QRM Process

Minimizing Risk in Sterilization Validation

Isolators have allowed Bayer Healthcare’s Shawnee, Kansas facility to run for three years without a single false positive.

By Bill Swichtenberg, Senior Editor

Sterility testing is an essential part of every sterilization validation, to rule out the presence of particulate, bacterial and fungal contamination. Personnel must wear isterile gowns that prevent microbial shedding. The result is a monotonous, careful process that can still be error-prone.

Ruling out contamination

Sterility testing proves the absence of possible contaminating organisms and helps ensure product safety and quality. Samples are tested for sterility by placing them in growth media, incubating them for at least 14 days and checking them for evidence of microbial contamination.

Each sterility study must be qualified by a Bacteriostasis and Fungistasis test to demonstrate that the test article itself is not inhibitory to the growth of microbial contaminants that could be present in the sample.

The environment for sterility testing should be similar in design to aseptic processing conditions. The USP states, “The facility for sterility testing should be such as to offer no greater a microbial challenge to the articles being tested than that of an aseptic processing production facility.”

While contamination is the ultimate nightmare for any manufacturing facility, a lab-induced false positive is a time-wasting worst-case scenario. “It’s easy to consider a retest, but it requires a specific cause and a lot of time and effort, and it reflects on your lab,” says Alan Dake, supervisor, Microbiology Laboratory, Quality Control/Quality Assurance for Bayer HealthCare, Shawnee, Kan.

Two years ago, the Bayer lab did all its sterility testing in a sterile cleanroom with a laminar flow hood for testing. While the setup worked well, the company saw an opportunity to upgrade its technology when the facility’s manufacturing services program was expanded. The new, larger facility would increase the amount of testing work required by the lab, so the lab had to be expanded as well.

“This was a chance to take advantage of new technologies to prevent false positives in sterility testing,” says Dake. Since the goal was to make the new and improved lab less prone to errors and easier for operators to work in, isolators reduced the risk of unrelated contamination coming from the lab, offered increased levels of sterility assurance and eliminated personnel from the aseptic area.

Bayer’s isolator configuration is actually two La Calhene isolators with separate sterilization cycles. They can be docked together and were designed with maximum docking configurations for greater operator flexibility when loading/unloading from one chamber to the other. “Hatchback-style” windows on the transfer unit are a key ergonomic improvement, considering the amount of material used for a single test session. An on-site ergonomics expert helped prevent other issues with such items as new non-PVC half-suits, neoprene floor mats and gloves acceptable for all operators.

“The isolator and loading configurations have resulted in both ergonomic and throughput efficiencies that we are very pleased with,” says Dake.

The transfer isolator is used to sterilize test materials so that they can be used later in an already sterilized workstation. Again, the goal is to prevent contamination. “Generally, we pick the worst location, such as the product vial or the point where it contacts the shelving, and wipe the contact points,” says Dake.

The isolators are completely enclosed HEPA-filtered chambers. They are interfaced with vaporized hydrogen peroxide (VHP) to sterilize the inner surfaces of the isolator as well as the supplies inside. The room to the isolator also has a separate air supply.

Sterility testing is accomplished from outside the isolator in the larger unit utilizing two half-suits. Operators enter the half-suit by ducking under the base and then standing up within the positively pressurized suit. Thus, the testing process is totally isolated from laboratory personnel and the potential for introduction of contaminants is minimized.

While isolators have simplified operation, running sterility tests still requires three months of extensive operator training, in which staff master the 38 pages of standard operating procedures required. “There is a lot to consider,” says Dake. “For example, you need to know how to load correctly, hook up and execute transfers, get the gas and evacuate.”

The decontamination/disinfection process after each sterility test is extensive. Some of the processes involved include: a pressure test, dehumidifying with VHP, and a condition-and-target phase. In all, the process takes approximately three and a half hours.

The isolator and procedures must be annually requalified, and any new materials or techniques validated before their use.

Of course, false positives can still occur, even in the most diligent sterility testing operations. However, Bayer has found that isolators help increase sterility assurance levels. “Three years without a false positive — we’re pretty proud of our record so far,” says Dake.

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