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.
Sep 01, 2012

Not surprisingly, industries operating in a free market tend to emulate and implement successful practices from divergent industries. This tendency is particularly true for technology-based industries such as biopharmaceuticals and software development—two industries that are customer-focused and rapidly changing. Although the term "platform" dates back hundreds of years, the concept of developing a platform or framework off of which subsequent products can be launched originated in software development. Current industry leaders in software development have implemented this concept with great success. Over the past decade or so, biopharmaceutical companies have applied platform processes to various aspects of their operations. The concept has gained considerable traction within the field of bioprocess development as an increasing number of groups have implemented it and begun touting its benefits in quick succession. However, as with any idea, there are benefits as well as disadvantages that need to be assessed prior to and concurrent with implementation.

TOUTING THE PLATFORM

The central argument in favor of a platform process, particularly in the context of bioprocess development, is that it expedites project timelines. By leveraging similarities between new molecules, a platform process enables resources to be deployed efficiently, reducing costs while also shrinking timelines. Everything from cell-culture expansion steps to filter sizing can be grouped together to form a comprehensive, thaw-to-formulation platform process. Particularly in the context of preclinical and early-phase clinical production needs, platform processes allow for rapid development of molecules. Even for late-phase clinical production needs, a platform process provides a starting point for subsequent development, readying a process for regulatory approval and eventual commercialization.

More specifically, platform processes also allow bioprocess development groups to focus on those aspects of the process that require greater evaluation or development such as viral clearance and bioreactor harvest criteria. For instance, viral clearance must be demonstrated under the conditions employed during purification steps to ensure the safety of the end product. Orthogonal steps capable of removing viral contaminants by alternate modes of action must be employed, with the performance of each step quantified. Because each molecule is different, with different physiochemical properties such as its isoelectric point (pI), and purified under slightly different conditions (i.e., buffers, pH, and conductivity), viral clearance must be demonstrated routinely. Similarly, specific cell-culture conditions can degrade the desired product based on culture duration (i.e., temperature and pH), cell viability, and the onset of apoptosis.

Determining how these and other factors affect product quality is vital to successful transfer and implementation of a GMP process. It is crucial to understand these operations because of their potential to affect release of the final product. Therefore, both operations need to be explored in detail. With a platform process in-hand, many noncritical operations can be ignored and run based on the platform, focusing instead on critical operations such as the two described above. This ability to prioritize effectively while maintaining a high level of process understanding is another benefit of platform technology.

Another realized benefit of employing platform processes is that it simplifies the complexity of the interactions taking place between groups inside and more importantly outside of the process development group. Groups such as quality assurance, quality control, logistics/supply chain, and manufacturing can all benefit from process development's use of platform processes. For instance, vendors for everything from growth media to chromatography resins can be assessed once (audited and certified by quality assurance) and relied upon routinely because multiple programs will use the same raw materials and consumables. Similarly, specifications defined by quality control and material numbers defined by logistics can be defined once and be used for multiple programs. Implementation of a platform process also espouses confidence in manufacturing groups because preparing and executing batch records are simplified. In other words, all of these groups external to process development benefit from standardized, well-defined workflows that have been previously tested and shown to be effective; a hallmark of a true platform process. In fact, the better the platform, the more these desirable characteristics can be achieved.