Pharma-Tech center design addresses unknowns
Clean process suites to meet cGMP and FDA regulations for pharmaceutical products by incorporating a flexible design
By Judy Keller
Designing a pharmaceutical cleanroom is usually a fairly straightforward task. The client explains what the room is for, and the designer ensures the space meets required codes for the appropriate cleanroom class. But what if the client doesn`t know exactly what will happen in the process suite because the products that could be tested there don`t yet exist?
That`s what happened when executives at Hosokawa Micron Powder System (HMPS/Summit, NJ) asked designers at CE&IC (Burlington, NJ) to create cleanrooms for its new $1 million, 60,000-square-foot Pharma-Tech center, which includes a 1,600-square-foot cleanroom facility. The center is a test lab, and even HMPS officials couldn`t tell CE&IC planners precisely what products and equipment would be in use on any given day. Still, they knew the rooms had to meet current good manufacturing practices (cGMPs) and the new, more stringent Food and Drug Administration (FDA) regulations for pharmaceutical products.
The facility`s purpose is to demonstrate pharmaceutical equipment, test the equipment on customers` products, and to perform small-scale pharmaceutical manu facturing. At times, HMPS clients will rent the space as a test lab for developing products. An equipment cleaning area with a separate outside entrance provides space to clean machinery that is brought back to the plant after rental to clients.
“We are offering new technologies to the market, and we needed this facility so they can test their products on our equipment,” explains product specialist Sharon Yeager. “We`re hoping this will be more than a showroom, though. We hope our customers will use our test facility to speed up their own product development processes.” She says that there is room for expansion in the process rooms once validation is completed. It`s possible that a glovebox environment will be installed, but for now, the focus is on HMPS` newest product line of pharmaceutical machinery.
The cGMP area incorporates International Society for Pharmaceutical Engineering (ISPE) and FDA baseline guide standards. It consists of two Class 100,000 process suites, a clean equipment storage area, an equipment washroom, material quarantine-and-release areas, an analytical testing laboratory, and a client conference room. The separate entrance foyer doubles as a gowning area. FDA validation of this test facility is expected to be completed by the fall and is under the supervision of CE&IC.
Yaeger explains that clients who must meet FDA codes have no room for error — they must ensure that each dosage of a drug is exactly the same every time it is produced. Understandably, they are going to be particular about the equipment they buy. HMPS process equipment made to pharmaceutical standards includes a spiral jet mill, a Pharmpaktor with flake crusher, a 160 UPZ impact mill, a vacuum dryer and a Stott filling machine. Clients can test their products on these machines in the new center.
The challenge? How to do this and keep it clean, safe, and in compliance with codes. The solution: two Class 100,000 cleanrooms. For Ed McAvoy, principal engineer at CE&IC, this particular facility was all in a day`s work. Still, he called this design “unique in the industry” because it is versatile space used as a test lab, and because cGMP and FDA regulations come into the picture. Validating the facility is a major design expectation, he says.
CE&IC designers started planning this facility by going straight to the written industry standards. “The cGMP, published FDA regulations and the baseline guidelines from the ISPE gave us a good idea of what we had to incorporate into the Pharma-Tech center,” McAvoy says.
CE&IC`s project director Paul Skinner agrees. “And then we do a lot of listening to see what else is needed,” he says. The result? A space finished in about eight months, coordinated with general contractor J. R. Prisco Inc. (Summit, NJ).
To enter the center, visitors and workers walk into a foyer, which is a gowning area with a closet and lavatory. After donning appropriate coveralls or lab coats, as well as head and shoe coverings, they proceed to the main corridor, which is common to all of the rooms in the facility.
Skinner explains that this corridor is positively pressurized relative to the two cleanrooms. A door separates the entrance area from the main corridor to the north. A conference room is on the east end of the main hallway, and the two process rooms are on the north side of the corridor, separated by automatic sliding doors. At the west end of the hall is the analytical lab. The southwest end of the corridor opens onto the clean equipment storage area, which has its own exterior door for emergency exit. Adjacent to this area is a material storage room with a sliding door and a wash room with a roll-up door. The wash area has a double door open to the outside.
McAvoy says the wash area serves as an air lock separating the interior environment from the outdoors. Equipment and raw materials can be brought in through exterior double doors, keeping the interior roll-up door closed.
“Sometimes the company rents out its equipment, and it is brought back for cleaning. The equipment can be washed in the washroom, and when it`s ready, passed on to the clean equipment storage room,” McAvoy says.
To keep the areas clean and to reduce the chance of cross contamination, the process area is divided into two rooms. The utility room is behind the process rooms, and all HVAC ductwork and support utilities are routed through this room to reduce the amount of exposed piping, conduit and ductwork in the process rooms. Each process room has a sink recessed into its north wall, as well as a utility panel and an electrical panel. McAvoy says these were designed for the pharmaceutical equipment, and allow various types of machinery to be plugged in.
One process room has support steel above the ceiling, and a large cabinet seven feet above the floor houses process equipment. All of this is custom.
“It allows the equipment to be suspended from above, and rolled out of the cabinet when needed for process operations, without taking up the space for a permanent structure,” McAvoy says. It also allows the equipment to be rolled out of the way when the room is cleaned.
Process room walls, floors and ceilings have smooth chemically resistant, cleanable surfaces coated with resin. The lighting and electrical devices are suitable for washdown and for electrical classification. The HVAC system is 100-percent outside air supplied through a roof-mounted air handling unit, which includes 30 percent prefiltration, 85 percent filtration, preheat coils, a steam-injection humidifier, cooling coils and a supply fan. Terminal HEPA filters are used in the process rooms and in the clean corridor and the clean equipment storage area. The rooms are not designed to meet specific particulate classification levels, as would be common in a semiconductor process room.
The supply airflow is held constant and the process rooms and lab have 18 to 20 air changes per hour on the exhaust side. The corridors are positively pressurized relative to the adjacent rooms, and the whole facility is positively pressurized relative to the outdoors.
This contains dust within the process rooms and reduces the amount of unconditioned air coming into the building. The design maintains a temperature between 67 degrees Fahrenheit and 73 degrees F in the process rooms and between 65 degrees F and 75 degrees F in the other rooms. None of the rooms in the facility are larger than 20-by-30 feet.
Each process room has dust collection flow, depending on the equipment used. The room exhaust air is controlled by a damper, which throttles the exhaust air when large amounts of dust flow are being exhausted.
HVAC display panels for each process room are located in the corridor. These panels display temperature, humidity and relative pressure between each process room and the hallway. “This way, if something is wrong, it is immediately noticeable,” McAvoy points out.
The existing plant hot- and cold- potable water systems were tapped into for the new center. Cold water is supplied to each process room, the lab, the washroom, the lavatory and the deionized water system. Backflow preventors are used at the sinks and the utility panel connections to protect the potable water system. Deionized water is provided to the utility stations in the process rooms and to the laboratory and the washroom. The deionized water is used for equipment washing and for the analytical lab; it is not ingredient water for finished products.
Deionizer beds are used to purify potable water, which is distributed in one-way, PVC piping to the use points. These are units that are regenerated offsite by a service company.
The process rooms also need liquid nitrogen for some of the equipment, which is evaporated and distributed to the utility panels in the process rooms. It is passed through a 1-micron filter and a coalescing filter before being supplied to the panels. At the panels, the nitrogen is divided into a process connection and a general connection. The process connection has a regulator, a 0.2-micron filter and a pressure gauge. The piping downstream of the filter is stainless steel, McAvoy says.
“Because of the process nitrogen, there is a danger of hundreds of CFMs leaking if a hose breaks. It could suffocate people,” McAvoy says. “Therefore, an oxygen detector or unit monitors the air and sounds an evacuation alarm if the oxygen level falls below 19 percent.”
Each room has a dedicated reheat coil — the corridor and clean equipment storage use one reheat coil and the entrance, conference room, material storage area, washroom and lab share another reheat coil. An average reading from the thermostats in the conference room and the lab controls this coil. There is no temperature or humidity measuring device in the material storage area. If temperature or humidity-sensitive materials are stored there, portable recorders can be used, McAvoy explains.
The cooling coil in the supply air handling unit is controlled to cool/dehumidify at 48 degrees F. Humidity is monitored in the two process rooms and an average is used to control the steam injection valve.
Each process room has two drains in the floor, Skinner says. One drain is for water containing potentially hazardous materials and the other for water. He says the water drain hooks up directly to the sewer system, while the other drain is connected to an underground storage tank that is serviced periodically by an outside company.
Remodeling the space took about eight months, and with a lot to do in a short amount of time, there was little room for error or time delays. Once the explosion-proof wall was in place, the walled-off area was a basic envelope for the other phases of construction, says Ed Friedhoff, construction supervisor at J.R. Prisco, the general contractor. He says the job called for lots of coordination between CE&IC, his company and HMPS.
A potential delay was the custom-made gasketed steel sliding doors for the process rooms, he says. But the project was finished on time despite some delays with the door order. He says the utility panels were all custom, and jokingly refers to construction as “a three-ring circus” with the mechanical and electrical subcontractors working to get each phase installed in time for the next.
Friedhoff describes this project as “an interesting job.” “We had a little of everything. A little concrete firewall, some structural steel and resins — all of which we had to worry about. We had to vent the resin vapors as it hardened; we had to call together a variety of companies to install each component on time. And we had to deal with a bunch of unknowns, but we all put our minds to it and did it,” he says.
HMPS officials are pleased with the new facility, and their enthusiasm was sparked by a great turnout at their grand opening in May. The company considers the new center key to its potential expansion in the pharmaceutical field.
Yeager believes that the facility`s design is all the better for having to conform to newer, stricter FDA guidelines, and she praised CE&IC`s reliance on the standards to create a versatile test lab. “It`s a wonderful working facility, with lots of things in a small space. And they did it without any of us knowing for sure what will be developed in there,” Yaeger says. “That`s the true beauty of all of this — the things that might happen because this lab is here.”
Judy Keller is a freelance writer in Milford, NH.
A profile of HMPS
Hosokawa Micron Powder System (HMPS/Summit, NJ), an ISO 9001-certified facility, is a single-source provider of integrated powder and particle processing systems. The company makes equipment that covers size reduction, agglomeration, compaction, drying, blending, mixing, classification, powder analysis, and hygienic weighing and filling. The on-site technologies offered in the new Pharma-Tech center include milling and granulation, mixing and vacuum drying, micronization, compaction, and bulk processing. In short, the new lab boasts everything necessary to prepare and mix raw materials for the pharmaceutical industry, as well as equipment that can mill it and compact it into pills or bulk package powders.
HMPS is part of Hosokawa Micron Group, which makes equipment and technology for powder and particle processing, product recovery, plastics processing and confectionery products. The company`s new Pharma-Tech facility is a remodeled area in a 60,000-square-foot building constructed in 1941, which also contains warehouse space and offices. The new center is separated from the rest of the building by a four-foot-thick cinder-block firewall. — JK
This spiral jet mill is just one example of the type of pharmaceutical equipment used in the Pharma-Tech center process suites. Photos courtesy HMPS.
A large cabinet, seven feet above the floor, houses process equipment, allowing the equipment to be rolled out of the way when the room is cleaned.
Automated programmable logic controllers (PLCs) in each process room are used to control all of the equipment in the lab.