The momentum is finally beginning to build behind continuous bioprocessing in the way it did with single-use a few years ago. Faced with rising cost pressures, increased competition and escalating productivity challenges, biopharmaceutical manufacturers are embracing the cost-efficiency, consistency and scalability that continuous bioprocessing offers compared to traditional batch processing.
Yet despite the myriad benefits, many biopharmaceutical manufacturers still have questions about how these new processes will be regulated. There is a widely held perception in the industry that the risk-based approach of regulatory agencies is at odds with innovation, yet it does not need to be. In fact, the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and to an extent other governmental bodies have tried hard to encourage innovation in the pharmaceutical industry – providing this innovation uses a risk-based approach. It is here that the industry should be focusing its efforts when it comes to innovation. If we can develop new technologies and techniques that are built on robust data, then the perceived regulatory roadblocks that hinder new approaches like continuous manufacturing will be quickly overcome.
Better relationships with regulators
There is a misinterpretation within the pharma industry when it comes to regulators; many see them as a hurdle to overcome, rather than the partners that they can be. Regulators challenge the industry to move forward, but we must meet them halfway with new concepts and approaches that they can respond to meaningfully.
Take the early forays into continuous bioprocessing, for example, where there was a lot of concern in the industry about not being able to denote a ‘batch’ when the process was running continuously, and the FDA simply wouldn’t find this acceptable. In fact, when we discussed it with the regulator, it proactively worked with us to come up with a number of possible solutions. When the industry sees the regulator as a hurdle to be overcome rather than a valuable partner and assumes its response rather than seeks it, something critical is lost. It’s this closed mindset that is the true blocker to innovation, not the regulators themselves.
Unleashed by technology
In the case of continuous bioprocessing, from a regulatory perspective the process isn’t inherently different from batch processing. The operations in continuous may be sequenced differently, but they are still the same operations which require the same safeguards, quality checks and standards as in the more ‘tried and tested’ batch systems.
It’s the continuous nature of the process that brings nuances and particular challenges, and where manufacturers and indeed regulators need to focus. Take the elimination of stop/start, as an example. Whereas in batch the manufacturer can collect the entire material and test it before moving to the next step, with continuous you don’t have that luxury. Material flows from one step to the next without stopping, which then raises concerns about the possibility of contaminants and out-of-specification material passing through the process. In fact, because a continuous line allows manufacturers to maintain a completely closed system, a continuous process can actually reduce the risk of contaminants – but only if the system is designed correctly and if manufacturers have the right information at their fingertips.
It is thanks to technology and in particular the use of data that we have been able to mitigate these risks and ensure that continuous processes conform to the principles of Quality by Design (QbD) and Quality Risk Management. If you can have automated process analytical technologies (PAT) gathering and interpreting data about the flow of material along each stage of the continuous line, you don’t need to stop, pool and test materials along the way – you have all the information you need and, more importantly, that the regulator will need.
Indeed, the FDA put out a guidance document as far back as 2004 in support of PAT as a means of driving quality, but the industry is still unsure of how this will be implemented in practice. We made the decision at Pall to invest heavily in PAT, automation and machine learning to ensure all our continuous innovations are supported by robust data, particularly around scale-up, as we believe the viability and value of the continuous approach is now irrefutable.
Building for the future
The growing interest in continuous bioprocessing is driven in part by the possibilities unlocked by PAT and automation technologies. This is only natural, given that continuous bioprocessing results in vastly more data and allows for the use of statistically relevant criteria for demonstrating consistent process operation.
To access these benefits, we will all need to address the growing skills gap created by the paradigm shift of technologies. The industry, including regulators and vendors, will need more people with experience designing and operating the new biopharmaceutical manufacturing operations. Increasingly we will also be competing with other industries for top engineering, data analysis and process development talent.
This is unsurprising given the pace of change and digital transformation we’re seeing. Every industry is transforming so rapidly that university programmes simply can’t adapt fast enough to be able to provide students with adequate practical understanding. Over the next five years we will see machine learning and PAT making huge changes to the manufacturing process. By the time educational establishments have adjusted their curricula to meet these changes, the industry will have moved on again.
Ultimately, we are all on the same team and our collective objective is universal: to manufacture vital medicines in a way that is safe, efficient and which provides the greatest possible benefit to the patient. All the pieces are there to make continuous bioprocessing a success for both manufacturers and regulators, with technology and data at the forefront. If as an industry we can take a more collaborative approach to working with regulators while embracing the possibilities offered to us by technology, we have a very bright future ahead of us.
Loe Cameron is Director of Analytics & Controls at Pall Corporation
