FDA Information Requests for Autoinjector Testing and Performance

By Rhizome Team

The FDA rigorously evaluates autoinjector performance and safety through detailed information requests during BLA and NDA reviews. These requests focus on critical aspects including device functionality, stability testing, risk analysis, and human factors validation to ensure patient safety and product reliability.

Understanding common FDA information requests helps manufacturers prepare comprehensive submissions and develop robust testing protocols. This analysis examines actual FDA-applicant interactions since 2022, providing insights into successful response strategies and regulatory expectations.

Here we examine specific examples where the FDA explicitly accepted applicant responses to autoinjector testing and performance requests, demonstrating effective approaches to addressing regulatory concerns.

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Based on the Drugs@FDA database and review memos, FDA (CDER) sends requests for information or information requests to BLA or NDA applicants related to a prefilled autoinjector's testing or performance. The applicant can respond with justifications or the additional information and the FDA will state whether the response was acceptable. Provide examples since 2022 of the request, the additional information, and where the FDA explicitly stated that the response was acceptable.

Answer

Overview of FDA Requests for Autoinjector Testing and Performance

The FDA (CDER) frequently requests information from BLA or NDA applicants regarding the testing and performance of autoinjectors. These requests often focus on:

  • Device functionality and performance: Dose accuracy, activation force, breakloose/glide force, and needle safety.
  • Stability and durability: Testing under aging, shipping, and storage conditions.
  • Risk analysis and mitigation: Identification of potential failure modes and corrective actions.
  • Human factors validation: Ensuring usability and safety for intended users, including untrained or specific patient populations.

Applicants typically respond with additional data, justifications, or modifications to address these requests. The FDA then evaluates the responses and explicitly states whether they are acceptable.

Examples of FDA Requests, Applicant Responses, and FDA Acceptance

1. REPATHA (Evolocumab) – Amgen Inc. (2022)

  • FDA Request: Clarification on drug compatibility testing of the autoinjector, including testing at the end of shelf life, risk analysis for device components, and performance testing after shipping and aging 1122126.
  • Applicant Response: Amgen committed to testing the fully assembled product at the end of shelf life, provided risk analysis and management information, and confirmed usability and durability through clinical data 1122126132.
  • FDA Acceptance: The FDA explicitly accepted the applicant's clarification on end-of-shelf-life testing and risk analysis, deferring final safety and effectiveness determination to the Human Factors/DMEPA review 1122130.

2. UDENYCA (Pegfilgrastim-CBQV) – Coherus Biosciences Inc. (2023)

  • FDA Request: Information on dose accuracy, breakloose/glide force, barrel compression force, aging/stability testing, and risk analysis 189.
  • Applicant Response: Coherus provided a Failure Modes and Effects Analysis (FMEA), verification and validation testing, and data on injection force, dose accuracy, and needle safety performance 1909293.
  • FDA Acceptance: The FDA explicitly accepted the responses, stating that the information was adequate and recommending approval 19495.

3. BIMZELX (Bimekizumab-BKZX) – UCB Inc. (2023)

  • FDA Request: Examination of 100 autoinjectors for failures during clinical-use studies and details on device failures, root causes, and corrective actions 179.
  • Applicant Response: UCB identified failure modes, implemented design and process mitigations, and conducted validation testing, including human factors studies and accelerated aging 1798788.
  • FDA Acceptance: The FDA deemed the responses adequate, concluding that the design and control strategies were sufficient and recommending approval 1788488.

4. NUCALA (Mepolizumab) – GlaxoSmithKline LLC (2022)

  • FDA Request: Data on injection timing, patient comfort, and stability testing for aged autoinjector batches 16871.
  • Applicant Response: GSK provided timing data, patient comfort information, and committed to submitting stability data 16871.
  • FDA Acceptance: The FDA accepted the approach and approved the device constituent parts with post-marketing commitments for additional data 16971.

5. HADLIMA (Adalimumab-BWWD) – Samsung Bioepis Co. Ltd. (2023)

  • FDA Request: Design verification, validation, and robustness testing, as well as human factors validation for usability and safety 1456.
  • Applicant Response: Samsung Bioepis provided design verification protocols, human factors data, and stability testing results 156910.
  • FDA Acceptance: The FDA found the responses adequate, supporting the usability of the autoinjector for adult populations, though concerns about pediatric testing remained 156910.

6. TYENNE (Tocilizumab-AAZG) – Fresenius Kabi USA (2023)

  • FDA Request: Revisions to storage instructions, recruitment rationale for human factors studies, and cap removal force specifications 100104.
  • Applicant Response: Fresenius Kabi revised the IFU, provided rationale for study recruitment, and updated cap removal force specifications 100104.
  • FDA Acceptance: The FDA explicitly accepted all responses as adequate 100104.

7. ADBRY (Tralokinumab) – LEO Pharma AS (2024)

  • FDA Request: Cytotoxicity, sensitization, and irritation testing, as well as performance data for the prefilled syringe after simulated shipping 144145146.
  • Applicant Response: LEO Pharma provided testing results and argued that sequential preconditioning exceeded regulatory guidance 145149152.
  • FDA Acceptance: The FDA accepted the simulated shipping testing but requested further data on needle safety activation force 145153.

Observations and Implications

  • Common Themes: FDA requests often focus on ensuring the safety, reliability, and usability of autoinjectors under various conditions. Stability testing, human factors validation, and risk analysis are recurring areas of interest.
  • Applicant Strategies: Successful responses typically include comprehensive data, adherence to regulatory standards (e.g., ISO), and proactive risk mitigation measures.
  • FDA Decisions: Explicit acceptance of responses demonstrates the importance of clear, evidence-based justifications and thorough testing.

These interactions highlight the FDA's rigorous approach to evaluating autoinjector performance and the critical role of detailed applicant responses in securing approval.