Certainly! Below is a comprehensive, non-duplicative list of requests for information, information requests, or deficiencies disclosed by CDER in review memos from 2024 and 2025 about injectable drugs or delivery devices in a BLA or NDA, specifically pertaining to drug quality tests or delivery device ISO tests. Where answers conflicted or overlapped, all relevant details are included and differences are noted.

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1. ALHEMO (Concizumab-mtci) – BLA 761315 (2025)

• Essential Performance Requirements (EPRs) in Stability Protocol and Release Specs:

  • CDER requested inclusion of EPRs (dose accuracy, activation force, hold force, injection time) in the post-approval stability protocol and in the drug product release specifications. The applicant’s initial response was deemed insufficient, and CDER reiterated the need for these EPRs to be included to ensure ongoing device performance monitoring post-approval.
  • Pertains to device performance testing and ongoing quality monitoring, related to ISO standards for combination products and injectable delivery devices.
  • ¹⁵²⁴

• Filing Review Checklist (Device/Combination Product):

  • CDER/CDRH checked for (and would request if missing):
    • Essential Performance Requirements defined by the sponsor
    • Design verification data and full test reports for verification/validation (including reliability, biocompatibility, sterility, shelf life, aging, transportation)
    • Description of quality systems (drug cGMP-based, device QSR-based, or both)
    • Control strategy for EPRs
  • ¹⁵

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2. NEFFY (Epinephrine Nasal Spray) – NDA 214697 (2025)

• Device Performance and Biocompatibility Deficiencies:
  • Lack of device performance testing of EPRs post-transportation simulation; FDA requested performance testing post-shipping to ensure device meets specifications (linked to ISO essential performance and reliability standards).
  • Missing biocompatibility test reports, specifically irritation testing per FDA guidance and ISO 10993-1/10993-23. FDA requested an irritation test report for the device.
  • Lack of fault tree analysis (FTA), design/process risk analysis, or trace matrix. FDA requested a FTA with a top-level failure mode of “failure to successfully deliver complete intended dose,” referencing ISO 14971:2019 (risk management for medical devices).
  • ²⁵³⁰

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3. YESAFILI (Aflibercept-jbvf) – BLA 761274 (2024)

• Facility and Device Quality/ISO-Related Requests:
  • CDER requested identification of facilities responsible for final assembly, kit assembly, and sterilization, and an updated 356h form.
  • Requested information supporting intraocular injection device specifications, including bacterial endotoxins (FDA guidance), sterilant residuals (ISO 10993-7), particulates (USP 789), ocular irritation (ISO 10993-23), and controls to assure future lots meet these specifications (release tests, quality agreements, etc.).
  • ¹⁸

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4. TYENNE (Tocilizumab) – BLA 761275 (2024)

• Quality Systems and CAPA Deficiencies:
  • CDER/CDRH requested summaries of GMP compliance approach and quality systems for the final finished combination products, including:
    • 21 CFR 820.20 (Management Responsibility)
    • 21 CFR 820.30 (Design Controls)
    • 21 CFR 820.50 (Purchasing Controls)
    • 21 CFR 820.100 (Corrective and Preventive Actions)
    • Other subparts related to device quality system regulation (QSR)
  • Requested CAPA procedure required elements for device constituent parts/combination products.
  • ¹⁷

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5. ENTYVIO (Vedolizumab) – BLA 761133 (2024)

• Device and Quality System Deficiencies:
  • CDER requested:
    • Full design verification reports for prefilled syringe and autoinjector, including real-time and accelerated aging testing, with statistical summaries and force traces.
    • Data demonstrating needle safety override force meets required confidence and reliability up to proposed shelf life (per FDA guidance for sharps injury prevention features).
    • Documentation of compliance with combination product cGMP requirements and base operating system.
    • Addressed deficiencies in prior cycles: needle clogging, CAPA, purchasing controls, cap removal force.
  • ^1481628

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6. ZURNAI (Nalmefene Hydrochloride Autoinjector) – NDA 218590 (2025)

• Device Filing Review – Verification and Validation Testing:
  • CDER/CDRH requested:
    • Design verification data included in the NDA/BLA or cross-referenced.
    • Full test reports for verification and validation testing (EPRs, reliability, biocompatibility, sterility, shelf life, aging, transportation).
    • Description of device manufacturing process and quality systems.
  • ⁷²⁶

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7. BRIXADI (Buprenorphine) – NDA 210136 (2024)

• Drug Quality Deficiencies:
  • Concerns about sterility: CDER requested additional information on the testing procedure or alternative test method to assess assurance of sterility throughout shelf life.
  • Lack of specification for factors affecting dissolution; requested assay/specification for release or stability, and found dissolution method deficient.
  • Concerns about inspectional findings at the testing site, calling into question the validity of supporting data.
  • ²⁷

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8. LIDOCAINE – NDA 209190 (2024)

• Drug Quality Deficiencies:
  • CDER requested discussion and control strategy for increasing trend in unknown impurity on stability.
  • Requested inclusion of vacuum test in stability specification for pouch integrity at every stability time point.
  • ²⁰

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9. ANKTIVA – BLA 761336 (2024)

• Drug Quality Deficiency:
  • CDER requested revision of container closure integrity testing method to detect breaches <20 µm and inclusion of appropriate routine positive controls.
  • ²³

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10. TERIPARATIDE – NDA 211097 (2024)

• Drug Quality Deficiencies:
  • Multiple information requests and deficiencies regarding drug product quality/method verification and verification of drug product quality methods.
  • ²⁹

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11. Filgrastim-txid – BLA 761126 (2025)

• Drug Quality Deficiency:
  • CDER requested summary data for "volume of injection" for ongoing real-time stability study to support proposed 24-month shelf life for both dose presentations.
  • ³⁵

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12. YORVIPATH (Palopegteriparatide) – NDA 216490 (2024)

• Device Dose Delivery and Statistical Control:
  • CDER requested design verification testing data to verify device meets new pen dose delivered specification.
  • Requested statistical control plan for lot release testing of device EPRs.
  • ⁵

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13. General/Other Notable Requests (from Multiple Products)

• Risk Management and Analysis:

  • CDER requested risk management plan documentation, hazard analysis, risk summary report, and fault tree analysis (FTA) for several products, referencing ISO 14971 (risk management for medical devices).
  • ³⁰³³

• CAPA Procedures:

  • CDER requested additional information on CAPA procedures to ensure compliance with 21 CFR 820.100, including analysis of processes, quality audit reports, complaints, and other sources of quality data.
  • ¹³²

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Summary Table

Product (Year)	Request/Deficiency Area	Description/Notes	Source(s)
ALHEMO (2025)	Device ISO/Quality	EPRs in stability protocol/release specs, V&V data, quality systems	1524
NEFFY (2025)	Device ISO/Quality	EPRs post-shipping, biocompatibility (ISO 10993-23), FTA (ISO 14971)	2530
YESAFILI (2024)	Device ISO/Quality	Facility identification, device specs (ISO 10993-7/23, USP 789)	18
TYENNE (2024)	Device ISO/Quality	Quality systems, CAPA, QSR elements	17
ENTYVIO (2024)	Device ISO/Quality	Design V&V reports, needle safety force, cGMP compliance, CAPA	1481628
ZURNAI (2025)	Device ISO/Quality	V&V data, test reports, quality systems	726
BRIXADI (2024)	Drug Quality	Sterility, dissolution, inspectional data	27
LIDOCAINE (2024)	Drug Quality	Impurity trend, pouch integrity/vacuum test	20
ANKTIVA (2024)	Drug Quality	Container closure integrity test method	23
TERIPARATIDE (2024)	Drug Quality	Method verification, quality IRs	29
Filgrastim-txid (2025)	Drug Quality	Volume of injection stability data	35
YORVIPATH (2024)	Device ISO/Quality	Dose delivery V&V, statistical control plan	5
Multiple	Device ISO/Quality	Risk management plan, hazard analysis, FTA (ISO 14971)	3033
Multiple	Device ISO/Quality	CAPA procedures (21 CFR 820.100)	132

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Conflicting/Additional Notes

• Some review memos (e.g., for ENTYVIO, EBGLYSS, WINREVAIR) state that no new deficiencies were issued in 2024, but prior cycles had device quality and CAPA-related deficiencies that were resolved ^{10111213141628}.
• For some products (e.g., ZURNAI), the review memo confirms that device EPRs and V&V data were reviewed and found appropriate, with no explicit new deficiencies, but the filing review checklist indicates what would be requested if missing ⁷²⁶.
• Some answers reference deficiencies or requests in prior cycles that were addressed before 2024/2025; these are included for completeness where the 2024/2025 memo references their resolution ¹⁶²⁸.

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References

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If you need the full text of any specific request/deficiency or further breakdown by product, please specify.