Page 242 - Biomedical Engineering and Design Handbook Volume 2, Applications

STERILE MEDICAL DEVICE PACKAGE DEVELOPMENT 221

Notice that these principles do not explicitly define the test parameters. However, the theory postu-
lated by von’t Hoff using the Q value (which states that a rise in temperature of 10°C will double
10
the rate of chemical reaction) is the most convenient method of estimating the approximate ambient
storage time equivalent at a selected accelerated aging temperature, despite the known limitations
and concerns for use on complex and dissimilar material structures.
For the aging study shown in the flowchart in Fig. 7.7, using an accelerated aging temperature of
55°C, the equivalent ambient storage time for 1 year is 26 days. Remember, the accelerated aging in
this protocol is treated as a separate entity and the combined effects of aging and distribution han-
dling are not determined. Caution must be taken not to accelerate the aging too much, since elevat-
ing the temperature of packaging materials could result in a mode of failure that might never be
observed in real life (i.e., material/product interaction, creep or deformation).

7.9.5 Defining the Shipping Environment—Environmental
Stress Testing
The parallel leg of the package validation protocol shown in Fig. 7.7 is based on the accepted fact
that sterile medical device packages do not typically lose their sterility simply by being stored on a
shelf. Package failures are a result of environmental extremes and dynamic events which may have
occurred during the manufacturing process, during shipping and handling to the sterilization facility,
or during distribution or transit to the point of end use. All of these processes may subject the fin-
ished package to forces involving handling shocks, vibration, high and low temperature, and humid-
ity extremes. The GMP for Medical Devices Part 820.130 states that “the device package and any
shipping container for a device shall be designed and constructed to protect the device from alter-
ation or damage during the customary conditions of processing, storage, handling, and distribution.”
There are optional methods available to satisfy this segment of the package validation process.
First, the package could be tested by simply shipping it to a destination using the anticipated ship-
ping mode (i.e., overnight parcel, common carrier). This method, although economical, does not lend
itself to a high degree of control and repeatability. Alternatively, laboratory simulations provide a
means of subjecting packages to the anticipated distribution hazards of shock, vibration, and
dynamic compression in a controlled and repeatable manner. Observations of the package perfor-
mance, as it is subjected to various hazards, can be accomplished in the laboratory, and corrective
action can be taken to alleviate any anticipated problems in a timely fashion. Laboratory methods
can be performed using standardized laboratory simulations such as ASTM D4169, “Performance
Testing of Shipping Containers and Systems” or International Safe Transit (ISTA) procedures like
Procedure 1A, 2A, or 3A. More information on the ISTA standards can be found at the ISTA Web
site, www.ista.org.
The standardized laboratory procedures sequence a number of distribution “elements” or
dynamic tests that use realistic test intensity levels. The ASTM method also allows the user who
has significant knowledge of his or her distribution system to design a test sequence which more
closely matches a specific shipping environment. This may allow for a laboratory simulation based
on actual field measurements, including, vibration, drops, temperature and humidity, and atmos-
pheric pressure.
The most common standardized distribution simulation test used for medical device package val-
idation is the ASTM D4169, Distribution Cycle #13. This method is designed for packages weigh-
ing less than 100 lb and being transported by air and motor freight (small parcel distribution system).
This test “provides a uniform basis of evaluating in the laboratory, the ability of shipping units to
withstand the distribution environment. This is accomplished by subjecting the packages to a test
plan consisting of a sequence of anticipated hazard elements encountered in the chosen distribution
environment.” A new method that has incorporated specific field data from the small parcel delivery
system (e.g., UPS, FedEx, DHL) has been published by ASTM and is entitled ASTM D7386-08
“Standard Practice for Performance Testing of Packages for Single Parcel Delivery Systems.” This
is thought to be a more realistic standardized simulation of the distribution environment to which
most medical device packages are subjected.