Whether for economic or strategic reasons, medical device manufacturers often outsource their production to another site or external company. In principle, when this occurs the legal manufacturer of the medical device is responsible for the biocompatibility evaluation. With various factors to be considered for the biocompatibility assessment when a manufacturing site is transferred, Dr Silvio Peng and Caroline Bachem from our Operations team share some advice on how to approach this scenario in our topical article below…
Clarify any design changes
Whilst the focus of the biocompatibility evaluation sits with the receiving site, the existing processes at the donor’s site can also be considered in the assessment. It must be clarified whether a design change is required at the same time as the transfer or whether the transfer has an influence on the product design. To this end, a site transfer is often utilised as an opportunity to re-evaluate the existing design – for example, the material used for the medical device.
Categorise and group the products / product families
With any biocompatibility evaluation, products / product families are first categorised and grouped as follows:
- They are categorised according to ISO-10993-1
- They are grouped based on:
- The raw material of the device
- The manufacturing processes on the receiving site used to manufacture the device
Within the group, a representative part is selected, with factors such as shape, geometry, blind holes, surface, and size of the part taken into consideration.
If the production of a complete product family or group is transferred, the grouping and selection of the representative part can be adopted for the biocompatibility evaluation at the receiving site.
Perform a thorough gap analysis
The most critical task within the biocompatibility evaluation is the gap analysis relating to the biological endpoints as per the category of the devices in scope according to ISO-10993-1. The gap analysis will help you to define whether testing is required or not and if so, what tests would be meaningful. When dealing with implants, patient exposure and indication is also taken into consideration for the gap analysis.
When transferring your manufacturing site, you need to determine the available biocompatibility data at the receiving site. It’s important to check whether the existing data at the receiving site still meet the current standards, and attention must also be paid to whether a chemical characterisation is available or not in the case of certain devices such as implants or externally communicating devices.
The ideal situation would have the receiving site already manufacturing comparable products, with the product to be transferred already falling into a group known to the receiving site. In this case, testing might not be necessary, and the assessment could potentially be completed with just a risk-based biocompatibility evaluation.
Test and evaluate
Based on the gap analysis, testing is then selected to generate data to address the endpoints as per ISO-10993-1. Initial testing typically includes testing for residues, or in vitro tests such as cytotoxicity. The testing for residues can be achieved by chemical characterisation which is designed to detect any potential residues on the medical device that might be biologically or toxicologically relevant. For more information on this, take a look at our fact sheet on the Analytical Evaluation Threshold (AET).
Data from the chemical characterisation is then used to perform a toxicological risk assessment and determine the need for potential further testing of the device (for example genotoxicity or in vivo studies).
When all available data has been considered, the biocompatibility evaluation is complete.
5 tips for a successful manufacturing site transfer
It is crucial to select your receiving site with detailed care and attention. Here are some key tips for successful manufacturing site transfer relating to biocompatibility:
- Consider if the receiving site already manufactures similar products with comparable manufacturing processes
- Assess the already available biocompatibility data on the receiving site to reduce the likelihood of further testing
- Consider transferring entire product families or groups rather than single products
- Allocate sufficient resource to the manufacturing site transfer to ensure adequate development of, and support for, the receiving site
- Factor in ample time within your project plan for the transfer – especially if a biocompatibility assessment including testing is required