Final Drafts of the ISO 11608 series were opened for voting by the National Standards Bodies on 6 October 2021. The official closing date is 1 December 2021 which means the new standards will likely become available early 2022. These standards, covering requirements, test methods, and design guidance for needle-based injection systems for medical use (NIS) are getting to the end of the most comprehensive update since 2012.

Since 2012 several new parts were introduced which created the need for a better alignment. Among the new parts is the new standard regarding On-Body Delivery Systems which are not adequately covered so far. When involved in such projects in the past, we always had to puzzle together requirements from different standards which made it cumbersome. Having most requirements defined in one single standard which was developed with the help of numerous experts in ISO Technical Committee 84 (ISO/TC 84) is obviously a huge advantage. confinis was heavily engaged in these discussions with three experts, namely Beat U. Steffen and Urs Widmer representing Switzerland, and our US office representing the United States of America.

What does “ISO/FDIS” mean? The FDIS (Final Draft International Standard) is circulated to all ISO members for an 8-week vote. The standard is approved if a two-thirds majority of the P-members of the TC/SC is in favor and not more than one-quarter of the total number of votes cast are negative. No technical changes can be made anymore.

Since the initial publication of ISO 11608-1 in 2000 (which focused on pen injectors for medical use), the standard has significantly expanded its scope to cover many aspects of needle-based injection systems (NIS) with the exception of products such as prefilled syringes.

After publication, the series will comprise of:

• ISO 11608-1 General requirements
• ISO 11608-2 Double-ended pen needles
• ISO 11608-3 Containers and integrated fluid paths
• ISO 11608-4 NIS containing electronics
• ISO 11608-5 Automated functions
• ISO 11608-6 On-body delivery systems
• ISO 11608-7 Accessibility for persons with visual impairment

The main changes of the final drafts currently under approval are summarized below:

ISO 11608-1: Needle-based injection systems

To ensure this “overarching” standard covers all possible NIS, ISO/TC 84 put a lot of effort and focus on aligning the various parts and eliminating duplicated topics. It covers fundamental aspects of safety and performance (i.e. dose accuracy) and references relevant “sub-standards” like the new ISO 11608-6 regarding On-Body Delivery Systems. It follows a risk-based approach but also expanded testing regimens to simulate aspects such as but not limited to life-cycle testing. The impact and requirements of the medicinal product to be delivered must be considered in the design input requirements. Minor modifications include moving all requirements and test methods concerning electronics to ISO 11608-4. Another one is the implementation of a choking hazard warning for small components and the associated test fixture.

ISO 11608-2:  Double-ended pen needles

Subtle changes were introduced to ISO 11608-2. We want to point out the determination of flow rate which was expanded to include proposed low ranges. Furthermore, the sample sizes were harmonized with those in the overarching standard. Obviously, compatibility between a needle and a specific NIS is crucial. Therefore, testing requirements to confirm this have been revised and now dose delivery and needle hub removal force. Finally, the samples required for functional compatibility have been reduced and guidance has been added regarding the requirements for the inner needle shield.

ISO 11608-3: Containers and integrated fluid paths
Since OBDS are now also explicitly covered by the ISO 11608 series, the scope of ISO 11608-3 has been expanded beyond defining cartridge geometry and performance to cover NIS Containers and integrated fluid paths. Cartridge geometry definition has also been moved to a non-mandatory annex. Changes implemented concern e.g. resealing reduction and the increased particle size for coring characterization. Requirements for soft cannulas and fluid line connections have been added.

ISO 11608-4: Needle-based injection systems containing electronics

As one of the driving forces for the initial version of this standard, confinis representatives were also heavily involved in this update. Some changes introduced are a consequence of the alignment with ISO 11608-1. Others represent a scope expansion to include all electronics on a NIS, not just those related to the delivery of the medicinal product.

The fact that medical electrical devices are already tightly covered in the IEC 60601-x series of standards made it fairly difficult to end up with a standalone standard with the scope it now has. Therefore, explicit references were included to the relevant standards of the IEC 60601-x series that are appropriate for electronic NIS, mainly those related to power input requirements and patient protection. A few other important changes implemented concern the minimum ingress protection from IP22 to IP52 and defined maximum temperatures for skin contact.

ISO 11608-5: Automated functions

Since the activities for the previous version of ISO 11608-5 were initiated somehow asynchronously, the revised text for ISO 11608-5 is now fully aligned with ISO 11608-1. Other changes implemented don’t look spectacular but are nevertheless important and concern areas such as automated needle insertion, dose delivery and accuracy, non-perpendicular needles, and fenestrated needles. Additional requirements included are defining and measuring automated dose delivery time.

ISO 11608-6: On-body delivery systems

This was a major piece of work, particularly also the alignment with ISO 11608-1 and ISO 11608-5. Its development also had a significant impact on ISO 11608-3 because more traditional container geometries may not be suitable for OBDS or would limit technical solutions unnecessarily.

What makes it different to other types of injectors is obviously the fact that they are attached to the body and therefore have increased requirements concerning everything related to that. It was also crucial to dissect the important differences to an infusion pump, i.e. dose accuracy vs. rate over time. Nothing is perfect but the result reflects the key aspects and differences to “traditional” NIS in a good way and will provide an important resource for everybody involved with OBDS.

Summary

Except for ISO 11608-6 regarding OBDS, the updates are not a revolution but a great evolution. Everybody involved in needle-based injection systems will be affected and should familiarize him- or herself with the new requirements.

We are happy and feel privileged to have contributed to these updates. A huge “Thank You” to all our co-experts for listening, discussing, questioning, proposing etc. always with a focus on safe devices for patients – that is what matters! The above summary provides top-level information but doesn’t replace a careful review and interpretation (yes, standards have to be interpreted!).

Author: Beat U. Steffen