Process Validation and Acceptance Activities for Medical Devices FDA Guidelines

(1)     Process Validation

Device quality, such as feature geometry, overall dimensions, material

Characteristics, and mechanical properties, are impacted by AM process

parameters, process steps, and raw material properties, as described in the sections
above.  In addition, for an identical device or component, quality may vary when
built using different AM machines, even when the same machine model,
parameters, process steps, and raw materials are used.  Therefore, knowledge of
how the variability of each input parameter and processing step affects the final
finished device or component is critical to ensuring part quality.  Where the
results of a process cannot be fully verified by subsequent inspection and testing,
the process must be validated with a high degree of assurance and approved
according to established procedures.²¹ In addition all documentation must
conform to the existing guidelines in the Quality System regulation for device
validation.  Process validation must be performed to ensure and maintain quality
for all devices and components built in a single build cycle, between build cycles,
and between machines, where the results of a process (i.e., output specifications)
cannot be fully verified by subsequent inspection and test.²²  Software also must
be validated for its intended use according to an established protocol²³ (i.e.,
software workflow).

For validated processes, the monitoring and control methods and data must be

documented.²⁴  This section provides some examples of methods for ensuring the consistency of quality. The list is meant to be representational of the type of
factors to consider when performing process validation.  It can be used as a
reference point but is not exhaustive.  The following examples may have the greatest applicability to powder bed fusion technologies, which comprise a large portion of AM medical devices.  Methods could include:

·   In-process monitoring of parameters such as:

o   temperature at the beam focus,

o   melt pool data,

o   build-space environmental conditions (e.g., temperature, pressure,
      humidity),

o   power of the energy delivery system (e.g., laser, electron beam,
      extruder), and

o   status of mechanical elements of the printing system (e.g., recoater,
      gantry)

In-process monitoring may also be helpful for processes that are not validated, but is not required. 

·   manual or automated visual inspection with defined acceptance criteria, ·   non-destructive evaluation (see Section V.E.3 Verification), and
·   test coupon evaluation (see Section V.E.4 Test Coupons).

Not every AM system will be able to perform all these measurements, either because the process does not use them or because of technological limitations. Test methods used for process monitoring and control must be validated.²⁵  For example, analysis should be conducted to confirm that test coupons used are representative of the final finished device or component and representative of a certain area within the build volume.

A single failed component or device in a build cycle may not necessitate the

rejection of all other devices or components within that build cycle.  The criteria for determining whether to reject a single device or component, or the entire build, should be established before testing.

(2)     Re validation

Changes to the device, manufacturing process, or process deviations should be
identified and analyzed for the potential risks they introduce.  Based on this
assessment, the change or deviation may trigger the need for revalidation of the
process.²⁶  Manufacturers should rely on existing FDA Guidance for their
regulatory pathway^27,28,29,30 when considering a change to a previously cleared or
approved device that uses AM.  Some examples of triggers for revalidation
specific to AM are:

·   software changes (e.g., change or update of build preparation software),

·   changes in material (e.g., supplier, incoming material specification, reused
      powder, new formulation) or material handling,

·   change in the spacing or orientation of devices or components in the build
      volume,

·   changes to the software workflow (see Section V.B.2 Digital Device
      Design to Physical Device),

·   physically moving the machine to a new location, and

·   changes to post-processing steps or parameters. 

(3)     Acceptance Activities

Acceptance activities are integral to process control.  Many AM technologies can produce more than one device or component simultaneously at different locations in the build volume.  Each of these devices or components can be copies of a single design or different designs.  This makes it more challenging to ensure
repeatability and consistency within a build cycle and across lots.

Some acceptance activities for individual devices or components can be

performed through non-destructive evaluation (NDE).  Specifically, NDE

techniques can be used for the verification of geometry, morphology, and some performance characteristics.  Techniques include, but are not limited to:

·   Ultrasound,

·   computed tomography (CT) or micro-CT,

·   xx-ray (in cases with simple geometry),

·   dye penetration,

·confocal microscopy, and
·   hyperspectral imaging.

Some techniques are not suitable for some materials, designs, or intended uses. General NDE testing protocols can be found from the ASTM and ISO
Committees on Nondestructive Testing. Protocols specific to AM can be found from the ISO/ASTM Committee on Additive Manufacturing Technologies.³¹  If an NDE technique is used in your process validation or acceptance activities, the choice of technique used should be discussed and documented.

(4)     Test Coupons

A test coupon is a representative test sample of the device or component.  The
design of test coupons and placement within the build volume can be especially
important for AM.  Coupons can be simple shapes suitable for destructive
mechanical testing, or they may contain one or more structural features (e.g.,
surface porosity, internal channels) representative of the component or device that
can be assessed using destructive techniques.  We recommend that coupons be
used to help with your process validation and to identify worst-case conditions in
your manufacturing process (e.g., worst-case orientation and location in build
volume).  Test coupons can also be used for in-process monitoring by placing
them in build volume locations that are known to have the worst-case outputs.
However, test coupons may not be needed if the process is validated per Quality

System requirements and coupon testing is not a process monitoring activity

defined in your quality system.  These test coupons can confirm that the build

cycle has met its performance specification for that portion of the build volume if
the test coupons meet the performance specifications.  For example, test coupons
may be placed at the edges of the build volume if edges are known to have less
optimal build quality.  They may also be placed randomly in between components
or devices to produce a sampling of the build quality.  Data to demonstrate that
test coupons are representative of the components, in-process devices, or finished
devices should be documented. Many factors can alter how well a test coupon

represents any given part in the build space.  When coupons are used, they should be validated to accurately and reproducibility represent the one or more printed parts within a specific build volume. 

Refrences:

²¹21 CFR 820.75(a)

²²See 21 CFR 820.75(a)

²³See21 CFR 820.70(i), and “General Principles of Software Validation; Final Guidance for Industry and Staff.”
²⁴See 21 CFR 820.75(b)(2) 

²⁵ See 820.72(a) and 820.250(a)

²⁶See 820.70(b) and 820.75(c)

²⁷Deciding When to Submit a 510(k) for a Change to an Existing Device

(www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm080235.htm)

²⁸30-Day Notices, 135-Day Premarket Approval (PMA) Supplements and 75-Day Humanitarian Device Exemption (HDE) Supplements for Manufacturing Method or Process Changes

(www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM080194.pdf)
²⁹Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process
https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm089360.pdf
³⁰Changes or Modifications During the Conduct of a Clinical Investigation

(www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm082158.pdf)

³¹http://www.astm.org/COMMIT/SUBCOMMIT/F42.htm