When viable vaccines began to be discovered amidst the height of the pandemic and Operation Warp Speed was initiated in May 2020, pharmaceutical manufacturers began scrambling to overhaul production capabilities at the drop of a hat to meet overwhelming demand from a restless quarantining society. The array of bottlenecks in the process of vaccine and pharmaceutical production these companies faced was daunting, ranging from labor shortages and production capacity to safety risks for the health of equipment operators. Thus, pharmaceutical manufacturers began seeking all opportunities to increase efficiency, including better management of buffers through inline buffer formulation – the standard for which is the industry-leading MOTIV™ IBF™ system, an award-winning proprietary technology from Asahi Kasei Bioprocess. At the time, IBF had already earned a solid track record for optimizing processes around pharmaceutical development but had not yet been widely implemented globally.

 

Traditional buffer preparation is a low value-adding activity, but it has a substantial impact on facility design, maintenance and human resources. Optimizations to the buffer preparation process have been too long overlooked, but improvements in just this single area can impact overall facility efficiency and safety. Inline buffer formulation differs from inline buffer dilution in that buffer formulation allows manufacturers to create complex buffer solutions, some with as many as 6 to 7 constituents, and this is done via precise flow control, pH, and conductivity measurement. IBF delivers buffers at required concentrations ready to be used by process equipment. An IBF system requires highly capable software to manage the required precision and to reduce waste. Despite all its clear advantages over traditional buffer management, and manual preparation, the adoption of IBF can still face headwinds as manufacturing processes are highly regulated. Any change to a component within the production process is an involved procedure that takes time and may lead to constituents sticking with what has always seemed to work just fine. 

 

The inline buffer formulation method is truly an unsung contributor in the pharmaceutical industry that uncovers optimizations in virtually every step of the manufacturing process. Combined with Asahi Kasei Bioprocess’ MOTIV equipment and OCELOT System Control automation software, it allows for a substantial decrease in labor hours and is much safer for operators as they no longer must deal with manually mixing powders on their own. In addition, traditional buffer management of powders requires a segregated space to eliminate cross-contamination. IBF eliminates the need for this space and mitigates the growing concern of powder inhalation and exposure substantially. With an automated system, human error is substantially mitigated and data integrity is maximized. It also dramatically decreases equipment footprint and allows manufacturers to create and use buffers as needed to dramatically reduce waste product.

 

Streamlining the buffer processes with an automated system can be a substantial contributing factor to help pharmaceutical manufacturers evolve towards Industry 4.0 – referring to the fourth industrial revolution with advances regarding the Internet of Things (IoT), cloud computing and analytics, as well as AI and machine learning. It will also take the automation we have today to the next level by delivering new levels of efficiency throughout manufacturing facilities. Pharmaceutical production based on Industry 4.0 factory design is manifested when these same ideas are applied to GMP compliance, validation and GAMP® requirements.

 

Industry 4.0 for pharmaceutical manufacturing is a framework that consists of many elements such as resources, information systems, organization, processes and culture as well as enablers like digital maturity and data integrity by design. This operational model is a methodology for processes from product development all the way up to commercial manufacturing.

 

Automated buffer formulation systems like the OCELOT proprietary automation system developed by Asahi Kasei Bioprocess that can be easily integrated to existing facility equipment combined with their MOTIV™ IBF™ system are an easy way to advance the automation of a manufacturing facility. These systems allow for the production of large quantities of buffer in very short amounts of time and with minimal footprint. Additionally, buffers can be produced on-demand to meet the needs of your surrounding equipment. In fact, one properly sized buffer formulation system can supply several unit operations at once and can do so without operator intervention. All these features assist in the evolution toward achieving higher tiers on the journey toward Industry 4.0.

 

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Chris Rombach is the VP of Sales and Marketing at Asahi Kasei Bioprocess America. Over his 30-year career Rombach has held various leadership and management roles in companies serving the biopharmaceutical industry. Rombach was a founding member of the BPSA, (Bio-Process Systems Alliance) and one of the early pioneers of single use systems.