“We know there are a lot of virtual companies in the pharmaceutical industry right now and the new CPST can provide unique services for these small pharma startups,” says Mark Gilbert, CPST general manager. “We’ll partner with these companies who only have a license for a drug to provide analysis, formulation, and cGMP sterile product manufacturing.”

The idea for the CPST started in the late 1980s, when the UK College of Pharmacy opened a small facility on campus to produce compounds for toxicology studies and for human and animal use under the FDA’s Good Manufacturing Practices (GMP). It was intended initially as a way for the College to support the research of its own faculty, but researchers from other universities and private industry soon began approaching UK for assistance with their own analysis and non-sterile and sterile clinical supply manufacturing. Since 1986, the CPST has completed more than 200 development projects that have lead to clinical trials.

In 2003, the state of Kentucky awarded a $7-million grant to UK toward a new pharmaceutical manufacturing facility. Using another $10 million from the University, the College of Pharmacy stopped sterile production at its on-campus site, retooled it for non-sterile production, and set about planning for the new CPST at the Coldstream Research Campus, nine minutes from central campus.

The first step was to hire a consultant who developed a business plan and brought together a team of six people, each with unique expertise: Gilbert, who is a pharmaceutical operations engineer with 30 years of experience, an architect, and others with expertise in FDA regulations, manufacturing operations, sterile, aseptic processing, and using isolators in pharmaceutical manufacturing.

Building in an Academic Setting

As the University of Kentucky is the owner of the new CPST and the major source of funding, Gilbert had to follow the University’s capital construction process.

“One of the things I quickly found out is that universities operate differently than business and industry,” Gilbert said.

Universities tend to use a bid-design/bid-build process where there can be two different firms working on a single project. Industry tends to use bid/design/build, where the one designer stays with the project through completion.

“The difference became apparent in our planning phase when we issued separate RFPs for design and construction,” he says. “Working with two different firms on a day-to-day basis was challenging.”

The new single-story, 20,000-sf stand-alone facility is expected to house as many as 35 professionals capable of simultaneously running 10 to 15 projects at different stages of development, and produce about 100 batches (each batch is 5,000 vials of injectables) of product annually. The facility will also offer production of sterile liquids for injection and freeze-dried injectables, a service rarely found outside of large pharmaceutical companies.

The CPST also has the ability to produce potent anti-cancer (cytotoxic) drugs and non-cytotoxic drugs in the same room at the same time.

“The biggest contaminant in a pharmaceutical facility is its people,” says Gilbert. “So we separate the people from the product.”

By using sealed rolling carts, called mobile isolators, and disposable versions of all materials that come in contact with products, scientists at the CPST will be able to work on multiple drugs without risk of cross-contamination. The isolators also prevent cross-contamination among products from different companies or researchers, a major concern when several projects are running simultaneously. In addition, the CPST has devised a unique system of using disposable equipment to further prevent cross-contamination.

“This means that everything that is used on a product or comes in contact with a product will be thrown away,” says Gilbert. ‘We won’t have any surfaces that could actually contaminate another product.”

The decision to work exclusively inside isolators saved hundreds of thousands of dollars in construction costs, because it allowed Gilbert to eliminate the need for ISO Class 5 space, which limits the amount of particulate in the air to no more than 100 particulates per cubic foot (cf) of air.

With the isolators, labs could be designed to Class 8 standards, which allow more conventional construction techniques and air handling that permits as much as 100,000 particles per cf of air. The isolators also allowed the facility to minimize the amount of Class 7 space (10,000 particles per cf of air), but some was included for flexibility if researchers wanted to do classic aseptic processing for formulation.

The building has five separate air-handling systems, and all spaces are separated by double-door air locks to maintain various internal pressures. Each of the labs is equipped with an isolator, where all sterile materials are handled.

Construction, Operation, and Approval

The core of the CPST contains a 5,800-sf manufacturing facility, an in-process lab and a full microbiological lab, with a combined total 1,000 sf. Warehousing and utilities occupy about 5,100 sf each, and 3,000 sf is dedicated to administration.

Building a “clean” facility is never easy; building one in a city like Lexington, Ky., where contractors and vendors have limited experience in building such facilities, is even more challenging.

“We are the only sterile manufacturing facility in the state, and there are not a lot of construction groups that know how to work in this environment,” says Gilbert. “So getting the facility up and running has required a lot more effort on our part.”

Constructing the framework of the building follows standard procedures. The second stage is clean construction, meaning stored ductwork and pipes are always capped to avoid exposure to the environment. In the third stage the walls are in, so maintaining a clean environment is crucial. No food or drink is allowed in production areas, and there is no smoking in the facility.

“We insisted that our contractors had to clean up every day and mop all the floors every week,” says Gilbert.

The final stage is installing equipment, so access to the building is restricted. Workers clean and sanitize regularly, and gowning requirements are imposed in the construction space itself.

In the end, you will need to be able to prove to the FDA that the facility and its occupants can do what you say they can do before production ever begins. That’s the validation process, which costs as much as 20 percent of the total cost of construction.

“Don’t underestimate validation processes and costs,” says Gilbert. “This is the part where working with the FDA becomes so critical, and it’s the hardest part of the job.”

The master validation plan—which includes all approved vendor submittals; factory acceptance tests; installation, operational, and performance qualifications; site commissioning; and about 1,000 standard operating procedures—acts as a roadmap for the facility, outlining every piece of equipment and how it will be used and maintained.

“Validation is not a one-time event,” says Gilbert. “This process has to be done constantly over the life of the facility. It is detailed, challenging, and slow.” Validation at UK’s new CPST is expected to be completed in the first quarter of 2007.

Gilbert stresses the importance of his team of experts at each phase from design and construction to outfitting and validation. “My best advice is, always bring in industry experts.”

By Lisa Wesel