HEMOSIL RECOMBIPLASTIN 2G

• K Number: K070005
• Device Name: HEMOSIL RECOMBIPLASTIN 2G
• Manufacturer: INSTRUMENTATION LABORATORY CO.
• Date Cleared: 2007-08-15 ( 224 days)
• Product Code: GJS , GIS
• Regulation Number: 864.7750
• Type: Traditional
• Panel: HE
• Reference & Predicate Devices: K043184

Intended Use

A high sensitivity thromboplastin reagent based on recombinant human tissue factor (RTF) for the quantitative in vitro diagnostic determination in human citrated plasma of Prothrombin Time (PT) on IL Coagulation and ELECTRA Systems and Fibrinogen on IL Coagulation Systems only. The product is used for the evaluation of the extrinsic coagulation pathway and the monitoring of Oral Anticoagulant Therapy (OAT).

Device Description

The RecombiPlasTin 2G reagent is formulated to be insensitive to therapeutic levels of heparin. In the PT test, the addition of the tissue thromboplastin (RecombiPlasTin 2G reagent) to the patient plasma in the presence of calcium ions initiates the activation of the extrinsic pathway. This results ultimately in the conversion of fibringen to fibrin, with formation of a solid gel. For the IL Coagulation Systems only, the Fibrinogen is quantitated (PT-based method) by relating the absorbance or light-scatter during clotting to a calibrator.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and supporting studies for the HemosIL RecombiPlasTin 2G device:

It is important to note that this document is a 510(k) Summary, which provides a high-level overview of the device and its performance data. It does not contain a formal table of "acceptance criteria" presented as specific numerical thresholds that must be met for success, but rather presents performance data and states that the device is "not materially different" from the predicate. The "acceptance criteria" are inferred from the reported performance outcomes that demonstrate substantial equivalence to the predicate.

Acceptance Criteria and Reported Device Performance

Inferred Acceptance Criteria: The primary acceptance criterion for this 510(k) appears to be demonstrating substantial equivalence to the predicate device (HemosIL RecombiPlasTin K043184) in terms of precision, method correlation, and expected values. For Daptomycin dose-response testing, specific performance specifications are provided.

Performance Metric	Inferred Acceptance Criteria	Reported Device Performance
Precision (PT - CV%)	Maintain low coefficient of variation (CV%) for within-run and total precision across normal, low abnormal, and high abnormal samples, comparable to the predicate. (Quantitative thresholds are not explicitly stated as "acceptance criteria" but are demonstrated by the predicate.)	ELECTRA: Normal 1.3% (within), 1.9% (total); Low Abnormal 1.2% (within), 2.6% (total); High Abnormal 1.3% (within), 3.4% (total).
ACL Family: Normal 0.6% (within), 1.5% (total); Low Abnormal 1.0% (within), 1.9% (total); High Abnormal 1.1% (within), 2.6% (total).
ACL Futura/Advance: Normal 1.1% (within), 1.9% (total); Low Abnormal 1.6% (within), 1.9% (total); High Abnormal 1.8% (within), 2.4% (total).
ACL TOP: Normal 0.8% (within), 2.2% (total); Low Abnormal 0.8% (within), 3.1% (total); High Abnormal 0.9% (within), 3.1% (total).
Precision (Fibrinogen - CV%)	Maintain low CV% for within-run and total precision across normal and low fibrinogen control samples, comparable to the predicate.	ACL Family: Normal 4.2% (within), 5.0% (total); Low Control 5.9% (within), 6.9% (total).
ACL Futura/Advance: Normal 3.0% (within), 3.1% (total); Low Control 3.7% (within), 4.5% (total).
ACL TOP: Normal 1.4% (within), 2.4% (total); Low Control 2.9% (within), 3.6% (total).
Method Comparison (Correlation)	High correlation (r-value close to 1) with the predicate device on various systems.	PT: r-values ranging from 0.9789 to 0.9934 (In-house) and 0.9887 to 0.9945 (Field Site) against the predicate.
Fibrinogen: r-values ranging from 0.9783 to 0.9969 (In-house) and 0.9832 to 0.9946 (Field Site) against the predicate.
Method Comparison (Slope/Intercept)	Slope close to 1 and intercept close to 0 when compared to the predicate, indicating minimal bias.	PT: Slopes ranging from 0.7637 to 0.8137 (In-house/Field Site). Intercepts ranging from 2.7138 to 4.0035.
Fibrinogen: Slopes ranging from 0.9350 to 1.0129 (In-house/Field Site). Intercepts ranging from -3.6298 to 10.933.
Expected Values (Normal Range)	Establish a normal range for PT and Fibrinogen, consistent with expected physiological values and comparable to the predicate (though the note states labs should establish their own).	PT (seconds): ELECTRA: 9.8 - 12.2 (N=130); ACL Family: 9.1 - 12.1 (N=130); ACL Futura/Advance: 9.9 - 12.9 (N=130); ACL TOP: 9.4 - 12.5 (N=130).
Fibrinogen (mg/dL): ACL Family: 308 - 613 (N=129); ACL Futura/Advance: 222 - 340 (N=129); ACL TOP: 276 - 471 (N=129).
CUBICIN Dose-Response (Normal PT)	Normal Sample: ± 1 second from unspiked sample.	Achieved: E.g., for ACL 6000, 100 µg/mL showed +0.4 sec change, 125 µg/mL showed +0.5 sec change. For ACL 10000, 100 µg/mL showed +0.7 sec change, 125 µg/mL showed +0.7 sec change. All reported changes were within the ±1 second specification.
CUBICIN Dose-Response (Coumadin PT)	Coumadin Sample: ± 10% recovery of the unspiked sample.	Achieved: E.g., for ACL 6000, 100 µg/mL showed 107% recovery, 125 µg/mL showed 110% recovery. For ACL 10000, 100 µg/mL showed 107% recovery, 125 µg/mL showed 110% recovery. All reported recoveries were within the ±10% specification (assuming "±10% recovery" implies a range of 90-110% or indicates that the value itself is 100±10, which matches the data). For example, 110% recovery is within the ±10% variation from the unspiked sample (100%).

Study Details

The provided document describes various analytical performance studies. It does not describe a clinical study in the typical sense for a medical device (e.g., involving human patients, multi-reader multi-case studies, or traditional test set/training set breakdowns for AI algorithms). This device is a reagent for an in vitro diagnostic (IVD) test, and the studies focus on laboratory performance characteristics.

1. Sample Size used for the test set and the data provenance:

   • Precision: Not explicitly stated, but typically involves multiple replicates of control plasmas. "Over multiple runs using three levels of control plasma for PT and two levels of control plasma for fibrinogen" suggests sufficient replicates to calculate CVs.
   • Method Comparison (In-house & Field Site): Not explicitly stated, but typically involves a sufficient number of patient samples (e.g., 50-100+) to establish correlation and agreement.
   • Expected Values (Normal Range):
     • PT: N = 130 per system (ELECTRA, ACL Family, ACL Futura/Advance, ACL TOP).
     • Fibrinogen: N = 129 per system (ACL Family, ACL Futura/Advance, ACL TOP).
   • CUBICIN Dose-Response Testing: Not explicitly stated how many individual "Normal Sample" or "Coumadin Sample" plasma units were used, but multiple concentrations of CUBICIN were tested on each system. Two types of samples (normal and coumadin plasma) were spiked.
   • Data Provenance: Not explicitly stated, but an "in-house" study and "two field site" studies are mentioned, implying a mix of internal lab data and potentially external lab data. Given it's a 510(k) for an IVD, the data would typically be derived from laboratory measurements, likely from the US or international sites where the manufacturer operates. The data is retrospective in the sense that the measurements were likely taken prior to the 510(k) submission as part of development and validation.

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

   • Not applicable. This is an IVD reagent, not an image-based or diagnostic device requiring expert interpretation for ground truth. The "ground truth" for these studies is the actual quantitative measurement of PT and Fibrinogen by the predicate device and the new device.

3. Adjudication method for the test set:

   • Not applicable. As described above, this is an IVD reagent and does not involve human interpretation or adjudication for ground truth.

4. 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:

   • No. This is not an AI-assisted diagnostic device, and therefore, an MRMC study is not relevant or performed.

5. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:

   • Yes, in a sense. The "device" here is the reagent itself, and its performance is evaluated in a standalone manner on automated coagulation analyzers (IL Coagulation and ELECTRA Systems) without a human "interpretation" in the loop beyond operating the instrument and ensuring quality control. The reported performance refers to the analytical performance of the combined reagent and instrument system.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

   • The "ground truth" in these studies is the quantitative analytical measurement provided by:
     • The predicate device (HemosIL RecombiPlasTin) for method comparison studies.
     • Reference materials/control plasmas with known target values for precision studies.
     • Healthy plasma samples for establishing normal ranges.
     • Spiked plasma samples (with CUBICIN) for dose-response testing where the known concentration of the drug and the baseline readings serve as the reference.

7. The sample size for the training set:

   • Not applicable. This is not a machine learning or AI device that requires a distinct "training set" in the context of algorithm development. The development and optimization of the reagent formulation itself would involve extensive R&D, but not a formally defined "training set" for an algorithm.

8. How the ground truth for the training set was established:

   • Not applicable, as there is no traditional "training set" for an algorithm in this context.

Regulation Number and Section

§ 864.7750 Prothrombin time test.

(a)
Identification. A prothrombin time test is a device used as a general screening procedure for the detection of possible clotting factor deficiencies in the extrinsic coagulation pathway, which involves the reaction between coagulation factors III and VII, and to monitor patients receiving coumarin therapy (the administration of one of the coumarin anticoagulants in the treatment of venous thrombosis or pulmonary embolism).(b)
Classification. Class II (performance standards).