STAGE 05 · AUTHORITY REVIEW
240 examiner questions across 6 jurisdictions. 1 needs Sarah's sign-off today.
PMDA · JPESCALATED
42
Open
28
Sent
14
Closed
Review clockday 47 / 120
KFDA · KRHEAVY
68
Open
19
Sent
8
Closed
Review clockday 47 / 168
TGA · AUACTIVE
31
Open
22
Sent
11
Closed
Review clockday 35 / 50
HSA · SGRELIANCE
8
Open
5
Sent
14
Closed
Review clockday 22 / 35
TFDA · TWACTIVE
28
Open
14
Sent
9
Closed
Review clockday 28 / 72
HK · MDDDONE
0
Open
2
Sent
5
Closed
Review clockapproved · day 8
ESCALATED · CRO DECISIONDEF-PMDA-2026-0117 · PMDA RFI #14⏱ RESPONSE DUE IN 4d 11h
PMDA proposes narrowing the indication to "adults ≥18 with cryptogenic stroke history."
Original IFU claim: "AF detection in adults · ambulatory." PMDA reviewer Dr. Y. Watanabe believes the trial population (847 patients, 74% with stroke history) does not generalize to the broader ambulatory adult population. SENTINEL flagged this as a structural label-narrowing decision per POL-LABEL-NARROWING-V1 — non-delegable, CRO sign-off required. Decision propagates to all 5 other jurisdictions via reliance.
Sarah Chen (CRO) sign-off · label narrowing is non-delegable
Severity
Critical · CRO escalate1
Major38
Standard156
Clarification45
Owner
A. Tanaka68
P. Nair42
M. Yang28
Dr. L. Wei22
T. Ribeiro14
SENTINEL66
Status
Awaiting human38
Agent drafting66
In review22
Sent to authority90
Closed61
SLA
Overdue3
< 3 days11
3-7 days42
> 7 days184
DEF-PMDA-2026-0117PMDA
CLINICAL · IFU · LABELNarrow indication to stroke-history population?
S. Chen · CROESCALATED4d 11h
filed 14 May
DEF-PMDA-2026-0118PMDA
CLINICAL · STATSSensitivity confidence interval methodology clarification
Dr. L. WeiIN REVIEW2d 18h
filed 16 May
DEF-KFDA-2026-0042KFDA
HTA · COST EFFICER threshold sensitivity for utility weight ±10%
M. YangDRAFTING2d 04h
filed 16 May
DEF-TGA-2026-0089TGA
MFG · QMSISO 13485 audit certificate — provide last 3 years
T. RibeiroDRAFTING3d 06h
filed 15 May
DEF-KFDA-2026-0043KFDA
CLINICAL · POPULATIONKorean subgroup analysis · n=87 patients · separate efficacy table
P. NairIN REVIEW4d 09h
filed 14 May
DEF-PMDA-2026-0119PMDA
CLINICAL · AERe-classify AE-2024-0117 narrative — additional detail requested
P. NairDRAFTING5d 02h
filed 13 May
DEF-HSA-2026-0023HSA
RELIANCE · ANCHORHSA confirms reliance on PMDA review · awaiting PMDA milestone
A. TanakaSENT--
closed 12 May
DEF-TFDA-2026-0067TFDA
LABELING · TRANSLATIONTraditional Chinese IFU — terminology alignment with TFDA glossary
A. TanakaDRAFTING6d 18h
filed 11 May
DEF-TGA-2026-0090TGA
CLINICAL · PMCFPMCF protocol v3 — sample size justification post WHO 2024 update
Dr. L. WeiIN REVIEW5d 14h
filed 13 May
DEF-KFDA-2026-0044KFDA
HTA · BUDGET IMPACT5-year budget impact model · Korean payer perspective
M. YangDRAFTING6d 02h
filed 12 May
DEF-PMDA-2026-0120PMDA
MFG · COMPONENTLithium cell vendor change — biocompatibility data
T. RibeiroDRAFTING7d 11h
filed 11 May
DEF-TFDA-2026-0068TFDA
SOFTWARE · SECURITYCybersecurity threat model — IEC 81001-5-1 alignment
A. TanakaSENT--
sent 09 May
DEF-KFDA-2026-0045KFDA
CLINICAL · SAFETYHospitalization rates · Korean cohort vs overall · table requested
P. NairDRAFTING7d 06h
filed 10 May
DEF-TGA-2026-0091TGA
LABELING · CLAIMS"Continuous monitoring" claim — substantiation required
A. TanakaIN REVIEW8d 02h
filed 10 May
DEF-PMDA-2026-0121PMDA
CLINICAL · SUBGROUPJapanese-only subgroup · n=124 · efficacy & safety tables
P. NairSENT--
sent 08 May
DEF-PMDA-2026-0117 · PMDA RFI #14 · DOSSIER §3.2.1 IFU
PMDA proposal — narrow indication to "adults ≥18 with cryptogenic stroke history."
PMDA · ORIGINAL QUESTION (translated from JA)
"Reviewing the LINQ-NEXT trial design and patient population, we note that 74% of the 847 enrolled subjects had a documented history of cryptogenic stroke. The trial inclusion criteria specified ambulatory adults with elevated AF risk, but the enrolled population was predominantly stroke-history patients. We propose that the approved indication should reflect the studied population: "adults aged ≥18 years with a history of cryptogenic stroke who require AF monitoring for secondary prevention." Please respond with either acceptance of this proposed language or scientific justification for the broader indication."
⬢ SENTINEL — analysis & recommendation
SENTINEL · CONFIDENCE 84%This is a structural label-narrowing proposal, not a documentation clarification. PMDA's interpretation is defensible — the enrolled population is skewed toward stroke history. However, the SAP pre-specified subgroup analysis for non-stroke-history patients (n=220) shows comparable AF detection sensitivity (94.1% vs 95.3% overall). Defensible to push back with the subgroup analysis, but the response adds 4-6 weeks to PMDA review via an RFI loop. Decision is non-delegable per POL-LABEL-NARROWING-V1 — cross-jurisdictional commercial consequences exceed agent authority. Surfacing both options for CRO sign-off.
Cross-jurisdiction propagation if accepted (Option A)
RELIANCE-DRIVEN
HSA auto-adopts PMDA language · TFDA follows · HK follows. 4 jurisdictions immediately narrow.
INDEPENDENT
KFDA running independent HTA · likely follows for consistency. TGA CO-OR scheme adopts PMDA. NMPA (post-CT) gets narrower indication baked in.
SENTINEL · response draftv2 · ready for sign-off
"Dear PMDA Review Panel,
Medtronic acknowledges the population skew noted in the LINQ-NEXT pivotal trial (n=847, 74% with cryptogenic stroke history). We respectfully propose to support the broader ambulatory adult indication by referencing the pre-specified non-stroke-history subgroup analysis (SAP §6.4), which enrolled n=220 patients without prior stroke and demonstrated AF detection sensitivity of 94.1% (95% CI 91.2–96.4), comparable to the overall trial population.
The subgroup was powered per SAP at α=0.05 and pre-registered in ClinicalTrials.gov NCT-04XXXXXX. We attach the subgroup-specific efficacy and safety tables (Appendix R-14-A) for your review.
We respectfully request that the approved indication retain the broader ambulatory adult language as proposed in our original submission §3.2.1, with appropriate post-market commitments for ongoing surveillance via the PMCF protocol (v3, attached).
Sincerely,
Medtronic Regulatory Affairs"
Sarah Chen (CRO) sign-off required · this response propagates to 5 jurisdictions
WORKFLOWPer-jurisdiction review status
▶
SENTINEL runs an independent review queue per jurisdiction. Each clock ticks independently. Reliance jurisdictions accelerate after the anchor (PMDA) signals approval direction.
PMDA · JP
120-day clock · day 47
DAY 47/120 · 42 Q OPEN · ESCALATED
KFDA · KR
168-day clock · day 47
DAY 47/168 · 68 Q OPEN
TGA · AU
50-day clock · day 35
DAY 35/50 · 31 Q OPEN
HSA · SG
35-day clock · day 22 · reliance
DAY 22/35 · 8 Q OPEN
TFDA · TW
72-day clock · day 28
DAY 28/72 · 28 Q OPEN
HK · MDD
approved · day 8
✓ APPROVED · DAY 8