There are a number of developments in both science and engineering technology that are leading the biopharmaceutical industry into a new age — the age of the “Flexible, Agile” facility. This transition is bringing with it a new set of operational and conceptual facility attributes that will be the cornerstone of the industry for the next 20 years.

The prime example of this new facility paradigm is the U.S. Department of Health and Human Services’ Biomedical Advance Research and Development Authority (BARDA) pandemic flu vaccine manufacturing business model, as stated in its recent request for proposal, “Centers for Innovation in Advanced Development and Manufacturing (ADM).”  This business model requires the very rapid, large-scale production of several new pandemic flu vaccines based on pandemic sample viruses (reference virus) obtained from new threats identified in the patient population. The U.S. Department of Defense has also adopted a similar model in its ADM program under a similar production paradigm.

Significant levels of funding are being earmarked by both of these programs to develop new, faster, more agile programs for the manufacture of biologic vaccines and therapeutics that will have a significant impact on shaping the “Facility of the Future” (FoF) business model.

This is where Bigfoot and Speed Racer come in to play.

When you look up the physical characteristics that most people identify with the legend of Bigfoot, the words most often used are “giant-like,” “large,” “enormous,” “slow,” and “bulky.”

These aptly describe the decade of the ‘90’s, where the biotech industry had its foundation. Large-scale facilities (10,000 to 20,000L) that were developed around a single platform became the foundation of the Industry’s growth and expansion during those years.

We saw dozens of facilities launched and licensed that were centered around the common platform, large-scale, low-titer, and low utilization operational approach. These “Bigfoot” characteristics served the Industry well for the short-term, allowing for the dynamic growth of market share and lower cost-of-goods when compared to their predecessor facilities.

We recognize that manufacturing capability is a critical function for the development, launching, and supply of the biopharma market with high quality therapeutics. The first step to reaching an understanding of future facility models is to understand the challenges presented by biopharma manufacturing. These challenges are discussed in a series of articles written by Odum, Witcher, and Zivitis in Pharmaceutical Engineering where the concept of decoupling of the major process, facility, and infrastructure attributes is developed, leading to an understanding of the agile nature of the FoF.

Enter Speed Racer.

Those of us who grew up with Speed Racer knew his characteristics well: he was fast, agile, mobile, and quick to respond to the challenge. This is the target of the bio-manufacturing industry today — a mature industry that has to be able to respond to constantly changing requirements as science and engineering technology advance. It is easy to see that the biopharma industry of today is very different and more complex than the industry that was birthed four decades ago around the batch process, stainless steel asset facility model.

We will have to measure the success of future facilities in terms of utilization, flexibility, and efficiency, as well as how they provide a platform that supports and facilitates the operational excellence required for reliably producing high quality product while meeting an ever-evolving set of regulatory compliance guidance. The Speed Racer model is going to allow this transition away from the current Bigfoot state, with new enabling technologies that will provide manufacturing platforms that meet the goals of being flexible with low capital unit operations changeovers, efficient movement to new markets, and a scale-out approach with smaller increments of capacity from highly productive processes to meet lower demand markets.

Of course, one says, “Sounds good; how will it work?”

Believe it or not, this evolution has been in progress for a decade. It is best represented by a simple graphic developed by the ISPE Biopharmaceutical Baseline Guide Team that focuses on the impact of process technology to confirm validated closed systems and thus reduce the dependency on classified spaces to ensure product protection.

In this simple figure, it is easy to see the transition of the Bigfoot (Case 1) into a form of the Speed Racer (Case 4) in terms of the size of the classified space that is driven by the ability to define process system closure in a validated state. When you couple this to the work being done by groups such as the BioPhorum, where the “ballroom” concept of manufacturing facility design basis is evolving, it becomes easy to see that where we were and where we are going are diametric opposites — Bigfoot and Speed Racer.

The transition of the Bigfoot model facilities is already in progress. Many companies are developing process models that allow for the implementation of a hybrid manufacturing model, where traditional stainless steel and current single use systems (SUS) are being implemented to give older facilities new life without incurring the huge costs of decommissioning.

Where the hybrid model is being implemented, the focus is again on utilization and efficiency. These facilities may take on a new, sometimes unconventional, look. SUS equipment will co-exist inside manufacturing areas in a kind of “mating dance” that results in improved overall facility utilization and lower operating costs.

For three decades, biologics manufacturers have relied on traditional manufacturing platforms that were rooted in integrated, large-scale Bigfoot-type facilities. These stainless steel-based technologies are not designed around flexibility or ease of adaptability, nor are they highly efficient in their utilization. Yet, as previously stated, they have served the needs of the industry well.

As companies expand their product pipelines, platform technologies change, and business models have to evolve. Many companies, bio-CMOs in particular, find themselves with a dilemma: how to meet these changing demands with their current, aging facility assets. Implementation of new enabling technologies like SUS and modular facility designs are changing the dynamic of manufacturing project delivery. CMOs will likely be on the leading edge of adapting these new technologies.

As we move further into the fourth decade of the biotechnology industry, we are likely to see many more Speed Racer facility models, utilizing SUS platforms, modular delivery approaches, and unique operational and business models that would have never been thought of back in the 1990’s. Bigfoot’s days are numbered. 

References

1. U.S. Department of Health and Human Services’ Biomedical Advance Research and Development Authority (BARDA) – Request for Proposal – Centers for Innovation in Advanced Development and Manufacturing,” (HHS RFP 11-100-SOL-00011).
2. U.S. Department of Defense – Request for Proposal – Advanced Development and Manufacturing (DoD RFP W911QY-11-R-0023)
3. “Next Generation Facility Forum” Pharmaceutical Engineering, volume 33, numbers 1, 2, 3; January – June 2013.
4. ISPE Pharmaceutical Baseline Guides, volume 6, “Biomanufacturing Facilities,” p. 156.

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Jeff Odum, CPIP is director of Operations at IPS. He can be reached at jodum@ipsdb.com.