Process validation for medical 3d-printing is a challenge for me. And for you? Let's share our experiences....

Process validation is a challenge for all engineers and all processes, but for 3d printing engineers, the challenge is even bigger. Although there are companies that 3d-print under GMP, the knowledge they created on how the validate the processes usually stay inside the company. In this article, I am going to tell you what we are considering in the process validation of 3d-printing. We haven't figured it out completely ourselves yet. It is a thought process and your input and comments are more than welcome. In the meantime, I will update the document as soon as we have new insights or details to share.

In general, we can say that 3D printing processes need to follow the same process validation steps as for any other technology. The basics steps are explained in my other article on process validation for Medtech starters. However, there are important differences as well. Batch sizes are smaller for once and may vary. Sometimes you only make one product (print), while another time you print 10 products on a building plate.

But even with small batch numbers and changing print designs, it is possible to measure the process performance by measuring the dimensions and compare this with the design. Scanners and software to do Quality Control are readily available on the market. Cpk's can be calculated and monitored like any process, measuring printing process capabilities. Choose critical dimensions to focus on. These are dimensions that are important to the device function, but could also be difficult to print areas such as holes, porous regions, overhangs etc.)

Both the FDA as well as ISO13485 require that all processes producing medical devices or parts thereof a regimen of process validation as part of the overall quality system.

Before starting with the process validation, the process should be clear. The 3d-printing process entails much more than just the printing itself. The process is divided in a software workflow and a printing workflow. The workflow is depending on the devices that are printed and the 3d-printing techniques, but here you can find an example.

Software Workflow

So, the first step is the validation of the software workflow. Different workflows are possible but below is described a possible and common software workflow.

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

3D-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 filament, powder or resin) and the printer can start printing. When the print is finished, the print needs to be removed from the building plate or out of the powder, depending on the technology. The post-printing activities can start, which could entail:

1. cleaning of powder
2. washing with IPA
3. post-curing or sintering
4. smoothing surfaces

But most importantly the operator and Quality Control need to check the quality of the print. Dimensional and visual inspections are the most common quality control checks.

Software workflow validation

The software workflow must be validated. First, all software programs used in this workflow needs to be validated. GAMP 5 guide is a commonly used guide to validate the software. This article will not go into detail on software validation.

Although software validation is most important, the complete workflow process can be validated during the PQ phase.

validation of the 3d-printing workflow

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

1. Risk analysis (use/class of device, contamination risk, critical functionality-parameters, shelf life, stability, the safety of operators, users, and patients, etc)
2. product specifications
3. biological considerations (e.g. degradation behavior of the resorbable implant)
4. workflow
5. material properties

Critical parameters

The critical process parameters for 3d printing are depending on the technology you choose.

For FDM (Filament Diffusion Modeling) the process should be validated for every type of material used. Process parameters to consider are

• temperature and humidity of the environment
• processing temperature
• printing speed
• layer thickness, layer adhesion
• movement of x-y position. For example, the maximum degree of overhang in any design should be determined

For SLA the process settings are different, but also here all process settings should be validated for each material

• material temperature
• temperature and humidity of the environment
• accuracy
• laser technology, the age of laser source

Sterilization validation

Like all medical devices, if a sterile product is required (e.g. implants), the sterilization process needs to be validated as well. As batch sizes are much smaller (vary from 1 to a couple of dozen prints per batch), validation of the sterilization process should also be adjusted. Often 3 batches are used for sterilization validation, but with these small numbers, one might choose to validate more batches.

Validation plan

A possible validation plan could be the IQ and OQ of the 3d-printer and the OQ and PQ of the process of a specific material and/or group of products. An example of this group of products are all surgical guides for maxillofacial operations.

The IQ is not different from most equipment IQ's.

the Engineering study is a challenging part. choosing the critical parameters (which parameters are critical and which are not or less critical). Designing the DOE

The equipment OQ could be the correct printing of a standard model

The process OQ could be the repeatedly correct printing of a group of different prints using a specific material. This could be done in different settings (high, midpoint, low). High could mean high temperature and high speed versus low temperature and low speed. The importance is to choose settings in different corners of the processing window

The PQ run should consist of the whole process run including the software workflow, 3d printing process, post-printing activities, packaging, and sterilization. The printing run could consist of the printing of one or several prints at standard settings by different operators, repeated 3 times. Statistics should show high-quality parts and low variation (high Cpk).

Documentation

One of the requirements of validation is the availability of the necessary SOP's (standard operating procedures), setting sheets etc. Procedures/work instructions should be made for:

1. start-up, running, and shut down procedures for the 3d printing process
2. maintenance of the 3d-printer
3. Quality control (in process control or IPC, visual or dimensional inspections, etc)
4. Control of print files and firmware
5. A procedure of handling bad prints and the disposition of these prints
6. Setting sheet with the allowable print settings
7. work instructions on post-printing activities
8. Packaging and packaging materials
9. Sterilization
10. Storage and transport
11. material specifications (filament or resin, packaging materials)
12. product specification (with details of the device, QC, packaging, storage labeling etc.)

About Sandra de Vos

Sandra de Vos has been working with (polymeric) medical devices for over 12 years now. She has set up a Quality Management System (QMS) from scratch to ISO 13485 certification, that included product development (DHF file), Risk analysis and process development (process and product validation). She is a certified Lead Auditor. 

Currently, she is the founder and CEO of Vosfox Medical. Vosfox Medical offers consulting services and contract manufacturing services (CMO) for medical device companies. 

Our CMO services include the use of our facilities and support to develop the production process and make it ready for clinical trials. We offer ISO Class 7 cleanroom, QA support, production process development and validation support, etc. We have several 3D printers in the cleanroom and we produce medical grade filaments (for FDM printing).

You can stay as involved as you wish and outsource what you want.

For more information please visit our website (Vosfoxmedical.com), mail me ([email protected]), or call +31-650281838. You can also comment on the article and help me improve this and future articles.