Evidence · idea-020

FDA (US Food and Drug Administration) De Novo (De Novo classification request) request DEN220027 (an FDA De Novo decision number), for the B·R·A·H·M·S sFlt-1/PlGF KRYPTOR Test System submitted by BRAHMS GmbH (part of Thermo Fisher Scientific), was granted and classified the device under 21 CFR (Title 21 of the Code of Federal Regulations) 862.1602, "Prognostic test for development or progression of preeclampsia," Class II (FDA device class II), product code QWH.

The labeled indication of the DEN220027 device is limited to women with singleton pregnancies between 23 weeks 0 days and 34 weeks 6 days of gestation who are hospitalized for hypertensive disorders of pregnancy (preeclampsia, chronic hypertension with or without superimposed preeclampsia, or gestational hypertension), as an aid in risk assessment for progression to preeclampsia with severe features within two weeks.

Roche's Elecsys sFlt-1/PlGF ratio assay received FDA 510(k) (premarket notification) clearance in 2025 for a preeclampsia-prognosis indication, meaning at least one assay has already reached this device type by 510(k) behind the De Novo. The Generator did not identify the K-number.

No FDA-cleared point-of-care or whole-blood sFlt-1/PlGF test, and no FDA-cleared point-of-care PlGF-only test, was identified by the Generator's web search; the Quidel Triage PlGF Test (a point-of-care PlGF assay marketed outside the US) is stated on the manufacturer's site not to be available for sale in the US.

The PRAECIS study (Thadhani R, et al., "Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy," NEJM Evidence 2022;1, EVIDoa2200161, DOI 10.1056/EVIDoa2200161) enrolled 1014 hospitalized hypertensive pregnant women at 18 US hospitals between 23 and 35 weeks, and reported that an sFlt-1/PlGF ratio of 40 or greater had sensitivity 81%, specificity 81%, positive predictive value 66% and negative predictive value 90% for progression to preeclampsia with severe features within two weeks.

The PROGNOSIS study (Zeisler H, et al., "Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia," N Engl J Med 2016, DOI 10.1056/NEJMoa1414838) reported that a ratio of 38 or lower ruled out preeclampsia within one week with a negative predictive value of about 99%.

A 510(k) for a new platform measuring the same analytes under 21 CFR 862.1602, with the predicate's indication unchanged, would be expected to require analytical performance data and a method-comparison and clinical-cutoff agreement study against a cleared predicate, rather than a new clinical outcome study. The Generator did not read the special controls of 21 CFR 862.1602 and does not know what they require.

Operation by nursing or other trained personnel on the obstetric unit would require the device to be categorized under CLIA (Clinical Laboratory Improvement Amendments) and the testing site to hold a certificate matching that categorization; the Generator expects a moderate-complexity categorization at launch and treats a CLIA waiver as a separate, later application requiring its own study.

CPT (Current Procedural Terminology) PLA code 0524U describes an obstetric (preeclampsia) sFlt-1/PlGF ratio immunoassay on serum or plasma reported as a risk assessment; PLA codes are assigned to a specific named test, and whether a new manufacturer's test could report under 0524U or would need its own code is not established.

CPT PLA code 0243U describes an obstetric (preeclampsia) placental growth factor time-resolved fluorescence immunoassay on maternal serum with a predictive algorithm reported as a risk score; it is a different test (a PlGF-based risk-score algorithm), not a code for the sFlt-1/PlGF ratio in this indication.

Laboratory tests performed on hospital inpatients are paid within the facility's inpatient DRG-based payment and are not separately payable, under Medicare's inpatient prospective payment system and, the Generator believes, under most state Medicaid inpatient payment methods; a test used only in this device's hospitalized indication therefore has no separate per-test payment.

TAM (total addressable market) component 1 of 4, birth volume and payer mix: NCHS "Births: Final Data for 2023" (National Vital Statistics Reports vol. 74 no. 1, March 2025; PMID 40961109) reports 3,596,017 US births in 2023, with Medicaid the source of payment for 41.5% of births.

TAM component 2 of 4, clinical fraction: US hypertensive disorders of pregnancy rose from 2.79% of deliveries in 1989 to 8.22% in 2020 (reported in "Trends in Hypertensive Disorders of Pregnancy in the United States From 1989 to 2020," PMID 35849460), with other CDC-cited estimates for 2019 ranging from 10.1% (birth certificates) to 15.9% (hospital discharge records). The Generator asserts no single figure; the spread is itself a finding about source dependence.

TAM component 3 of 4, the in-indication subset: the fraction of pregnancies with a hypertensive disorder that are hospitalized for it between 23+0 and 34+6 weeks with a singleton pregnancy is not known to the Generator; no figure is asserted.

TAM component 4 of 4, price per test: no price per cartridge is asserted. The Generator assumes the hospital's reference point would be its current reference-laboratory send-out cost for the same test, which was not looked up.

Addressable share: the Generator assumes the addressable market is the subset of US hospitals with obstetric units that do not run a cleared sFlt-1/PlGF assay on an in-house analyzer; no count or share is asserted and no primary research supports one.

Obstetric units at US hospitals number in the low thousands; American Hospital Association survey data or the CDC Levels of Care Assessment Tool would give a count, and the Generator extracted none.

Reference laboratories list the sFlt-1/PlGF ratio as an orderable test, including ARUP Laboratories (test 3017909, "Preeclampsia Risk Assessment (sFlt-1/PlGF Ratio)") and Mayo Clinic Laboratories (test code PERA).

Assumption, not a fact: at hospitals that currently send this test out, the result returns too late to inform decisions taken during the triage or early-admission episode (admission versus discharge, transfer to a higher level of care, antenatal corticosteroid timing), so that an on-unit result would change management.

Assumption, not a fact: hospital laboratory directors would approve, and obstetric nursing staff would perform, a moderate-complexity point-of-care immunoassay on the labor-and-delivery unit, including the quality-control and competency obligations that come with it.

FTO (freedom to operate), named family 1: US patent US10302657B2, "Dynamic of sFlt-1 or endoglin/PlGF ratio as an indicator for imminent preeclampsia and/or HELLP syndrome," was identified on Google Patents in a search for sFlt-1/PlGF preeclampsia patents. The Generator did not determine its assignee (believed to be Roche, unconfirmed), claims, legal status or expiry, or whether its claims read on a single-timepoint ratio as used in this intended use.

FTO, named family 2: US patent 10,357,469, "Diagnostic assay and treatment for preeclampsia," was identified in a USPTO (United States Patent and Trademark Office) full-text link returned by a web search. The Generator did not determine its assignee, claims, legal status or expiry.

FTO, earliest art and field coverage: foundational patent families on measuring sFlt-1 and PlGF to diagnose or predict preeclampsia, associated with Beth Israel Deaconess Medical Center (co-inventor S. Ananth Karumanchi), exist; a Spanish family member ES2440651T3 ("Method to diagnose preeclampsia") was seen, but no US family member number was identified. The Generator believes the earliest of these families date from the early 2000s and may have expired, and has not checked. Beyond the numbers in this and the two preceding claims, no patent search was performed; the FTO field for point-of-care cartridge immunoassays, on-cartridge plasma separation and ratio reporting is otherwise unexamined.

Mechanism and analytical-risk reasoning (Generator's own, flagged as reasoning rather than finding): because PlGF is low in the patients the test is meant to flag, the ratio's error is dominated by imprecision at low PlGF concentrations, so a whole-blood cartridge must match central-laboratory precision near its lower limit of quantitation or it will misclassify around the cutoff; named failure modes are low-end PlGF imprecision, hematocrit and hemolysis effects on plasma separation, lot-to-lot cutoff drift, and non-commutability with the predicate's calibration. None has been characterized because the device does not exist.

No device of this candidate's design exists as a prototype, and no analytical or clinical data exist for it; every performance property attributed to it in this file is design intent.

Assumption, not a fact: a hospital would buy a reader and cartridges for this indication on its own operating economics (length of stay, avoided transfers or readmissions) in the absence of a separately payable per-test fee.

Competitive position: the two cleared incumbents in this device type are central-laboratory assays from Thermo Fisher (BRAHMS KRYPTOR) and Roche (Elecsys); the Generator identified no company pursuing a US point-of-care sFlt-1/PlGF test, which is a web-search absence and not evidence of an empty field.

Neither open macro-trend seed was relied on: this device contains no machine-learning function, and its payers in this indication are predominantly Medicaid and commercial plans rather than Medicare.

No domain dossier exists in this repo for preeclampsia or hypertensive disorders of pregnancy: the knowledge-base/domains directory as of 2026-09-28 holds README.md, _template.md and twelve dossiers on other clinical areas.