A BPI Theater Roundtable at Interphex 2016

SANOFI(WWW.SANOFI.COM)

On Tuesday, 26 April 2016, Eric S. Langer (managing partner of BioPlan Associates) chaired a morning roundtable titled “Deciding on Single-Use vs. Stainless Steel Strategy: What the CMOs Know That Biopharma Needs” as a follow-up to a similar discussion held last year. Langer brought together a panel of four contract manufacturing organization (CMO) industry experts:

• Daniel Vellom (senior director of global technology innovation at Sanofi Pasteur)
• Sue Behrens (senior director of process technology at IPS–Integrated Process Solutions, Inc.)
• Bill Hartzel (director of strategic execution at Catalent Pharma Solutions)
• John Ward (vice president of engineering at Patheon).

Langer began this session by asking, “What do CMOs really know, and how can they share that with end users?” He introduced the panel as a “brain trust” of bioprocessing and single-use technology knowledge. CMOs are paid to be more efficient and test new technologies. Bioprocessors have been trying to decide whether to stay with stainless steel equipment or switch to single-use technologies. But they have come to realize that it isn’t an either–or decision. Integration of both approaches depends on product volume and the amount of flexibility needed. Stainless steel is still the workhorse of bioprocessing, but disposables can be more efficient for smaller batches or in particular stages of product development. Single-use innovation is driving stainless steel innovation now in regard to automation, compactness, and reliability. Users want incremental improvements in stainless steel sensors, integration, actuators, and diaphragms; the top four improvement needs for disposables concern product sensors, connectors, purification devices, and chromatography products.

Daniel Vellom(Sanofi Pasteur)

From his position in the vaccines division of Sanofi, Vellom described the vaccine industry as conservative when considering new technologies. Manufacturers are safety conscious, especially those making vaccines for infants. Production technologies have evolved over the 200 years since Edward Jenner started vaccinating against smallpox, through the early 20th-century creation of childhood vaccinations, and on to 21st-century modalities. Companies needed a way to make vaccines quickly, so they have begun moving from stainless steel to disposables, which require less time for implementation and changeover. Most use a hybrid of single-use and stainless steel processing.

Vellom listed as current major focuses the standardization of disposables so that they fit together, ongoing concerns over leachables and extractables, the need to establish good relationships with suppliers, and training development for installing and using disposable equipment. He pointed to multiple benefits of working with single-use systems as well as some challenges, which include manual set-up and cumbersome change control.

John Ward (Patheon)

Ward addressed the question of whether to use stainless steel or single-use technologies (or both together) by posing other questions: What are your objectives and timelines? Is it a new facility? What amount of capacity do you need? How high is your throughput? How much product change-over are you doing?

For new facilities, companies might save capital with single-use systems, but single-use components can be expensive. If a company already has manufacturing capacity in place, then it might be able to eliminate the need for some of those components.

“Hybrid systems can optimize what you have already and reduce the cost of purchasing single-use supplies,” Ward said.

“If you are operating around the clock and moving a high volume of fluid through as fast as possible, stainless steel could be a better choice. If you are running at a more moderate pace, then single-use systems might be preferable.”

His company looked at two different operating paradigms: a high-changeover system for early stage products and another for commercial products. Although the hybrid equipment turned out to be similar, the number of changeovers and the skill sets of the workers were very different. “You also should consider how many products are being produced in a facility,” Ward cautioned. To decide which way to go, he advises looking at three systems — buffer/media preparation, product holding, and product contact — and then deciding based on the amount of product made and associated expenses.

Bill Hartzel (CatalentPharma Solutions)

Hartzel described how his company aligned its business and manufacturing strategies, including addressing the question of single-use or stainless steel systems. Catalent realized that small-to-midsize companies dominate the discovery phase of biopharmaceutical development, with larger companies handling phase 2 and 3 clinical stages and beyond. Speed is a priority especially for small organizations.

Meanwhile, proteins are becoming more complex, so this CMO needed to make sure that its manufacturing ability could keep up with product modalities. It began with a transgenic product and stainless steel manufacturing equipment. In 2011, Catalent needed to expand. Having already purchased stainless steel bioreactors, the company decided to sell them and commit to single-use technologies. In one year it had a single-use system up and running, producing good manufacturing practice (GMP)–compliant material and generating revenue. The single-use system gave Catalent the ability to make product and turn around batches more quickly with reduced risk, and it simplified process design. Disposables gave this company the ability to offer its small customers the speed they desired.

Hartzel agreed with Ward that a good, strong partnership with single-use suppliers is necessary because “you are outsourcing your validation.” He added that training on correct use of new equipment is essential.

Sue Behrens(IPS)

Behrens recalled that last year she had talked about what her company was deciding about which type of systems to use. So this year, she followed up by reporting on what IPS chose. She said that the biopharmaceutical industry is still figuring out when to use disposables and when stainless steel is still preferable.

Last year she talked about the old assumptions people had about single-use technologies. “Are these valid reasons to choose one over the other?” Behrens posed, along with her own answers:

• Single-use technology is more flexible, and flexibility is important (both true).
• Disposables are more affordable (debatable; it depends on the product and the amount being made).
• Single-use technology facilitates open architecture (IPS did not see a difference between single-use and stainless steel in the ability to use open architecture).
• Disposables provide for closed systems (but you can have a closed system with either option).
• Reliable supply is vital (IPS hopes that all systems have reliable suppliers).
• Single-use technology is faster to implement than stainless steel (absolutely true).

Looking across the bioprocessing space, Behrens sees single-use technologies used in media and buffer preparation and in aseptic filling, whereas stainless steel is used to handle large volumes such as for large-scale fermentation. A mix of both is used for cell culture, chromatography, and filtration. She advises companies to base such decisions on their own specific projects rather than on someone else’s assumptions or fancy show designs.

Questions and Answers

What one thing in the past 12 months has further stimulated single-use adoption? It has not been one thing but rather several things: the ability to make hybrids, the advent of new components, and new layouts. Meanwhile, companies are discovering the limitations of stainless steel.

After companies have worked with one supplier and qualified its bags (e.g., for extractables/leachables), how can a new supplier compete? When a biopharmaceutical company begins to design and build a new facility, it will explore different choices and evaluate new suppliers. It will give them the chance to qualify and show that they have enough of the right inventory available. New suppliers should not give up. When a process moves from one phase to the next, the product sponsor often needs a different set-up at a different scale.

What key factors would drive a company to change from single-use to stainless steel? The scale of manufacturing might necessitate a particular stainless steel element such as a large bioreactor.

How do you put together a hybrid system? Is an innovation still missing? Panelists said that the industry currently has this capability. “Pay special attention to sensors and connections,” was their advice, “and make sure that monitoring is taking place appropriately.”

Alison Center is editorial assistant (acenter@bioprocessintl.com) for BioProcess International, PO Box 70, Dexter, OR 97431. Recordings of many of these full presentations are available online at www.bioprocessintl.com/Interphex2016.