230
Chapter 15: Use of Standards in Medical Device Global Regulatory Strategy
Replacement heart valves can be made
of various materials. Mechanical heart valves
usually consist of one or two tilting discs or
“leaflets” operating inside a ring or housing.
The discs often are made of ceramic, such as
pyrolytic carbon the housings also can be made
of ceramic or a metal, such as titanium. Tissue
heart valves use animal-derived tissue, such as
bovine pericardium or an intact porcine valve.
The tissue is treated during the manufacturing
process, often with glutaraldahyde or a simi-
lar fixative. Most surgically-implanted valves
also have a “sewing ring,” often of polyester, to
enable the surgeon to suture the prosthetic valve
into the patient’s native tissue annulus.
However, for this case study, assume the
device manufacturer wants to incorporate
the latest technological innovations. To treat
patients at a high risk of complications in tra-
ditional open-heart surgery, the valve will be
delivered via a catheter. The catheter will be
introduced into the patient’s groin, will pass
through the femoral artery and up through
the aorta. The valve then will be released from
the catheter and fixed in place of the patient’s
native aortic valve. The valve itself will need to
be flexible and compressible to be loaded onto a
catheter. To avoid potential risks associated with
tissues of animal origin, the manufacturer has
decided to manufacture the valve housing and
leaflets from a polymer material.
The manufacturer intends to offer this valve
to patients worldwide and has developed a reg-
ulatory strategy to begin clinical studies in the
US and then use those data to submit market-
ing applications in other regulated countries.31
The manufacturer will adhere to a rigid
design control process that will include ade-
quate periods of time to define user needs and
develop design input leading to design output.
Further, the manufacturer will schedule a series
of design reviews to act as gating mechanisms
throughout the development process. As certain
milestones are reached during design and test-
ing, these reviews will either confirm the design
is meeting expectations and move activities into
the next phase, or direct the design and devel-
opment team to return to the previous phase for
retesting or design revision. The development
team will be expected to establish an overall
protocol for verifying and validating the design,
relying on state-of-the-art thinking about valves
and the most appropriate available standards
and guidance.
Because the manufacturer intends to study
and market the valve first in the US, the devel-
opment team should be knowledgeable about
FDA expectations. FDA first published Draft
Guidance for Industry and FDA Staff, Heart
Valves—Investigational Device Exemption (IDE)
and Premarket Approval (PMA) Applications
in 1994.32 The guidance was revised and reis-
sued in 2010. ISO first published ISO 5840
Cardiovascular implants—Cardiac valve pros-
theses in 1996.33 The standard was revised in
2005 and reaffirmed in 2010. This standard
has since been revised by ISO 5830-2:2015
Cardiovascular Implants—Cardiac Valve
Prostheses—Part 2: Surgically Implanted Heart
Valve Substitutes.34
The manufacturer, then, would use guid-
ance documents and standards in parallel in the
development process. ISO 5840 provides an
excellent outline of general requirements, even
specifying design input, output and transfer,
and risk management.35 The standard goes on
to identify further general requirements, such
as material property assessment, hydrodynamic
performance assessment, structural performance
assessment, etc., with some specific require-
ments defined in the annexes.
The FDA guidance provides more detail
in some areas and is intended to be compli-
mentary to ISO 5840. Specific requirements
are identified for in vitro testing, including
durability, fatigue, dynamic failure mode and
cavitation. Similar levels of detail are provided
for preclinical animal testing, along with specific
recommendations on how to submit the data in
IDE and PMA applications. As expected, the
guidance provides a great deal of information
about clinical testing, including objective per-
formance criteria. Finally, there is a section on
labeling. The appendices also provide a wealth
of detail regarding shelf life, cavitation, verifica-
tion of Bernoulli’s principle and a protocol for
echocardiographic assessment.
Chapter 15: Use of Standards in Medical Device Global Regulatory Strategy
Replacement heart valves can be made
of various materials. Mechanical heart valves
usually consist of one or two tilting discs or
“leaflets” operating inside a ring or housing.
The discs often are made of ceramic, such as
pyrolytic carbon the housings also can be made
of ceramic or a metal, such as titanium. Tissue
heart valves use animal-derived tissue, such as
bovine pericardium or an intact porcine valve.
The tissue is treated during the manufacturing
process, often with glutaraldahyde or a simi-
lar fixative. Most surgically-implanted valves
also have a “sewing ring,” often of polyester, to
enable the surgeon to suture the prosthetic valve
into the patient’s native tissue annulus.
However, for this case study, assume the
device manufacturer wants to incorporate
the latest technological innovations. To treat
patients at a high risk of complications in tra-
ditional open-heart surgery, the valve will be
delivered via a catheter. The catheter will be
introduced into the patient’s groin, will pass
through the femoral artery and up through
the aorta. The valve then will be released from
the catheter and fixed in place of the patient’s
native aortic valve. The valve itself will need to
be flexible and compressible to be loaded onto a
catheter. To avoid potential risks associated with
tissues of animal origin, the manufacturer has
decided to manufacture the valve housing and
leaflets from a polymer material.
The manufacturer intends to offer this valve
to patients worldwide and has developed a reg-
ulatory strategy to begin clinical studies in the
US and then use those data to submit market-
ing applications in other regulated countries.31
The manufacturer will adhere to a rigid
design control process that will include ade-
quate periods of time to define user needs and
develop design input leading to design output.
Further, the manufacturer will schedule a series
of design reviews to act as gating mechanisms
throughout the development process. As certain
milestones are reached during design and test-
ing, these reviews will either confirm the design
is meeting expectations and move activities into
the next phase, or direct the design and devel-
opment team to return to the previous phase for
retesting or design revision. The development
team will be expected to establish an overall
protocol for verifying and validating the design,
relying on state-of-the-art thinking about valves
and the most appropriate available standards
and guidance.
Because the manufacturer intends to study
and market the valve first in the US, the devel-
opment team should be knowledgeable about
FDA expectations. FDA first published Draft
Guidance for Industry and FDA Staff, Heart
Valves—Investigational Device Exemption (IDE)
and Premarket Approval (PMA) Applications
in 1994.32 The guidance was revised and reis-
sued in 2010. ISO first published ISO 5840
Cardiovascular implants—Cardiac valve pros-
theses in 1996.33 The standard was revised in
2005 and reaffirmed in 2010. This standard
has since been revised by ISO 5830-2:2015
Cardiovascular Implants—Cardiac Valve
Prostheses—Part 2: Surgically Implanted Heart
Valve Substitutes.34
The manufacturer, then, would use guid-
ance documents and standards in parallel in the
development process. ISO 5840 provides an
excellent outline of general requirements, even
specifying design input, output and transfer,
and risk management.35 The standard goes on
to identify further general requirements, such
as material property assessment, hydrodynamic
performance assessment, structural performance
assessment, etc., with some specific require-
ments defined in the annexes.
The FDA guidance provides more detail
in some areas and is intended to be compli-
mentary to ISO 5840. Specific requirements
are identified for in vitro testing, including
durability, fatigue, dynamic failure mode and
cavitation. Similar levels of detail are provided
for preclinical animal testing, along with specific
recommendations on how to submit the data in
IDE and PMA applications. As expected, the
guidance provides a great deal of information
about clinical testing, including objective per-
formance criteria. Finally, there is a section on
labeling. The appendices also provide a wealth
of detail regarding shelf life, cavitation, verifica-
tion of Bernoulli’s principle and a protocol for
echocardiographic assessment.