# Usage: curl -sSL https://seed.show/medtech.fda.clearance | bash -s <install-path>
# <install-path> is the directory where the file should land.

set -euo pipefail
[ -z "${1:-}" ] && {
  echo "install requires a path: curl -sSL https://seed.show/medtech.fda.clearance | bash -s <install-path>" >&2
  exit 1
}
TARGET="$1"
mkdir -p "$TARGET"
DEST="$TARGET/seed-fold.vQE4jn.folded.md"

cat > "$DEST" <<'PORTDOWN_7281EC23'
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This is a `.folded.md` archive — a directory packed into one markdown
file. The markers below are load-bearing; don't edit them directly.

To unpack (requires bash — if you have no shell, tell the user):
  1. curl -sSLf https://fold.dom.vin/skill | bash -s <INSTALL_DIR>
  2. <INSTALL_DIR>/fold/scripts/unfold <this-file>
     (or: unfold <this-file>  if fold/scripts is on your PATH)
-->

---
fold: true
marker: 1eef45
at: 2026-05-07T16:16:18Z
root: seed-pack.qsPozl
---

<!--fold:1eef45@file path="README.md" mode="644"-->
# FDA Medical Device Clearance — Agent Context

**What not to hallucinate:** FDA 510(k) "clearance" and FDA "approval" are specific legal determinations with different evidentiary standards — they are not interchangeable terms. Never describe a cleared device as "FDA approved." Review timelines and Q-Sub program slot availability are guidance targets, not guarantees — point to sources.md for current FDA guidance rather than stating specific numbers as current fact.

---

## Mental model: risk-proportionate regulation

FDA classifies medical devices by risk. Classification determines the entire regulatory pathway, the evidentiary bar, and the timeline to market.

**Class I — Low risk, general controls.** Most Class I devices are exempt from premarket review entirely. General controls (labeling, misbranding prohibition, establishment registration) apply. Examples: tongue depressors, elastic bandages, handheld surgical instruments.

**Class II — Moderate risk, special controls + 510(k).** Special controls (performance standards, post-market surveillance requirements, patient registries, specific labeling requirements) supplement general controls. The premarket pathway is 510(k) premarket notification — clearance based on substantial equivalence to a predicate device. Roughly 80% of devices that go through premarket review use this pathway. Examples: powered wheelchairs, infusion pumps, pregnancy test kits.

**Class III — High risk, PMA.** Premarket Approval requires valid scientific evidence — typically clinical trials — demonstrating reasonable assurance of safety and effectiveness. The most stringent pathway; reserved for devices that support or sustain human life, are of substantial importance in preventing impairment, or present unreasonable risk of illness or injury. Examples: implantable pacemakers, cochlear implants, HIV diagnostic tests.

The single most important question at session start: **what class is this device, and has FDA already classified it?** Use the Product Classification Database first (see sources.md). If a predicate exists, the path is almost always 510(k). If it's novel and low-to-moderate risk with no predicate, the path is De Novo. Novel and high risk is PMA.

---

## What agents get wrong

### 1. 510(k) is clearance, not approval

Agents routinely describe 510(k) as "FDA approval." It is **clearance** — a determination of substantial equivalence. These are legally and substantively different: approval requires FDA to find the device safe and effective based on clinical evidence; clearance requires showing the device is **as safe and effective as a legally marketed predicate device**.

Substantial equivalence has a specific standard: (a) same intended use as the predicate, and (b) same technological characteristics — or different technological characteristics that don't raise new questions of safety or effectiveness and the device is at least as safe and effective as the predicate. FDA issues a Substantially Equivalent (SE) determination letter for cleared devices.

The predicate chain matters. A valid predicate must be:
- A device legally marketed before May 28, 1976 (the Medical Device Amendments enactment date), or
- A device that was itself cleared through 510(k), creating a traceable chain to a preenactment device, or
- A device reclassified from Class III to Class II or Class I, or
- A device cleared through De Novo (De Novo clearance establishes a new device type and can anchor future 510(k) predicates)

**The mistake:** agents assume any cleared device can serve as a predicate. The chain must be traceable. If the predicate's predicate is broken or the chain terminates at a device that wasn't preenactment or properly cleared, the submission fails — FDA issues a Not Substantially Equivalent (NSE) determination.

### 2. De Novo vs. 510(k) vs. PMA — novel devices need De Novo, not 510(k)

When a device is novel and no legally marketed predicate exists, 510(k) is not available. Agents frequently recommend 510(k) for novel devices; submissions get rejected with an NSE determination, leaving the sponsor without a path.

**De Novo** is the correct pathway for novel devices that are low-to-moderate risk — Class I or Class II if appropriate special controls can be established. De Novo creates a new device type and its associated regulatory controls. Once cleared via De Novo, that device becomes a legally marketed predicate for future 510(k) submissions in that category.

Decision tree:
1. Legally marketed predicate exists? → 510(k)
2. No predicate, device is likely Class III risk? → PMA (or seek Breakthrough Device Designation to expedite)
3. No predicate, device is likely Class I or Class II risk with appropriate controls? → De Novo

**The mistake:** agents skip De Novo entirely or conflate it with 510(k). They're separate submission types with different review standards, different outcomes, and different downstream implications for the predicate chain.

### 3. SaMD — Software as a Medical Device is a distinct regulatory category

Software that meets the device definition under 21 USC 321(h) is regulated as a medical device. The 21st Century Cures Act (2016) carved out specific software functions (administrative, general wellness, CDS meeting specific criteria), but the carve-outs are narrower than they appear.

FDA's Digital Health Center of Excellence (DHCoE) coordinates SaMD oversight. The IMDRF SaMD framework (which FDA has adopted) defines SaMD by intended use and significance of information provided to clinical decisions — from informing clinical management to driving clinical management decisions. Higher significance of information + higher state of healthcare situation = more stringent regulatory category.

Software subject to enforcement discretion (FDA has published a list) is not exempt from the device definition — FDA is simply not actively enforcing. That distinction matters for liability, QMS, and post-market obligations.

**The mistake:** agents advising on healthcare software don't ask whether the software meets the device definition. Clinical decision support tools, diagnostic aids, monitoring software, and many mobile medical apps are SaMD requiring premarket review. Assuming enforcement discretion applies without analysis is a compliance risk.

### 4. PCCP — AI/ML devices that change behavior require a Predetermined Change Control Plan

FDA finalized the PCCP framework (2024 guidance). AI/ML-enabled devices designed to change their behavior — model retraining, algorithm updates, performance threshold shifts — cannot ship updates under the original cleared indication without a PCCP in the original submission describing: (a) the types of changes anticipated, (b) the methodology for implementing changes, and (c) the performance specifications that must be maintained.

Without a PCCP, each significant algorithm change requires a new 510(k) or PMA supplement. For ML systems that continuously learn or require frequent retraining, this is operationally impractical.

**The mistake:** agents advising on AI-based medical devices treat the FDA submission as a one-time event. For adaptive AI systems, the PCCP is part of the initial submission scope — scoping it post-clearance means either freezing the algorithm or triggering new submissions for every update.

### 5. QMS — clearance does not authorize commercialization alone

510(k) clearance (or PMA approval) is necessary but not sufficient for commercial distribution. Manufacturers must comply with 21 CFR Part 820 — the Quality System Regulation (QSR). FDA amended Part 820 in 2024 to align with ISO 13485:2016; the updated rule is the Quality Management System Regulation (QMSR). The two are substantively similar but the QMSR formally incorporates the ISO 13485 structure.

QMS requirements cover: design controls, document controls, purchasing controls, production and process controls, corrective and preventive action (CAPA), complaint handling, records, and internal audits. Design History File (DHF), Device Master Record (DMR), and Device History Record (DHR) are specific required artifacts.

**The mistake:** agents treat clearance as the finish line. A cleared device distributed without a compliant QMS is in violation regardless of cleared status. FDA can take enforcement action — warning letters, injunctions, import alerts — against companies with compliant clearances but non-compliant QMS.

### 6. Predicate selection — the technological characteristics analysis is not optional

Agents often pick a predicate based on superficial similarity (same anatomical target, similar name) without working through the substantial equivalence analysis. The comparison must cover: intended use (primary, secondary, conditions of use, user population), technological characteristics (materials, design, energy source, software), and performance data (bench, animal, clinical as applicable).

If the new device has different technological characteristics, the submission must demonstrate those differences don't raise new safety or effectiveness questions and that the device performs at least as well as the predicate. This analysis is done in the 510(k) Substantial Equivalence Comparison — a required section.

**The mistake:** assuming technological similarity without documenting it. FDA reviewers look specifically for the comparison matrix.

### 7. Combination products — device + drug or device + biologic changes everything

If a product combines a device with a drug (drug-device combination, e.g., a drug-eluting stent) or a device with a biologic (e.g., a tissue-engineered scaffold), it is a combination product regulated under 21 CFR Part 3. The Office of Combination Products (OCP) at FDA determines the primary mode of action, which in turn determines the lead center (CDRH for device-led, CDER for drug-led, CBER for biologic-led).

The lead center's regulatory framework governs, but the other centers provide input. A device-led combination product still needs the drug constituent assessed under CDER's framework. This is significantly more complex than either standalone product.

**The mistake:** agents advise on the device component without flagging that the product is a combination product requiring OCP jurisdictional determination before selecting a submission pathway.

---

## Key stable facts

| Fact | Detail |
|---|---|
| Class I | General controls only; most exempt from premarket review |
| Class II | General + special controls; 510(k) pathway |
| Class III | General controls + PMA; clinical evidence required |
| Substantial equivalence | Same intended use + same (or non-inferior different) technological characteristics |
| De Novo | For novel low-to-moderate risk devices; creates new device type; De Novo-cleared device becomes predicate |
| PCCP | Required for AI/ML devices with anticipated algorithm changes; finalized 2024 |
| QSR/QMSR | 21 CFR Part 820; now aligned to ISO 13485:2016 as of 2024 |
| SaMD | Full device framework applies; IMDRF framework adopted by FDA |
| EU parallel | CE marking under EU MDR 2017/745; separate notified body; no mutual recognition with FDA |
| Combination products | OCP determines lead center; primary mode of action governs pathway |
| Breakthrough Device | FDA designation that speeds review for breakthrough devices; reduces but doesn't eliminate evidentiary requirements |

---

## What AI is changing

### FDA's AI/ML framework for SaMD

FDA's 2021 AI/ML Action Plan and the 2024 PCCP final guidance represent a new regulatory model for adaptive devices. The core challenge: traditional device regulation assumes the device as cleared is the device that remains in distribution. AI/ML devices that learn or update break this assumption.

The PCCP addresses this by authorizing specific types of changes in advance — the clearance covers both the current algorithm and the defined envelope of future changes. This is a meaningful regulatory innovation: it shifts the oversight model from change-by-change approval to prospective change management within defined performance bounds.

**Continuous learning devices** (algorithms that update in deployment, not just in retraining cycles) are not yet fully addressed by the PCCP framework. FDA has signaled these require additional guidance. An agent advising on a truly continuously learning device should flag this as an open regulatory question.

### Digital health and DTx

Digital therapeutics (DTx) — software that delivers therapeutic interventions — are regulated as SaMD when they meet the device definition. FDA cleared the first DTx (for substance use disorder) in 2017; the category has grown but remains incompletely defined. DTx for mental health, cognitive rehabilitation, and chronic disease management are active clearance categories.

Mobile Medical Apps (MMAs) are a subset of SaMD — apps that meet the device definition and run on mobile platforms. FDA has published guidance on which apps it intends to regulate (those that are accessories to regulated devices or that transform a mobile platform into a regulated device).

### What stays human

Clinical validation — the design, execution, and interpretation of clinical studies supporting substantial equivalence or PMA approval — is not automatable. The study design must match the device's intended use and risk profile; IRB review and informed consent are legal requirements; adverse event reporting during studies triggers specific FDA obligations.

Post-market surveillance (PMS) and complaint handling are legally required ongoing activities with specific documentation obligations. Complaint handling under 21 CFR Part 820 requires evaluating every complaint to determine if it's an MDR-reportable event (Medical Device Report under 21 CFR Part 803). These processes require human judgment, regulatory expertise, and institutional accountability — not just workflow automation.

---

## How to use this context

1. Classify the device. Use the Product Classification Database (sources.md).
2. Identify whether a predicate exists. If yes: 510(k). If no: De Novo (low-moderate risk) or PMA (high risk).
3. Determine if the product is a combination product. If yes: OCP determination first.
4. For software: determine whether it meets the SaMD definition before advising on pathway.
5. For AI/ML devices: flag PCCP in the initial submission scope.
6. Scope QMS requirements from day one — clearance is not commercialization authorization.

Fetch `sources.md` for current FDA guidance URLs. Fetch `workflow.md` for the 510(k) clearance lifecycle and PMA milestone sequence.
<!--fold:1eef45@file path="sources.md" mode="644"-->
# FDA Medical Device Clearance — Source URLs

Fetch these at the start of a session for current guidance. FDA updates these pages; the URLs below are stable entry points, but the underlying content evolves. Do not state specific review timelines or program details as current fact — fetch the source.

---

## Core premarket pathways

**510(k) Premarket Notification — Overview**
https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-notification-510k

**510(k) Substantial Equivalence Decision-Making — Guidance**
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/refuse-accept-policy-510ks

**De Novo Classification Request**
https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/de-novo-classification-request

**PMA — Premarket Approval Application**
https://www.fda.gov/medical-devices/premarket-submissions-selecting-and-preparing-correct-submission/premarket-approval-pma

**Breakthrough Device Designation**
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-devices-program

---

## Digital health and SaMD

**Digital Health Center of Excellence (DHCoE)**
https://www.fda.gov/medical-devices/digital-health-center-excellence

**Software as a Medical Device (SaMD) — FDA Policy and Guidance**
https://www.fda.gov/medical-devices/digital-health-center-excellence/software-medical-device-samd

**Mobile Medical Applications — FDA Guidance**
https://www.fda.gov/medical-devices/digital-health-center-excellence/device-software-functions-including-mobile-medical-applications

**Digital Therapeutics — FDA Perspective**
https://www.fda.gov/medical-devices/digital-health-center-excellence/digital-health-innovations

**IMDRF SaMD Framework (adopted by FDA)**
https://www.imdrf.org/documents/software-medical-device-samd-key-definitions

---

## AI/ML and PCCP

**Artificial Intelligence and Machine Learning in SaMD — Action Plan**
https://www.fda.gov/medical-devices/software-medical-device-samd/artificial-intelligence-and-machine-learning-software-medical-device

**Marketing Submission Recommendations for a Predetermined Change Control Plan for AI/ML-Enabled Devices (Final Guidance, 2024)**
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/marketing-submission-recommendations-predetermined-change-control-plan-artificial-intelligencemachine

**AI/ML-Based Software as a Medical Device — Discussion Paper and Request for Feedback**
https://www.fda.gov/media/122535/download

---

## Quality Management System

**Quality Management System Regulation (QMSR) — 21 CFR Part 820 (2024 Amendments)**
https://www.fda.gov/medical-devices/postmarket-requirements-devices/quality-system-qs-regulationmedical-device-good-manufacturing-practices

**ISO 13485:2016 — Medical Devices QMS (ANSI/AAMI reference)**
https://www.iso.org/standard/59752.html

---

## Classification and product codes

**Product Classification Database**
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm

**Device Classification Panels**
https://www.fda.gov/medical-devices/classify-your-medical-device/device-classification-panels

**510(k) Database (search cleared devices for predicate research)**
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm

**De Novo Database (search De Novo-cleared devices)**
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm

---

## Combination products

**Office of Combination Products (OCP)**
https://www.fda.gov/combination-products

**Request for Designation (RFD) — Determining Lead Center**
https://www.fda.gov/combination-products/jurisdictional-information/request-designation-rfd

---

## Post-market requirements

**Medical Device Reporting (MDR) — 21 CFR Part 803**
https://www.fda.gov/medical-devices/postmarket-requirements-devices/medical-device-reporting-mdr-how-report-medical-device-problems

**Post-Market Surveillance (522 Studies)**
https://www.fda.gov/medical-devices/postmarket-requirements-devices/postmarket-surveillance-studies-522-studies

---

## EU parallel (CE marking)

**EU MDR 2017/745 — EUR-Lex**
https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX%3A32017R0745

**EUDAMED (European Database on Medical Devices)**
https://ec.europa.eu/tools/eudamed/

**EUDAMED SaMD Guidance**
https://www.mdcg.eu/

---

## Primary statute

**Federal Food, Drug, and Cosmetic Act — Device provisions (21 USC 301 et seq.)**
https://www.fda.gov/regulatory-information/laws-enforced-fda/federal-food-drug-and-cosmetic-act-fdc-act
<!--fold:1eef45@file path="workflow.md" mode="644"-->
# FDA Medical Device Clearance — Workflow Reference

Two pathways dominate: 510(k) for Class II devices with a predicate, PMA for Class III. De Novo is the third pathway for novel low-to-moderate risk devices. Each has a distinct lifecycle. What follows is the step sequence for each, with the key decision and documentation artifact at each stage.

---

## 510(k) Clearance Lifecycle

### Stage 1: Device Concept and Device Definition

**What happens:** Define the device's intended use, indications for use, and contraindications. This language is load-bearing — the intended use statement anchors the substantial equivalence analysis, the labeling, and the post-market surveillance scope.

**Key decision:** Is this a device under 21 USC 321(h)? Software, combination products, and instruments with diagnostic claims all need this threshold analysis before anything else.

**Artifact:** Intended Use / Indications for Use document (draft). For software: SaMD classification determination.

---

### Stage 2: Classification Determination

**What happens:** Determine whether FDA has already classified a device of this type. Search the Product Classification Database by device name, product code, or panel. A product code maps to a regulation number (21 CFR Part 860–892), a device class, and a predicate pool.

**Key decision:** Has FDA classified this device type? If yes: Class I (likely exempt), Class II (510(k) unless also exempt), or Class III (PMA). If the device type has no product code and no regulation, it may be unclassified — which means it defaults to Class III until reclassified (or cleared via De Novo).

**Artifact:** Classification summary with product code, regulation number, and predicate pool identification.

---

### Stage 3: Predicate Search and Selection

**What happens:** Search the 510(k) Database and De Novo Database for devices with the same intended use and substantially similar technological characteristics. A predicate must be a legally marketed device — meaning it was marketed before May 28, 1976, or was cleared through 510(k), or was cleared through De Novo, or was reclassified.

**Key decision:** Which predicate best anchors the substantial equivalence argument? Multiple predicates can be used; this is called a "split predicate" — using one predicate for intended use and another for technological characteristics. FDA has cautioned against split predicates in some contexts; the argument must still be coherent.

**Artifact:** Predicate device summary — cleared device name, K-number or DEN-number, cleared intended use, and cleared technological characteristics.

---

### Stage 4: Substantial Equivalence Analysis

**What happens:** Compare the new device to the predicate on intended use and technological characteristics. If technological characteristics differ, document that the differences don't raise new safety/effectiveness questions and that performance data shows equivalence or superiority to the predicate.

**Key decision:** Do technological differences require performance data beyond bench testing? Materials differences may require biocompatibility testing (ISO 10993). Software differences require software documentation (level of concern). Energy-based devices require electrical safety testing. This determination scopes the testing program.

**Artifact:** Substantial Equivalence Comparison (required section of the 510(k) submission — typically a comparison table with side-by-side analysis).

---

### Stage 5: Testing and Verification

**What happens:** Execute the testing program required to support the substantial equivalence claims. Categories:
- **Bench testing:** performance testing, dimensional testing, mechanical testing, electrical safety (IEC 60601 for electrical medical devices)
- **Biocompatibility:** ISO 10993 series for devices with patient contact
- **Software/cybersecurity:** IEC 62304 for software lifecycle, FDA cybersecurity guidance for networked devices
- **Sterilization validation:** if applicable (ISO 11135, ISO 11137, etc.)
- **Animal/clinical:** if technological differences require in vivo evidence

**Key decision:** Is clinical data required? FDA reviewers may request clinical data even for 510(k) submissions if bench testing is insufficient to characterize equivalence. For AI/ML devices: performance testing must include the PCCP validation methodology.

**Artifact:** Test protocols and test reports (form part of the 510(k) submission).

---

### Stage 6: 510(k) Preparation

**What happens:** Assemble the 510(k) submission. The standard 510(k) format includes: cover letter, table of contents, executive summary, device description, substantial equivalence comparison, proposed labeling, sterility/biocompatibility information, performance testing, and software documentation (if applicable).

Traditional 510(k) vs. Abbreviated 510(k) vs. Special 510(k):
- **Traditional:** full submission; most common
- **Abbreviated:** relies on FDA-recognized consensus standards; reduced data requirements where standards apply
- **Special:** for modifications to a manufacturer's own previously cleared device

**Key decision:** Does the device qualify for the Abbreviated pathway (recognized standards exist and are followed)? This can reduce submission size and review burden.

**Artifact:** Complete 510(k) submission package (eCopy submitted via CDRH eSubmitter or eStar system).

---

### Stage 7: FDA Review — Acceptance and Substantive Review

**What happens:** FDA first performs an Administrative Review (Refuse to Accept — RTA check) to confirm the submission is complete. A complete submission enters substantive review. FDA may issue an Additional Information (AI) request; the clock stops while the submitter responds. The submitter has up to 180 days to respond to an AI request before the submission is considered withdrawn.

**Key decision:** When FDA issues an AI request, prioritize speed and completeness. An AI response that triggers a second AI request signals a fundamental issue with the predicate or the equivalence argument — may need to reconsider predicate selection.

**Artifact:** AI response package. All FDA correspondence goes through the CDRH eSubmitter system.

---

### Stage 8: Clearance

**What happens:** FDA issues a Substantially Equivalent (SE) determination letter. The device is now legally marketed for the cleared intended use. The clearance letter specifies the cleared intended use and the predicate device used for comparison.

**What the SE letter is not:** it is not a safety finding, not an endorsement, not a performance certification. It is a determination that the device is as safe and effective as the predicate. FDA makes this explicit in its communications.

**Artifact:** SE letter (keep permanently — it establishes legal market authorization and anchors any future 510(k) submissions from this company that use this device as predicate).

---

### Stage 9: Post-Market Requirements

**What happens:** Post-clearance obligations are ongoing and indefinite:

- **QMS compliance:** 21 CFR Part 820 (QMSR) — design controls, document controls, CAPA, complaint handling, internal audits. Active from first commercial distribution.
- **Medical Device Reporting (MDR):** 21 CFR Part 803 — mandatory reporting of deaths, serious injuries, and certain malfunctions to FDA within specified timeframes (30 days for most; 5 days for events requiring immediate action).
- **Establishment registration and device listing:** annual registration with FDA; device listing required within 10 days of first commercial distribution.
- **Labeling compliance:** cleared labeling must match distributed labeling; changes to intended use or indications require a new 510(k).
- **Post-market surveillance:** FDA can order 522 studies if post-market performance data is needed.

**Key decision:** What changes to the cleared device require a new 510(k) vs. internal design change documentation? FDA's guidance on modifications to cleared devices (the 510(k) decision-making guidance) is the reference. A change that could significantly affect safety or effectiveness requires a new 510(k) — this is a judgment call with legal consequences.

---

## PMA Pathway Milestones — Class III Devices

PMA is required for Class III devices: those that support or sustain human life, are of substantial importance in preventing impairment, or present unreasonable risk. The timeline is longer and the evidentiary bar is higher.

### Pre-Submission (Q-Sub) — Before Anything Else

Before committing to a PMA clinical program, request a Q-Sub (pre-submission meeting) with FDA. Q-Sub is a formal feedback mechanism: submit questions about study design, endpoints, predicate approach, or device classification; FDA responds in writing. Q-Sub responses are not binding, but they establish FDA's current thinking and reduce rework risk.

**Use Q-Sub for:** IDE design discussion, clinical trial endpoints, manufacturing scale-up questions, novel material biocompatibility questions, and software validation approach.

### IDE — Investigational Device Exemption

To conduct significant-risk device studies in the US, an IDE is required. IDE application includes: the investigational plan, investigator agreements, IRB approvals, informed consent procedures, and device manufacturing information. FDA has 30 days to review an IDE; after approval, the clinical study can begin.

Nonsignificant risk (NSR) studies do not require an IDE from FDA — IRB approval alone suffices. The sponsor (not FDA) makes the initial NSR/SR determination; IRB reviews and concurs.

### PMA Clinical Study

Clinical study design for PMA must demonstrate reasonable assurance of safety and effectiveness. Key elements:
- Primary endpoint aligned with intended use and clinical outcomes meaningful to patients
- Adequate controls (comparator device or standard of care)
- Sample size sufficient for statistical power
- Pre-specified analysis plan

FDA will not accept a PMA supported only by registry data or retrospective analysis for novel high-risk devices — prospective controlled study data is typically required.

### PMA Application Preparation

PMA includes: device description, summary of safety and effectiveness (SSED), nonclinical studies, clinical studies, manufacturing information (full manufacturing audit — unlike 510(k)), proposed labeling. The manufacturing section must demonstrate the manufacturing process produces a device consistent with the clinical study device.

### PMA Review and Panel

FDA reviews the PMA application (180-day review clock after filing acceptance). For novel or high-risk devices, FDA convenes an advisory panel — external experts who publicly evaluate the evidence and recommend approval, conditional approval, or non-approval. The panel recommendation is advisory; FDA is not bound by it, but departures from panel recommendations require written justification.

### PMA Approval Conditions

PMA approval frequently comes with conditions: post-approval studies (PAS) to collect additional real-world performance data, restricted distribution requirements, mandatory labeling updates, or required registry participation. Conditions are legally binding — failure to meet them is a basis for withdrawal of approval.

### Post-Approval Requirements

PMA holders must submit:
- Annual reports updating manufacturing, labeling, and post-market safety data
- PMA supplements for changes to the device, manufacturing, or indications (some supplements require FDA approval before implementation; others are 30-day notices)
- Medical Device Reports (MDR) under the same 21 CFR Part 803 requirements as 510(k)-cleared devices

---

## De Novo Pathway Summary

De Novo is not a subset of 510(k) — it's a separate pathway for novel devices that lack a predicate and are low-to-moderate risk.

Key distinctions:
- Submitter demonstrates the device is Class I or Class II risk with appropriate special controls
- FDA review establishes a new product code, regulation, and special controls — creating the regulatory infrastructure that didn't previously exist
- Once cleared via De Novo, the device becomes a legally marketed predicate for future 510(k) submissions

The De Novo submission contains similar elements to a 510(k) (device description, performance data, proposed labeling) plus a proposed classification and proposed special controls. FDA has 150 days from filing to act on a De Novo request.

---

## Common Cross-Pathway Requirements

These apply regardless of pathway:

| Requirement | When | Regulation |
|---|---|---|
| Establishment registration | Before commercial distribution | 21 CFR Part 807 |
| Device listing | Within 10 days of first commercial distribution | 21 CFR Part 807 |
| QMS (QMSR) compliance | From first commercial distribution | 21 CFR Part 820 |
| MDR reporting | Upon awareness of reportable event | 21 CFR Part 803 |
| Labeling compliance | At all times | 21 CFR Part 801 |
| Unique Device Identification (UDI) | Labeling and GUDID database | 21 CFR Part 830 |
<!--fold:1eef45@end-->
PORTDOWN_7281EC23

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' "$DEST"
SEED_EXTRACTED=$(find "$TARGET" -type f -not -path "$DEST" 2>/dev/null | wc -l)
if [ "$SEED_EXTRACTED" = "0" ]; then
  echo "seed: archive contained no files — refusing to delete the source" >&2
  echo "  archive preserved at: $DEST" >&2
  exit 1
fi
rm -f "$DEST"

echo "" >&2
echo "✓ seed unpacked → $TARGET ($SEED_EXTRACTED files)" >&2
find "$TARGET" -type f | sort | while IFS= read -r _sf; do
  echo "  ${_sf#${TARGET}/}" >&2
done
echo "" >&2
if [ -f "$TARGET/SKILL.md" ]; then
  echo "This seed contains a skill (SKILL.md). Install it in your agent's skills directory." >&2
  echo "" >&2
fi
echo "Install the seed skill if not already installed:" >&2
echo "  https://seed.show/skill" >&2
echo "" >&2
echo "Publisher prompt:" >&2
sed 's/^/  /' >&2 <<'__SEED_PROMPT_END_AC1F2B__'
You have FDA medical device regulatory context across three files. Read README.md first — device classification is load-bearing, clearance vs. approval is a hard distinction, and the what-agents-get-wrong section covers the seven most common failures. Read workflow.md for the 510(k) clearance lifecycle and PMA milestone sequence. Fetch sources.md for current FDA guidance URLs — point to sources rather than stating timelines as current fact. Start by asking: what device are we classifying, or what regulatory question are we working through?
__SEED_PROMPT_END_AC1F2B__
exit 0