Recently, I have heard the term game changer used to describe single-use technologies (SUTs). Whether this is hyperbole or reality remains to be seen. But it does bring baseball to my mind. After all, it’s finally spring, games began in April, and optimism reigns supreme — at least in some major-league cities. I was struck recently by an article in my home-town Washington Post by venerated columnist Thomas Boswell, who wrote in March about hope for the future of our losing but still beloved Washington Nationals: “Beginning now, February’s mandatory baseball optimism turns gradually into March realism. By April, dreams must translate into performance. That transition can happen quickly” (1)
As both a baseball fan and executive director of the Bio-Process Systems Alliance (BPSA), the trade association of the Single-Use industry, I have observed over the past four years this very transition: from optimism and hope about the potential of SUTs as biopharmaceutical process platforms to incremental realization of their myriad benefits by pharmaceutical providers and then to a new point (now) at which I regularly hear “It’s a game changer.” So we may have reached that transition point.
For these manufacturing systems, it’s March, the regular season has begun, and by all accounts SUTs are contenders. There is no such thing as a sure thing — even for perennial winners like the New York Yankees. Certainly, however, indicators suggest that SUTs will continue to emerge as reliable and affordable enabling technologies within a complex future drug market that is just now coming into focus. When considering their potential as game changers in tomorrow’s drug manufacturing business, it is important to see the entire field in the context of what preceded SUTs and how the drug market is rapidly changing right now. The Run-Up to SUTs
For perspective, it’s important to acknowledge that the now-ubiquitous blood bag is the antecedent of SUTs. Over recent decades, flexible polyvinyl chloride (PVC) bags have for the most part replaced the use of glass bottles for storing blood and its components. PVC bags enable greater stability than glass for both the separation of blood and safe transfusion of its components. Blood bags are classically “single-use” devices and alleviate the need and costs associated with washing and sterilizing reusable containers. As a huge added benefit, PVC bags double the shelf life of blood products to the benefit of patients, donors, and emergency rooms worldwide. So these were very much a game changer, providing for extension of blood life, which saves patient lives every day.
Inclusive of blood bags, the market for PVC in medical applications is on a 5–6% growth curve. As reported by BCC Research, the US market for plastic healthcare packaging should reach 3.8 billion pounds of products in 2010 (2) and is expected to increase to nearly 5 billion pounds in 2015, with a five-year compound annual growth rate (CAGR) of 5.6%. PVC is the second-largest segment in that study and expected to increase from 845 million pounds in 2010 to nearly 1.1 billion in 2015 (a CAGR of 5%.)This study details the use of plastics in packaging healthcare products segmented by pharmaceutical and medical packaging, including medical products used by practitioners in hospitals, clinics, home healthcare operations, and so on. Examples include syringes, blood and intravenous solution bags, diagnostic kits, tubing, trays, and other items. Their growth is most likely fueled by affordability, safety, ease of use, and trust in the products coupled with externalities such as an aging population, a related explosion of healthcare related needs, and across-the-board scrutiny of healthcare costs and economics. The same set of drivers holds true for anticipated continued growth of SUTs.
At work now is a process I characterize as “raging incrementalism.” Biocontainers are becoming a standard in biotechnology and biopharmaceutical applications — e.g., as storage and process containers for buffers, cell culture media, and cell harvesting. Slowly but with increasing rapidity, SUTs based on extruded plastic films, molding technologies, and cleanroom manufacturing environments (with historical ties to blood-storage advances and plastics processes) are gaining acceptance as the preeminent flexible processing platform. Man on first! Moving the Runners: Pharma’s Face in 2016
Moving that base-runner up — the next step in single-use adoption — is very much steeped in the growing demand for new drugs. It is often said that the era of the blockbuster drug is coming to an end and that boutique bio-based therapies are the wave of the future. As in any boutique, those new drugs will not necessarily serve the masses, but instead will be targeted at different diseases in certain DNA-marked populations.
Development of unique drug classes is a formidable, expensive, and risky endeavor. So it is no surprise that the biopharmaceutical industry can be quite methodical — even conservative — in adopting new technologies. The risks are just too great. Very few bases are stolen in this game. When making a new drug or therapy, a company can commit between US$500,000,000 to a billion dollars, with no guarantee that the product in development will be relevant or marketable after three to five years.
Comparing the relative sophistication of targeted therapies to what was available a mere 20 years ago is a bit like comparing Star Trek and Wagon Train. Manufacturing close to patients will be essential for the success of many products. Processes and delivery devices will change. Microneedles, magnetically targeted carriers, nanoparticles, and polymer capsules will be part of our 2016 toolkit. Drs. McCoy and Crusher would be right at home beaming down here from their Enterprise starships. The era of personalized medicine is here, indeed. It is steeped in a variety of externalities, including whether or not it can be profitable to manufacture small lots of drugs for limited patient pools. There are many, many unknowns. What is known, however, is that as new drugs evolve, so will the supply chain. New product types and modes of healthcare delivery; increased emphasis on outcomes and importance of emerging markets; and greater public scrutiny, regulatory oversight, and environmental pressures all factor in here. By 2016, it has been estimated, bioengineered vaccines and biologics will account for 23% of the global drug market, measured by value (3).
Fundamentally, the commercialization of new biological therapies occurs at only a fraction of a percent for every project that initiates from an initial DNA molecule. Because the odds of making it from concept to full commercialization are small, a market need has been created to test the most possible concepts at the lowest possible cost, given the continuing expense and dearth of available capital. The drive for economy and efficiency will be relentless in this new pharma world. Current models for manufacturing (and distributing) medicines aren’t necessarily suited to it. To compete, companies will be loathe to tie up capital in equipment that is irrelevant to market demands. Rapid reconfiguration of existing manufacturing lines f
or different products using flexible, low-cost, configurable manufacturing platforms will be key. Enter SUTs, and the bases are loaded. Sliding into Home: Not How But When?
The question is no longer if, but rather when SUTs will emerge as the dominant biomanufacturing platform. Given the future face of the biopharmaceutical industry, polymeric SUTs offer much to recommend. Understanding that polymers can be comparable to stainless steel (fixed, capital-intensive facilities) will drive their adoption. Among their beneficial features are cost-effectiveness, safety and quality, operating efficiencies, environmental impact, and supply chain diversity.
Cost-Effectiveness: SUTs reduce capital expenditures and facility footprints. They are adaptable to patient-proximity manufacturing, which is particularly important in epidemic and bioterrorism vaccine deployment.
Safety and Quality: SUTs reduce cross-contamination product loss and cleaning and validation efforts while improving sterility assurance.
Operating Efficiencies: SUTs reduce labor costs, allow faster drug campaign turn-around times, improve process flexibility, and accelerate speed to market.
Green Benefits: SUTs reduce the use of SIP (steam-in-place) and CIP (clean-in-place) hot water consumption required to revalidate traditional steel systems.
Supply Chain Diversity: Sufficient, qualified vendors now exist to ensure timely supply and service of components and systems.
Those advantages help to explain why 60% of contract manufacturing organizations (CMOs) have already implemented SUTs. SUTs have now advanced from “the technology of the future” to the mainstream over the past four years, at least at the CMO level. That bodes well for the industry at large.
The ultimate wide-scale adoption of SUTs will still be based on performance, price, safety, risk, and user-comfort factors. The extent to which SUTs become a real game-changer — and how fast it happens — will depend on many factors, not the least of which is the ultimate performance of these systems compared with traditional facilities. As we have seen, the benefits are comparable at a greatly reduced economic scale. And the runners score!
Making sense of the future pharma game and its complex rules will require sorting out as the future of pharma reveals itself. The role SUTs will play will become clearer as the market evolves. The First International Single-Use Summit
Recognizing the need for a business-specific conference on these topics, BPSA has put together a compelling program for a July 2011 gathering in Washington, DC: the first International Single-Use Summit (ISUS), www.bpsalliance.org/summit.html. Unlike a technical meeting, ISUS will be an exclusive two-day business information and networking event that will cover most of the topics addressed herein — and more. Key officials from PhRMA, the Department of Defense, the US FDA, BenVenue Laboratories, CRB Consulting Engineers, the Baylor Research Institute, Genentech, BioPlan Associates, and Promethera Biosciences have been invited, with presenters from Asia, Europe, and South America as well as North America.
ISUS will provide a unique perspective for our industry. Will SUTs knock it out of the park or settle for a utility role? Time will tell, but many forces are at work here, and multiple benefits are waiting to be captured, which all bodes well for an SUT pennant run. As Yogi Berra once said, “You can observe a lot by watching.” I hope to see you in July at ISUS, where we can discuss our respective observations.
Kevin D. Ott is executive director of the Bio-Process Systems Alliance in Washington, DC and principal of Ott Consulting LLC in McLean, VA; 1-202-721-4125; firstname.lastname@example.org; www.bpsalliance.org
1.) Boswell, T. 2011. Nats Keeping High Hopes to Themselves. The Washington Post 1.
2.) Report PLS009F 2000. Medical Plastics, BCC Research, Wellesley.
3.) 2011. Pharma 2020: Supplying the Future, PricewaterhouseCoopers LLP, New York.
4.) Kapp, T. 2010. Roadmap to Implementation of Single-Use Systems: A BPSA White Paper for Manufacturing Decision-Makers within End-User Organizations. BioProcess Int. 8:S10-S19.
5.) Langer, ES. 2010. Seventh Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, BioPlan Associates, Inc., Rockville.
6.) Ott, KD. 2011. Flexible Vinyl by the Numbers, Flexible Vinyl Alliance, McLean.
7.) BPSA Irradiation and Sterilization Subcommittee 2008. Guide to Irradiation and Sterilization Validation of Single-Use Bioprocess Systems. BioProcess Int. 6:S10-S22.
8.) BPSA Extractables and Leachables Subcommittee 2008. Recommendations for Extractables and Leachables Testing. BioProcess Int. 6:S28-S39.
9.) BPSA Technology Committee 2008. Complete BPSA Component Quality Test Matrices. BioProcess Int. 6:48.
10.) BPSA Disposals Subcommittee 2008. Guide to Disposal of Single-Use Bioprocess Systems. BioProcess Int. 6:S24-S27.
11.) Caine, B. 2010. The Impact of Single-Use Technologies, BioProcess Systems Alliance, Washington.