FDA 510(k) Deep Dive
Understanding the regulatory framework: three active clearances, exact cleared indications, predicate device history, and the legal basis for off-label clinical use
FDA-Cleared Indication
FDA regulatory data. Based on publicly available 510(k) summaries, Federal Register notices, and device classification records.
Understanding 510(k) Clearance
A 510(k) is a premarket notification submitted to the FDA to demonstrate that a new device is 'substantially equivalent' to a legally marketed predicate device. It is NOT an approval — the FDA does not 'approve' 510(k) devices. Instead, the FDA 'clears' them for marketing.
510(k) clearance does NOT require clinical trials demonstrating efficacy
The manufacturer must show 'substantial equivalence' to an existing legally marketed device (the predicate)
Substantial equivalence means the new device has the same intended use and similar technological characteristics, OR different technological characteristics that do not raise new safety/efficacy questions
Over 95% of medical devices reach market through the 510(k) pathway
Medicinal leeches are regulated as Unclassified Pre-Amendment medical devices under product code NRN
Three Active Clearances
As of 2026, there are three active 510(k) clearances for medicinal leeches in the United States. All three share the same cleared indications but differ in species labeling, market share, and clearance history.
Ricarimpex SAS (Eysines, France)
- Clearance Date
- June 21, 2004
- CBER Tracking (since 12/30/2024)
- BK251211
- Species (on label)
- <em>Hirudo medicinalis</em> (on label)
- Species Note
- Per Siddall et al. (2007), the leeches commercially supplied as H. medicinalis are actually <em>Hirudo verbana</em> — a separate species described in 1820 but conflated with H. medicinalis until molecular taxonomy resolved the distinction.
- Predicate Device
- Pre-amendments (grandfathered — 1976 Medical Device Amendments)
First modern 510(k) clearance for medicinal leeches. Established the predicate chain for all subsequent clearances.
Biopharm UK Ltd. (Hendy, Wales, UK)
- Clearance Date
- February 19, 2014
- CBER Tracking (since 12/30/2024)
- BK251217
- Species (on label)
- <em>Hirudo verbana</em>
- Species Note
- First clearance to use the taxonomically correct species name on the label, reflecting the Siddall et al. molecular taxonomy.
- Predicate Device
- K040187 (Ricarimpex)
European supplier with established distribution in NHS hospitals. Brought taxonomically updated labeling to the US market.
Carolina Biological Supply Company (Burlington, NC, USA)
- Clearance Date
- August 7, 2015
- CBER Tracking (since 12/30/2024)
- BK251218
- Species (on label)
- <em>Hirudo verbana</em>
- Species Note
- Continued the updated species labeling convention established by K132958.
- Predicate Device
- K040187 (Ricarimpex)
Only US-based 510(k) holder. Primarily known as an educational supply company; medicinal leech distribution is a secondary product line.
Cleared Indications — Exact Language
The FDA-cleared indications for medicinal leeches are narrowly defined. All three 510(k) clearances share identical indication language:
“Removing pooled blood beneath skin grafts where there is no other mechanism of adequate venous drainage”
This indication covers the use of leeches in post-operative flap salvage — specifically venous-congested tissue flaps and replantations where microsurgical venous anastomosis has failed or is not technically feasible.
“Restoring circulation in blocked veins by removing pooled blood (venous congestion relief)”
This broader indication encompasses venous congestion relief in various clinical settings, including digit replantation, free flap transfer, and pedicled flap reconstruction.
Off-Label Context
510(k) vs FDA Approval
Many patients and clinicians confuse '510(k) clearance' with 'FDA approval.' They are fundamentally different regulatory pathways:
| Feature | 510(k) Clearance | PMA Approval | De Novo Classification |
|---|---|---|---|
| Regulatory standard | Substantial equivalence to predicate | Reasonable assurance of safety and effectiveness | Low-to-moderate risk; no predicate exists |
| Clinical trials required? | Not typically (bench/performance testing may suffice) | Yes — usually large, randomized trials | Sometimes (risk-based determination) |
| Average review time | 3–6 months | 12–24 months | 6–12 months |
| Cost to manufacturer | $10,000–$30,000 (FDA fee) + testing | $300,000+ (FDA fee) + $1M–$75M (clinical trials) | $100,000–$200,000 |
| Device class | Typically Unclassified Pre-Amendment | Class III | Class I or II (reclassification) |
| Examples | Medicinal leeches, pulse oximeters, powered wheelchairs | Heart valves, breast implants, cochlear implants | AI diagnostic software, novel wearables |
Predicate Device History
The 510(k) pathway depends on a chain of predicate devices tracing back to legally marketed devices from before May 28, 1976 — the date the Medical Device Amendments were enacted.
Medical Device Amendments
Congress enacts the Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act. Devices marketed before this date are 'grandfathered' as legally marketed pre-amendments devices.
Medicinal Leeches Grandfathered
Medicinal leeches were in documented clinical use in the United States well before 1976 (and for centuries prior). This establishes them as legally marketed pre-amendments devices — the foundation of the predicate chain.
K040187 — Ricarimpex (First Modern Clearance)
Ricarimpex SAS submits the first 510(k) for medicinal leeches, citing the pre-amendments predicate. FDA clears the device on June 21, 2004, establishing modern cleared indications.
Siddall et al. — Species Reclassification
Molecular phylogenetic analysis by Siddall et al. (Proceedings of the Royal Society B) demonstrates that commercially supplied '<em>Hirudo medicinalis</em>' are actually <em>Hirudo verbana</em>. This does not affect clearance status but prompts updated labeling in subsequent submissions.
K132958 — Biopharm Leeches
Biopharm Leeches (UK) receives 510(k) clearance using K040187 as the predicate. First clearance to label the species as <em>Hirudo verbana</em>.
K140907 — Carolina Biological
Carolina Biological Supply receives 510(k) clearance, also citing K040187 as predicate and labeling species as H. verbana.
CBER Jurisdiction Transfer
Effective December 30, 2024, regulatory jurisdiction for medicinal leeches transfers from CDRH (Center for Devices and Radiological Health) to CBER (Center for Biologics Evaluation and Research) via Federal Register notice FR Doc. 2024-31266.
Product Classification & Codes
Medicinal leeches are classified under a specific FDA product code and regulation number:
Product Code
NRN
Leeches, Medicinal
Device Class
Unclassified Pre-Amendment
Pre-amendment device — unclassified through rulemaking; regulated through 510(k) premarket notification
CFR section
None (Pre-Amendment)
Pre-amendment unclassified devices have no device-specific CFR regulation. Regulated through the 510(k) premarket-notification pathway.
Review Panel
General & Plastic Surgery
FDA Product Classification database review-panel assignment for product code NRN.
Review Organization (current)
CBER
Center for Biologics Evaluation and Research (transferred from CDRH effective December 30, 2024)
Submission Type
510(k)
Premarket notification — substantial equivalence to predicate device
CBER Jurisdiction Transfer (2024)
On December 30, 2024, the FDA published Federal Register notice FR Doc. 2024-31266, transferring regulatory jurisdiction for medicinal leeches from CDRH (Center for Devices and Radiological Health) to CBER (Center for Biologics Evaluation and Research).
What It Means
- +Future 510(k) submissions and regulatory correspondence will be handled by CBER rather than CDRH
- +CBER typically oversees biological products (blood, vaccines, gene therapy) — the transfer reflects the biological nature of medicinal leeches
- +Administrative change in which FDA center handles oversight
- +Aligns leech regulation with other biological-origin therapeutic products
What It Does NOT Mean
- —Does NOT change the legal marketing status of any currently cleared device
- —Does NOT require new clinical trials or re-submission of existing 510(k) clearances
- —Does NOT change cleared indications or intended use
- —Does NOT affect clinicians' ability to use leeches (on-label or off-label)
- —Does NOT reclassify leeches from their Unclassified Pre-Amendment status to any other class
Off-Label Use Framework
The majority of clinical applications discussed on this website represent off-label use — conditions outside the two FDA-cleared indications. This is important to understand, but it does not make these uses illegal or inappropriate.
Off-label prescribing is legal: The FDA regulates device marketing claims, not the practice of medicine. Once a device is legally marketed, clinicians may use it for any condition they deem medically appropriate.
Off-label use is common: An estimated 20–30% of all prescriptions in the United States are for off-label indications. This figure is even higher in certain specialties (oncology, pediatrics, psychiatry).
Evidence varies by condition: Some off-label uses (e.g., osteoarthritis) have multiple RCTs supporting efficacy. Others (e.g., hypertension) have only preliminary or low-quality evidence.
Burden shifts to treating clinician: For off-label use, the prescribing clinician assumes additional responsibility for clinical justification, informed consent, and documentation.
Institutional policies may vary: Some hospitals have specific protocols for off-label device use, including ethics committee review, enhanced consent processes, and outcome tracking requirements.
Off-Label Conditions Covered on This Site
Off-LabelOsteoarthritis (knee, thumb base)
Off-LabelChronic venous insufficiency
Off-LabelHypertension
Off-LabelPain syndromes (low back pain, lateral epicondylitis, myofascial pain)
Off-LabelPost-thrombotic syndrome
Off-LabelNon-healing wounds (outside flap/graft context)
Off-LabelCardiovascular conditions
Off-LabelStroke rehabilitation
Off-LabelAll clinical specialty applications (cardiology, neurology, etc.)
Institutional Compliance Checklist
Hospitals and clinical facilities using medicinal leeches should verify compliance with the following requirements. This checklist covers both FDA-cleared and off-label use scenarios.
Supply Chain & Sourcing
- Leeches sourced from an FDA 510(k)-cleared supplier (K040187, K132958, or K140907)
- Supplier provides Certificate of Analysis or compliance documentation per batch
- Cold chain or appropriate shipping conditions maintained during transit
- Receiving inspection procedure in place (viability check, count verification)
- Backup supplier identified in case of primary supplier disruption
Single-Use & Biohazard Disposal
- Each leech used on only one patient — NEVER reused (FDA requirement)
- Post-use leeches euthanized per institutional protocol (typically 70% ethanol immersion)
- Disposed of as regulated medical waste (biohazard — bloodborne pathogen exposure)
- Sharps/biohazard containers available at point of use
- Waste disposal documentation maintained per state and federal regulations
Infection Control
- Prophylactic antibiotics ordered per institutional protocol (fluoroquinolone or TMP-SMX — NOT cephalosporins due to Aeromonas intrinsic resistance)
- Patient screened for antibiotic allergies before prophylaxis initiation
- Aeromonas infection monitoring protocol in place (wound surveillance for 7–14 days post-treatment)
- Culture and sensitivity testing ordered if signs of infection develop
- Staff trained on Aeromonas risk and resistance patterns
Informed Consent
- Procedure-specific informed consent obtained and documented
- For off-label use: consent explicitly states that the use is outside FDA-cleared indications
- Known risks discussed: bleeding (expected), infection (Aeromonas), allergic reaction, scarring
- Alternative treatments discussed and documented
- Patient provided written information about what to expect during and after treatment
Documentation & Quality
- Medical record documents: indication, number of leeches applied, application sites, duration, blood loss estimate
- Lot/batch number of leeches recorded in medical record (traceability)
- Prophylactic antibiotic name, dose, route, and duration documented
- Outcome documented: congestion relief, wound status, any complications
- Adverse events reported per institutional and FDA MedWatch requirements