📡 Module 01 · Signal Detection

Signal Detection AI

Disproportionality analysis on FAERS, VigiBase, EudraVigilance datasets. PRR, ROR, EBGM, BCPNN scoring with signal prioritization matrix and longitudinal signal tracking.

Active Signals

47

across 8 products

▲ +5 this quarter

Strong Signals (PRR>2)

14

requires regulatory action

Standard threshold

Cases This Quarter

12,485

FAERS + spontaneous

▲ +18% YoY

Mean Time to Signal

38

days (industry P50: 62)

▼ -24 vs P50

🔍 Top Signals by Disproportionality ScoreFAERS · Last Quarter

PRR (Proportional Reporting Ratio), ROR (Reporting Odds Ratio), EBGM (Empirical Bayes Geometric Mean). PRR > 2 and chi-square > 4 typically warrants signal investigation.

Product	Adverse Event (MedDRA PT)	Cases (N)	PRR	ROR	EBGM	Chi-Sq	Signal Strength	Action
ASC-301	Pneumonitis (immune-mediated)	142	4.82	5.14	3.71	68.4	Strong	RMP update
ASC-301	Cytokine release syndrome	89	3.21	3.42	2.84	42.7	Strong	Label review
IMD-118	Hepatic enzyme increase	218	2.74	2.91	2.48	38.2	Strong	DSUR add'l data
CDM-188	Acute kidney injury	94	2.18	2.31	1.94	22.4	Moderate	Watch list
IMD-256	Injection site reaction (severe)	312	1.92	2.04	1.78	16.8	Moderate	Track quarterly
NEU-378	Suicidal ideation	28	1.48	1.56	1.32	7.2	Weak	Routine PV
ASC-512	Peripheral neuropathy	56	1.34	1.42	1.22	5.4	Weak	Routine PV

📊 Signal Volume Trend (12 months)

🎯 Signal Prioritization Matrix

⚡ AI Signal Insight

The ASC-301 pneumonitis signal (PRR 4.82) crossed the regulatory action threshold this quarter. Disproportionality is consistent with the immune-related adverse event profile expected of this MOA class, but case severity is trending upward (12 fatal cases YTD vs 4 in prior year).

Recommended action: Initiate ad-hoc PSUR addendum to FDA and EMA within 15 days. Update RMP module SVII to add pneumonitis as an Important Identified Risk.
Risk minimization: Consider DHCP letter (Dear Healthcare Provider) communicating early-detection protocol and corticosteroid management.
Cross-product check: The CDM-188 AKI signal is approaching threshold (PRR 2.18) but not yet actionable; recommend stratified analysis by age and concomitant nephrotoxic medications.

📋 Module 02 · ICSR Operations

ICSR Triage & Processing Engine

Individual Case Safety Report intake, classification (seriousness, expectedness, causality), MedDRA coding accuracy, and expedited reporting (E2B R3) workflow management.

ICSRs This Month

4,182

total inbound

▲ +12% MoM

Expedited Cases

348

15-day reporting

▲ +24 YoY

Mean Processing Time

5.8

days (target: ≤7)

▲ within SLA

MedDRA Coding Accuracy

96.4%

vs industry 92%

▲ Best-in-class

📥 Case Intake by Source

⏱️ Processing Cycle Time

🎯 Case Classification Distribution

Classification Dimension	Volume (N)	% of Total	Expedited?	Health Authority Report Required	SLA Status
Serious, Unexpected, Related (SUSAR)	348	8.3%	15-day	FDA + EMA + PMDA + NMPA	On track
Serious, Expected, Related	784	18.7%	Periodic	PSUR cycle	On track
Serious, Unexpected, Not Related	412	9.9%	Quarterly	Annual report	On track
Non-serious, Related	1,847	44.2%	Periodic	PSUR cycle	On track
Non-serious, Not Related	685	16.4%	Routine	Annual report	On track
Pregnancy / Lactation Reports	68	1.6%	15-day if serious	Pregnancy registry	2 late
Special Populations (Peds/Elderly)	38	0.9%	Case-by-case	Stratified analysis	On track

⚡ ICSR Operations Insight

Case volume is up 12% MoM, primarily driven by ASC-301 launch ramp (now 38% of total inbound). Current operating model shows healthy SLA compliance but is approaching capacity at 4,200 cases/month.

Capacity gap projected Q3 2026: Volume will exceed 5,500 cases/month at current launch trajectory. Recommend onboarding additional 4 FTEs to PV ops or expand FSP partnership with Accenture/Cognizant.
Pregnancy registry late cases (2): Both due to delayed source-document submission from clinical sites. Recommend automated reminder workflow at 5-day mark.
Automation opportunity: 64% of non-serious cases follow predictable MedDRA coding patterns — recommend NLP-based auto-coding with PV reviewer QC, estimated 40% reduction in processing time.

⚠️ Module 03 · Risk Management

Risk Management Plan (RMP) Builder

EU RMP (template by EMA), US REMS, and ICH E2E equivalent for other regulators. Safety specification, pharmacovigilance plan, and risk minimization measures across the product lifecycle.

🎛️ Product Profile

Product Selection

RMP Version

Regulatory Scope

Risk Category Filter

📋 RMP Module ChecklistEU Format

✓

Part I: Product OverviewComplete

✓

Part II SI: Epidemiology of indication & target populationComplete

✓

Part II SII: Non-clinical safety findingsComplete

✓

Part II SIII: Clinical trial exposureComplete

!

Part II SIV: Populations not studied in clinical trialsPregnancy data pending

✓

Part II SV: Post-authorisation experienceComplete

✓

Part II SVI: Additional EU requirements for safety specificationComplete

!

Part II SVII: Identified & potential risksUpdating w/ pneumonitis

✓

Part II SVIII: Summary of safety concernsComplete

✓

Part III: Pharmacovigilance planComplete

○

Part IV: Plans for post-authorisation efficacy studies (PAES)Drafting

✓

Part V: Risk minimisation measuresComplete

✓

Part VI: Summary of activities in the RMP by productComplete

○

Part VII: Annexes (PSP, study protocols)In review

🚨 Safety Specification — Risk Inventory

Risk	Category	Severity	Frequency	Risk Minimisation Measure	Status
Immune-mediated pneumonitis	Important Identified	Severe	3-8%	aRMM: HCP guide + Patient card	High priority
Cytokine release syndrome	Important Identified	Severe	2-5%	Routine + monitoring algorithm	High priority
Hepatic toxicity	Important Identified	Moderate	5-12%	Routine + LFT monitoring	Watch
Use in pregnancy	Missing Information	Unknown	N/A	Pregnancy registry (PASS)	Watch
Long-term safety (>5 yr)	Missing Information	Unknown	N/A	PASS observational study	Watch
Severe infections	Important Potential	Severe	<2%	Routine PV + screening	Routine

⚡ RMP Strategic Insight

The v3.0 RMP draft for ASC-301 should be submitted to EMA at least 60 days before MAA filing. Three areas require attention before sign-off:

Pneumonitis additional Risk Minimisation Measures (aRMM): Finalize HCP educational guide and patient alert card. Submit aRMM materials with the RMP for PRAC review.
Pregnancy registry PASS protocol: Currently in draft. Need PRAC-acceptable design — recommend ENCePP-compliant prospective registry, 5-year follow-up.
Part IV PAES: Confirmatory phase 4 PFS study required as condition of conditional approval. Lock protocol design before MAA submission to avoid post-approval delays.

⚖️ Module 04 · Aggregate Reporting

PSUR/PBRER & Benefit-Risk Assessment

Periodic Safety Update Reports and Periodic Benefit-Risk Evaluation Reports (ICH E2C R2). Aggregate safety data analysis with structured benefit-risk framework (UMBRA, PrOACT-URL).

Active PSURs

8

across portfolio

Next PSUR Due

42

days (ASC-301)

▲ Critical

Benefit-Risk Score

+2.4

favorable (ASC-301)

▲ Stable

DLP Compliance

100%

data lock point on-time

📅 PSUR/PBRER Schedule (12 months)

Product	PSUR Period	Data Lock Point	Submission Due	Days Remaining	Status	Lead Author
ASC-301	2026-Q2/Q3	2026-09-30	2026-12-29	42	Authoring	PV Lead - Oncology
IMD-118	2026-H2	2026-12-31	2027-03-31	134	Planning	PV Lead - Immunology
IMD-256	2026-H2	2026-12-31	2027-03-31	134	Planning	PV Lead - Immunology
CDM-188	2026-Q3/Q4	2026-12-31	2027-02-14	89	Planning	PV Lead - Cardiomet
RD-901	2026 Annual	2026-12-31	2027-03-31	134	Draft outline	PV Lead - Rare
NEU-378	2026 Annual	2026-12-31	2027-03-31	134	Draft outline	PV Lead - CNS

⚖️ Benefit-Risk Profile (ASC-301)

UMBRA framework: quantified benefit and risk dimensions, weighted composite score.

📊 Safety Profile Evolution

Cumulative AE incidence rates per 100 patient-years.

⚡ Benefit-Risk Strategic Brief

ASC-301 benefit-risk profile remains favorable (+2.4) across all subpopulations. The pneumonitis signal is mitigated by early-detection protocol and corticosteroid management — overall mortality benefit (HR 0.68 vs SoC) substantially exceeds risk.

PSUR conclusion language: Recommend wording: "Benefit-risk profile remains positive in the approved indication. Additional risk minimisation measures introduced for immune-mediated pneumonitis have been effective in case management."
Subgroup analysis: Elderly patients (>75 yrs) show 1.6× pneumonitis risk — recommend dedicated subsection in PSUR and consideration of label update.
Strategic positioning: Benefit-risk strength supports planned expansion into earlier-line setting (Phase 3 ASC-301 1L combination). Use PSUR data as supporting evidence in pre-IND meeting.

🏗️ Module 05 · PV Operating Model

REMS Strategy & Global PV Operating Model

FDA Risk Evaluation and Mitigation Strategies (REMS) design, ETASU components, and global pharmacovigilance operating model diagnostic.

REMS Programs

2

active (ASC-301, IMD-118)

PV FTE Count

142

global team

▲ +12 YTD

CRO/FSP Spend

$18.4M

annual (ICSR processing)

PV Maturity Score

3.8

/5 (industry P50: 3.6)

▲ Above peer

🛡️ REMS Component Selector — ASC-301

REMS Element	Selected	Rationale
Medication Guide	Required	Pneumonitis & CRS risk communication
Communication Plan (DHCP)	Required	Initial launch + per signal
ETASU – Prescriber Certification	Conditional	Specialist oncologists only — under FDA review
ETASU – Patient Enrollment	Not required	Risk profile does not warrant patient registry as ETASU
ETASU – Lab Monitoring	Conditional	Pulmonary function tests baseline + Q3 months
Implementation System	Required	REMS portal + audit trail
Timetable for Submission of Assessments	Required	18mo, 3yr, 7yr post-approval

🌐 Global PV Operating Model Maturity

📊 PV Function Diagnostic

PV Function	Maturity (1-5)	FTE Count	Outsourcing Mix	Key Gap	Priority
Case Intake & Triage	4.2	38	42% FSP	Volume surge readiness	Medium
ICSR Processing & MedDRA	3.9	52	68% FSP	NLP auto-coding not yet adopted	High
Signal Detection & Management	3.6	14	10% FSP	EBGM tool not integrated with Argus	High
Aggregate Reporting (PSUR/PBRER)	4.0	12	25% FSP	Authoring efficiency	Medium
Risk Management (RMP/REMS)	3.8	8	5% FSP	aRMM measure tracking	Medium
QPPV & Regulatory PV	4.4	10	0% FSP	None — strong	Maintain
Medical Safety & Benefit-Risk	3.5	8	0% FSP	Benefit-risk framework standardization	High

⚡ PV Operating Model Roadmap

Composite PV maturity of 3.8/5.0 places organization in industry P60. Three high-leverage transformation initiatives:

Year 1 — NLP-based ICSR auto-coding: Reduce processing cycle time 40% and FSP spend 18%. Total $4.2M investment, 11-month payback.
Year 1 — Integrated signal detection platform: Replace standalone EBGM tool with Oracle Empirica or Aris Global cloud-native solution integrated with Argus.
Year 2 — Benefit-risk methodology standardization: Adopt UMBRA framework across all PSURs and major safety reviews. Establish Medical Safety Council with quarterly cadence.

Expected impact: Maturity 3.8 → 4.3, ICSR cycle time 5.8 → 3.4 days, signal detection time 38 → 22 days, $5.8M annual cost takeout by Year 3.