Regulatory Overview – Pediatric Pulmonary Valve

Executive Summary

U.S. pediatric pulmonary valves are Class III devices and typically require PMA. For rare pediatric populations, HDE/HUD can be leveraged to demonstrate safety and probable benefit. Programs addressing significant unmet needs can seek Breakthrough Device designation to accelerate interactions across IDE and PMA. Typical programs progress from Early Feasibility (IDE) to Pivotal IDE with long-term follow-up commitments (often up to 10 years).

At-a-Glance

Pathway	Core Proof	Where It Fits
PMA	Safety & Effectiveness	Standard for Class III valves
HDE/HUD	Safety & Probable Benefit	Rare pediatric populations (<8,000/yr)
Breakthrough	Superior benefit / unmet need	Expedited FDA interactions
IDE	Clinical study authorization	EFS → Pivotal clinical evidence

Device Classification

Pulmonary valve prostheses are Class III devices. FDA expects robust preclinical (bench + animal) and clinical data, with durability under repeated balloon expansions for growth-accommodating concepts, and hemodynamic performance (gradients, regurgitation) across the labeled size range.

PMA: What Must Be Proven

Longitudinal safety & effectiveness (freedom from reintervention, survival, NYHA symptoms as applicable).
Acceptable hemodynamics (peak/mean gradients, regurgitation) at implant and across follow-up.
Durability across repeat expansions (for growth-accommodating designs) without structural failure.
Validated manufacturing & quality (Design Controls, Process Validation, Sterility, Biocompatibility).

PMA Package – Typical Contents

Bench + Fatigue/Accelerated Wear; Hydrodynamics; Simulations.
Animal data demonstrating tissue response and function.
Clinical (pivotal IDE) results with independent core lab.
Risk management (ISO 14971) & Human factors (as applicable).
Labeling (IFU, MRI info), Post-approval study plan.

HDE / HUD (Rare Pediatric Pathway)

For devices addressing conditions affecting <8,000 individuals in the U.S. per year.
Standard is safety and probable benefit (not full effectiveness).
Profit permitted for pediatric indications under HDE (with caps/conditions).
Useful when randomized trials are impractical due to small populations.

When to Use HDE

Consider HDE for highly specific pediatric anatomies or rare RVOT reconstructions where a PMA-sized dataset is infeasible. The PMA route remains preferred when broader commercial indications or international harmonization are planned.

Breakthrough Device Designation

For devices that provide more effective treatment/diagnosis for life-threatening or irreversibly debilitating diseases.
Unlocks expedited, interactive review during IDE and PMA.
Can reduce review cycles and align on pivotal endpoints earlier.

Implications for Growth-Accommodating Valves

Programs showing credible evidence of reduced reoperation burden via repeat expansions and sustained hemodynamics can qualify. This can streamline endpoint alignment and statistical analysis plans with FDA earlier in development.

IDE & Clinical Evidence Plan

Early Feasibility Study (EFS): initial safety and performance; often single-arm with staged expansion plans.
Pivotal IDE: prospective multicenter; durability and reintervention endpoints; core-lab adjudication.
Follow-up: long-term (often up to 10 years) to satisfy durability requirements.

Illustrative Cadence

FIH → Pivotal start: ~26 months in recent programs.
Pivotal duration to primary endpoint: typically 2–5 years depending on design and endpoints.
Post-approval study: additional 5–10 years follow-up.

Budget & Capitalization

Pivotal IDE program cost typically $10M+ (device-specific).
Additional CMC/quality scale-up & post-market commitments add materially to spend.

Program Timeline

Preclinical + EFS: ~12–24 months.
Pivotal IDE to PMA decision: ~24–48 months (device- and data-dependent).

Common Risks

Expansion durability, thrombosis/neo-intimal hyperplasia.
Manufacturing validation & supply chain readiness.
Enrollment pace in narrow pediatric anatomies.

EU MDR (CE Mark)

Higher evidentiary and post-market surveillance requirements under MDR vs. legacy MDD.
Clinical evaluation alignment with U.S. pivotal can de-risk dual submissions.
Ongoing PSUR/PMCF expectations post-CE mark.

Harmonization Tips

Design pivotal endpoints to serve both FDA PMA and EU MDR clinical evaluation.
Engage Notified Body early to validate acceptability of pediatric evidence.

Submission Checklist (PMA/HDE)

Clinical: SAP, core lab plan, adjudication charter, data monitoring plan.
Preclinical: hydrodynamics, fatigue/accelerated wear, biocompatibility, sterility, shelf-life.
Quality: design history file, process validation, supplier controls, UDI/labeling.
Risk: ISO 14971 file, usability/human factors (if applicable), cybersecurity (if applicable).
Post-market: PAS/PMCF protocols and registries.

Project Sources (internal)

Osprey Intel research and analysis (regulatory timelines, costs, MDR, IDE→pivotal cadence).
Valve Competition – Autus vs. Medtronic (HDE example, competitive positioning).
Autus Valve notes (Breakthrough Device designation; FIH→pivotal timing; 10‑year follow‑up).
VC/IC memo & valuation models (budget signaling for pivotal execution).

Note: This page summarizes regulatory content from the project files to support the Consolidated Deep Dive Dashboard.