Josh Hays (upstream technology director, MilliporeSigma), BPI Theater @ INTERPHEX, April 26, 2016, 1:20–1:40 pm

Over the past 10 years, upstream processing has undergone a considerable evolution. Single-use technologies up to the 2,000-L scale have become the “gold standard” to deliver a fast, flexible, and cost-effective solution for production of recombinant proteins in a current good manufacturing practice (CGMP) environment. Cell culture media advances through speed and flexibility enhancements as raw-material modifications (along with supply continuity and reduced overall cost of operation) have also been paramount in shaping how manufacturing will look as the industry moves forward.

Although speed and flexibility in manufacturing are important, bioprocessors face a growing need to mitigate risk. This presentation by Josh Hays offered examples about how single-use upstream products are being developed with risk mitigation in mind. He examined ways that his company’s complete product and equipment portfolio aims to deliver fast, simple, inexpensive, and safe solutions that are superior to what “conventional” stainless steel equipment offers. Hays also identified a relevant single-use cell culture platform for a multiproduct facility, primarily focusing on a platform that benefits from a clear definition of the design space, from bench to production scale, to minimize process development efforts.

Hays commented that “When you look up the term risk, you will find a definition such as ‘to expose someone or something to danger.’ This fits well with the biopharmaceutical industry in many ways because its members are always striving to reduce risk to patients. Similarly, these manufacturers need to look at their own internal processes to mitigate their own risks and thereby lower that of their patients. Looking at it another way, poor management of risk can lead to a contamination event in a manufacturing facility, and that in turn could lead to devastating financial loss: US$1 billion is arguably a conservative estimate.”

So how do manufacturers reduce their risk? Hays explained that, as with many things, a holistic approach to the entire process is the key. For example, viral safety could be addressed quite early in a development process with teams looking at virus-resistant cell lines or perhaps pretreating components for viral reduction by way of high-temperature, short-time (HTST) treatment or dedicated viral filtration. A shift to a single-use manufacturing strategy is an increasingly effective strategy as well, eliminating the need for cleaning and therefore drastically reducing the risk of cross-contamination. Sterile, single-use sampling and connectivity are proven technologies to lower the risk associated with those operations.

Hays concluded by emphasizing that regardless of how users choose to approach their individual risk, they should focus on the big picture of their entire bioprocess.

Further Reading

Bai Y. Strategies to Mitigate Technology Transfer and Clinical Manufacturing Risks: Downstream Purification Case Studies. BioProcess Int. 12(6) 2014: S42–S47.

DeSain C. Risk-Based Quality Management Systems: What Are We Waiting For? BioProcess Int. 4(3) 2007: 12–18.

Hutchinson N. Understanding and Controlling Sources of Process Variation: Risks to Achieving Product Critical Quality Attributes. BioProcess Int. 12(9) 2014: 24–29.

Lannon KA. Quantitative Risk Assessment of Bioaccumulation Attributable to Extractables and Leachables in Cellular Immunotherapy Biomanufacturing. BioProcess Int. 13(10) 2015: 28–37.

Locwin B. Quality Risk Assessment and Management Strategies for Biopharmaceutical Companies. BioProcess Int. 11(11) 2013: 52–57.

Mollah AH. Application of Failure Mode and Effect Analysis (FMEA) for Process Risk Assessment. BioProcess Int. 2(10) 2005: 12–20.

Noferi JF, Worden DE, Dillon RL. Regulatory Risk Management: The Paradigm Continues To Evolve. BioProcess Int. 2(2) 2005: 14–18.

Samavedam R. A Risk-Based Life-Cycle Approach to Implementing Disposables for Facility Flexibility. BioProcess Int. 11(4) 2013: S30–S35.

Listen to the full presentation at www.bioprocessintl.com/Interphex2016