20th Anniversary Issue: From the Editors

Founded in the middle of 2002, BPI published its first issue in January of 2003. Our 20th-anniversary issue thus takes the form of a state-of-the-early-21st-century industry report. Assembling this content has reinforced our appreciation of the remarkable paths that this industry has taken and continues to take — and our journey alongside it. Having worked as editors in this industry since August 1988 (Montgomery) and September 1996 (Scott), we’ve found it difficult to maintain a chronological grasp of developments — especially given how myriad transformations can arise from the uptake and incorporation of new technologies.

In the mid 1990s, the hot topic was validation — and for a time, biopharmaceutical publications were inundated with manuscripts on the topic as the industry grappled with the regulatory requirements. In this century, of course, the arguably disruptive topic has been single-use technology (SUT) — which now seems to permeate applications throughout drug development and manufacturing.

BPI’s 10th-anniversary issue in June of 2012 was written largely by our editorial team. It was organized — as we had been used to doing overall — based on the “pillars” of bioprocess development: upstream production, downstream processing, manufacturing, and operations. We reviewed equipment and technologies that had been introduced within the publication’s first decade, highlighting a range of advances within those categories.

In the past few years, however, we have become less satisfied in relying on that pillar-based organization of content. The general issue themes still help focus our editorial and advertising endeavors. But the messages emerging from your industry — exemplified by this issue’s contributions — have focused increasingly on integration, communication across the former “silos,” alignment of instrumentation and methods, and speed. Staff across all functions are working together to move programs toward clinical testing, regulatory review, and marketing. Addressing such issues as developability and scalability so seriously and early in development would have seemed like a distraction 20 years ago. Now those considerations are a necessity.

So for this issue, we stepped away from the old organization by pillars to a scheme that represents relationships and activities among the interconnected working groups across a more mature biopharmaceutical industry. That makes it an interesting read, even if it was somewhat of a challenge to organize. Like unraveling a sweater, just choose any strand of yarn and pull.

The Journey So Far
Quality Systems: Early discussions of quality by design (QbD) and process analytical technology (PAT) were exploratory, with somewhat murky suggestions for implementation. In January 2007 and March 2008, respectively, our process-control and process-design supplements mostly brought shrugs and head-scratching from potential advertisers. Now we all routinely refer to critical process parameters and quality attributes (CPPs, CQAs), design of experiments (DoE), and PAT tools. A focus on scalability of processes and understanding of parameters under the new paradigm has catalyzed development of scalable processing equipment, ultimately aiding in technology transfer and enabling the launch of modular processing suites/factories around the world. Regulatory harmonization efforts continue to gain momentum in ways that many people thought could not happen two decades ago.

SUT: BPI’s first SUT-focused supplement, developed in partnership with the Bio-Process Systems Alliance, came out in 2007. A decade later, SUT had become so integrated into your work that we couldn’t justify singling it out in a special issue alone. By now, of course, SUTs are ensconced as major tools for cutting costs, speeding development, streamlining manufacturing, and so on. Some speakers in early panel discussions said flat-out that standardization of such components could never happen. Yet we now see progress toward exactly that, especially with connectors and fittings, and we’ve learned through recent experience how a supply-chain crisis intensifies the need for more interchangeable options. Some products and processes still call for fixed, stainless-steel equipment, and some companies are finding that end-to-end disposable solutions fit their needs. Meanwhile, hybrid options seem to be the most widespread solution for design of facilities and operations.

Intensification: As technologies new and revised (notably, perfusion) now enable reductions in overall processing scale by improved upstream production titers, and with disposable and modular units able to handle downstream processing, continuous processing has been revisited more widely and seriously. Authors and speakers present models of how such processes would look for different modalities. Meanwhile, processes have become more compact, technologies more flexible, and equipment better adapted for new product classes. For many thought leaders, the continuous concept may be less realistic or constructive to explore than is a focus on intensification through optimized unit operations connected to one another only where it makes sense to do so.

Advanced Therapies: The main subject category that was missing from BPI at its founding was cell and gene therapy. For March 2011, we turned our attention to the need to bring knowledge from commercial biopharmaceutical development into that sector, helping it move from small-scale research and hospital applications toward a regulated industry. The initial challenge had been whether such products even could be dealt with as commercial products. How could they be regulated and made affordable? Now companies are working toward creating off-the-shelf cell and gene therapies, even moving modalities from autologous to allogeneic to reduce costs and ease both distribution within established networks and to larger patient populations.

Pandemic: A cumulative legacy of solid knowledge and technology helped prepare the biopharmaceutical industry to respond quickly to the COVID-19 pandemic. It may be too early to call this a true tipping point, but the pandemic’s impact on our industry has been significant and will be long-lasting. It has tested our predictions about the value of continuous/intensified processes, highlighted the importance of emergency authorizations, and boosted formulation and delivery of mRNA therapeutics and antibody development — all while highlighting weaknesses in the global supply chain and revealing gaps in communication about bioprocess technologies and clinical testing to a broader population. The industry undoubtedly has much to be proud about in its responses to the continuing crisis. But take note of some cautionary statements in this issue against applying the lessons learned too broadly.

Businesses that were hard hit by quarantines and layoffs now are suffering from a lack of qualified personnel, when levels of training and recruitment into the industry already had been less than ideal. So several authors herein note the critical need for knowledge management, talent recruitment, and effective training programs. Some relief may come from the industry “4.0” initiatives transforming processes through automation — with the additional benefit of reducing contaminant risk through human exposure — and an evolution from digitization toward digitalization. Compliance with 21 CFR Part 11 regarding digital records was a challenge 20 years ago; tremendous leaps in the information-technology sector since then have made it less of a question now and more of a basic assumption.

The Big Picture
In planning for this issue, the four editors sent a long list of possible topics to as many contacts as we could: suppliers, end users, consultants, and contractors. We asked for manuscripts on topics of choice or answers to interview-style questions. The responses were overwhelming — literally so, in that we ended up exceeding our initial paper order at the printer. So you will see more related articles and multipart conclusions in our coming issues this fall. If you think that we’ve left out a critical topic, please let us know.

For our 20th anniversary, in classic BPI style, we gave ourselves the gift of a complex and weighty project. It could not have succeeded without a powerhouse editorial staff — namely Maribel Rios and Brian Gazaille — and contributions of our sales, production, marketing, and administrative teams. As the two remaining founders of the publication, we have been blessed with a staff stability that’s increasingly rare in publishing and evidenced by the results you hold in your hands. It brings the weight of all our combined years of learning about the industry to everything we do.

The picture that work has created here is of a dynamic and mature industry that continues to reinvent itself in response to the times — an industry made up of people who truly care about getting therapies to patients who need them quickly and affordably. The image is also a “busy” one thanks to the many interconnected companies and groups driving innovations in bioprocesses, biotechnology, and biologic drug products around the world. BPI as a publication could not have thrived over these past 20 years without the invaluable input from our readers, authors, advisors, and advertisers. On behalf of our editors and sales team — and those who have pursued this journey with us — we thank you. And we can’t wait to see what you’re going to do next.