Bucking the Trend - A perspective on why platform processes are not and should not define the future of bioprocess development efforts. This article is part of a special section on biopharmaceutical t

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Bucking the Trend
A perspective on why platform processes are not and should not define the future of bioprocess development efforts. This article is part of a special section on biopharmaceutical trends.


BioPharm International
Volume 25, Issue 9, pp. 54-56

PITFALLS, REMORSE, AND THE PATH FORWARD

Just as with any other beneficial procedure or method, there are complications and problems that result from over-reliance of the singular platform approach. For instance, proponents of platform processes often argue technical knowledge can be acquired and developed by continually improving the platform. This notion is a fallacy as often platform improvement is discouraged due to the effect these changes would have on external groups already operating in the platform framework. Furthermore, implementing subtle improvements become less and less likely as these potential changes require greater justification. Recognizing that innovation arises from a series of small, seemingly inconsequential steps, the inertia around modifying platform processes can lead to stagnation and inefficiencies over time.

In addition, with a singular platform process in place, molecules with "platform friendly" physical and/or chemical properties may be favored over other molecules. That choice might not appear damaging, but the link between a molecule's manufacturability and its efficacy is weak or nonexistent. So, funneling molecule after molecule through development based primarily on its ability to conform seems ineffective and out-of-touch, thereby questioning the validity of the system that spawned this result. Such a system is unable to self-correct as the bias for conformity is difficult to eliminate. A troubling extension of this bias is that certain molecules are effectively killed if they do not fit the platform or require significant development. This action is appalling because it represents a true disservice to patients and the very business of biotechnology. To terminate a program with potential life-saving properties because it does not fit the cookie-cutter mold is beyond egregious. When development groups refuse to work outside of the platform environment, their failure is everyone's failure.

With the profound long-term effect platform processes and the mindset that goes hand-in-hand with its uninterrupted implementation can have on bioprocess development, a different approach is needed. An approach is needed that leverages the technical knowledge and overall skill set not only to develop new processes, but also troubleshoot existing processes. Such expertise requires continued exposure to an ever-expanding assortment of unit operations, techniques, and methodologies. Think of it as a scientist's repertoire or toolbox that is continually updated and employed. Every method and every unit operation has to be mastered such that it can be reworked and reconfigured as needed.

Every set of conditions tested is another data point, and as data points are collected into a comprehensive database, decisions can be made for new processes. It is important to note that not all aspects of each unit operation or method have to be identified upfront before implementation. Such characterization comes over time, as certain parameters are locked down and others are varied to understand the design space and identify where the process can potentially fail. Instead, the focus can be on functionality and utility—what purpose might a particular step play and how. For example, defining the expectations for a capture step (i.e., purity, aggregation, and profile of impurities) can instantly exclude or highlight certain types of resin based on their performance. Applying this very notion systematically across all unit operations can identify weak spots that merit greater scrutiny while also providing several possible avenues to explore concurrently.

A key responsibility for development groups that can often be overlooked is troubleshooting; assisting manufacturing and technical services groups in addressing unexpected issues. Troubleshooting by definition requires a systematic approach to identify the source of a particular failure or potential problem. Underlying that logical, structured approach is technical knowledge, without which troubleshooting cannot be accomplished. A modular platform approach would in effect, expose development groups to a whole assortment of operations and methods, thus enhancing their overall technical knowledge and ability to troubleshoot. For example, exploring multiple ways in which cell lines can be transfected and screened can lead to a better understanding of how particular cell lines behave and what triggers might disrupt productivity or product quality. Similarly, experience with multiple formulation buffers can lead to the development and implementation of screening tools aimed at delivering the right formulation for a specific mode of administration, concentration, and stability. Working in a modular framework essentially builds a layered, powerful database that can be employed to rapidly develop processes without forgoing actual development, as the singular platform approach does.

CONCLUSIONS

The benefits of developing and instituting platform processes are undeniable because the versatility of the platform drives cost-effectiveness and overall efficiencies, especially for routine operations. However, once established, a platform approach can be difficult to modulate as incremental changes are heavily scrutinized particularly by key stakeholders outside of development. As a result, a singular platform technology can lead to stagnation if not routinely challenged and refined. An alternative approach, one that has a longer timeframe in mind, is to develop expertise around many distinct unit operations that can be assembled into different combinations. By pairing an understanding of the capabilities and limitations of each unit operation from seed train operations to ultrafiltration and chromatography, with platform evaluation techniques, new processes can be quickly constructed. By constructing a framework that is more modular in form than true platform technologies, a whole host of molecules can be produced, purified, and formulated rapidly without sacrificing efficiencies and process robustness. Monoclonal antibodies may be prevalent today, but that may not be true several years from now as technologies advance and the industry inches closer to personalized medicine demarked by the use of many different types of therapeutic molecules. Being ready for any molecule that comes out of research is not only prudent, but fundamentally a core responsibility shared by all development groups.

ACKNOWLEDGMENTS

The author would like to Luca Di Noto and Derek Adams for support and feedback during preparation of the manuscript.

PRATIK JALURIA, PHD, is an associate director in upstream development at Alexion Pharmaceuticals, Cheshire, CT,
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