The challenges of process validation for medical 3d-printing

The validation of 3d printing processes is challenging. Challenging for all processes, but 3D printing processes have additional challenges. Companies have already validated their 3d-print process, but their knowledge is often kept secret. In this article, I share with you our experience so far.

3D printing processes must follow the same process validation steps as any other production process. Different 3D printing processes, such as SLS, SLA, FDM or bioprinting, have each their challenges. This article will describe the general topics with sometimes remarks for specific printing processes. The FDA and ISO13485 require all processes for the production of medical devices or components to be validated. This should be done according to the ISO/ASTM52930 and ISO/ASTM52920 norms.

Before starting with the validation, one needs to define the product specifications. These specifications are the basis of your acceptability criteria. Examples are dimension, mass, functionality, mechanical strength etc. The acceptable tolerances must be known.

Secondly, make a process flow diagram that clearly shows which process steps are required to produce your product. Then decide which steps need validation. When verification is possible, consider verification instead of validation. Read more about this in the article Process validate

 

Software Workflow

So the first step is the validation of the software workflow. The software workflow is depending if your devices are unique or if you use 3D printing as low volume mass production. In this case, you may consider if the software workflow is part of the validation when you always use the same print file. When the print file is part of the production process, e.g. for unique single products, the workflow could be as follows:

A medical scan (e.g. CT or MRI) results in a DICOM file. The exciting part of the scan is selected using rendering techniques. A device is designed using CAD software to fit the patient specifically with the DICOM data as input. This file is exported in a format that slicing software can slice (G-code file). The sliced data is fed to the 3d printer.

Software validation can be done according to GAMP 5 or ISO 8002 series. This article will not go into detail on software validation.

Printing and post-printing workflow

The 3D printing workflow starts with the transfer of the G-code file to the 3D printer. The material is fed into the printer (e.g. the treatment, powder or resin), and the printer can start printing. This assumes that all settings are part of the G-code. When applicable, the printed components can be removed, and post-printing activities can be done. Examples are powder removal, washing and curing, sintering, or smoothing surfaces.

The operator or Quality Control will check the print quality as described in the product specifications. Dimensional and visual inspections are the most common quality control checks.

Preparing printer for next job

Before the next job can be started, the printer needs to be prepared. This can be cleaning, changing or reusing resin, sieving, testing and adding virgin powder, or changing filament. All these activities require validation when 100% verification is not possible.

Validation of the 3d-printing and post-printing workflow

The exact test plan for validation is for every workflow different, but some theses to consider are:

1. Pre-requisites
   1. Draw the flow diagram
   2. Perform a process Risk Analysis (consider, for example, contamination risk, process parameters, manual tasks, shelf life, stability, and the safety of operators). For more info on risk analysis, see this article.
   3. Define the product specifications
2. Define critical parameters. For this process, development might be needed, especially for new processes.
   • Usually, not all parameters are critical. Select the essential parameters for performing the Design of the Experiment.
   • Consider parameters such as temperature, intensity and time of the laser, particle size, resin type etc.
   • Consider the effect of post-printing activities on product quality. E.g. solvent residue, contamination, effect sandblasting on dimensions, warping due to curing.
3. Define what will be 100% verified and what requires validation. For low-volume production, 100% verification might be more economical.
4. If more than one part is printed per run, one should establish if and what the effect is of the location on the build plate and the distance between parts.
5. Define whether the build plate contains the same number and types of parts for every run or whether this varies. If this is variable, these need to be validated (e.g. 1-10 parts per display, only part A or mixing parts A, B, C, and D).

Validation of cleaning and preparing printer

When the print is removed from the build plate, the following activities may need to be considered.

1. Pre-requisites
   1. Perform a risk analysis on all cleaning and printer preparation activities.
   2. Make sure that all these activities are defined in the flow diagram.
   3. Define specifications of the cleaning/preparation activities
2. Cleaning build plate (influence cleaning technique on roughness, build-plate particles contaminating the parts, solvent residue etc., reusing powder). Most powders are expensive, so the powder is often sieved and reused. This process must be validated, monitored and controlled. How much virgin material is added, and what is the influence of 90% versus 40% virgin material on process parameters and product properties? SLA printing of resins may cause microparticles in the resin. Does this influence the properties of the products
3. Cleaning of the machine when changing from one raw material to another must be validated. Therefore when you can use dedicated equipment or tools, the cleaning validation can be avoided or reduced. For example, using a building platform and resin tank for one resin type.

Packaging, Sterilisation and Test method validation

Like all medical devices, the packaging and, when applicable, the sterilisation process must also be validated. As batch sizes are much smaller (vary from 1 to a couple of dozen prints per batch), validation of the packaging and sterilisation process should probably be adjusted. The standard validation method is often the validation of three (PQ) batches. However, for tiny quantities, three batches might not provide enough data to obtain your required confidence levels, and more PQ runs can be necessary.

Just like with all processes, the Quality Control tests must be validated. The attribute testing (Pass/Fail) and the variable quality control tests must be validated.

Documentation

The following documentation should be created during the validation of the 3D printing process, when applicable. Combining topics in one plan, protocol or instruction is possible. This

1. Validation plan
2. IQ, OQ, PQ protocol and summary report
   • When several products need to be validated (using the same 3D printer), using test cases might be useful. These test plans contain, line by line, all activities which need to be checked or done. Different columns with test nr, reference (proof) test, expected result, actual result, Pass/FAIL, Deviation and date of execution with signature can be part of the test case. Operators or junior engineers can easily reuse and execute these test cases.
3. Validation summary report
4. Work instruction for the start-up, running and shut-down procedures for the 3d printing process
5. Equipment instruction with info about maintenance and calibration of the 3d-printer
6. Quality control (in-process control or IPC, visual or dimensional inspections, etc.)
7. Control of print files
8. A procedure for handling bad prints, out of specification, and the disposition of these prints
9. Setting sheet with the allowable print settings (when deemed useful).
10. Work instructions on post-printing activities, cleaning and preparing the printer for the next run.
11. Packaging and packaging materials
12. Sterilisation
13. Storage and transport
14. material specifications (filament or resin, packaging materials)
15. product specification (with details of the device, QC, packaging, storage labelling etc.)