Innovative technologies are helping biopharma move towards round the clock production. But fully continuous, end-to-end manufacturing will only become a reality when systems are easier to combine on the factory floor, reports a new study, which set out to determine whether “technology enablers,” i.e., bioprocess systems designed to support 24/7 production, are changing drug manufacturing and helping industry move away from batch-mode production.

And the short answer is “yes,” says Andrew Zydney Ph.D., director of the membrane science, engineering, and technology center at Penn State University, with single pass tangential flow filtration (SPTFF), an alternative to batch ultrafiltration, being a good example.

“SPTFF is already being used to minimize tankage constraints in existing facilities by concentrating the eluent from chromatography columns so that they can be handled by existing tanks even as the product titer increases,” he explains. “SPTFF is also being used to pre-concentrate feed streams before chromatography to increase the dynamic binding capacity and thus the effectiveness of the chromatography step.

“New work in our lab and elsewhere has demonstrated the use of SPTFF modules for inline buffer exchange, and providing exciting opportunities to adjust pH and conductivity, in addition to product concentration, as part of fully continuous downstream processes.”

Anurag Rathore PhD, from the Indian Institute of Technology, Delhi, who co-wrote the study agrees, describing SPTFF as one of “the most exciting enablers of recent times.”

Fully continuous processes

So, industry is using continuous systems. However, to date few fully round the clock production processes have been developed. According to GlobalData, the FDA has only approved six fully continuous processes, all of which are used to make small molecule drugs. There are many reasons for the paucity of continues processes, including concerns about initial investment costs, industry reluctance to change, and fear of additional regulatory hurdles being examples.

Another factor is the technical challenge of combining systems from different suppliers, notes Rathore.

“While hardware solutions for individual unit operations exist, integrating equipment from multiple vendors remains a challenge and so does performing monitoring and control of the process as a whole,” he says. “Most companies use process and analytical equipment from multiple vendors and most of these operate on proprietary software. This makes their integration a challenge. To address this, the technology sector’s focus needs to shift to process integration, monitoring, and control.”

Whether this happens will depend on demand and biopharma’s willingness to work with suppliers, according to Zydney.

“These are difficult topics for technology suppliers to work on. Many of the key questions can only be addressed if you have access to a fully integrated continuous bioprocess that is making a real product from a commercially relevant cell line at commercially relevant titers,” he points out. “Thus, some of these problems can probably only be effectively addressed through collaborative efforts between technology suppliers and end users, often supplemented by more fundamental academic studies. These partnerships can be challenging to set up, but they are invaluable for addressing these complex challenges associated with monitoring and controlling a fully integrated process.”

Or, as Rathore puts it, “Unless biopharma end users pool together to force the vendors to follow the same standards, it will not happen.”

 

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