K Number
K113349

Validate with FDA (Live)

Date Cleared
2012-07-11

(240 days)

Product Code
Regulation Number
866.5240
Reference & Predicate Devices
N/A
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

Human CH50 reagent pack for use on the SPA plus. These reagents are intended for the quantification of total classical complement activity (CH50) in human serum on the Binding Site SPAPLUS analyser. Measurement of complement activity aids in the diagnosis of immunological disorders, especially those associated with deficiencies of complement components. The test results are to be used in conjunction with clinical findings and other laboratory tests. Human CH50 calibrator set for use on the SPA plus The Human CH50 calibrator set is intended for use on the SPAPLUS in conjunction with the Binding Site Human CH50 reagent pack (product code: NK095.S) for the determination of total complement activity. Human CH50 controls for use on the SPA plus. The Human CH50 controls are intended for use in conjunction with the Binding Site Human CH50 reagent pack for use on the SPAPLUS (product code: NK095.S).

Device Description

Not Found

AI/ML Overview

This looks like a 510(k) clearance letter for an in vitro diagnostic (IVD) device, not a typical AI/ML-driven medical device. Therefore, many of the requested elements (like sample sizes for test sets, number of experts, adjudication methods, MRMC studies, standalone performance, training set details) are not directly applicable in the same way they would be for an AI algorithm that processes images or other complex data.

However, I can extract the acceptance criteria and performance information as typically presented in IVD submissions, focusing on analytical performance rather than diagnostic accuracy determined by human experts.

Here's the breakdown based on the provided text, interpreting "acceptance criteria" as the performance specifications and "reported device performance" as the results confirming those specifications:

1. Table of Acceptance Criteria and Reported Device Performance

The provided document (a 510(k) clearance letter and Indications for Use) does not contain the detailed acceptance criteria or the study results. This information is typically found in the 510(k) submission itself, often in sections detailing analytical performance studies (e.g., precision, accuracy, linearity, interfering substances). The clearance letter only confirms that the FDA reviewed the information and found the device substantially equivalent.

To illustrate what such a table would look like for an IVD, and as an example if this information were available in the submission, here's a hypothetical structure:

Performance CharacteristicAcceptance Criteria (Hypothetical)Reported Device Performance (Hypothetical)
Precision (Within-Run CV)≤ 5%Sample A: 2.5%, Sample B: 3.1%
Precision (Total CV)≤ 8%Sample A: 4.8%, Sample B: 5.9%
Accuracy (Bias vs. Reference)Mean Bias ≤ 10%Mean Bias: 3.7%
Linearity (R-squared)> 0.980.995
Interfering SubstancesNo significant interference (≤ 10% change) for common interferents at specified concentrations.Met for hemoglobin, bilirubin, triglycerides (details would be in submission).
Detection LimitUndisclosed range, but sufficient for clinical utility.5 CH50 U/mL (for example)
Range (Analytical Measurement Range)10 to 100 CH50 U/mL10 to 100 CH50 U/mL (confirmed)
SpecificityNo cross-reactivity with indicated substances (e.g., C-reactive protein, other complement components)Confirmed lack of significant cross-reactivity.

2. Sample Size Used for the Test Set and Data Provenance

This information is not provided in the clearance letter or the Indications for Use. For an IVD like this, "test set" would refer to the clinical samples used for analytical verification and validation studies.

  • Sample Size: Unknown from this document. IVD studies typically use a range of samples for different studies (e.g., dozens for precision, hundreds for accuracy, specific spiked samples for interference).
  • Data Provenance: Unknown from this document. Such studies often use samples collected from various clinical sites, and the country of origin would be part of the detailed study reports within the 510(k) submission. They are typically prospective or retrospective clinical samples, chosen to represent the target patient population.

3. Number of Experts Used to Establish Ground Truth and Qualifications

This specific type of "expert ground truth" as it applies to AI/ML algorithms (e.g., radiologists interpreting images) is not applicable here. For an IVD measuring a biomarker like CH50, the "ground truth" is established through:

  • Reference Methods: Comparing the device's results to a recognized, often more laborious or expensive, reference method for CH50 measurement.
  • Certified Reference Materials: Using materials with known, assigned CH50 values.
  • Clinical Outcomes/Pathology (indirectly): While CH50 levels are used in the diagnosis of immunological disorders, the "ground truth" for the device's measurement itself is analytical accuracy, not a clinical diagnosis established by interpreting the results alone.

4. Adjudication Method for the Test Set

Not Applicable in the context of expert adjudication for an IVD measuring a specific analyte. Adjudication applies to subjective interpretations, not quantitative measurements compared to a reference.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

Not Applicable. MRMC studies are used for evaluating human reader performance, often with imaging devices, and are not relevant for a quantitative in vitro diagnostic like a CH50 reagent pack.

6. Standalone Performance

Yes, in a way. An IVD device's performance is its standalone performance. The studies performed to support this 510(k) would have demonstrated the analytical performance of the "Human CH50 reagent pack for use on the SPAPLUS" system as a whole, without human interpretation of raw data (other than running the instrument and interpreting the quantitative result displayed).

7. Type of Ground Truth Used

The ground truth for an IVD measuring a specific analyte like CH50 would typically be established by:

  • Reference Methods: Comparison against established, often gold-standard, laboratory methods for CH50 (e.g., standard hemolytic assays).
  • Calibrators and Controls: Using materials with precisely assigned values, traceable to international standards if available.
  • Spiked Samples: Samples engineered with known concentrations of the analyte to test linearity and recovery.

8. Sample Size for the Training Set

Not Applicable. This is an IVD reagent and calibrator/control set, not an AI/ML algorithm that requires a "training set" in the computational sense. The "training" for such a system involves the chemical and biological formulation of reagents, optimization of the analytical method, and instrument calibration, not machine learning model training.

9. How the Ground Truth for the Training Set was Established

Not Applicable for an IVD reagent system. The concept of "ground truth for a training set" specifically applies to machine learning algorithms.

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an abstract symbol resembling a stylized human figure or bird in flight, composed of flowing lines.

10903 New Hampshire Avenue Silver Spring, MD 20993

The Binding Site Group, Ltd. c/o Ms. Marianne Sender, Regulatory Affairs 8 Calthorpe Rd, Edgbaston Birmingham, B15 1QT United Kingdom

JUL 1 1 2012

Re: K113349

Trade/Device Name: Human CH50 reagent pack for use on the SPAPLUS Human CH50 calibrator set for use on the SPAPLUS Human CH50 controls for use on the SPAPLUS Regulation Number: 21 CFR §866.5240

Regulation Name: Complement components immunological test system Regulatory Class: Class II Product Code: DAE, JIX, JJY Dated: July 6, 2012 Received: July 11, 2012

Dear Ms. Sender:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must or any I outhal the Act's requirements, including, but not limited to: registration and listing (21

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Page 2 - Ms. Marianne Sender

CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

ia m chan

Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Devices Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K113349

Human CH50 reagent pack for use on the SPA pLus Device Name: Human CH50 calibrator set for use on the SPA plus Human CH50 controls for use on the SPA plus

Indications For Use:

Human CH50 reagent pack for use on the SPA plus.

These reagents are intended for the quantification of total classical complement activity (CH50) in human serum on the Binding Site SPAPLUS analyser. Measurement of complement activity aids in the diagnosis of immunological disorders, especially those associated with deficiencies of complement components. The test results are to be used in conjunction with clinical findings and other laboratory tests.

Human CH50 calibrator set for use on the SPA plus

The Human CH50 calibrator set is intended for use on the SPAPLUS in conjunction with the Binding Site Human CH50 reagent pack (product code: NK095.S) for the determination of total complement activity.

Human CH50 controls for use on the SPA plus.

The Human CH50 controls are intended for use in conjunction with the Binding Site Human CH50 reagent pack for use on the SPAPLUS (product code: NK095.S).

× Prescription Use (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510K K113349

§ 866.5240 Complement components immunological test system.

(a)
Identification. A complement components immunological test system is a device that consists of the reagents used to measure by immunochemical techniques complement components C1q , C1r , C1s , C2 , C3 , C4 , C5 , C6 , C7 , C8 , and C9 , in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these proteins aids in the diagnosis of immunologic disorders, especially those associated with deficiencies of complement components.(b)
Classification. Class II (performance standards).