FDA ISO 11608 Requirements for Prefilled Syringes

By Rhizome Team

For pharmaceutical companies developing prefilled syringes and needle safety devices, understanding FDA's specific requirements for ISO 11608 testing is crucial for regulatory compliance. ISO 11608 specifies requirements and test methods for needle-based injection systems, including k-factor analysis of dose volume and preconditioning requirements.

The distinction between FDA requirements for different device types—prefilled syringes versus autoinjectors and prefilled pens—can significantly impact development timelines and testing strategies. Knowing when ISO 11608 testing is explicitly required versus when it's voluntarily submitted helps sponsors plan appropriate development programs.

This analysis examines FDA review documents from the past five years to determine whether the agency has explicitly required ISO 11608 testing or conformance for prefilled syringes and PFS/NSD products, excluding autoinjectors and prefilled pens from consideration.

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Has the FDA explicitly required ISO 11608 testing or conformance for any prefilled syringe or PFS/NSD for NDA or BLA approval in the last five years? Do not include autoinjector or prefilled pen results. This might include k-factor analysis of dose volume, or the preconditioning requirements specified in ISO 110608.

Answer

Comprehensive Answer:

Based on a thorough review of FDA approval and review documents for prefilled syringes (PFS) and prefilled syringes with needle safety devices (PFS/NSD) submitted for NDA or BLA approval in the last five years (excluding autoinjectors and prefilled pens), there are conflicting interpretations in the available evidence regarding whether the FDA has explicitly required ISO 11608 testing or conformance for these products.

Majority Finding: No Explicit FDA Requirement

The majority of reviewed FDA documents and analyses indicate that:

  • The FDA has not explicitly required ISO 11608 testing or conformance for PFS or PFS/NSD as a condition for NDA or BLA approval in the last five years.
  • Where ISO 11608 is mentioned, it is typically:
    • Listed by sponsors as a "recognized" or "applicable" standard, but not cited by the FDA as a requirement for approval.
    • Referenced in the context of autoinjectors or prefilled pens, which are excluded from this question.
    • Not associated with explicit FDA requests for k-factor analysis, dose accuracy, or preconditioning per ISO 11608 for PFS/NSD.
  • The FDA has instead required or referenced other ISO standards for PFS/NSD, such as:
    • ISO 11040 series (e.g., ISO 11040-4/8) for glass syringes and injectability
    • ISO 80369 (connectors)
    • ISO 23908 (sharps injury protection)
    • ISO 10993 (biocompatibility)
    • ISO 7886 and ISO 7864 (syringe and needle testing)
  • In cases where sponsors voluntarily conformed to ISO 11608 (e.g., YESAFILI, SOGROYA), FDA reviewers acknowledged the conformance but did not state it was required for approval. In some cases, the FDA explicitly noted that conformance to ISO 11608 was not mandatory 456711121314151617181920212223252627.

Conflicting Evidence: Some FDA Acceptance of ISO 11608 Testing

A minority of sources point to specific cases where the FDA has explicitly referenced and accepted ISO 11608-1 testing for PFS/NSD as part of the NDA/BLA review process:

  • LANREOTIDE ACETATE (NDA 215395, 2022):
    • FDA review documents reference testing "per ISO 11608-1 clause 10.6" (cold storage preconditioning) and "per ISO 11608-1 clause 10.9" (vibration), and these results were accepted as valid for the PFS/NSD constituent 8.
  • BIMZELX (BIMEKIZUMAB-BKZX, BLA 761151, 2023):
    • FDA reviewer comments state: "Dose accuracy testing was completed per FDA recognized standard ISO 11608-1 for a single dose, fixed dose device. This is acceptable."
    • Preconditioning requirements from ISO 11608-1:2014 were used for verification testing of the PFS constituent, and the FDA explicitly acknowledged and accepted this standard 10.

In these cases, the FDA did not merely accept ISO 11608-1 testing as supplementary; the review documents show that such testing was explicitly referenced and accepted as the basis for demonstrating device performance and conformance for PFS/NSD products (not autoinjectors or pens). The specific ISO 11608-1 requirements cited include preconditioning (cold storage, vibration) and dose accuracy testing, which may include k-factor analysis 810.

Summary of Conflicting Interpretations

  • Most FDA reviews do not show an explicit requirement for ISO 11608 testing/conformance for PFS/NSD; instead, other ISO standards are cited as required.
  • A few recent cases (notably LANREOTIDE ACETATE and BIMZELX) show the FDA explicitly referencing and accepting ISO 11608-1 testing for PFS/NSD, including preconditioning and dose accuracy requirements.
  • In all cases, there is no evidence that the FDA has required ISO 11608 for autoinjectors or pens in these contexts, and such devices are excluded from this answer.

Conclusion

The prevailing evidence suggests that the FDA has not generally or systematically required ISO 11608 testing or conformance for prefilled syringes or PFS/NSD in NDA or BLA approvals over the last five years. However, there are a small number of documented cases where the FDA has explicitly referenced and accepted ISO 11608-1 testing for PFS/NSD as part of the approval process, including preconditioning and dose accuracy testing. Thus, while not a universal or routine requirement, explicit FDA acceptance of ISO 11608-1 for PFS/NSD has occurred in select cases 456781011121314151617181920212223252627.

References:
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