Page 229 - Biomedical Engineering and Design Handbook Volume 2, Applications

208 MEDICAL DEVICE DESIGN

the established design and operating limits and tolerances. Part 2 of the ISO standard addresses all
of the issues in validation such as equipment qualification, process development, process perfor-
mance qualification, process control, and process certification and revalidation.

7.7.6 Installation Qualification (IQ)
An equipment installation qualification (IQ) is important because all production facilities have specific
requirements for utilities, cleanliness, ambient temperature and humidity, and other variables. For this
reason, the equipment should be installed in its intended production location before qualification. In
addition, all equipment change parts and accessories are assembled and checked out for proper fit. This
phase of the validation includes verifying that the equipment will perform its intended function, estab-
lishing calibration and maintenance procedures, and identifying monitoring and control issues.
Standard operating procedures (SOPs) must be written for calibration, maintenance, and repair.
Facilities management has confirmed that the equipment has been properly installed, and that it
performs in accordance with the manufacturer’s specification. We can now begin to produce finished
packages on the new equipment.

7.7.7 Operational Qualification (OQ)
In the operational qualification (OQ) the process parameters are challenged to ensure that they will pro-
duce sterile barrier systems that meet all defined requirements under all anticipated conditions of man-
ufacturing. This step is designed to show and document that the equipment can run at its operating limits
and to determine its performance capabilities relative to the manufacturer’s specifications. This is the
most critical and time-consuming phase of the validation process. It requires a large amount of perfor-
mance testing and evaluation. Tests must be chosen that measure relevant performance characteristics of
the package for important attributes such as seal strength and integrity. ISO provides examples of tests
that may be used for measuring these attributes, including ASTM F88, ASTM D903, and ASTM F1140
for seal strength, and several methods such as internal pressure, dye penetration, gas sensing, and vac-
uum leak tests for package integrity, which have been discussed previously. These are physical test meth-
ods that ISO acknowledges can be used for demonstrating the integrity of the sterile package.
The first step in this phase of the validation is to establish the upper and lower ranges of the process
parameters, which produce acceptable package performance. This may be accomplished by testing
packages produced from a matrix of process parameter variable combinations, or by a design of exper-
iments (DOE) which will only test packages produced at the extreme range of the process parameters.
Where limited quantities of packages are available, one combination of process parameters may be
used to produce packages based on historical experience, and then tested for strength and integrity. If
these process parameters do not produce packages meeting the prescribed performance specifications,
then the process parameters are adjusted until acceptable packages are produced. The flowchart in
Fig. 7.2 depicts the process for establishing the machine process parameters.
The packages are produced under standard operating conditions and on the process equipment
that has completed an IQ.
Through the rigorous step of OQ, the manufacturing department has now documented the machine
process parameters and established the package performance specifications for the package system
being developed.

7.7.8 Performance Qualification (PQ)
When the optimum machine process parameters have been established in the OQ, it is essential to
determine the effects of sterilization, storage, and shipping and handling on the performance of the
critical package attributes. This can be accomplished by measuring the seal strength and integrity
after each of the individual processes and the accumulative effects of all these processes. This step