Navigating the Mandatory Electronic Submission Era Without Losing Time — or Cash

Prepared by Vital Compliance | Updated 17 June 2025

Executive Snapshot

Beginning 1 October 2025, every De Novo request must be submitted via eSTAR — the FDA's structured Electronic Submission Template and Resource. Traditional PDF and eCopy submissions will be automatically rejected.

Used correctly, eSTAR auto‑validation can:

  • Eliminate the Refuse‑to‑Accept (RTA) review
  • Trim ~30 days from review time
  • Reduce consulting spend by ~15%

However, startups that underestimate eSTAR's structured logic — especially in sections like software, cybersecurity, and biocompatibility — often trigger blocking errors, delay launch, and burn cash.

1 | Regulatory Timeline & Enforcement Dates

  • 1 Oct 2024

    Optional eSTAR available for De Novo filers.

    → Pilot workflows early and identify gaps.
  • 1 Jul 2025

    Weekly FDA webinars begin.

    → Submit technical questions to eSTAR team.
  • 1 Oct 2025

    Mandatory eSTAR submission begins.

    → PDF/eCopy submissions will be rejected outright.
  • Q1 2026

    eSTAR template refresh expected.

    → Likely additions: QMSR fields, SBOM slot upgrades.
  • Q2 2026

    FDA inspections begin referencing eSTAR metadata.

    → Align DHF structure early.

2 | De Novo vs. 510(k) vs. PMA — Choosing Wisely

How they compare:

  • Predicate Status:
  • 510(k): Yes
  • De Novo: No predicate, moderate risk
  • PMA: No predicate, high risk
  • Clinical Data:
  • 510(k): Bench + limited clinical
  • De Novo: Some clinical often required
  • PMA: Substantial clinical required
  • FY 2025 User Fees:
  • 510(k): $22k ($5k small biz)
  • De Novo: $115k ($28k small biz)
  • PMA: $483k ($120k small biz)
  • Review Days (avg):
  • 510(k): 180
  • De Novo: 150
  • PMA: 320
  • Class Outcome:
  • 510(k): Class II
  • De Novo: Class I or II
  • PMA: Class III
  • eSTAR Requirement:
  • 510(k): Not yet, encouraged
  • De Novo: Yes — by 1 Oct 2025
  • PMA: Planned for 2026

Tip:

De Novo status offers first-mover predicate advantage and market differentiation — but only with 0.5 FTE regulatory ownership for 6 months.

3 | eSTAR Deep Dive — Structure, Validation, and Traps

3.1 eSTAR Anatomy

  • Interactive PDF with embedded validation
  • Key Sections:
  • Admin Info
  • Declarations of Conformity
  • Device Description
  • Software / Cybersecurity
  • Performance Testing
  • Labeling
  • Auto‑generated Attachments Index

3.2 Common Validation Gates

  • Missing Required Field:

    → Blocking error

    → Fill field and re‑validate.
  • Wrong File Type (e.g., not PDF/A-1B):

    → Blocking error

    → Convert and re‑attach.
  • Inconsistent Logic:

    → Warning

    → Fix contradictory answers (e.g., claim “no software” but upload SBOM).
  • Oversized File Attachments (>1 GB):

    → Warning

    → Compress or split into families.

4 | Building the eSTAR Evidence Package

Key Evidence Categories & Format Tips

  • Risk Management File
  • ISO 14971 plan, hazard log, risk report
  • Max: 50 MB PDF
  • Bench Testing
  • Mechanical, electrical, software V&V
  • Group by test type
  • Clinical Data
  • Protocol, stats plan, full report
  • One PDF per study
  • Biocompatibility
  • Toxicology + chemical characterization
  • Combine where feasible
  • Labeling
  • IFU, packaging, quick-start
  • Max: 10 MB per doc
  • Cybersecurity
  • SBOM (JSON + PDF), threat model, VMP
  • Zip the JSON and PDF summary

Pro tip:

Use PDF/A, standardized filenames, and bookmarks for docs >15 pages.

5 | Cybersecurity & SBOM — Section 524B Compliance

  • eSTAR Section 15 captures:
  • SBOM (JSON format, zipped)
  • Threat model
  • Vulnerability Management Plan (VMP)
  • Penetration testing summary
  • Declaring “no software”?

    → eSTAR disables cyber uploads — ensure your device description supports this.

6 | Human Factors & Use-Related Risk

  • Complete optional HF Addendum to help reviewers.
  • Include:
  • A Top 5 Critical Tasks table (with use-error summary)
  • The full Human Factors Validation Report under Performance Testing

7 | Cost & Resource Modeling for Lean Teams

Your Options

  • DIY eSTAR Build
  • Upfront: $0 tools + $8–12k internal time
  • Duration: 12–16 weeks
  • Best if in-house regulatory talent exists
  • Fractional Regulatory Lead + DIY Testing
  • Cost: $5–8k/month
  • Duration: 10–12 weeks
  • Ideal for lean teams needing coaching
  • Turn‑Key De Novo Package
  • Cost: $60–90k
  • Duration: ~14 weeks
  • Choose if under pressure to launch
  • Hybrid Model
  • Split: ~$25k internal, ~$25k external
  • Duration: 12 weeks
  • Offers speed + knowledge transfer

8 | Case Study — 208-Day De Novo Win (11-Person Startup)

  • No RTA hold letters due to aggressive eSTAR pre-validation
  • Only one AI (Additional Information) round — not two
  • Total review time: 208 days vs industry average of 300+
  • External spend: $115k
  • Achieved by using a fractional regulatory lead for just six weeks

9 | Common Pitfalls — and Fixes

  • ❌ Treating eSTAR as “just a form”

    ✅ Draft your evidence under eSTAR headings from day one
  • ❌ Oversized attachments get rejected

    ✅ Compress, split by family, or use FDA File Transfer Service
  • ❌ SBOM submitted in Excel

    ✅ Convert to CycloneDX JSON, zip it, and add PDF summary
  • ❌ No De Novo rationale attached

    ✅ Include flowchart: predicate search → risk logic → De Novo justification
  • ❌ Missing draft UDI plan

    ✅ Even premarket devices must attach a UDI placeholder

10 | Action Checklist — First 90 Days

✅ Appoint eSTAR/De Novo project owner

✅ Download latest eSTAR template version

✅ Map your DHF to eSTAR section headings

✅ Draft ISO 14971 risk file

✅ Generate alpha SBOM + gap analysis

✅ Schedule HF formative study

✅ Book optional FDA Q‑Submission for questions

✅ Run dry eSTAR validation to debug early

✅ Apply for small business fee waiver (if eligible)

11 | Conclusion

The shift to mandatory eSTAR for De Novo isn't just regulatory — it's strategic. Done right, it gives you first-predicate advantage, faster reviews, and fewer consulting headaches.

Start now.

Structure your evidence by eSTAR section from Day 1, automate SBOM, and validate early. Avoid RTA surprises, conserve capital, and reach market faster than those clinging to PDFs.

Need help? Vital Compliance offers fixed-fee De Novo packages and fractional regulatory leadership to get you eSTAR-ready — fast.