Imminent start needed as ‘Legacy Tyvek’ might be running out of stock.
Three years ago, DuPont announced new production lines for the production of “Transition” Tyvek (type 1059B and 1073B). The new production process is more efficient, and with the new facilities, DuPont can guarantee supporting the growing demand of the medical device industry. The upcoming years DuPont may be able to deliver the old (now called “Legacy”) Tyvek, but they give no guarantee. In time, shortage of Legacy Tyvek is foreseen.
Although the technical specifications of Transition and Legacy Tyvek are virtually the same, the new production methods and locations are considered a substantial change. As this issue affects almost all medical device companies, one may expect that this change is processed at a central location. From DuPont’s side, this is the case, and DuPont has gone through great efforts to provide the industry with test data on the main properties of the material, comparing Transition Tyvek with Legacy Tyvek (see their specific website: http://www.areyouready.tyvek.com). Looking at the regulatory authorities, for example in USA and Canada, there is one central party processing the change, and who have provided guidance on how to proceed. However, for the EU, every Notified Body processes the change in its own way.. In this blog, the implications for these three main regions will be discussed.
EU (Notified Body) requirements
Starting with the EU, five major Notified Bodies provided guidance on their expectations. In short, they expect the manufacturer to show that the packaging system with the Transition Tyvek still complies to the ISO 11607 standards. This sounds simple, but generates a lot of work!
To show that the packaging system complies to all requirements of the ISO 11607-1, we went through the standard and determined for which clauses the existing evidence might no longer hold. In general, three main subjects will require attention:
• Compatibility with the sealing and forming processes (clause 5.1.9);
• Compatibility with the sterilization process (clause 5.3); and
• The sterile barrier system shall maintain sterility until the point of use or until the expiry date (clause 6.1.4).
Starting with the first bullet point, we see no way to completely avoid testing. With the change of Tyvek, the existing sealing validation is no longer valid. Hence, the OQ and PQ will need to be repeated. In case the OQ shows that the seal window is (almost) unchanged, one might be able to rationalize that a reduced PQ is sufficient. Otherwise, the PQ needs to be fully redone.
On the second point, DuPont provided test results on the seal strength of Tyvek for different types of packaging, after sterilization by Ethylene Oxide or Gamma irradiation (and for some types of packaging also for other sterilization methods). When DuPont data is available on one of the tested combinations of packaging and sterilization method, it should be possible to write a rationale based on the DuPont data. In case you are planning a sterilization revalidation, it is a good idea to use Transition Tyvek in the validation and add the data also to the Tyvek change.
Accelerated aging, the third point, is also a sensitive subject. DuPont provided accelerated aging data (up to 10 years) and real time aging data (1 year, 3 years end of 2017) on the seal strength, packaging integrity and microbial barrier for the main sterilization methods. We see no problem in levelling this data as proof, for up to 5 years shelf life. For more than 5 years, the number of samples tested by DuPont is too low to draw valid conclusions. It is recommended to combine this with real time aging of your own products.
For reason that a change of a material is a significant change, your Notified Body will expect to receive a Change Notification when changing to Transition Tyvek. Depending on the classification of the devices and the policy of your Notified Body, the documentation will be reviewed during the next audit or will require approval upfront. Upfront approval is likely for Class III devices and in case a sterilization validation had to be performed. Remember that the change should be documented as a change of a critical component, and processed according to the Design Change procedure! As for all changes, a risk analysis needs to be part of the change process.
USA (FDA) requirements
Looking at the USA, the situation is more straightforward. The FDA has send DuPont already in 2015 a general statement on the change of Tyvek. FDA determined that the performance of the new Tyvek material is functionally equivalent to the existing Tyvek material, something no Notified Body will ever do. FDA declared that it is generally not necessary to submit a new 510(k) or PMA supplement for a change solely on the Tyvek transition. FDA does require to properly perform and document the change, i.e. conduct a Risk Analysis, evaluate the impact of the change on packaging and sterilization processes, update the Device Master Record, and provide the rationale for acceptance of Transition Tyvek. Interestingly, this explicitly opens the door for rationales. Still, the DuPont data does not cover the validation of the specific sealing process used by a manufacturer. Thus, as in the EU, the sealing process will need to be revalidated. The difference is that the change will generally not be reviewed by FDA.
Canada (Health Canada) requirements
For Canada, the situation is more complex. Health Canada already in 2015 requested all manufacturers of Class III and IV products to inform them by a prescribed form whether Tyvek is used, and if so, how severe the implications will be. In case the DuPont data can be leveled, or if the change does not have a significant impact, no further action is required. However, when it is concluded that there might be a negative impact on the device sterility over the stated shelf-life, the manufacturer must submit a Medical Device License Amendment Application and provide the validation reports. It is up to the manufacturer to determine the significance of the impact, so eventually, the change process is very similar to the situation in the EU and USA.
The change to Transition Tyvek is a major project for all manufacturers using Tyvek. Looking at our customers, we do not get the impression that the urgency is felt. This might be because everything is already prepared, but more likely because the deadline is not announced yet. Yes, there is still Legacy Tyvek for sale, and yes, DuPont has already postponed their planned date for the closure of Legacy Tyvek. However, better start preparing!
Jan-Paul van Loon & Sheila Jaime