Designing an aseptic and sterile manufacturing facility that meets regulatory requirements takes expertise. Designing it to operate efficiently is even more challenging. Process architects are an important part of the team that can help you meet that challenge with confidence.
A slender vial containing just a few milliliters of clear liquid: for the billions of people who received a vaccine over the last few years, this has become a familiar sight. Yet few know the scale of manufacturing complexity required to ensure that the product inside that tiny vial is safe and effective.
Even within the industry, it’s not easy to see the whole picture. Process engineers understand the unit operations and specialized equipment necessary to support aseptic and sterile manufacturing; mechanical teams understand the HVAC requirements of a high-classification cleanroom; owners understand the business case behind their production targets.
What’s the secret to fitting all of these dynamic pieces together in a compliant and efficient aseptic manufacturing ecosystem? It comes down to the combined knowledge of the project team and their ability to collaborate toward a meaningful outcome. The most capable of these teams include process architects.
The word they share in common indicates the overlap between these two roles: when it comes to process, both are responsible for owning compliance and efficiency. Where they differ is in their field of view, and it’s this difference that makes them so valuable to a project owner.
Process engineers are focused on the manufacturing process—its unit operations, the equipment it requires, and so on. The process engineer asks, “What does this process have to be in order to deliver a safe and effective product?”
Process architects take that manufacturing-level view and map it to the facility level, bringing an architectural and an operational understanding to bear on the whole picture. While every project has an architect, many don’t have a process architect—and that makes all the difference when it comes to achieving compliance while maximizing efficiency. The process architect asks, “What will this building have to be in order to accommodate this process in the most efficient way possible?”
Process engineers and process architects are close collaborators. Just as two eyes enhance depth perception, these two roles work in concert to see the project and its interdependencies more clearly.
The goal of this collaboration between process engineers and process architects is to synthesize a global view of the whole facility with a granular view of its many moving parts.
Whether working on a retrofit or a large-scale greenfield project, the process architect’s impact is greatest during the early phase of capital delivery. That’s when they’re able to help define and deliver on what the facility must be, what it can be, and what it wants to be. The earlier they’re involved, the greater their opportunity to help turn that vision into a reality.
Facilities that support aseptic operations are among the industry’s most highly scrutinized and complex buildings. To maintain regulatory compliance, project teams must advance the facility’s business case while navigating an exceptionally sophisticated matrix of requirements.
The European Union’s revised Annex 1: Manufacture of Sterile Medicinal Products, released earlier this year, is a major component of that regulatory matrix. It’s been fourteen years since the last Annex 1 revision; during that time, the industry has developed and adopted many new best practices. To ensure that those best practices would be adequately codified into the 2022 revision, regulators invited experts from across the industry to closely scrutinize interim working drafts and provide feedback. The result is a regulatory document that reflects today’s expectations of a safe and reliable aseptic and sterile manufacturing operation.
The new Annex 1 requires manufacturers to establish a robust contamination control strategy (CCS). This CCS should go far beyond equipment selection to include details like personnel gowning and flows, material and product flows, and waste handling—all factors that impact a facility’s design. The process architect can work with project teams to proactively address these factors from day one, helping to protect patients from contamination and ensure ongoing regulatory compliance (recent high-profile FDA Form-483s show the consequences of inadequate CCS).
This could mean planning for:
Appropriate background classifications and airlocks.
Room classifications and airlock strategies differ depending on variables like equipment technologies and target production scale. A high-speed fill line within an open isolator has different requirements than a low-speed fill isolator with a decontamination chamber for ready-to-use (RTU) components, for example. The process architect can help project teams understand these variables and their impact on the facility design.
Once room classifications are aligned with the manufacturer’s approach to process closure, process architects and process engineers can collaborate to right-size the material and personnel airlocks. This may include planning for appropriate pressurization to protect the fill room, designing adequate space to accommodate wipe down and gowning activities, segregating material and personnel traffic for safety, and understanding where to establish bidirectional versus unidirectional flows based on the risk to production, operational bottleneck, and spatial efficiency.
Small-scale, low throughput filling can require fewer airlocks and less circulation space depending on the mode of operation. Facility layout for large, high speed filling lines can be optimized with loading and unloading operations in lower classification rooms, however overall footprint requirements are significantly larger. Understanding the client requirements and cross functional coordination is key.
More sophisticated equipment and more systems to support it.
To accommodate the equipment typical of advanced aseptic manufacturing, including isolators, automated fill lines, lyophilizers, robotics systems, automated visual inspection, and automated packaging lines, project teams need to do more than plan for adequate room in the production area. They also need to consider the support systems that come with this equipment.
Those systems often require large secondary mechanical spaces outside of the manufacturing area. These spaces can span multiple levels, each with its own access requirements to support maintenance, calibration, engineering, validation, and quality assurance. It’s vital that project teams design sterile and aseptic facilities with these requirements in mind. Here, too, a process architect can help.
Equipment for an aseptic fill line with a lyophilizer can span multiple levels and areas. Room HVAC and isolator HVAC may be on different levels with support requirements and ductwork penetrations requiring additional consideration. Lyophilizers can have multi-story hydraulic rams that require special considerations for installation and maintenance. Refrigeration and vacuum systems need to be in close proximity to the lyophilizer chamber with interconnected piping and cabling closely coordinated.
Success is a compliant aseptic manufacturing facility that’s aligned with higher-order business goals. There’s no single way to get there, though; in fact, there may not even be an objective “best” way.
Instead, there are many levers to pull, each with its own escalating impact on how a facility operates. A process architect can work alongside process engineers, mechanical teams, and everyone involved in the delivery lifecycle to understand which of those levers to pull. From a business perspective, the goal is to:
Navigate impactful business decisions, such as ready-to-use vs. bulk components.
In contrast to the bulk alternative, RTU components require relatively little preparation and support areas, which leads to a smaller footprint for cleanrooms. These benefits come with tradeoffs, though. Storing RTU components requires more space compared to bulk components, for example. Then there’s the cost of goods: manufacturers spend more per vial when RTUs are involved, which could become unsustainable at large volumes.
Working with the project team, a process architect can help manufacturers weigh this business decision through the lenses of capital expenses, operational expenses, and cost of goods.
Understand the project’s capacity requirements.
What are the facility’s throughput goals during its first year of operation? What about year five, ten, or twenty? With insights from their collaborators on the project team, process architects can help business owners establish an appropriate internal or external expansion strategy based on their capacity requirements over time and translate that strategy into spaces allocated for future development.
Use that understanding to establish guardrails and guide project decisions.
Because they are deeply familiar with the project’s long-term commercial vision, process architects can help project teams design appropriate support and ancillary spaces. A parking lot that’s scaled for today’s workforce, for example, could become a serious constraint in five years, when the owner anticipates doubling the facility’s workforce.
The process architect can help project teams ensure that the facility can accommodate all of its required functions within its fixed footprint, now and far into the future. That could mean, for example, evaluating the manufacturer’s shift strategy to right-size its parking lot and cafeteria, or optimizing its warehouse by relying on just-in-time deliveries from an offsite location.
Deliver a facility that balances short-term needs with long-term flexibility.
During a facility’s lifetime, it’s likely that new products, technologies, and aseptic processes will emerge. How can today’s project teams help owners ready themselves to seize these new opportunities and generate value from their investment for decades to come?
The process architect can help to answer this question. They collaborate with project delivery experts to think through details such as ceiling height, hallway dimensions, level changes—anything that may constrain future changeovers or inhibit the speed and flexibility with which a facility can adapt, grow, and meet the needs of a rapidly evolving market.
Your process architect has the expertise to visualize design documents as living, breathing spaces through which people, materials, manufacturing equipment, and product flow. These visualizations, and the bottlenecks that they uncover, are one of the project team’s most powerful tools for building efficiency and flow into the final design.
A key component of the process architect’s approach is understanding the relationship between efficiency and compliance. Consider, for example, the costs and benefits of meeting stringent regulatory requirements through engineering-based solutions versus procedural design.
Engineering control: By “engineering out” the risk of contamination, owners can be assured of a safe and robust aseptic manufacturing operation—but they’ll find themselves operating a facility that’s much larger and more expensive than necessary.
Procedural control: It takes much less space to manage contamination via operating procedures. From a regulatory perspective, though, an overdependence on procedural control elevates the risk of contamination.
A process architect can find the ideal balance. The key to launching a facility that maximizes its risk management approach while minimizing inefficiency is to strategically leverage both control mechanisms. A process architect, with their view of the facility as a global system of interconnected parts, can help you refine this approach until it’s perfectly tailored to your unique regulatory and efficiency needs.
For example, consider using temporal segregation in bidirectional airlocks. This strategy can save space when footprint is limited, and it can reduce HVAC loads and minimize circulation spaces within processing areas. For temporal segregation to pay off, though, it needs to make sense in terms of risk to process and operational cadence.
That’s where a project team that includes process architects can provide valuable guidance. They can assess when temporal segregation makes sense, such as in an advanced therapy medicinal product (ATMP) filling operation with small throughput batches at a low cadence, and when it could be problematic, such as in a vaccine filling operation that must handle large, high-cadence batches.
In addition to balancing regulatory, commercial, and operational efficiency strategies during the design and delivery of an aseptic manufacturing facility, the project team is also thinking through how end users will experience that facility—and what impact that experience might have on critical factors like compliance, productivity, safety, labor retention, and corporate image. The process architect can help the project team assess these factors and their potential effects.
One of the best examples of this mindset in action is the concept of adding glass walls to aseptic production spaces. On its surface, this decision may seem like nothing more than a cosmetic flourish, but a process architect would integrate that glass wall in the right way to offer multiple benefits:
Compliance: Annex 1 stipulates that aseptic manufacturing facilities must address contamination risks in part by minimizing the number of operators in classified cleanroom areas. By allowing anyone who’s not critical to the production operation to see into the cleanroom without having to physically enter it, a glass wall becomes an important compliance-related asset.
Business development: Designing a facility whose look and feel reflects its state-of-the-art operations is an important business driver for CDMOs. Glass walls could play a key role here by giving potential clients the opportunity to assess production areas without compromising critical environments.
Operator comfort and productivity: Well-placed glass walls can expose operators to daylight and offer views of varying distances—two factors that The International Well Building Institute list as critical to employee health and comfort and could impact productivity. In addition to creating a healthier environment, features like this may help manufacturers attract and retain an engaged workforce—a vital advantage, given the labor shortages impacting today’s biotechnology market.
Operational efficiency: By combining strategically placed windows with appropriate cleanroom communication devices, manufacturers can streamline communication between operators and remove the temptation to use airlocks for conversations. Over time, this small change can lead to significant gains in efficiency and a reduced compliance risk.
Sustainability: In its LEED certification assessments, The U.S. Green Building Council awards points based in part on a facility’s strategic use of daylight to reduce or replace electrical lighting.
By viewing aesthetic details like these through different lenses, the process architect can help project teams ensure that every decision, no matter how significant or seemingly minor, is aligned with overall facility objectives.
Whether you’re optimizing an existing aseptic manufacturing line or building a new facility from the ground up, integrating a process architect will help your team achieve successful regulatory outcomes, strong operational efficiencies, and long-term commercial success. In the end, these advantages add up to one thing: a life-saving product that costs less to make.
Reach out to our team of process architects to discuss how they can bring these advantages to your next aseptic manufacturing project.
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