Nice Insight is in conversation with Kimo Sanderson, at Asahi Kasei Bioprocess America, to discuss the company’s “technology of the decade.”

Inline buffer dilution (IBD) has been recognized as a game changer and a highly optimized solution to this critical processing step. Kimo Sanderson, Vice President of Marketing and Client Services at Asahi Kasei Bioprocess America, lends his leading industry insights with Pharma’s Almanac to better describe the methods behind this crucial function.

The expertise to process large-molecule biologic compounds well has become both a core skill and a strategic path to success for many of today’s most prominent biopharmaceutical companies. Bioprocessing on a commercial scale has been a technological reality for years, but as the world’s appetite for biologic therapeutic agents continues to grow, there has been tremendous pressure to optimize capacity and address any manufacturing “bottlenecks.”

Process-Related Bottlenecks

Any unit operation that slows down the overall process can be considered a bottleneck. Angelo DePalma, Ph.D., industry analyst and journalist, finds that in practical terms, the definition may be expanded to difficult, risky or expensive functions. Although bottlenecks can occur due to facility-related barriers, including utility-related obstacles, most of the attention has been focused on downstream process-related bottlenecks.¹

Better Buffer Process And Control

Inline buffer dilution — the mixing of buffers from concentrates — cuts down on both prep time and storage, leaving scarce manufacturing space for adding capacity. The pros of inline dilution include increasing the existing tank space but also reducing the validation and cleaning of related, larger tanks.² Thousands of liters can be required for protein capture, polishing, concentration and virus removal steps, with each step needing specific buffer compositions.² Asahi Kasei Bioprocess America, in particular, has successfully worked to remove the bottleneck from the buffer process.

In 2012, the company’s IBD System was named Downstream Processing “Technology of the Decade” by BioProcess™ International. Asahi Kasei’s singular multi-stage blending methodology was also awarded a patent in acknowledgment of its technical innovation.³ Kimo Sanderson commented on this tactical issue, saying, “Downstream unit operations remain challenged by the increasingly higher titers from upstream processes creating a bottleneck that is further amplified by manufacturing suites with fixed installation capacity.” He notes, “that the potential of continuous processing to unlock manufacturing efficiencies is gaining favor.” In order to achieve this, there will need to be an alternative to the current methods. “New technologies will be required to support these initiatives,” predicts Sanderson.

Automation And Sensing Make The Difference

One area ripe for technological improvement is the use of automation to drive the production of buffers for downstream unit operations. “Historically, buffers have been produced by relatively manual batch compounding. This approach is labor-intensive and requires time-consuming post-run quality control analysis to ensure accuracy.” He notes that this is also an issue: “Since the resulting buffers reside in large tanks, operational costs such as tank cleaning and validation accumulate while manufacturing facilities lose valuable floor space.”

“These concerns,” continues Sanderson, “inspired the development of a standard, automated IBD system featuring patented buffer-blending technology that delivers buffers on-demand to the downstream process.” Sanderson notes that the IBD’s “process analytical technology (PAT) controls pH and conductivity simultaneously, resulting in precise buffers that are released directly to the downstream process.”

One remedy for buffer-volume-related problems has been “inline conditioning” (ILC). In such systems, buffers are created by an algorithm-controlled machine that accurately produces most, if not all, buffers applicable to a process from their individual chemical ingredients rather than from conventional concentrates. ILC simplifies buffer making and makes the process more robust. Both labor effort and storage space can be saved — by up to 70% — as the buffer goes straight to the chromatography skid, for example.¹

This significantly reduces the footprint of the buffer prep area. As a result, at-strength buffers are blended in a more precise manner, from up to 20X salt solution concentrates, after which they are sent to other, existing equipment, for example, bioprocess chromatography systems.³ More importantly, “the quality and reproducibility of the PAT-driven buffers can also improve yields in purification steps,” adds Sanderson. As pharma executives face growing pressures to drive down costs of biotherapeutic manufacturing, yield improvement will become the next driver for the industry uptake of IBD.

Because the buffer blend is not based on mass or volume estimates, but rather critical process parameters, the accuracy of the dilute buffer output is uncoupled from the formulated concentrate buffers.⁴ “The quality and reproducibility of the buffers can also improve yields in purification steps,” says Sanderson. In the near future, Sanderson predicts that “continuous, automated buffer production will be a key component of tomorrow’s continuous processes.”

Through continued technological innovation, the biopharmaceutical industry has a renewed opportunity to solve capacity and quality issues through the adoption of advanced methods, including automated inline dilution.⁵ In particular, Asahi Kasei’s IBD system integrates QbD principles into fluid processing, and validates buffer processing in real time through its PAT-based analytics platform. Such capabilities inject accuracy, yield improvement and proactive compliance into the operations surrounding this critical-path process — something few biopharmaceutical processors can forgo to remain competitive.

References

1. DePalma, Angelo. “Easing Bioprocess Bottlenecks.” Genetic Engineering and Biotechnology News. GEN. 1 June 2015. Web.
2. Malone, Thomas, and Michael Li. “PAT-Based In-Line Buffer Dilution.” BioProcess International. 1 Jan. 2010. Web.
3. “IBD™ Wins Prestigious ‘Technology of the Decade’ Award.” Asahi KASEI. 14 Dec. 2012. Web.
4. DePalma, Angelo. “Leveling Downstream Process Bottlenecks.” Genetic Engineering and Biotechnology News. GEN. 1 May 2010. Web.
5. Patterson, Brandon J. “Automated In-Line Dilution – A QbD Manufacturing Method.” Journal of GXP Compliance 12.5 (2008): 21-33. Web