A Facilities Expert Answers Audience Questions On Construction And Validation

By Tyler Menichiello, contributing editor

If you missed April’s Pharmaceutical Online Live event on facility design and validation, don’t worry — you can watch the entire recording or check out my summary of key takeaways here. It was an engaging hour of discussion on everything from single-use systems to modular facility design and more. Unfortunately, we didn’t have enough time to answer every question that came through from our audience. However, some of them were just too good not to address, so I asked our bioprocessing facility expert, Herman Bozenhardt, to share his thoughts in writing. Below are his answers to some of these questions.

How do you ensure that facility design supports ongoing process validation? What role does environmental monitoring play in facility validation?

Design must be grounded in GMP techniques and reviewed by the organization’s QA, sterility assurance, and outside experts. Good design is driven by good process knowledge, with a focus on providing operators with the tools and opportunity to be successful. All great technology will fail if operators cannot perform the tasks easily and cleanly.

Consult the design best practices in the ISPE guidelines. The environmental monitoring data is the facility qualification —  if you don’t achieve standards, the facility will fail. Proper layout and HVAC design (symmetrical air flow and proper air-change rates) is key.

How do you determine the hourly and daily water needs for a facility?

There are two main approaches. The first is to use SuperPro Designer from Intelligen, a tool that provides flow volumes in a dynamic model. You can run cases with different delivery systems and tank storage setups. It's great for optimizing design and managing cost and space in utility areas.

The second approach is to build a spreadsheet that outlines all necessary water use — water for injection (WFI), purified water to WFI conversion (PW to WFI), WFI to clean steam conversion, clean-in-place (CIP) water, steam-in-place (SIP) cycles, wash water, buffer water, media water, etc. — and calculate the total over the course of your standard process batch length. If you have to add additional processes, then you’ll need to calculate that too. You must account for every aspect, including the water needed to wash floors. Your answer is only as good as the details you can provide. It’s also a good idea to add a reasonable “fudge factor” in your calculations.

What are your thoughts on ancillary support rooms — e.g., personal airlock (PAL) and material airlock (MAL)?  I still see gowning rooms that are too small to allow for proper gowning, especially in Grade A/B spaces.

Gowning rooms are designed by folks who want to minimize square footage (to cut the facility price) and who never have to use them. Gowning rooms that serve as PALs need to have space for all gowning supplies and spares, a bench for sitting during gowning (not as a grade transition), waste containers, and enough room for a maximum of 4 people.

MALs are another story! MALs need to be able to contain all the equipment: single-use systems (SUS), piping, totes, bins, and operating material to be brought in. It must also be sized to take waste out, which means all the SUS unraveled, disassembled, and bagged, all the used totes, and any potential equipment that needs to be cleaned or repaired. The other challenge with MALs is sizing them to accommodate maintenance equipment — hoists to pull an agitator, scaffolding to fix a ceiling fixture (e.g., a broken sprinkler head or a leaking tri-clamp joint), and a scissor lift to wash the ceiling and hard-to-access points.

The smartest way to size PALs is to have the modular panel company build you a “mock-up” PAL in your warehouse or on their site. Then, you can test it out with your operators and mechanics. All you need are four walls and a set of in-and-out doors. This is a simple and effective way to avoid building a “telephone booth” PAL and facing criticism.

If there is a shared return corridor between modular clean rooms, how do you address crossover between waste and final product flow out of the clean area?

You separate the clean supply corridor from the dirty return corridor! This is standard in 2025. Clean materials and equipment come into the process suite through the MAL, and waste travels out on the opposite side.  Product needs to exit 180 degrees from the waste flow — any crossover or mixing of these flows will cause regulatory issues (look at the Emergent BioSolutions 483 from April 2021).

 If you have a facility like the one you describe (with a single, shared corridor), you need a temporal break in the corridor. Take time to clean the corridor (walls, floors, and ceilings) before bringing in the clean SUS, seed culture, equipment, or other ingredients. Then, execute the process. Hold waste in the suite until the end of the shift when all corridor traffic is done. Double-bag the waste and sanitize the exterior before removing it. Afterwards, you must re-sanitize the corridor. Alternatively, you can have a decontamination (chemically or via autoclave) step in the process suite so the waste is neutralized or benign upon exit.

Modular facilities are good for some applications, but not for all. Integrating the modules into building systems can be problematic, especially for automation (e.g., building management systems, process control systems, environmental monitoring systems, etc.) and HVAC. Further, design can be suboptimal because you have to fit these utility systems within the constraints of a module. 

Another problem is the difference in building standards and codes between countries. Amgen faced disaster after having modules built in China and shipped to their plant in East Greenwich, Rhode Island. 

 First of all, it was a mistake to go to China for a modular build just to save a few dollars. The quality is poor, the GMP practices and finishes were lacking, and the 12-hour time difference made coordination very difficult. This is a process that requires close design coordination between the process owner, the QA department, the design engineer, and the constructor.

The module is as big as you specify it — there are no rules or constraints. It can have as many or as few chases above, behind, or within the walls as you want. Instrument and power cables go inside interstitial chases. Piping generally goes above the ceiling into the larger chases (four-inch or six-inch) and then out to the user.

HVAC and automated systems’ controls and wiring can be placed in the chases. It all comes down to design and working with a knowledgeable partner. Our last project was all wireless, with a modem placed above the ceiling. Alternatively, if you don’t want to go wireless, you can use two-inch chases to route data and control lines (e.g., category-six cables, twisted-pair signal cables, or multiconductor lines) to each piece of equipment.

The bottom line is this: Never chase cheap. It will cost you more in the end and destroy the timeline for product introduction. This video about the Locus Biosciences facility touches on some of these aspects. The facility was built in nine months.