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Global Medical Device Regulatory Strategy
Fortunately, there is an FDA APDS guidance
document. The guidance references several
horizontal and vertical standards. In addition,
a summary of safety and effectiveness data
(SSED) for a similar device or precedent, if one
exists, may be examined. From these documents
and the referenced standards, a fairly compre-
hensive list of standards can be obtained that
might cover the majority of, if not all, preclinical
testing requirements and bench performance
objective performance criteria, EMC, biocom-
patibility, sterility assurance, packaging, shelf
life, shipping, software and human factors.
The various research and development,
engineering, quality and clinical cross-functional
groups within the organization will need to
ensure all regulatory requirements are met. In
addition, a discussion about standards should
occur since standards play a significant role in
helping establish and communicate baseline
expectations at each APDS product lifecycle
stage. A few examples of the applicable numerous
horizontal and vertical standards for disparate
APDS components are discussed below.
Since the APDS insulin set component
is inserted under the patient’s skin, regulators
would be interested in the set materials’ bio-
compatibility. Certain parts of the ISO 10993
series may be examined to understand and
meet APDS biocompatibility requirements
within a risk management process. An FDA
blue book memo, entitled Use of International
Standard ISO 10993, Biological Evaluation of
Medical Devices Part 1: Evaluation and Testing,
can be consulted in parallel.27 A manufacturer
will need to provide biocompatibility testing
result summaries, since the standard, itself,
does not include pass/fail criteria. ISO 11137
Sterilization of Health Care Products—Radiation
helps in understanding sterility testing and
validation requirements. The device system’s
sensor component, which is a single-use dis-
posable device, is intended to be inserted under
the patient’s skin and remain there for up to six
days. In addition to the sensor, the pump, trans-
mitter, reservoir, and infusion set also are sterile
components. ISO 11137 provides baseline
requirements for the electron beam steriliza-
tion process and validation used to sterilize
all components provided as sterile, regardless
of whether they are for single or multiple use.
ISO 11607 Packaging for Terminally Sterilized
Devices, ASTM D4169 Standard Practice for
Performance Testing of Shipping Containers and
Systems and ASTM D642-00 Standard Test
Method for Determining Compressive Resultant
of Shipping Containers, Components and Unit
Loads were applied to sensor packaging. For the
manufacturer to ensure baseline packaging and
shipping requirements are met for this sterile,
single-use device, these three standards were
applied to validate the sensor is packaged for
device sterilization and protection adequately.
Packaging standards for device components
provided sterile, as opposed to those provided
non-sterile differ. IEC 62366-1:2015, discussed
previously, helps analyze, specify, design, verify
and validate the device’s usability for safety.
Finally, ISO 14155:2011 is applied in global
APDS clinical investigation. ISO 13485 for
quality systems and ISO 14971 for risk man-
agement also would apply.
Standards cited in the discussion above are
not intended to be comprehensive. This case study
is intended to demonstrate the breadth of stan-
dards applicable to a typical, complex, highest-risk
IVD device system. Identifying, understanding
and applying relevant standards may help the
manufacturer’s cross-functional team develop
a device that eventually will meet regulatory
requirements in the US and other countries.
Case Study: Use of Standards in Developing
a Hypothetical Replacement Heart Valve
The replacement heart valve provides another
case study of the application of both vertical and
horizontal standards in developing a medical
device. Heart valves are high-risk devices, Class
III in the US28 and under the EU MDD.29
Heart valves are in constant contact with the
patient’s blood and can cause death or serious
injury if they fail. The widely publicized failures
of the Shiley Heart Valve in the 1980s led to
heightened awareness of valves by all stakehold-
ers, including doctors and patients, regulators and
manufacturers. Concerns about the Shiley Heart
Valve and other devices were factors in enacting
the Safe Medical Devices Amendment of 1990.30
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
19
16
20
17
21
18
22
Global Medical Device Regulatory Strategy
Fortunately, there is an FDA APDS guidance
document. The guidance references several
horizontal and vertical standards. In addition,
a summary of safety and effectiveness data
(SSED) for a similar device or precedent, if one
exists, may be examined. From these documents
and the referenced standards, a fairly compre-
hensive list of standards can be obtained that
might cover the majority of, if not all, preclinical
testing requirements and bench performance
objective performance criteria, EMC, biocom-
patibility, sterility assurance, packaging, shelf
life, shipping, software and human factors.
The various research and development,
engineering, quality and clinical cross-functional
groups within the organization will need to
ensure all regulatory requirements are met. In
addition, a discussion about standards should
occur since standards play a significant role in
helping establish and communicate baseline
expectations at each APDS product lifecycle
stage. A few examples of the applicable numerous
horizontal and vertical standards for disparate
APDS components are discussed below.
Since the APDS insulin set component
is inserted under the patient’s skin, regulators
would be interested in the set materials’ bio-
compatibility. Certain parts of the ISO 10993
series may be examined to understand and
meet APDS biocompatibility requirements
within a risk management process. An FDA
blue book memo, entitled Use of International
Standard ISO 10993, Biological Evaluation of
Medical Devices Part 1: Evaluation and Testing,
can be consulted in parallel.27 A manufacturer
will need to provide biocompatibility testing
result summaries, since the standard, itself,
does not include pass/fail criteria. ISO 11137
Sterilization of Health Care Products—Radiation
helps in understanding sterility testing and
validation requirements. The device system’s
sensor component, which is a single-use dis-
posable device, is intended to be inserted under
the patient’s skin and remain there for up to six
days. In addition to the sensor, the pump, trans-
mitter, reservoir, and infusion set also are sterile
components. ISO 11137 provides baseline
requirements for the electron beam steriliza-
tion process and validation used to sterilize
all components provided as sterile, regardless
of whether they are for single or multiple use.
ISO 11607 Packaging for Terminally Sterilized
Devices, ASTM D4169 Standard Practice for
Performance Testing of Shipping Containers and
Systems and ASTM D642-00 Standard Test
Method for Determining Compressive Resultant
of Shipping Containers, Components and Unit
Loads were applied to sensor packaging. For the
manufacturer to ensure baseline packaging and
shipping requirements are met for this sterile,
single-use device, these three standards were
applied to validate the sensor is packaged for
device sterilization and protection adequately.
Packaging standards for device components
provided sterile, as opposed to those provided
non-sterile differ. IEC 62366-1:2015, discussed
previously, helps analyze, specify, design, verify
and validate the device’s usability for safety.
Finally, ISO 14155:2011 is applied in global
APDS clinical investigation. ISO 13485 for
quality systems and ISO 14971 for risk man-
agement also would apply.
Standards cited in the discussion above are
not intended to be comprehensive. This case study
is intended to demonstrate the breadth of stan-
dards applicable to a typical, complex, highest-risk
IVD device system. Identifying, understanding
and applying relevant standards may help the
manufacturer’s cross-functional team develop
a device that eventually will meet regulatory
requirements in the US and other countries.
Case Study: Use of Standards in Developing
a Hypothetical Replacement Heart Valve
The replacement heart valve provides another
case study of the application of both vertical and
horizontal standards in developing a medical
device. Heart valves are high-risk devices, Class
III in the US28 and under the EU MDD.29
Heart valves are in constant contact with the
patient’s blood and can cause death or serious
injury if they fail. The widely publicized failures
of the Shiley Heart Valve in the 1980s led to
heightened awareness of valves by all stakehold-
ers, including doctors and patients, regulators and
manufacturers. Concerns about the Shiley Heart
Valve and other devices were factors in enacting
the Safe Medical Devices Amendment of 1990.30