When contemplating new biopharmaceutical development and manufacturing facility construction, there are three commonly pursued industry options, Conventional, Modular, and Podular. Prior to embarking on a capital-intensive building project, it should be considered whether one of these three is a preferred approach.
There is credible evidence to suggest that offsite prefabrication of a facility shell/utilities core and its modular equipment platform offers advantages over more conventional “fixed” facility installation approaches, although making the right decision will be a more nuanced process.
The difference between conventional, modular, and podular biopharma facilities
Strictly speaking, “Conventional” implies minimal incorporation of modularity (reconfigurability of processing units), while podularity (intra- or inter-facility transportability) takes modular concepts to another level by modularizing the entire factory unit.
The following differentiates the three approaches (conventional, modular, podular) in more detail:
- Conventional
- Brick-and-mortar facilities designed to last 20 or more years with all major utilities embedded into the building infrastructure
- Operating equipment is permanently anchored into the facility’s substructure, mandating major renovation for equipment reconfiguration and/or upgrades
- Modular
- Brick-and-mortar facilities designed to last 20 or more years with all major utilities embedded into the building infrastructure
- Operating equipment is prefabricated offsite and the skid-mounted platforms are subsequently integrated into the facility enabling reconfiguration and equipment upgrades without major renovation
- Podular
- Brick-and-mortar warehouse-like facilities designed to last 20 or more years with basic utilities, such as water and electricity, embedded into the building infrastructure
- Autonomous shells (PODs) and modular, skid-mounted equipment platforms are prefabricated offsite and shipped for local onsite assembly. Utilities such as HVAC, process control and hepa filtration systems are pre-integrated into the PODs
- Inter- and intra- facility reconfiguration of the entire operational factory is enabled
Benefits of prefabricated modular/podular biopharma facility construction
The benefits of prefabricated modular/podular construction in the reduction of project timelines were highlighted in a January 2019 LinkedIn post from Dennis Powers. Although the article does not explicitly differentiate between modular and podular, the referenced technology fits the aforementioned definition for podular. The economics associated with these various approaches is a topic for another discussion. However, because cost analyses are complex, albeit necessary, one needs to thoroughly vet the underlying assumptions and ensure that the supporting data sets used are not unfairly biased to favor one approach versus the other.
Some of the benefits cited in the referenced posting are highlighted below:
- Lower onsite project complexity
- Compressed timelines through the application of parallel vs. sequential construction practices
- Reduced financial risk since investment decisions can be made nearer to when the capacity is required
- Creation of repurposable assets (PODs) helping to mitigate obsolescence
- Additional benefits:
- Staged launch: Initial launch at some fraction of the peak market forecast, followed by scale-out or tech transfer to a pre-existing brick and mortar facility
- Technology transfer: Mitigate risk by replacing the time, expense and variability of traditional tech transfer with the expense associated with shipping and revalidation of the facility (more on that below)
Which of the three approaches to choose is dependent upon a company’s unique set of circumstances and should also be informed by a thorough examination of the intended use and desired life expectancy of the facility, as this will determine the optimal degree of flexibility/adaptability. Quality, costs, and timelines are of course equally important considerations, and as is often the case, the pros and cons of each approach need to be carefully assessed. In the end, one may find that a hybrid solution provides the best option for success.
For facilities incorporating only batch manufacturing technologies or if a dedicated single product manufacturing plant is envisioned (and projected to remain unchanged for a significant length of time), conventional construction concepts may be warranted assuming that the detailed cost analysis favors this approach. However, given the pace of technological change in the first quarter of the 21st century, especially as related to manufacturing equipment and ever-evolving digital platforms, designing for maximum flexibility would appear, in my view, to be a better choice.
Reconfiguring equipment modules or transporting equipment trains from one site to another is a reasonably well-established practice in both API and DP manufacturing and can be applied to both conventional brick and mortar and prefabricated modular buildings. As mentioned previously, major renovation will be required in the former case. Less established, but certainly not unprecedented, are the design of autonomous factories that are reconfigurable within a site or transportable en-masse from one location to another.
Factory transportability and the trend of miniaturizing production facilities in biopharma
I am very intrigued by the concept of factory transportability — a positive consequence of combining modularity with podularity. At one end of the spectrum, numerous efforts have been made to create benchtop-size drug production units that can be transported on the back of a truck or in some cases on an individuals’ back (see MIT/DARPA and DARPA/Panacea). These are truly amazing advances that “one only dreamed about” a short 10 or 15 years ago. We are most likely only seeing the tip of the iceberg.
At the other end of the spectrum — and of special interest to me — is the evolving paradigm to miniaturize, modularize and podularize modern-day production facilities to enable relocation of the units virtually anywhere in the world. There are many examples where these concepts have been brought to life over the past five years or so.
The following are illustrative and represent variations of the same concept:
- Lonza (Pharmaceutical Technology Lonza) and Pfizer (FiercePharma Pfizer) separately partnered with GE Healthcare and their KUBio (GE Lifesciences KUBio) manufacturing solution, to build facilities based on single-use bioprocessing technologies integrated into a prefabricated shell. These ‘factories in a box’ are stacked onsite like Legos to create a >15,000 m2 multi-purpose site.
- Pfizer (PCMM) partnered with G-CON Manufacturing and GEA to install a prefabricated autonomous oral solid dose manufacturing facility in a pre-existing Pfizer warehouse. The facility was designed to enable disassembly and relocation to another site, although this is not currently being considered. The continuous manufacturing unit has been approved by the FDA to manufacture commercial supplies of Daurismo (glasdegib) with additional projects expect to follow in the future
- Merck (FLEx) partnered with G-CON to build the Formulation Laboratory Experimental Center (FLEx) as multi-modality, podular development and production spaces that can be moved within or outside FLEx so that the area can be reconfigured or presumably swapped out and transported to another location without requiring renovation.
Companies that wish to build new development and manufacturing facilities generally want their investment to be an enduring one, though now at a time when the pace of technological change is occurring at rates never before seen. Consequently, it makes sense that building facilities that are adaptable in ways that can accommodate evolving technology paradigms, user requirements, and circumstances require design elements that incorporate principles to enable maximum flexibility.
In summary, I’m very bullish on the utilization of modularity in our industry and would like to see the concept of podularity explored even further. I am also interested to see whether the combined concepts of miniaturization, modularity, and podularity can be utilized to address a range of issues including: drug shortages, high supply chain/inventory costs, patient access to medicines, the containment of highly potent/toxic compounds, and the increasing demand for local manufacturing. My final comment is to encourage those of you contemplating biopharmaceutical manufacturing capital construction projects to carefully consider all available options, design with the future in mind, and respectfully push back on the ever-present “this is the way we’ve always done it” mindset.
