VIAL TRANSFER CART
DESIGN: Designing Transfer Carts for ISO
class 5 conditions to meet regulatory requirements including Annex 1
regulations effective May 2010
Hank Rahe
Technical advisor for Containment Technologies Group.
Schaefer
Technologies, Inc.
4901
Phone:
Email: kschaefer@schaefertech.us
http://www.schaefer-technologies.net
Abstract:
This paper addresses that FDA has found
several pharmaceutical companies not maintaining ISO class 5 (class A)
conditions within transfer carts. Implementing a solution has not been a simple
task. The author discusses an approach for designing a transfer cart that will
satisfy ISO Class 5 (class A) requirements.
During one
FDA inspection, a seemingly simple
question brought on a major modification for many parenteral
manufacturing operations. Are ISO class 5 (class A) conditions being maintained
during the transfer of vials from the filling line to the freeze dryer?
What had been the industry norm and practice
for many years was suddenly being challenged and most companies did not have
the data to answer the offhanded question. Testing was quickly conducted to
prove that such a question did not have merit. Surprising to many industry
experts, the results showed that ISO class 5 (class A) conditions were not
being maintained in the environment where partially stoppered vials were
transported. Panic arose on two fronts. The first concern was product integrity
and second was finding a solution to the problem. The level of concern was
somewhat mitigated by the fact that manufacturers felt that the problem would
be relatively simple to correct.
However, the design of a new cart has not
been a simple task. Many design attempts fail because of the many constraints
and variables. A successful design requires unique engineering skills and an
understanding of the facility and process.
Requirements of a transfer
cart
Design
The design of a new cart requires
unidirectional airflow, which has the ability to remove particulate that is
generated when the thousands of vials are jarred against one another during
movement of the cart and maintain these conditions while the cart is being
moved from the filling line to the freeze dryer. Also, fitting the new cart
into the existing space proved to be a formidable task.
Space
Most current parenteral
manufacturing facilities are built with a minimal amount of space in the
sterile block. Designs are driven by the expense of construction and the cost
of maintaining high-–quality spaces. A majority of parenteral
manufacturing facilities have filling lines located separately from the freeze
dryers within the sterile block. Products that are to be freeze dried, are transported from the filling line to the freeze
dryers, through less air–quality zones within the sterile block. At the filling
line, products are put into vials that are then partially stoppered and placed
onto trays. The trays are then loaded into the transfer carts and transported
to the freeze dryer. The carts currently in use are static, in terms of
air–handling systems and in most cases are not constructed to be gas tight. Two
major design flaws in the transfer cart, currently in use, surfaced when
questioned by FDA officials. The first flaw is the lack of an air system that
could maintain unidirectional airflow during transport and the second is the
lack of integrity in the construction of the cart.
Finding a solution
The answer was to build a cleanroom
on wheels and to incorporate the advantages of an isolator by making the
environment gas tight. This solution required complex engineering and an
understanding of the human interaction demanded by the process. Several
companies attempted to make a cart that would offer a solution, but failed
because of a lack of understanding of process interactions. The technical
details that had to be considered included were the understanding of the proper
airflow velocities, pressurization and patterns to deliver product protection
within the carts and the limitations created by the physical facilities.
Because the facilities were designed to be as small as possible, the space in
the filling line, loading areas and the freeze dryer, ISO class 5 (class A)
zones are very limited. These space constraints played a major role in the
functional requirements of the new cart design. Time constraints also played a
large role because of regulatory demands to get the problem fixed. This meant
development of an acceptable solution had to be done quickly.
The functional requirements call for an
understanding of the space available to load, unload and manipulate the carts.
The space constraints include not only the loading and unloading zones, but
also the route the carts travel from the filling lines to the freeze dryers,
with special concern for turns and door openings. Once the facility constraints
are defined, then the size of the transfer cart can be determined. The cart,
which consists of the product chamber and support systems, is designed, in most
cases, to maximize the number of trays in the product chamber. The larger the
product chamber, the more support systems required. Thus, the optimum solution
requires a balance of the two variables that maximize the vial load of the
cart. Additional considerations include the ergonomics of moving trays loaded
with vials, while using proper aseptic techniques during the loading and
unloading operations.
The tray–loading area at the end of the
filling line typically has ISO class 5 (class A) unidirectional flow coverage
provided by hanging, or ceiling HEPA–filtered units. The coverage patterns
within these zones change as different objects are placed in this area. The
larger cart may change the loading position for the operator which can create
different airflow dynamics. Testing for any potential change is critical and
should include mapping the area for airflow using a smoke test that is
videotaped. Operator technique and proper ergonomics for loading the trays,
which weigh more than 10 kg is important. Smoke testing can identify
positioning problems. The smoke testing can only be conducted when the sterile
block is “down” which limits the amount of time for testing. To compensate for
this short window, well designed tests and schedules are required.
The unloading of vials at the freeze dryer
and reloading after the freeze dry is completed, requires a review of this
workstation as well. Videotaping of smoke patterns provides the best
documentation that neither the cart nor freeze dryer is compromised during
these operations and also provides an operator training tool.
The carts operate in the sterile block and
must have surfaces that can be cleaned and sanitized which presents a design
challenge. The surfaces must be of high quality and designed to eliminate any
potential contamination points. From the wheels, to the interior chamber,
consideration of good aseptic design for all components was needed. Testing of materials of construction is
important, to assure that they are compatible with the products used for
cleaning and sanitizing the cart. The quality in the finish of the surfaces to
be cleaned must be considered from two points. First is having a surface finish
that can be cleaned to the proper level and the second having a surface finish
that can withstand normal activities. The adhesives and gaskets must withstand
the harsh chemicals to which they are exposed. The method of application of the
cleaning and sanitizing materials should be considered when testing for compatibility.
A majority of operations still use manual cleaning and sanitizing of the
exterior and interior of the carts. The racks should be removable, since many
times they are autoclaved. The design of the rack system is another important
feature to consider if it is to be autoclaved, it must
fit into an existing autoclave.
The gray side mechanical components required
for the air handling system are made up of blowers,
HEPA filters and a uniform
airflow membrane, were also a challenge. The system had exacting performance
criteria required to fit into limited space. The system should be tested to
assure that the product is maintained within the defined temperature range.
Verification of the temperature profile of the cart and the product should also
include complete testing of conditions while on battery power. The test
protocol should include a profile of both performance and heat load.
While in motion, the carts use a
battery-powered system to support the unidirectional airflow systems and
controls. Assurance of adequate power to run the air handling system required a
control system that monitored battery usage and would sound an alarm in time to
place the system on normal AC power, before the product was compromised. The
value of the products being transported can range into millions of dollars and
any out of specification event would result in the loss of the load.
When stationary, the carts use normal power
AC power, accomplished by simply plugging the cart into a power source.
Planning for adequate staging may require facility modifications because of the
number and increased size of the carts. The power sources and energy loads need
to be considered. The batteries must be charged, either by an onboard system or
at a charging station. Because of the critical area in which the carts operate,
the onboard system located in the gray zone of the cart is preferable.
A successful design
The many constraints and variables described
above are just a few examples of why the design of a transfer cart for freeze–dried
products is anything but simple and why many design attempts fail. A successful
design that will meet regulatory expectations requires unique engineering
skills and an understanding of both the facility and the process. To achieve
this, the pharmaceutical manufacturer must partner with the cart manufacturer
to evaluate the unique nature of the facility and develop the proper solution.
SIDEBAR:
CHARACTERISTICS OF A ISO
CLASS 5 CART
¨
Gas tight environment.
¨
Proper space availability to load, unload, and
manipulate.
¨
Well-designed smoke test.
¨
High quality, cleaned surface.
¨
Good aseptic design.
¨
Removable racks.
¨ Monitored battery usage.
Copyright © 2011 Schaefer Technologies Inc. All Rights reserved.