Building a facility to produce vaccines is among the most challenging endeavors an organization can undertake. Timelines are long, budgets are likely to be tight, and the technology is ever-changing.

IPS designs up to a dozen such facilities every year, leveraging a blend of technical, healthcare, and architectural talent to create pharmaceutically elegant facility designs that meet customers’ production capacity, project timeline, and project budget objectives.

Here, we examine challenges faced by pharmaceutical companies when designing a facility to produce vaccines — be it an active pharmaceutical ingredient (API) manufacturing facility or an aseptic fill/finish facility. We also discuss how IPS can help customers overcome those challenges.

What is a “Pharmaceutically Elegant” Facility?

In aseptic facility design, the pharmaceutical industry strives for quality by design, taking a holistic view of the entire process to confirm each element meshes well.

Consider material flows (e.g., personnel flows, work-in-process staging areas), which are commonly overlooked or undervalued, despite being vital to sustainable day-to-day facility operation. If material flows are not optimized during facility planning, the facility ends up implementing a lot of makeshift, workaround solutions.

To avoid these sometimes-disastrous situations, IPS has developed a three-level facility concept: clean utilities and the black utilities on the first level, process areas on the second level, and a technical space for HVAC equipment on the third level. This multi-level facility design helps to segregate personnel flow and material flows, thereby improving overall GMP segregation within the facility.

IPS also commonly uses bridge truss construction to eliminate columns within the process area. Traditional facility designs include columns every 32 feet or so, and process equipment must be arranged to fit around the columns. Bridge truss construction techniques permit very long spans with no columns, so we're able to design the optimal process configuration for equipment and flows within the space.

Additionally, in a three-level facility, a company can plan for expansion in linear fashion — when the process area footprint is expanded, the utility and HVAC areas can be expanded accordingly. If a company builds, for example, a single story with utilities located to one side of the process area, expansion tends to disrupt flows.

Vaccine Manufacturing Facility Design Challenges

The pharmaceutical landscape is littered with facility projects that have run over schedule and/or over budget. A project with a three-year timeline can stretch to four or five years for any number of reasons (e.g., shifting capacity requirements, inaccurate schedule/resource estimates, equipment delivery delays, or facility/equipment over-design). 

Within this design context, a project team’s ability to make good decisions quickly and stick to those decisions is a key driver helping minimize budget and schedule risk. 

Technologies in the aseptic fill/finish arena are continuously evolving. The process for selecting “best available” technologies within a company requires a careful review of the technology itself (maturity, robustness, availability) and a detailed review of the overall costs (initial capital + consumables + operating costs) associated with the technology. Beyond this internal review, additional benchmarking may be required. Unfortunately, the timeline required for this complete analysis far exceeds the time available in a typical concept design activity. Therefore, the concept design is handcuffed from the very beginning by sub-optimal technology selection.

Ideally, technology vetting within a company is an ongoing process conducted by a relatively small cross-functional team of qualified individuals, who research each technology and formulate its cost implications and its quality benefits. This allows the organization as a whole to agree upon what technologies should be implemented for subsequent projects in advance of the “next” project kick-off – a huge advantage from almost every project management perspective.

Further complicating the task of technology sourcing is that timelines for readiness of technology/equipment may not be apparent. While some projects feature timelines adaptable to this uncertainty, organizations more often must pursue aggressive timelines for their facilities.

Consider that the lead time for a primary packaging aseptic filling line currently runs 18 to 24 months, depending on the vendor. Thus, after the order is placed, the equipment may not arrive on site for about 20 months, after which it must be installed, commissioned, qualified, and tested. In addition to technology comparisons and qualification, timeline challenges include site selection and land acquisition, where tax advantages or the permitting process in certain locations can complicate decisions.

In responding to these challenges, it’s vital to note that “siloed” decision-making between departments contributes to a disjointed or less-than-optimal facility design. Companies end up following a congressional political process: everybody receives a little bit of what they request, and the result may not be the elegant facility they initially envisioned.

At the heart of many of these decisions — and compromises — are budget concerns. What gets nixed when costs start rising? Generally, the first thing squeezed out by budget concerns is additional space in the facility.

Recently, an IPS customer received a “standard configuration” facility design and pushed back for unidirectional flows everywhere. The design was updated to include new corridors and expand corridor width, among other tweaks. However, the revised cost estimate revealed the project was too expensive to move forward due to the additional space requirements. This is one reason IPS attempts to avoid the “value engineering” (VE) activity; we’d rather design to a defined cost basis from the beginning so we can make the right tradeoffs.

Chopping up a completed design by way of “VE” has a domino effect where technologies or layout do not function, or mesh, as well as initially planned. Consider a person ordering a family sedan from a dealership. The customer receives the car and decides it’s too expensive or too large, so the dealership cuts off the front and back bumpers, eliminates the headlights, and removes the doors. The sedan technically remains a car, but it no longer works as intended. It would have been better to order a more compact sedan in the first place.

The COVID-19 Effect

The facility decision-making processes and related timelines take on heightened importance under the current pandemic conditions, as well as the likelihood of other outbreaks in the future. IPS is tremendously busy working on different products related to COVID-19, thriving under an intensified sense of schedule awareness as our team works to enable companies involved with Operation Warp Speed (i.e., tries to bring facilities and additional manufacturing capacity online as quickly as possible).

In this scenario, the lead time between one vendor and another has greater impact on both the selection process and the project. For instance, if one vendor claims it can deliver a production line in 18 months and another vendor says 22 months, that’s a considerable advantage for the first vendor. 

However, the rush to deliver production lines as quickly as possible has the side effect of dismissing production innovations. Specifically, there exist many technologies with potential to be highly valuable, but the accelerated timeline prompts organizations to focus on proven, available technologies. For example, cutting-edge technologies, such as container integrity inspection, may be eliminated from consideration right away unless a company already knows it needs to include that technology in the planned facility.

How IPS Gives Customers an Advantage

IPS overcomes the above challenges for customers using tools developed in-house for efficient and accurate facility capacity analysis and financial evaluation. These tools include software for designing bulk pharmaceutical API manufacturing facilities, as well as a series of templates that allow us to accurately model different production capacity requirements for fill/finish facilities.

IPS’ proprietary tools are the result, in part, of our in-house experts’ experience and industry connections. We have cultivated a group of SMEs with industry experience focused on biopharmaceuticals and aseptic fill/finish, many of whom have extensive owner-side experience. Thus, we can begin each project with a firm understanding of owner requirements and an accurate interpretation of regulatory requirements. 

In addition to maintaining relationships with all major pharma equipment vendors, IPS technical staff strive to constantly evaluate new technologies, regularly comparing and contrasting what we have available from various vendors to understand the differences between their offerings. This way, when clients approach us with ideas for a new facility, we have something more to offer: “Have you heard about X yet? It has potential to be a great fit here.”

This vast knowledge base enables IPS to customize its services to meet unique client project needs, whether it’s starting a project from scratch or resurrecting one whose initial concepts have failed. For example, IPS recently completed a facility in Europe, initially envisioned as a RABS facility, that wasn't feasible within the allowable facility footprint. We redesigned the facility using an isolator-based approach that did fit and continued to provide engineering, procurement, construction management, and validation (EPCMV) services for the entire project.

IPS’ SME group can support the equipment design, fabrication, and testing process, or simply pass off the design if the client has adequate internal resources to continue where we leave off. Engagement throughout the process — including involvement in design review meetings, GMP reviews, design qualification meetings, factory acceptance testing (FAT), and site acceptance testing (SAT) — develops for us a more well-rounded understanding of all the moving parts comprising a successful production facility.

Perhaps most important, IPS is trusted by the FDA as a contributor to its DG330 course. We conduct a module training new inspectors on RABS and isolator systems. From the SME side and the architectural side, we've trained more than 600 inspectors.

This collaboration gives us great exposure to FDA upper management, helping us to understand the agency’s current focus and what it would like to focus on in the future. Regular FDA interaction also informs our facility design and the various discussions we have with clients.

Conclusions

Designing a facility to manufacture vaccines is a time-consuming, expensive process, laden with difficult decisions and a cacophony of voices in the room — some with competing priorities.

A company’s ability to leverage engineering and architectural expertise, industry experience, and a network of vendor connections directly impacts critical factors like budget expenditure, project timeline, and success in regulatory navigation.

This article originally appeared on CellAndGene.com.