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The objective of this review is to better align the various parts of the standard and to define a new class of device coming to the market, On-Body Delivery Systems, which are not adequately described in the current revision of the standards. CDP develops and verifies many needle-based injection systems on behalf of our clients and our manufacturing capability also gives us insight into the challenge of moving from building a handful of devices to building thousands of products. The Final Draft International Standard will soon be published, and I’d like to share some of the proposed changes.
It’s important to note that the current status of these standard parts is ‘draft’, and the details of these documents may well change before publication, assuming that the various international bodies approve the publication of these standards. That said, let’s get into some detail.
Since the publication of ISO 11608-1: Pen Injectors for Medical Use – Requirements and Test Methods in 2000, the standard has expanded to cover many aspects of needle-based injection systems (NIS). The various parts of the published standards now cover General Requirements (11608-1 since 2012), Needles (11608-2), Finished Containers (11608-3), Electronic and Electromechanical Injectors (11608-4) and Automated Functions (11608-5). These standards were then joined by 11608-7 (Accessibility for persons with visual impairment) in 2016, which covers design guidance for improving accessibility to NIS for visually impaired users. These parts of the standard come under the remit of ISO Technical Committee 84 (ISO TC84) – a committee that is focussed on defining the requirements and test methods to ensure safe and effective devices are made available to the widest number of people. I’ve had the privilege of being one of the UK’s representatives to this committee since 2013 and so I’ve had a front-row seat for a lot of these discussions. So, what changes should device manufacturers and designers be anticipating?
In this revision of the 11608 family, TC84 has worked to align the various parts, to ensure every potential NIS is addressed in the collection of parts, that they integrate well, and that topics are not duplicated. Therefore ISO 11608-1 is the “parent” part – the fundamental section of the standard that establishes the requirements and test methods for all NIS devices covered by the whole standard. The revision to part one includes the introduction of On-Body Delivery Systems (OBDS, more fully described in ISO 11608-6) and several new concepts. These concepts include primary function, the functions of the device that allow for it to be used safely and effectively, and functional stability, which expands testing regimens to simulate whole-life testing for reusable devices. In addition, the design specification for the NIS must consider the impact and requirements of the medicinal product and the guidance on risk-based design approaches has been expanded.
There are also several smaller modifications to ISO 11608, including moving all requirements for electronics and EMC testing to ISO 11608-4, the addition of a choking hazard warning for small components and the associated test fixture. A section has also been added to the document giving guidance on design verification with reference to ISO 13485.
The changes to ISO 11608-2 (Double-Ended Pen Needles) are more subtle. The determination of flow rate has been expanded to include suggested flow ranges and the sample sizes have been brought into line with the requirements in ISO 11608-1. The testing requirements to confirm compatibility between a needle and a specific NIS have been revised to include dose delivery and needle hub removal force. In addition, the samples required for functional compatibility have been reduced and guidance has been added regarding the requirements for the inner needle shield.
The scope of ISO11608-3 has now been expanded beyond defining cartridge geometry and performance to cover NIS Containers and Integrated Fluid Paths. Again, this change has been predicated by the development of OBDS. The requirement for resealing the cartridge has been reduced from 1.5x the intended use to a minimum of 1.0x the intended life and the particle size for coring characterisation has increased from 50um to 150um or larger. General requirements for soft cannulas and fluid line connections have also been added – another feature of the standard that can be traced back to introducing the OBDS class of device. Cartridge geometry definition has also been moved to an informative annex, meaning it’s no longer mandatory.
I’ve had no direct visibility of the updates to ISO 11608-4 but colleagues from the dedicated work group have summarised the two high-level changes as an expansion of the scope to include all electronics on a NIS (not just those concerned with the delivery of the drug product) and that medicinal product delivery whilst connected to mains power (for recharging the battery) will be permitted. The challenge for part 4 has been to reference the parts of IEC 60601 which are appropriate for NIS. Therefore, part 4 references IEC 60601 explicitly, adopting the general requirements, means of patient protection and power input requirements from the relevant components of the standard. The minimum ingress protection has been increased from IP22 to IP52, allowable temperatures for skin contact are defined, failure obvious to the user after free fall preconditioning is permitted and the use of NIS in oxygen-rich environments has been defined.
The revised text for ISO 11608-5 now explicitly directs the reader to ISO 11608-1 for general requirements and focuses on automated needle insertion and dose delivery. Requirements for fenestrated needles (needles with holes in the side) have been defined and the implications of non-perpendicular needle and cannula insertion are explored. The dose accuracy test has been modified for needles with automated insertion and defining and measuring automated dose delivery time is now a requirement.
This review includes the introduction of ISO 11608-6 defining the requirements for OBDS. This part of the standard initially expanded quickly as new terms and definitions were added but many of the new concepts have been adopted into the following component documents: 11608-1 (General Requirements), 11608-3 (Container and Integrated Fluid Paths), and 11608-5 (Automated Functions). The crucial difference between an OBDS and an infusion pump is that the performance of the OBDS is defined by dose accuracy for a fixed volume and an infusion pump is defined by the rate at which the medicinal product is delivered. OBDS are also distinct from other NIS types in that they are attached to the body, whereas traditional NIS are held by the user for the duration of the delivery. The requirements and design guidance reflect this difference in use and the concept of a delivery profile (as a characterisation tool, not a performance requirement) has been included to help device builders better understand their products.
This summary only scratches the surface of the comprehensive review of ISO 11608 and on the current timeline these changes will not be published until late 2022, but if your development programme extends beyond that date I hope you found this summary helpful. The draft standards can be purchased from the ISO web store if you’d like to better understand the scope of the changes and what the implications may be for your device development and verification programme. If you’re a device developer and are struggling with device performance, CDP has expert teams to help overcome these problems. I’d like to thank my colleagues from ISO for their assistance in drafting this summary. In particular, Robert Nesbitt, Director of Portfolio Strategy at Abbvie and project leader for the ISO 11608-1 review, and Bibi Nellemose and Lars Brogaard from Danish Standards, whose tireless efforts as TC84’s secretariat keep the whole process running smoothly.
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