cGMP facility gives hospital “orphan drug”-making arm, keeps Danny Thomas' dream of helping ailing children stay alive
By Mark A. DeSorbo
More than 50 years ago, a struggling actor with just $7 in his pocket knelt down in a Detroit church before a statue of St. Jude, the patron saint of lost causes, and asked, “Show me my way in life.”
Someone was definitely listening that day, for the now well-known entertainer found the inspiration and support to open St. Jude Children's Hospital (Memphis, Tenn.) in 1962.
And in the 12 years since his death, Danny Thomas' prayers are still being answered.
In mid-November 2001, site work began on a 65,000-square-foot pharmaceutical manufacturing facility that will soon allow St. Jude to produce small batches of compounds and experimental gene and cell therapies to treat such rare and catastrophic children's disorders as leukemia, solid tumor forms of cancer and infectious diseases.
Dr. Elaine Tuomanen, chair of the St. Jude Infectious Disease Department, says having a facility that employs current good manufacturing practices (cGMPs) will be a unique and extremely valuable resource for laboratory researchers.
“With this capability, we take a very big step from the bench to the patient and assure our mission to translate ideas into real medicines,” she adds.
Some of those real medicines, known as “orphan drugs,” are clinically effective against certain diseases, but not lucrative for big drug makers to produce, explains James Knight, St. Jude's director of quality assurance for therapeutic production.
“Big pharmaceutical companies do not touch them because they are too expensive. It's the number of patients that make these drugs 'orphan drugs.' There might be 12 children in the world that need a certain treatment, which could be as much as $100,000 a dose,” he adds. “One of the major functions of the facility is to produce orphan drugs in house. It's very, very expensive, but producing such therapies falls in line with our mission.”
Approximately half of the $36 million facility, scheduled to open March 15, will be dedicated ISO Class 7 cleanroom space, and cleanroom suites, Knight adds, will be equipped with ISO Class 5 or better biological safety cabinets.
“We will have several different production suites in the manufacturing area,” he says. “This gives us the opportunity to manufacture vaccines and other biologicals for clinical trials in a controlled cGMP environment. There are few facilities like this around, so we'd like to think this is really a cutting edge technology center for production of vaccines and other biological products to save children's lives.”
The facility will have more than ample space to store raw material and for cell quarantines and enough open space to prevent cross-contamination. About a third of the building will be used for actual manufacturing.
The HVAC air handling system will include separate air handling systems for the various areas to isolate the areas and minimize potential for cross-contamination. Five air handling systems serving classified process areas will be 100-percent-outside-air units for contamination control.
The floors are chemical-resistant terrazzo, and the surface contains quartz aggregate. Walls are Epiflex made by General Polymers. They are a five-layer construction with a flexible epoxy coating over dry wall with two urethane coats.
A reverse osmosis water system was designed to United States Pharmacopoeia standards and will provide purified water to steam generators and autoclaves and glass washers in USP purified water, which is sterilized using ozone and ultraviolet light. Water will be stored in a central tank and circulated to users in the building by a circulating pump. System piping will be constructed of orbitally welded 316L stainless-steel tubing.
“We will validate all the systems and all the equipment, air handling, the water system and production equipment,” says Knight, a pharmaceutical veteran who has worked with Baxter International Inc. (Deerfield, Ill.) and Schering-Plough Corp. (Kenilworth, N.J.).
Validation will not ever be a small task, especially when raw materials, processing and patient treatments by every batch need consistent and comprehensive documentation. Therapies are derived from single genetic mutations or by cellular reactions. From there, treatment ideas are tried until there's a model to show the idea has merit. This can involve hundreds of repeated steps, each time making a slight change to the material.
Keeping a construction project of this magnitude on track, Knight says, is difficult, but Austin Co., a Schaumburg, Ill-based design-builder, has been “staying on top of things” with very few setbacks.
Each production suite will be isolated with individual airlocks and each suite will have a higher pressure than the airlock. “We have areas of high pressure and low pressure,” Knight says. “We will have bio safety level III labs on each floor.”
Cleanroom personnel will wear full bunny suits, hair covering, booties and gloves. In some cases, personnel will also be required to wear beard covers and facemasks.
Presently, St. Jude has about 4,000 square feet of manufacturing space that is divided among several locations and used for producing AIDS vaccines and gene therapy products. Those environments will be consolidated in the new facility.
“The key thing is with an on-site lab, St. Jude can make batches of material faster and modify them more frequently than they can by sending the work to an outside service,” says Knight. “The lab truly shows its worth when it's time to produce the substance in volumes necessary for treating patients, instead of just mice.” III
Key facts
Size of facility: 65,000 square feet, approximately half of which will be ISO Class 7 cleanroom space equipped with ISO Class 5 or better biological safety cabinets.
Purpose of facility:The facility will allow St. Jude to produce small batches of compounds and experimental gene therapies to treat such rare and fatal children’s disorders as leukemia, solid tumor forms of cancer and infectious diseases.
Designer: Austin Co. (Schaumburg, Ill.)
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