Cleanrooms & Facilities

To assess current trends in cleanrooms and engineering & facilities, BioPharm International turned to Parrish Galliher, founder and chief technology officer, Xcellerex, Inc.; Jim Maslowski, owner, PDC Aseptic Filling Systems; Morgan Polen, vice president, application technology, Lighthouse Worldwide Solutions; and Benoît Verjans, commercial director, Aseptic Technologies.

Q: What trends do you see emerging in cleanrooms or in facility design?
Galliher: There has been a trend for some time now to use modular, pre-fabricated cleanrooms with more open operations. Our modular turnkey production train with "micro" cleanrooms is really the ultimate manifestation of this trend.
Maslowski: Companies are looking for ways to reduce the size and quantity of their cleanrooms. They are exploring technologies that allow them to process without the cleanroom.
Polen: I see more designed-in monitoring apparatuses and fixtures as part of the tooling and cleanroom design. These are no longer an afterthought, based upon where the tool is going.
Verjans: Reduction of complexity to overcome important cost and work hurdles.

Q: What have been the most important recent accomplishments in cleanrooms or facility design?
Polen: The stipulation for the monitoring of 5.0-µm particles for a minimum of 1 m³ for EU regulations, and the alignment of this with ISO 14644. Finally, the Europeans "get it."
Verjans: The introduction of new barrier systems such as isolators and RABS to reduce the complexity of cleanrooms as well as the risk attached to operators being close to products.

Q: Will the industry ever make significant moves toward operating in "grey" or unclassified space, using fully closed systems? Would regulators be comfortable with this approach?
Maslowski: I am aware of companies that have explored this concept. I'm not sure if regulators would be comfortable with it. If it validates, they should. I think the question is more appropriately, Will customers feel comfortable with a supplier that is first to make the leap?
Polen: I hope not. The reason the spaces should be classified is not due to the ideals of automation or control, but due to the fact that things break, interventions occur, machines and panels leak. The real world happens, and you need the background to be controlled, to help manage the risk. Regulators probably won't consider that; they simply don't spend enough time in the real world. Their world is the best-case world that is far removed from the day-to-day.
Verjans: Quality by design may help. Now, grey or unclassified is probably hard to get approval for, but Class C or D may become the standard.
Galliher: This is an evolution that will continue to progress as regulatory agencies become more comfortable with the idea. Further upstream, where processes can be more easily closed, this will happen faster. Our modular platform encloses the unit operations in a controlled environmental module, allowing the operating team to move freely in the space around it, which could be considered a hybrid of grey and classified space.

Q: Are you seeing any significant interest in making biotech facilities more environmentally friendly?
Verjans: I do not believe it will be the key driver. New technologies such as the closed vial and sterile syringe technologies will reduce environment impact by reducing the container washing associated with standard glass vials.
Galliher: This is definitely a consideration in all new plants and processes. Historically, there was some concern that disposables would introduce an environmentally unfriendly dimension to biomanufacturing. But studies are showing that the actual carbon footprint for a disposable operation is reduced compared to stainless steel facilities, mainly due to the dramatic reduction in energy required to purify water.
Maslowski: If disposables count as environmentally friendly, yes. Disposables reduce water usage and the energy needed to prepare WFI. Disposables also limit CIP, thus reducing the cleaning chemicals and their eventual processing and disposal.
Polen: Somewhat. I have seen facilities that are idle being completely shut down if not used for a few days. The start up cost is higher, but in the long run, why run the HVAC in an area that is not being used?

Q: What is the future of cleanroom and facility design?
Galliher: We think our modular architecture radically changes the way companies will look at cleanroom and biomanufacturing facility design. By enclosing each unit operation in its own controlled environmental module, we effectively shrink the cleanroom and place the operator outside the clean space. Operators can move freely from one operation to another, all within the same shared space. This adds efficiencies and flexibility that simply cannot be contemplated with conventional design.
Polen: More well thought-out designs, and better energy management. The use of computational fluid dynamics (CFD) to optimize airflow patterns. Increased monitoring of areas to characterize and set real process control limits.
Verjans: Put a barrier inside and adopt new technologies which are easier and safer.