed and matched to give exactly the capacity required for any given process or batch size, and because the capsules can be used within a holder — which we call a 'chassis' — in standard bottom-in/bottom-out or bottom-in/top-out configurations, as well as having the useful function of being able to be operated with two different grades of capsules within a single chassis, users who have already installed the system are very enthusiastic," explained Ian Sellick, director of marketing.
Figure 4. Flexible filter: The design of this
On a broader scale, the notion of a "process-in-a-box" (http://www.ChemicalProcessing.com/articles/2007/185.html) is now a reality, according to Sellick. "It is now perfectly feasible to have a complete process delivered as a disposable system, within certain capacity constraints. A process requiring up to 1,500-or-so-liter capacity at any given hold stage can be readily provided. If greater capacity is required, large biocontainers can be manifolded together and interconnected using simple, reliable sterile connectors."
From a practical point of view, such a system comes as a series of pre-sterilized sub-assemblies. Each is joined together — usually when that part of the process is reached — using sterile tube connectors. "Once a part of the process is finished, the tubing is sealed and cut maintaining the sterility of the system or a sterile disconnect device is used," he adds.
A significant benefit of the single-use approach is that identical systems can be used at early clinical stages as well as for large-scale manufacturing with no change in materials of construction, says Sellick. "Scale-up by multiplexing is the perfect solution to planning larger-scale manufacturing without having to risk capital at an early stage of the product lifecycle."
Different Economy, Different Challenges
Disposables actually may benefit from today's downturn. Weakness of the overall global economy coupled with growing scrutiny of healthcare costs in the U.S. and elsewhere will impact bioprocessing, explains Sellick. It inevitably will prompt increased attention to the costs of manufacturing and delivering pharmaceutical products to patients — and so provide a potent driver to reevaluate process economics. "This in turn should lead to the development and adoption of new technologies that will be to the long-term benefit of everyone. Process economics will really be the watchword," he concludes.
Seán Ottewell is Chemical Processing's Editor at Large. You can e-mail him at email@example.com.