White Paper

Modular, Flexible, Or Both? Key Considerations In Biomanufacturing Facility Design

scalable cleanroom

By Maik W. Jornitz and Sidney Backstrom, G-CON Manufacturing, Inc.

Discussions are widespread about the paradigm shift in the manufacturing site design and flexibility needs of the biopharmaceutical industry.1, 2, 3 The motivations behind these facility organization changes are manifold — for instance, new drug developments, higher expression rates, and changes in process technologies, especially the implementation of single-use systems. In addition, the transformation of treatment to more individualized therapies raises different aseptic processing standards and logistics concerns. Last but not least, there are purely economic reasons for reducing the cost of goods sold.

These, and other, factors are driving a new focus on capacity and process utilization, on facility flexibilities and robust containment options respectively. Ultimately, we are witnessing a shift from large-scale, single product-dedicated brick-and-mortar facilities to multipurpose, versatile ones. Successful facility layouts may also be copied in a cloning approach, to rapidly establish sites in multiple regions of the world.

The shift in facility design requirements resulted in the development of modular, or building block, facility design. Often, though, the term “modular design” is interchangeably used with “flexible facility”, which requires reevaluation, as flexibility may be interpreted in different ways. The article will review when a facility should be described as modular or flexible, or as modular and flexible.

Facility Designs Of The Past, Present, And Future

In addition to traditional brick-and-mortar facilities, there are a range of alternative facility designs, including modular container, modular stick-built, isolator (or containment-based), and autonomous cleanroom POD designs (Figure 1). Most of these designs are modular, which offers advantages over traditional approaches, especially in speed of construction.

Figure 1: POD infrastructure

Having said this, most modular designs utilize the same HVAC superstructure above the cleanroom area as traditional facility designs, and the HVAC system is a major constraint to flexibility. When it is designed as a superstructure, it is difficult to change, difficult to scale up or down, and difficult to repurpose. Thus, modularity loses its flexibility as soon as the facility is assembled and interconnected to the HVAC system. For example, if you want to scale up the cleanroom area, you must open the interconnected space and add the necessary cleanroom space. But by doing so, the existing process is interrupted by the opening and by the pressure cascade rebalancing required.

Each style of facility design has its own unique purposes, benefits and disadvantages (Table 1). Often, these designs are utilized in a hybrid mode and so are not necessarily entirely independent. These facility designs are tools in the toolbox of drug manufacturers and their supporting engineering firms, and questions should be asked before making a choice.

  • What is the purpose of the facility?
  • What are the requirements to fulfill the purpose?
  • How will process technology evolve and influence the current facility layout?
  • Will the cleanroom infrastructure be at the same facility in a few years?

Ultimately, the design choice boils down to the particular need of the application and end-user requirements, and these needs and requirements must be carefully observed to determine the optimal long-term solution. In addition, the final design requires thorough analysis of the total cost ownership and all financial facets of the facility, cleanroom infrastructure, and process equipment — not just the cost per square foot.


Table 1: Strength and weakness analysis of different facility designs

Facility Design



Brick and Mortar

  • Extensive experience level with such facilities
  • Dedicated product segregation
  • Large area design possibility
  • Difficult to repurpose
  • One product lifecycle
  • High CAPEX
  • Time-to-run: Up to 4 years
  • Inflexible
  • Large HVAC superstructure
  • Difficult to decontaminate, if necessary


  • Cheap
  • Extensive experience level with such facilities
  • Large area design possibility
  • Time-to-run: 12-18 months
  • Wall systems must be protected against cracks to avoid potential mold contamination
  • Creates dust problem during construction
  • Built on site with high amount of FTEs
  • Fixed and inflexible structure

Modular Container

  • CAPEX: 70-90% of traditional built
  • Time-to-run: 18-24 months
  • Off-site build-up
  • Interconnected to one large facility, losing its flexibility
  • Large HVAC superstructure
  • Shipping costs
  • Not scalable

Modular Built

  • CAPEX: 50% lower than traditional built
  • Time-to-run: 6-18 months
  • Build into a shell building
  • Potentially scalable
  • Interconnected to one large facility, losing its flexibility
  • Large HVAC superstructure
  • On-site build-up

Isolator or Controlled Environment Module

  • CAPEX: 50% lower than traditional built
  • Time-to-run: 12-18 months
  • Modules are repurposable
  • Possible to decontaminate
  • Scalable w/o interruption of existing processes
  • Size limitations make the use of larger equipment difficult
  • BSL containment limitations
  • Centralized HVAC

Autonomous POD

  • CAPEX: 40-50% of traditional built
  • Time-to-run: 6-12 months
  • Moved into a shell building with long-time FTE involvement at building site
  • PODs are repurposable
  • Easy to decontaminate
  • Scalable w/o interruption of existing processes
  • Shipping costs
  • Equipment size excursions require project POD
  • Shell building could be restrictive


Listing critical design parameters in a decision matrix will help you determine which of one of the tools to use for your project and/or a section of your project. As mentioned previously, a facility does not necessarily have to use a single design approach throughout; often, a hybrid solution of two or even three of the options listed is required. For example, cell therapeutic or antibody conjugate processing often occurs in production isolators surrounded by a Class B environment, which can be any type of cleanroom. Autonomous cleanroom POD solutions are most commonly connected to a modular-built corridor system. A one-size-fits-all approach will not necessarily make a modern facility more viable, despite being used for many years in the design of large-scale production processes. The intensification and miniaturization of manufacturing processes necessitates more innovative and flexible facility and infrastructure designs.

Modularity and Flexibility Are not Necessarily Interchangeable

Modularity and flexibility need to be distinguished from one another. The terms are used interchangeably, but they are often totally unrelated. Modular facilities designs are excellent concepts that, as described above, can be deployed faster than traditional facility layouts. Yet, most modular facilities become inflexible when interconnected, very much resembling traditional facilities.

For example, modular container systems are built off-site and ultimately interconnected to become a total facility at the final location. These systems are well-established and mirror large-scale traditional facilities, except that the construction happens off-site and assembly on-site. These facilities compared favorably to traditional sites on the basis of faster time-to-run. Today, these facilities are not just labeled as modular, but also flexible, which a questionable characterization. What is so flexible about modular containers interconnected to a single facility, often dedicated to a single product? Modules lose their modularity upon interconnection.

Likewise, modular stick-built facilities are called modular, but are they flexible? Probably not, as observed by Alain Pralong in a recent paper: “Until now, modular facilities have reproduced traditional architecture with regard to embedding utilities piping and HVAC ducts in the interspace between the physical module limits and the suspended ceiling making refurbishment, if required, extremely complicated.”4 These modular facilities are as flexible as traditional facility designs. Therefore, modular and flexible should not be used in the same context.

So, how should we define a flexible facility? Flexibility is often related to two major factors: multiproduct/multipurpose processing and scalability. Other factors are mobility and the ability to achievable product-lifecycles from the same process and infrastructure.

“Processing flexibility” is often used in conjunction with single-use equipment technologies.5 These units have a multitude of technological and economic benefits, such as serving as the first containment barrier, which creates the potential flexibility of multiproduct processing. However, the reliance here is on the robustness of the single-use processes. In the event of a breach, the containment duty shifts to the surrounding environment — the cleanroom space. This means if you want to maintain the flexibility of production, the surrounding environment needs to be easy to clean and sanitize. This includes the HVAC system, which must be compact to achieve a validated sanitization process. This can only be achieved when the cleanroom space has separate, independent HVAC units.

Scalability is another aspect of facility flexibility, meaning that processes and facility components must “flex” with capacity demands. The facility needs to increase production capacities quickly if product demand soars, and as easily ramp down if demand falls —all while maintaining product quality. In such an instance, the process and surrounding environment must be robust but repeatable. Scaling of the cleanroom space should not influence or interrupt existing, running processes, but rather must be achieved without stoppage.

Figure 2 shows an example of autonomous cleanroom units that can be docked against each other without interrupting the existing processes. These units also enable a “cookie cutter” approach to facility design, transplanting units to multiple regions of the world.

Figure 2: Scalable cleanroom units docked against each other for cell therapy purposes



Flexibility and modularity are not necessarily equivalent. It is important to review the various modular design offerings carefully and determine which generate a traditional facility layout or provide little or no flexibility. Single-use technology can provide flexibility in the form of multiproduct processes and easy scalability; however, its reliance on containment very much limits its flexibility.

True flexibility comes with autonomy of the critical cleanroom space. Autonomous, compact cleanroom systems, like PODs, can be painlessly decontaminated and sanitized, controlled, and reused. The cleaning and repurposing of autonomous cleanroom spaces make these most suitable for multiproduct processing. Furthermore, these systems can be deployed quickly and, if needed, moved.

The one-size-fits-all approach to biopharmaceutical facility design often leads to suboptimal solutions. The long-term needs of process and facility infrastructures must be thoroughly analyzed to determine the ideal — often hybrid — solution. Utilize the best tools from your toolbox and determine the total cost ownership, not just, erroneously, the cost per square foot.



  1. H. L. Levine, J. E. Lilja, R. Stock, H. Hummel, S. D. Jones (2012) Efficient, Flexible Facilities
for the 21st Century, BioProcess International 10(11)
  2. Hodge G. Hodge (2009) The Economic and Strategic Value of Flexible Manufacturing Capacity. ISPE Strasbourg Conference, 28–29 September 2009, Strasbourg, France.
  3. A. Shanley, P. Thomas (2009) Flexible Pharma: Puzzling Out the Plant of the Future, PharmaManufacturing.com
  4. A. Pralong (2013) Single-use technologies and facility layout – a paradigm shift, Biopharma Asia Magazine, Vol 2, Issue 1
  5. R.B. Holtz, D. Powers (2012) Integration of a Single-Use Platform Process within an Innovative Facility Design, BioPharm International Supplement, Vol 25, Issue 11

About The Authors

Maik W. Jornitz, president of G-CON Manufacturing, is a distinguished technical expert with close to 30 years of experience in bioprocesses, especially sterilizing grade filtration and single-use technologies, including regulatory requirements, integrity testing, systems design, and optimization. Jornitz has published multiple books, book chapters, and over 100 scientific papers. He is vice chair of the PDA Science Advisory Board, Marketing Advisory Board and member of the Audit Committee, as well as an advisory board member of the Biotechnology Industry Council and multiple science journals. He received his M.Eng. in bioengineering at the University of Applied Sciences in Hamburg, Germany, and accomplished the PED program at IMD Business School in Lausanne, Switzerland.

Sid Backstrom is the director of business management for G-CON Manufacturing. He functions in multiple areas for G-CON including contract negotiations, partnerships, risk and insurance, regulatory, sales and marketing, management, company policies and procedures, etc. Backstrom has also provided consulting services to Gradalis, Inc., Strike Bio, Inc. the Mary Crowley Cancer Research Center, and a number of other related entities. He has sat on the Business Advisory Board to Path4 venture capital firm based in Austin, Texas, a firm that specializes in the life sciences musculoskeletal sector with a focus on early-intervention orthopedic solutions. Backstrom received his B.S. in finance and his J.D. from the Louisiana State University.