(56 days)
Immunoassay for the in vitro quantitative determination of human prolactin in human serum and plasma.
Sandwich principle. Total duration of assay: 18 minutes (37 °C).
• 1st incubation (9 min.): 10µL of sample, a biotinylated monoclonal prolactin- specific antibody (75 µL), and a monoclonal prolactin-specific antibody labeled with a ruthenium complex (75 µL)** react to form a sandwich complex.
•2nd incubation (9 min.): after addition of streptavidin-coated microparticles (40 µL), the complex becomes bound to the solid phase via interaction of biotin and streptavidin.
**Tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)2+3)
•The reaction mixture is aspirated into the measuring cell where the microparticles are magnetically captured onto the surface of the electrode. Unbound substances are then removed with ProCell. Application of a voltage to the electrode then induces chemiluminescent emission which is measured by a photomultiplier (0.4 second read frame).
•Results are determined via a calibration curve which is instrument specifically generated by 2-point calibration and a master curve provided via the reagent bar code.
The provided text describes the Elecsys® Prolactin Assay, an immunoassay for the quantitative determination of human prolactin. The document is a 510(k) premarket notification summary, aiming to establish substantial equivalence to a predicate device, the Enzymun® Prolactin Assay.
Here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a set of predefined thresholds that the device must meet for approval. Instead, it presents various performance characteristics and compares them to the predicate device. The implied acceptance is that the new device's performance is comparable to or better than the predicate.
Given the comparative nature, I will present the performance metrics shown for the new device (Elecsys® Prolactin Assay) and the predicate device (Enzymun® Prolactin Assay) for comparison. The "acceptance criteria" here is implicitly that the Elecsys® Prolactin Assay performs acceptably in these categories, and its performance is at least equivalent to the predicate.
| Feature | Implicit Acceptance Criterion (Compared to Predicate) | Elecsys® Prolactin Assay Performance | Enzymun-Test® Prolactin Assay Performance (Predicate) |
|---|---|---|---|
| Precision | Comparable or better CV% at different levels (Low, Mid, High) | Within-Run %CV: Low: 2.4%, Mid: 1.9%, High: 2.4%Total %CV: Low: 3.1%, Mid: 3.4%, High: 3.3% | Within-Run %CV: Low: 2.1%, Mid: 2.4%, High: 1.9%Total %CV: Low: 4.5%, Mid: 2.7%, High: 2.2% |
| Lower Detection Limit | Comparable to or lower than the predicate device | 10 µIU/mL | 27.56 µIU/mL |
| Linearity | Comparable range and deviation from linearity | 10-10,000 µIU/mL (with a deviation from a linear line of ±10%) | 27.56-6,360 mIU/mL (with a deviation from a linear line of ±10%) |
| Method Comparison (vs. Predicate) | Strong correlation (r value close to 1) and low SEE, reasonable slope and intercept | Least Squares: y = 1.14x - 33.36, r = 0.9986, SEE = 40.088, N = 99Passing/Bablok: y = 1.101x - 19.40, r = 0.9986, SEE = 9.001, N = 99 | Least Squares: y = 0.79x + 2.63, r = 0.996, SEE = 3.764, N = 76 (Note: This refers to the predicate's comparison, likely to another external method, not the Elecsys device). This entry seems to be separate from the Elecsys vs. Enzymun. |
| Interfering Substances | Demonstrate no interference at clinically relevant levels | Bilirubin: 25 mg/dLHemoglobin: 1 g/dLLipemia: 1500 mg/dLBiotin: 30 ng/mLRheumatoid Factor: 1700 µIU/mL (no interference shown for Elecsys, "no interference" for predicate) | Bilirubin: 64.5 mg/dLHemoglobin: 1 mg/dLLipemia: 1250 mg/dLBiotin: 100 ng/mLRheumatoid Factor: no interference |
| Specificity (Cross-reactivity) | Demonstrate minimal or no cross-reactivity with related hormones | HGH, HPL, HCG, TSH, FSH, LH: 0.00% cross-reactivity at tested levels | HGH, HPL, HCG, TSH, FSH, LH: 0.00% cross-reactivity at tested levels |
| Calibration Stability | Acceptable stability for routine lab use | A calibration is recommended every 7 days if kit is not consumed; 4 weeks with same reagent lot if reagent is consumed within 7 days. | Full calibration required every 2 weeks. One-point calibration required every run. |
2. Sample Size Used for the Test Set and the Data Provenance
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Precision Test Set (N):
- Elecsys® Prolactin Assay: 60 samples at each level (Low, Mid, High), totaling 180 measurements for precision.
- Enzymun® Prolactin Assay (Predicate): 119 samples at Low and Mid levels, 120 at High level, totaling 358 measurements for precision.
-
Method Comparison Test Set (N):
- Elecsys® Prolactin Assay vs. Enzymun-Test® Prolactin: 99 samples (for both Least Squares and Passing/Bablok).
-
Interfering Substances & Specificity: The sample sizes for these tests are not explicitly stated as 'N' values for each substance but rather as the tested levels at which no interference or cross-reactivity was observed. These are likely conducted using controlled spiked samples rather than a large clinical cohort.
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Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given the nature of these in-vitro diagnostic studies, they are typically prospective laboratory-based studies using controlled samples and clinical specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This type of in-vitro diagnostic device (immunoassay) does not typically rely on human expert review (e.g., radiologists, pathologists) to establish "ground truth" in the same way an imaging AI device would.
- Ground Truth Determination: For assays like this, the "ground truth" for method comparison and performance evaluation is generally the results from a well-established, validated reference method (like the predicate device in this case, or a recognized gold standard). Precision, linearity, and interference are evaluated based on analytical measurements against known values (e.g., spiked samples, reference materials).
- Experts: While laboratory experts (e.g., clinical chemists, medical technologists) are involved in performing and validating such tests, they are not "establishing ground truth" through their interpretation in the context of this summary. Their role is to execute the assays and interpret the analytical data according to established protocols.
4. Adjudication Method for the Test Set
Not applicable for this type of device. Adjudication methods (like 2+1, 3+1) are common in scenarios where human interpretation (e.g., reading medical images) contributes to establishing a ground truth that might be subjective or require consensus. For an immunoassay, the results are quantitative measurements, and the "truth" is either the chemical standard or the result from a validated reference method.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance
Not applicable.
- This device is an automated in-vitro diagnostic assay. It does not involve "human readers" interpreting output in the same way an imaging AI would.
- There is no "AI assistance" component in the context of human interpretation for this device. The device provides a quantitative measurement.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the performance characteristics presented (precision, linearity, detection limit, method comparison, interference, specificity) are inherently standalone performance of the Elecsys® Prolactin Assay system (reagents plus instrument). It operates as an automated system producing quantitative results without human interpretive input for the measurement itself. Human-in-the-loop aspects would involve a clinician interpreting the result in the context of a patient's overall health, but not in the measurement process itself.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for this device's evaluation primarily relies on:
- Analytical Standards/Reference Materials: For parameters like precision, linearity, and detection limit, the "ground truth" is based on the known concentrations of prolactin in control samples or reference materials.
- Reference Method (Predicate Device): For method comparison, the results from the predicate Enzymun-Test® Prolactin Assay serve as a reference ("ground truth") to demonstrate comparable performance.
- Spiked Samples: For interference and specificity studies, the "ground truth" involves known concentrations of interfering substances or related hormones added to samples, and results are checked against expected prolactin values.
8. The Sample Size for the Training Set
The document does not explicitly mention "training set" or "validation set" in the context of machine learning, because this is not an AI/ML device. The described assays are chemical/immunological systems.
However, if we interpret "training set" as the data used to initially develop, optimize reagents, and establish preliminary assay parameters, that information is not provided in this 510(k) summary. These summaries typically focus on the final validation studies.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as this is not an AI/ML device with a "training set" that requires ground truth establishment in the described manner. The "ground truth" for the development and optimization of such assays would involve rigorous analytical chemistry techniques, established reference methods, and internal validation steps guided by scientific principles and regulatory requirements for in-vitro diagnostics.
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| 510(k) Summary | |
|---|---|
| Introduction | According to the requirements of 21 CFR 807.92, the following informationprovides sufficient detail to understand the basis for a determination ofsubstantial equivalence. |
| 1.Submittername,address,contact | Boehringer Mannheim Corporation2400 Bisso LaneP.O. Box 4117Concord, CA 94524-4117(510) 674 - 0690 extension 8415FAX 510 687 - 1850 |
| Contact Person: Mary KoningDate Prepared: November 21, 1996 | |
| 2.Device name | Proprietary name: Elecsys® Prolactin AssayCommon name: Electrochemiluminescence assay for the determination ofprolactin.Classification name: System, Test, Prolactin |
| 3.Predicatedevice | We claim substantial equivalence to the Enzymun® Prolactin Assay(K900695). |
| 4.DeviceDescription | Sandwich principle. Total duration of assay: 18 minutes (37 °C).• 1st incubation (9 min.): 10µL of sample, a biotinylated monoclonal prolactin-specific antibody (75 µL), and a monoclonal prolactin-specific antibodylabeled with a ruthenium complex (75 µL)** react to form a sandwichcomplex.•2nd incubation (9 min.): after addition of streptavidin-coated microparticles(40 µL), the complex becomes bound to the solid phase via interaction ofbiotin and streptavidin.**Tris(2,2'-bipyridyl)ruthenium(II) complex (Ru(bpy)2+3) |
| 4.DeviceDescription | •The reaction mixture is aspirated into the measuring cell where themicroparticles are magnetically captured onto the surface of the electrode.Unbound substances are then removed with ProCell. Application of a voltageto the electrode then induces chemiluminescent emission which is measuredby a photomultiplier (0.4 second read frame).•Results are determined via a calibration curve which is instrumentspecifically generated by 2-point calibration and a master curve provided viathe reagent bar code. |
| 5.Intended use | Immunoassay for the in vitro quantitative determination of human prolactin inhuman serum and plasma. |
| 6.Comparisonto predicatedevice | The Boehringer Mannheim Elecsys® Prolactin Assay is substantiallyequivalent to other products in commercial distribution intended for similaruse. Most notably it is substantially equivalent to the currently marketedEnzymun® Prolactin Assay (K900695).The following table compares the Elecsys® Prolactin Assay with thepredicate device, Enzymun® Prolactin Assay. Specific data on theperformance of the test have been incorporated into the draft labeling inattachment 5. Labeling for the predicate device in provided in attachment 6.Similarities:•Intended Use: Immunoassay for the in vitro quantitative determinationof prolactin•Sample type: Serum and plasma•Antibody: Same pair of mouse monoclonal prolactin antibodies•Solid phase binding principle: Streptavidin/Biotin•Assay standardization: World Health Organization Standard (WHO)#84/500 |
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Differences:
Comparison
to predicate device cont.
| Feature | Elecsys® Prolactin | Enzymun-Test® Prolactin |
|---|---|---|
| Detection method | Electrochemiluminescence | ELISA/1-step sandwichassay |
| Instrument required | Elecsys® 2010 | ES 300 |
| Calibration Stability | A calibration isrecommended every 7days if kit is notconsumed; 4 weeks withsame reagent lot if reagentis consumed within 7days. | Full calibration requiredevery 2 weeks. One-pointcalibration required everyrun. |
Performance Characteristics:
| Feature | Elecsys® Prolactin | Enzymun-Test® Prolactin | ||||
|---|---|---|---|---|---|---|
| Precision | Modified NCCLS (µIU/mL): | Modified NCCLS (µIU/mL): | ||||
| Level | Low | Mid | High | Low | Mid | High |
| N | 60 | 60 | 60 | 119 | 119 | 120 |
| Within-Run: Mean | 229.8 | 1843.5 | 4662.1 | 10.1 | 28.3 | 63.0 |
| % CV | 2.4 | 1.9 | 2.4 | 2.1 | 2.4 | 1.9 |
| Total: Mean | 229.8 | 1843.5 | 4662.1 | 10.1 | 28.3 | 63.0 |
| % CV | 3.1 | 3.4 | 3.3 | 4.5 | 2.7 | 2.2 |
| Lower DetectionLimit | 10 µIU/mL | 27.56 µIU/mL |
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Performance Characteristics:
Comparison
to predicate device, (cont.)
| Feature | Elecsys® Prolactin | Enzymun-Test® Prolactin |
|---|---|---|
| Linearity | 10-10,000 µIU/mL (with adeviation from a linear line of±10%) | 27.56-6,360 mIU/mL (with adeviation from a linear line of±10%) |
| MethodComparison | Vs Enzymun-Test® ProlactinLeast Squares$y = 1.14x - 33.36$$r = 0.9986$$SEE = 40.088$$N = 99$Passing/Bablok$y = 1.101x - 19.40$$r = 0.9986$$SEE = 9.001$$N = 99$ | Vs Enzymun-Test® ProlactinLeast Squares$y = 0.79x + 2.63$$r = 0.996$$SEE = 3.764$$N = 76$ |
| Interferingsubstances | No interference at: | No interference at: |
| Bilirubin | 25 mg/dL | 64.5 mg/dL |
| Hemoglobin | 1 g/dL | 1 mg/dL |
| Lipemia | 1500 mg/dL | 1250 mg/dL |
| Biotin | 30 ng/mL | 100 ng/mL |
| RheumatoidFactor | 1700 µIU/mL | no interference |
| Specificity | Level tested | % Cross-reactivity |
| Level tested | % Cross-reactivity | |
| HGH | 200 mU/mL | 0.00 |
| HPL | 100 ng/mL | 0.00 |
| HCG | 1000 IU/mL | 0.00 |
| TSH | 500 µIU/mL | 0.00 |
| FSH | 2 IU/mL | 0.00 |
| LH | 1 IU/mL | 0.00 |
| HGH | 2 mU/mL | 0.00 |
| HPL | 100 ng/mL | 0.00 |
| HCG | 625 IU/mL | 0.00 |
| TSH | 50 µIU/mL | 0.00 |
| FSH | 38 IU/mL | 0.00 |
| LH | 12.5 IU/mL | 0.00 |
§ 862.1625 Prolactin (lactogen) test system.
(a)
Identification. A prolactin (lactogen) test system is a device intended to measure the anterior pituitary polypeptide hormone prolactin in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of disorders of the anterior pituitary gland or of the hypothalamus portion of the brain.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.