January 6, 2020 PAP-Q3-19-CL-009
Strategic facility planning (SFP) is a proactive mechanism for establishing facility goals based on the strategic objectives of the organization.1 It enables optimization of facility design and function and leads to more efficient and productive facilities that are also easier to manage.
SFP can be performed on a company-wide basis to identify capability gaps and facility needs within the scope of available financial resources across the entire organization. It can also be applied on the specific facility level.
At the heart of SFP is the development of an understanding of the organization and the purpose of the facility. To start, potential future developments that may impact production are identified using various analytical techniques, such as systematic layout planning (SLP); strengths, weaknesses, opportunities and threats analysis (SWOT); strategic creative analysis (SCAN); and scenario planning. Using this information, a strategic facility plan can be developed and implemented.
A master plan is necessary for a campus or single facility. A facility master plan includes specifics about the types and numbers of spaces within the facility, material and personnel flows, and utility and warehousing needs. Other considerations include regulatory aspects, security strategies, and transportation planning — the result is a facility that functions more efficiently and has optimized the space needed.
Strategic facility planning is critical to understanding the options for a go-forward roadmap, especially when working in a capital-constrained environment. This approach allows companies to identify potential future growth projections and, on the flip side, plan for unforeseen business challenges before these items become critical for executive decision making.
SFP also helps companies avoid the trap of simply repeating what has been done in the past — something that can happen all too easily.3 Despite the fact that techniques, technologies, processes, and the skills of the workforce rapidly evolve, little often changes in facility design and implementation — particularly in the pharmaceutical industry. New state-of-the-art facilities, while incorporating these changes, still often fail to truly support the company’s objectives, because they are often developed using tactical, project-based approaches to planning without the long-range master planning influence.
To be able to support business now and into the future, facilities must be adaptable and designed to incorporate new technologies and ways of working as they are introduced into the marketplace. The intention of SFP is to study the “what if” and determine what concerns need to be incorporated into the development of the facility.
Given the comprehensive regulatory environment, increasing competition, and growing pricing pressures that drug manufacturers face, SFP has become even more imperative. SFP provides the framework for the design and construction of the facilities so that they have a greater assurance of meeting regulatory requirements and provide a higher level of protection and safety for operators and patients.
Proper SFP takes into account the specific space needs for handling potent and cytotoxic compounds, the layout and air filtering for cleanrooms, and locker/gowning areas required in biologic facilities. This has the downstream advantage of defining the spaces requirements up front so, as equipment, material, and personnel flows for minimizing the risk of cross-contamination in multi-product facilities are later defined, there is sufficient space allocated to alleviate concerns. It also addresses the unique space requirements for raw material receiving and distribution within the plant, as well as buffer preparation and other pre-process activities.
Drug manufacturing plants have specialized needs with respect to utilities (e.g., water for injection (WFI), process gasses, liquid nitrogen) that can be more effectively planned for using the SFP approach. The same is true for support areas for sampling, quality control/quality assurance, product release, and storage
While cell and gene therapies are often considered together, manufacturing requirements for these advanced therapy medicinal products (ATMPs) can be quite different.
In vivo gene therapies, in which the viral vector serves as the delivery vehicle that is administered to the patient, require manufacturing facilities that are in many ways analogous to smaller, more traditional monoclonal antibody (mAb) facilities. This is particularly true for viral vectors produced via suspension or adherent cell culture in bioreactors, which is the direction in which the industry is moving. Both viral vectors and mAb production involve upstream and downstream unit operations that are generally scalable and can often be standardized to some degree.
Cell therapies, including gene-modified cell therapies, on the other hand, are more complicated, particularly those that are patient-specific (autologous). The cells themselves are the product, and each type of therapy or product line is unique and can be based on many different cell types. However, within a given product, each patient therapy will typically use the same cell type by design. The processes also tend to be unique, preventing standardization. In most cases, they involve extensive manual manipulations performed in grade A biosafety cabinets and incubators located within grade B cleanrooms, although there is some movement toward the use of isolators. There are a lot of unique processes at the moment because we are at the inception of this submarket, so each company is researching to find the best method for their target indication, while also continually learning from their predecessors. The cell therapy industry is trying to move toward more standardization in equipment and methods, but it is in its infancy and too new to be able to pin down “the models” yet.
As such, the design of a cell or gene therapy facility depends greatly on the therapy itself and the process used to make it, the targeted indication, and whether the product is patient-specific or an off-the-shelf allogeneic. These factors directly impact the scale and throughput of the facility.
It is essential from a strategic facility planning perspective to understand the scope of the initiative and the throughput required. Factors that must be considered include the load on support spaces, such as the space needed for delivery of reagents for processing, QC labs, and warehousing, as well as the headcount needed to operate the facility and the expected material and personnel flows, number and types of cleanroom suites, and utility demands (share or dedicated). Any potential for cross-contamination must also be addressed.
A key component of SFP is considering the potential business risk associated with different facility solutions for a given organization. One of the decisions that companies must make is whether to build a single, large facility with the capacity to produce multiple products or to construct multiple, smaller facilities each dedicated to a single product.
Both approaches have advantages and disadvantages. The cost for multiple facilities tends to be higher, but the potential for cross-contamination is alleviated. There are also significant complexities introduced when producing multiple cell and gene therapies in a single building, particularly from a physical separation standpoint. It is necessary, particularly with viral vectors, to have production areas separated by hard walls. While difficult, it can be accomplished. In some cases, the decision is dictated by the available real estate and amount of capital for the project.
Overall, a campus comprising standalone facilities with dedicated equipment and utilities, redundant capabilities, and backup power tends to present a lower risk than a single, larger building with a shared utility infrastructure.
Another benefit afforded by SFP is the data generated as a result of the in-depth needs analysis. This information can be used when evaluating existing sites. Having an in-depth understanding of the specific needs for a facility simplifies the evaluation process and makes it easier to determine if an existing building or spaces are suitable.
In general, for cell and gene-modified cell therapies, it is recommended that manufacturers do not look to adapt existing mAb/biologic manufacturing sites. In vivo gene therapies may be an exception, given that viral vector manufacturing typically parallels mAb bioprocessing.
Customization of such existing facilities can be problematic for many reasons. The infrastructure around traditional mAb facilities is often unsuitable for supporting the higher-grade air classifications, air flows and specific layout /room requirements for cell therapy manufacturing. The physical arrangement/layout of mAb facilities is often not designed to accommodate the additional headcount, personnel flows, and locker/gowning needs of cell therapy plants; the proportions of the facilities and the associated space requirements are distinctly different. For autologous therapies in particular, the larger spaces with hard piping and large stainless-steel bioreactors would not be relevant.
Of course, for large biopharmaceutical companies with extensive existing facilities, it may be more economical and practical to remodel a site that is already within their network. For most start-ups and emerging biotech companies, however, finding an appropriate building or piece of real estate for the establishment of a completely new facility is recommended. Of note here, there are probably some unused or poorly utilized mAb spaces that may be more economical to build out tenant improvements (TI) and repurpose to new therapies; SFP can define these opportunities
Even when using the strategic facility planning approach for cell and gene therapy facilities, the greatest challenge remains the nascent nature of the sector. With just a handful of gene and cell therapies approved and on the market, the technologies and processes for commercial manufacturing remain under development — the only certainty is that equipment and systems will be advancing at a rapid pace. Commercial processes used today may look nothing like those used just five years from now.
As a result, it is essential to “future proof” the designs for cell and gene therapy facilities to ensure that the designs are sufficiently flexible to accommodate new technologies.
The first step in doing so is to employ process engineers that thoroughly understand the type of therapy that will be manufactured and all the regulatory requirements that will be applicable based on where the treatment will be manufactured and sold. This is critical to ensure that the necessary controls will be in place to enable validation of the initial production runs without any issues and that the facility design will be approvable by the different regulatory bodies.
The second step is to build into the design of the facility flexibility for updating infrastructure in a manner that will not impact the operation of the plant. Utilities and supporting equipment, for example, should be platform-based or located in the floor above cleanrooms and production suites to allow easy access independent of the process. The replacement of old equipment or addition of new technologies can be largely completed without impacting the operational schedule of the plant. Shutdown of the cleanroom/suite should only be needed to make the final connections.
Another consideration is the use of closed equipment to enable the downgrading of the environment of the production area — such as the use of isolators instead of biosafety cabinets. Taking this approach, if feasible for the processes, can lead to operational savings and provide greater flexibility with respect to the processes that can be performed in the production areas. Of note, this does allow down-classifying the room, but isolators tend to be individually designed and custom manufactured (as opposed to off-the-shelf), and, because there is limited access with them, they are not as easy for manual cell manipulations as a BSC.
Incorporating space for scale-out of processes is also important. For personalized medicines, it is not practical to create a room that can accommodate 20 stations if only four to six are initially required. Rather, it is essential to establish the right station size while including adjacent spaces where additional stations can be established in the future. The adjacent suites should have separate air handling to avoid cross-contamination but could leverage other shared services.
At CRB, we believe that, whether you are planning for the short term or embarking upon long-term planning, having quality information allows you to understand the relationship between your business requirements and your facility requirements. The result is smarter and more cost-effective facility decisions.
Our Strategic Facility Planning (SFP) team provides current and relevant data analytics of space utilization and space layout strategies that allow clients to manage their facility assets effectively and efficiently. This aligns the facility strategy with the client’s sales projections, business planning and the required capital expenditures.
CRB's SFP team employs state-of-the-art data consolidation, management and reporting systems that help streamline data collection and analysis while leveraging existing client and in-house building databases (BIM, Revit, CAFM) as appropriate. This information is used to perform facility asset inventory and space utilization and capacity planning analyses. We also can assist with metrics and benchmarking and conduct gap analyses.
With respect to strategic planning, we can help clients with all types of projects, including facility growth, scenario, real estate, relocation, and master planning, as well as tactical space planning and optimization for use in facility programming and conceptual design. CRB is also well positioned to help with operational improvement, such as process improvement workflow and space utilization planning.
For cell and gene therapy SFP, we have constructed an extensive database containing information on the 200+ projects that we have completed in the ATMP space (gene therapy, cell therapy, viral vectors, and related products) during the last decade. Analysis of this large data set provides us with a growing understanding of the nuances associated with different types of cell and gene therapy facilities and also helps CRB rapidly identify real estate opportunities — both existing facilities/buildings and empty sites — that can accommodate these unique facilities.
We consider the potential buildings and sites holistically, taking into consideration planned capital projects, the needed infrastructure, the sustainability objectives of the company, and various other aspects. A strategic plan is then developed for the specific facility (or campus) that incorporates all these inputs and validates a path forward.
CRB’s vision is to be the leader in the overall design and construction space for cell and gene therapies. To that end, we have established an all-encompassing offer that includes design architects working in collaboration with mechanical, electrical, plumbing, and process design teams to develop the optimum layout that enables the best use of space based on client business goals.
Most importantly, we listen to our clients and work hard to understand their needs — both today and into the future — in order to design flexible, efficient AMTP facilities that can be readily modified with newer technologies as they are developed and thus remain state-of-the-art manufacturing centers well into the future.
References
David Keith, AIA, is an architect with over 30 years of industry experience. David’s expertise in strategic facility planning started with G. D. Searle and progressed through acquisitions by Pharmacia and Pfizer to Director of Strategic Facility Planning for Pfizer. Additionally, David has worked with leading biotechs, pharmas and real estate developers including Abbott, J&J, Genentech and Phase 3 Real Estate before joining CRB. David is Director of Strategic Facility Planning for CRB and his unique blend of experience provides him with 360-degree visibility into the client’s long-range planning needs. From this vantage point he provides the roadmap for the trip as the client navigates internal and external drivers that influence and guide the development of a strategic facility plan.
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