Roadmapping Future Technology

Bioproduction – the process of manufacturing biopharmaceuticals or their precursors – has experienced persistent, yet discontinuous technological progress ever since the release of the first blockbuster biologics. Major technological advances have taken place in various aspects of bioproduction, from cell biology and gene integration to bioprocess media and chromatographic technologies.

However, due to regulatory, cost, and other risk factors, it can be difficult to implement new bioprocess technologies. New technologies are typically introduced early in a new product development lifecycle and can take months or even years to be implemented for manufacturing’s benefit. Even in the earliest stages of a new product development cycle, there is a propensity to design bioprocesses strictly on well-known technologies, which is sometimes heralded as a “platform process” – in a sense, “if it ain’t broke, don’t fix it.”

With such potential difficulties integrating new bioproduction technologies into existing processes, it behooves development teams and decision-makers to carefully consider their technology selections with the entire potential product lifecycle in mind. Aspects under consideration might include scale-up and scale-down performance, the physical operations and space required, the number of processes to which the technology can be applied, and how the selection might limit or expand future processing platforms. One might also consider market aspects, such as assurance of supply and delivery lead times, possible alternative and replacement technologies and, perhaps most important, the costs of implementing those technologies at some later date, if needed.

Let us consider the narrow example of selecting technologies for cell culture harvest and clarification. Traditionally, for vessels above 10,000 L, harvest was performed with stainless-steel disc stack centrifuges and post-centrifugal depth filters (1). As cell biology and culture technologies improved, product titers also improved. Increased titers, combined with flexibility and regulatory considerations, helped drive a shift in bioprocesses from large CIP/SIP stainless steel to smaller single-use equipment, particularly for bioreactors. At smaller volumes and moderate titers and cell densities, the stainless steel centrifuges could be replaced with single-use depth filters, reducing the facility engineering capital and operations.

But adopters of single-use depth filtration now face a rising challenge: upstream culture technologies have continued to intensify and single-use reactors are available in larger sizes (e.g., 5,000 L). These improvements portend the end of some large stainless steel bioreactors, promising to be more flexible and cost-effective than massive stainless steel vessels for multi-product facilities addressing smaller indication populations. However, the cell culture volumes and intensities are beginning to stretch the capabilities of single-use depth filtration to the edge of being tenable in performance, economics, or both.

Although some processes are locked into traditional single-use depth filters, there are alternatives available at varying levels of maturity and impact. For example, several companies have developed filters to be paired with flocculants, enabling harvest of relatively high-density cultures; a potential tradeoff is that the addition of flocculants may cause additional purification and development burdens, as well as potentially result in lower product yields. Alternatively, new filtration modalities, such as tangential flow filtration, have been (re)introduced. These have considerable implications in the residual of the bioprocess, potentially requiring development work across multiple bioprocess unit operations (e.g., moving to perfusion-based upstream). These and other technologies are available, but each one comes with additional risks, challenges, or burdens. These would become less daunting if the technology’s necessity was realized from the start.

This brief example of selecting harvest technology, though trite, highlights that there are numerous risks and challenges in adopting new technologies. Effort should be made at the time of initial selection to consider the long-term ramifications. A technology, once known, is subject to an endowment effect in which its perceived value and ease are exaggerated and the relative value and ease of unknown technologies are downplayed. 

How do we, as an industry, mitigate the risks and costs of choosing inappropriate technologies for the short and long term without exhaustive, expensive research efforts? One avenue is through industrial forums, such as the BioPhorum Group (BPOG), the International Society of Pharmaceutical Engineers (ISPE), and the Bio-Process System Alliance (BPSA). Technology roadmapping plays a heavy part in these forums, helping end-users to identify future technological bottlenecks and allowing vendors to collaboratively tune in. Overall, a level of transparency and communication between vendors and users is established, creating a more efficient marketplace for new technologies to arise in a timely fashion.

But having technologies is not the same as implementing technologies. Beyond roadmapping needed technologies, it is also critical to collaboratively consider other hurdles. In particular, the obstacles to regulatory implementation need to be addressed. By working hand-in-hand, vendors, users, and regulators can leverage forums and other collaborations to establish best practices that satisfy regulations while shaping the future of regulatory requirements. If we can become more efficient, informed, and decisive about planning and implementing the right new technology today as we look toward the future, the industry, the product, and – most importantly – the patient will be better for it.

Leverage Proven Technology to Speed Path to FIH

GPEx^® Lightning is a fast, flexible way to shorten the path to production of phase 1 material. During this talk, we share the latest data leveraging GPEx® Lightning to generate highly stable, highly productive cell pools.

Download