The Waisman Clinical BioManufacturing Facility (WCBF) at the
University of Wisconsin-Madison is a state-of-the-art cleanroom facility that
conducts GMP manufacturing of cell therapeutics, gene therapy vectors, and
biologics for phase I/II human clinical trials.
The WCBF serves researchers as they enter early development of novel
biological therapies and catalyzes the advancement of therapies into human
clinical trials. With broad and comprehensive capabilities, the WCBF
specializes in assisting researchers and companies with the entire process of
developing a manufacturing process and producing and testing materials for
human clinical trials.
The WCBF knows how important it is to maintain
strict cleanroom cleanliness and sterility in their Class 7 and 8
cleanrooms. That is because, if contaminated with microorganisms, the
products the WCBF manufactures can adversely harm patients. In addition,
the steep price of product rejects and recalls makes it crucial to ensure high
product yields.
“We are committed to ensuring that our operations
are performed to the highest quality principles, in compliance with the FDA and
other regulatory requirements,” says Chuck Valliere, Quality Control Specialist
(Gowning Training), WCBF, noting that a failed batch of cell-based products can
cost upwards of $100,000.
The bane of cleanroom operators like the WCBF is
microorganisms. Microorganisms introduced into a cleanroom environment
need only three things to grow: moisture, food and temperature – all of which
exist in a cleanroom. Consequently, all incoming air, water, chemicals,
and materials must be filtered or sterilized to meet high standards of purity
and microbiological control, so as not to contaminate processes or products in
production. Also to be “filtered,” in a sense, is the cleanroom operator,
who, most will agree, is the dirtiest thing to enter a cleanroom.
Keeping the operator’s dirt and germs out of the
sterile cleanroom environment and away from sensitive products and processes is
the main objective of the sterile cleanroom suit. The suit needs to
protect the environment from viable particles such as bacteria and yeasts, and
non-viable particles such as hair, dead skin cells, and dandruff. To that
end, it is critical for cleanroom operators to select cleanroom suits that
provide not only the highest levels of inherent sterility, but also the
greatest chances of maintaining that sterility through the gowning process.
The ability to maintain sterility through the
gowning process is one reason the WCBF turned to a new approach to sterile
gowning with Clean-Don technology from Kimberly-Clark Professional.
Sterile Gowning: Room for Improvement
Ask any cleanroom operator and chances are he or she
will find something about sterile gowns that could be improved. In
fact, Kimberly-Clark Professional did just that, spending the better part of
two years interviewing cleanroom operators, visiting them in their workplaces
and evaluating the features and functions of traditional sterile cleanroom gowns
to identify areas in which there was potential room for improvement.
Key findings of that research:
The sterile cleanroom gowning
process takes between 5 and 10 minutes for the vast majority of cleanroom
operators.
- Almost one-third of cleanroom
operators indicate that cleanroom coveralls are the most difficult part of
the six-step gowning process, and that donning coveralls takes an average
of 30 percent of the entire gowning process time. - Cleanroom operators are
disposing of an average of 10 percent of their sterile cleanroom garments
every week due to exterior contamination during the gowning process. - Most new cleanroom operators
need 30 hours of initial training on cGMP donning procedures before they
are allowed in the cleanroom itself, and an average of 6 hours of ongoing
training each week. - More than 50 percent of
cleanroom operators reported garments ripping out or billowing due to poor
fit. - One-third of cleanroom
operators report being unsure of their garment’s sterility due to the appearance
of its packaging. - Approximately 87 percent of
cleanroom operators would consider switching to a new garment if it was
more comfortable and offered less risk of contamination.
The issue of garment comfort was also
addressed. Scientific research in the workplace has revealed that a
moderate variation in body temperature can greatly reduce concentration and
increase risk-inducing behavior. Workers unable to maintain a
thermo-neutral zone, or comfort zone, have a higher tendency to become injured
and need time off from work, thus reducing productivity. In fact, more
than 40 percent of cleanroom operators polled during Kimberly-Clark’s research
report employees need to exit the cleanroom due to overheating on a regular
basis.
Cleanroom workers at the WCBF echoed
Kimberly-Clark’s research findings.
“We’ve always used disposable cleanroom gowns
because reusable gowns have a high initial investment,” says Bill Kreamer,
manufacturing and maintenance specialist, WCBF. “But even our traditional
disposable cleanroom gowns had problems and were not as convenient as we would
have liked.”
Kreamer notes that, not only were their old
disposable cleanroom gowns costly and their packaging bulk made them difficult
to store, they also required a tremendous amount of “precise handling,” such as
rolling up the arms and legs to keep them off the floor during gowning.
Designing a New Gowning Approach
A multi-functional product development team at
Kimberly-Clark Professional set out to design a new approach to sterile gowning
that would eliminate the problems identified during the company’s
research. The resulting Clean-Don Technology provides the following
features:
- A patent-pending snap
technology that features built-in snaps which gather up legs and arms to
lower the risk of the garment touching the floor, then automatically
release as the garment is put on. This eliminates problems
associated with traditional cleanroom garments, in which the garments’
arms and legs typically dangle freely as the operator dons the garment,
thus increasing the chance that those dangling arms and legs may touch the
floor, thus contaminating the garment. This problem with traditional
garments is particularly acute with individuals who are on the shorter,
yet portlier side, meaning they often have to go up one garment size and
therefore would have an even more difficult time keeping the longer
dangling arms and legs of the garment from touching the floor. - An innovative inside-out fold
pattern that presents the inside of the garment as the package is opened,
reducing the risk of touching and contaminating the outside of the
apparel. - A highly visible blue line
along the inside of the garment that signals the proper place to grasp
while gowning, helping workers avoid touching the exterior of the garment. - Thumb loops that help keep
the garment from riding up the arm and help to maintain the glove/garment
interface. - A unique process to package
the new garments for sterility assurance. The technology uses a
vacuum seal process to allow the breathable SMS fabric to be sterilized
with Gamma irradiation. The unique look and irradiation indicators
on each package help to confirm irradiation and sterility. - A roomy design that is less
likely to rip out than ANSI minimums since it provides 12 percent more
chest room and six percent longer body length. At the same time, the
garments’ elastic waist and back reduce loose-fitting material that could
contact work surfaces or billow out, forcing air to exit the garment at
its extremities. - An SMS (Spunbond Meltblown
Spunbond) material that provides a cloth-like feel and is 25 times more
breathable than TYVEK.
Kreamer, who is responsible for testing new personal
protective equipment for use in the WCBF cleanrooms, notes that the new gowning
approach is more convenient for their employees and has a better cost-in-use.
“The novel packaging has a number of benefits for
us,” he explains. “First of all, the vacuum packaging makes the garments
more compact and easier to store. As you open the package, the garment
stays in a compact shape, preventing it from unfolding and touching the floor,
which would be unacceptable in our sterile environment. It is also
packaged inside-out, with a stripe to indicate which side is which. This
helps prevent our cleanroom employees from contaminating the sterile outside of
the garment during the gowning process and saves steps and valuable time during
the gowning process.”
The WCBF estimates that the new gowning approach
allows employees to gown up in about three-quarters of the time they used to
spend on the gowning process with their previous disposable gowns.
“Our employees like the convenience of having the
gowns already prepared for entry,” Valliere adds. “They also like the fit
over our previous gowns, as well as the integral thumb loop. The
durability of the material also makes the gowns more resistant to tearing than
our previous cleanroom garments.”
Validation & Training: Inculcating the New
Approach
One of the necessary steps when validating a new
sterile cleanroom gown is to carefully review the garment’s
certification. Be sure to ask the garment supplier for the following:
Certificates of Conformance –
these verify that a specific product lot conforms to all specifications
before the lot is released. Physical characteristics should be
tested in accordance with relevant ASTM standards. Particles should
be tested in accordance with relevant IEST standards.
-
Certificates of Irradiation –
these document the minimum and maximum dosage of irradiation that a
product received. Look for sterilization validation documentation
that confirms that the doses have been verified, the loading patterns were
sufficient, and that the process is audited on a regular basis.
In most pharmaceutical companies, a variety of
functions will need to be involved in the approval process for a new cleanroom
gown. First, safety must approve the use of a new product. Each
local safety officer must ensure that the product will not violate any EPA or
OSHA regulations or permits. Any changes to processes are also concerns
for regulatory personnel, as they may impact the company’s FDA license.
After acceptance by safety and regulatory, Quality must be included and will
play a key role in testing and accepting the new product or process.
Quality Assurance personnel are involved in reviewing all of the procedures and
process records, testing the product to ensure its sterility, and approving the
final selection based on the data. The Quality Control organization will
inspect all incoming sterile products, policing the environment and reporting
the result. The purchasing department is the final step in the process
and often provides rubber-stamp approval for ordering the products already accepted
by the other players.
Most pharmaceutical companies will conduct a new
garment validation process for three to nine months, during which time the new
garments would be worn in a controlled area, though not necessarily in the
actual cleanroom in which the garment is designed to be worn.
In many pharmaceutical companies, a new sterile gown
also will need to undergo testing on three lots before validating and approving
it. In some cases, a change to the standards of practice for that
environment will also be required.
At the WCBF, cleanroom workers received training in
the new gowning procedures as part of their annual aseptic gowning
qualification. In order to pass, employees need to demonstrate three
consecutive acceptable gownings. Personnel environmental monitoring was
also conducted.
Conclusion
Validating a new sterile cleanroom garment is not a
task to be undertaken lightly. However, the WCBF found that this new
approach to sterile gowning can help improve the gowning process, reduce
opportunities for operator error, and minimize the risk of contamination —
providing a strong incentive for switching.