← Product Code [CFN](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/CFN) · K120750 # HUMAN IGM CSF KIT (K120750) _The Binding Site Group , Ltd. · CFN · May 17, 2013 · Immunology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/CFN/K120750 ## Device Facts - **Applicant:** The Binding Site Group , Ltd. - **Product Code:** [CFN](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/CFN.md) - **Decision Date:** May 17, 2013 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.5510 - **Device Class:** Class 2 - **Review Panel:** Immunology ## Intended Use Human IgM CSF kit for use on SPAPLUS is intended for the quantitative measurement of human IgM in cerebrospinal fluid (CSF) samples using the SPAPLUS analyser. Measurement of this immunoglobulin aids in the assessment of the body's lack of ability to resist infectious disease in conjunction with other clinical and laboratory findings. ## Device Story The Human IgM CSF kit is an in vitro diagnostic reagent system designed for use on the SPAplus analyzer. It measures human IgM concentrations in cerebrospinal fluid (CSF) samples. The device utilizes immunoturbidimetric technology to quantify IgM levels. It is intended for use in clinical laboratory settings by trained personnel. The output is a quantitative IgM value, which healthcare providers use alongside other clinical and laboratory data to assess a patient's immune status and ability to resist infectious diseases. ## Clinical Evidence Bench testing only. Precision evaluated per CLSI EP05-A2 (n=84 for serum, 5-day study for CSF). Linearity evaluated per CLSI EP06-A (R2=0.99-1.00). Analytical sensitivity (LoD 0.0322 mg/L, LoQ 0.2463 mg/L) and specificity (no interference from hemoglobin, bilirubin, acetaminophen, or aspirin) established. Method comparison with predicate (n=58) yielded y=1.08x-0.02. ## Technological Characteristics Turbidimetric assay; sheep anti-human IgM antibody. Measuring range 0.3–7.0 mg/L (1/1 dilution) and 3.0–70.0 mg/L (1/10 dilution). Instrument: SPAPLUS analyzer. Calibration/controls traceable to ERM-DA470k. Reagent stability: 18 months closed, 2 months open, 30 days on-board at 8-12°C. ## Regulatory Identification An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. ## Predicate Devices - Siemens (Dade Behring) N Latex IgM (k032014) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} 1 # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY A. 510(k) Number: k120750 B. Purpose for Submission: New Device C. Measurand: Immunoglobulin M D. Type of Test: Turbidimetry, Quantitative E. Applicant: The Binding Site Group, Ltd. F. Proprietary and Established Names: Human IgM CSF Kit for use on $\mathrm{SPA}_{\mathrm{PLUS}}$ G. Regulatory Information: 1. Regulation section: 21 CFR§866.5510 – Immunoglobulins A, G, M, D, and E immunological test system 2. Classification: Class II 3. Product code: CFN, Method, Nephelometric, Immunoglobulins (G, A, M) 4. Panel: Immunology (82) {1} # H. Intended Use: 1. Intended use(s): Human IgM CSF Kit for use on $\mathrm{SPAPLUS}$ is intended for the quantitative measurement of human IgM in cerebrospinal fluid (CSF) samples using the $\mathrm{SPAPLUS}$ analyzer. Measurement of this immunoglobulin aids in the assessment of the body's lack of ability to resist infectious disease in conjunction with other clinical and laboratory findings. 2. Indication(s) for use: Same as Intended Use 3. Special conditions for use statement(s): Prescription use only 4. Special instrument requirements: $\mathrm{SPAPLUS}$ analyzer # I. Device Description: The kit contains the following materials: Human IgM CSF Reagent $\mathrm{SPAPLUS}$ (1 x 60 tests), Liquid Human IgM CSF $\mathrm{SPAPLUS}$ Calibrator set 1-6 (6 x 1.0 mL), Lyophilized IgM CSF $\mathrm{SPAPLUS}$ High Control (2 x 1.5 mL) and IgM Low Control (2 x 1.5 mL) IgM CSF Reaction Buffer $\mathrm{SPAPLUS}$ (1 x 60 tests) # J. Substantial Equivalence Information: 1. Predicate device name(s) and 510(K) number(s): Siemens (Dade Behring) N Latex IgM (k032014) 2. Comparison with predicate: | Similarities | | | | --- | --- | --- | | Item | Device Human IgM CSF Kit for Use on SPAPLUS | Predicate Siemens N Latex IgM | | Intended use | For the quantitative measurement of human IgM in cerebrospinal fluid | In vitro diagnostic reagents for the quantitative determination of IgM in | | | | in vivo | | Type of use | In vitro diagnostic reagents for the quantitative determination of IgM in cerebrospinal fluid | in vivo | {2} | Similarities | | | | --- | --- | --- | | Item | Device Human IgM CSF Kit for Use on SPA PLUS | Predicate Siemens N Latex IgM | | | (CSF) samples using the SPA PLUS analyzer. Measurement of this immunoglobulin aids in the assessment of the body's lack of ability to resist infectious disease in conjunction with other clinical and laboratory findings. | human cerebrospinal fluid (CSF) and in paired CSF/serum samples by means of particle-enhanced immunonephelometry using the BN* Systems. The determination of IgM aids in the evaluation of the patient's immune system. | | Analyte | Human IgM | Same | | Sample type | CSF | Same | | Reference range | <1.3 mg/L | Same | | Differences | | | | --- | --- | --- | | Item | Device Human IgM CSF Kit for Use on SPA PLUS | Predicate Siemens N Latex IgM | | Method | Turbidimetry | Nephelometry | | Instrument | SPA PLUS | BNII system | | Antibody | Sheep anti-human IgM | Rabbit anti-human IgM | | Measuring range | 0.3 – 7.0 mg/L (at 1/1 sample dilution) | 0.13 – 4.2 mg/L | | | 3.0 – 70.0 mg/L (at 1/10 sample dilution) | | | Stability | Open vial: 2 – 8°C for 2 months | Open vial: 2 – 8°C for 4 weeks | | | On-board: 30 days | On-board: N/A (should not be left open on a BNII system) | # K. Standard/Guidance Document Referenced (if applicable): CLSI guideline EP05-A2 "Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition". CLSI guideline EP06-A "Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline". {3} L. Test Principle: The determination of soluble antigen concentration by turbidimetric methods involves the reaction with specific antiserum to form insoluble complexes. When light is passed through the suspension formed a portion of the light is transmitted and focused onto a photodiode by an optical lens system. The amount of transmitted light is indirectly proportional to the specific protein concentration in the test samples. Concentrations are automatically calculated by reference to a calibration curve stored within the instrument. M. Performance Characteristics (if/when applicable): 1. Analytical performance: a. Precision/Reproducibility: For CSF samples, the precision was evaluated based on CLSI EP05-A2 by testing three pooled samples with low (0.524 mg/L), mid (1.258 mg/L), and high (6.291 mg/L) IgM concentrations. The study was done over 5 days with 2 runs per day; each sample was run in duplicate within each run. The results are summarized in the following table: | Sample | Mean Conc. (mg/L) | Within-Run | | Between-Run | | Between-Day | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | SD (mg/L) | CV % | SD (mg/L) | CV % | SD (mg/L) | CV % | SD (mg/L) | CV % | | Low | 0.524 | 0014 | 2.7 | 0.012 | 2.3 | 0.014 | 2.7 | 0.023 | 4.4 | | Mid | 1.258 | 0.008 | 0.7 | 0.015 | 1.2 | 0.014 | 1.1 | 0.022 | 1.7 | | High | 6.291 | 0.031 | 0.5 | 0.096 | 1.5 | 0.086 | 1.4 | 0.133 | 2.1 | To supplement the CSF precision data, three pooled sera samples with low, mid, and high IgG concentration were assayed in duplicate with 2 runs per day for 21 days $(n = 84)$ using three reagent lots and three instruments. Results are summarized below: | Mean Conc. (mg/L) | Within-Run | | Between-Run | | Between-Day | | Between-Lot | | Total | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | SD (mg/L) | CV % | SD (mg/L) | CV % | SD (mg/L) | CV % | SD (mg/L) | CV % | SD (mg/L) | CV % | | 0.450 | 0.02 | 3.9 | 0.01 | 2.5 | 0.04 | 9.5 | 0.05 | 10.4 | 0.05 | 10.6 | | 1.123 | 0.02 | 1.8 | 0.03 | 2.6 | 0.10 | 9.2 | 0.11 | 9.6 | 0.11 | 9.7 | | 5.175 | 0.11 | 2.2 | 0.09 | 1.8 | 0.39 | 7.6 | 0.41 | 8.0 | 0.42 | 8.1 | b. Linearity/assay reportable range: Linearity: The linearity study was conducted based on CLSI EP06-A by analysis of a dilution series of pooled CSF sample. Each dilution was tested in triplicate. The observed values were graphed against the expected values and linear regression was performed. The results are summarized in the following table. {4} | Sample range (mg/L) | Slope | Intercept | R2 | % Recovery | | --- | --- | --- | --- | --- | | 0.231 – 7.688 | 0.992 | -0.103 | 0.999 | 86.6 – 100 | | 0.221 – 7.378 | 0.994 | -0.046 | 0.999 | 81.8 – 108 | | 0.229 – 7.643 | 1.011 | 0.019 | 1.00 | 98.5 – 115.3 | The claimed measuring range of the assay is $0.3 - 7.0\mathrm{mg / L}$ (at 1/1 sample dilution). Antigen excess (hook effect): The susceptibility of the assay to antigen excess was investigated. The results demonstrated that the assay is not susceptible to antigen excess up to a concentration of $60\mathrm{mg / L}$ . c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceability: The calibrators, the internal reference standards (IR) and controls are traceable to reference standard ERM-DA470k. IR is used to control calibration between batches. The table below summarizes the target values for calibrators and controls: | | Target Value (mg/L) | | --- | --- | | Calibrator | | | Calibrator 1 | 0.300 | | Calibrator 2 | 0.600 | | Calibrator 3 | 1.200 | | Calibrator 4 | 2.400 | | Calibrator 5 | 4.700 | | Calibrator 6 | 7.000 | | Controls | | | High Control | 4.00 | | Low Control | 1.80 | # Stability: Closed vial stability: The real time stability of IgM CSF kit was performed using three batches of kits stored under the recommended temperature at $2 - 8^{\circ}\mathrm{C}$ . Data were collected at point 0, 6.5, 10, 13 and 19 months. The results support stability of the kits under the recommended storage of $2 - 8^{\circ}\mathrm{C}$ for 18 months. Open vial stability: The study was done to evaluate the reagent stability after first opening. Three batches of kits were stored at $2 - 8^{\circ}\mathrm{C}$ after first opening. Data were collected at 1, 2, and 3 months. The results support that the reagents are stable once opened for 2 months when stored at $2 - 8^{\circ}\mathrm{C}$ . On-board stability: On-board stability of IgM CSF was done by placing the kit in the {5} reagent carousel of the $\mathrm{SPA}_{\mathrm{PLUS}}$. The reagent carousel was covered and cooled to $8 - 12^{\circ}\mathrm{C}$. A calibration curve was generated on Day 0 and validated with the IgM CSF kit controls. The test data were collected at Day 0, Day 14, and Day 35. The results support that the reagents are stables up to 30 days on-board the $\mathrm{SPA}_{\mathrm{PLUS}}$. d. Detection limit: The limit of blank (LoB) for this assay was determined by testing instrument diluent. The limit of detection (LoD) was determined by testing CFS sample with low IgM concentration. Sixty (60) replicates of each sample were run, and the mean and standard deviation for each of the samples was calculated. $\mathrm{LoD} = \mathrm{LoB} + 1.645 \times \mathrm{SDs}$ where SDs is the standard deviation of the replicate samples. The LoQ was determined by testing the lowest calibrator fluid with assigned concentration at 0.293 mg/L. The results are summarized in the following table: | LoB | LoD | LoQ | | --- | --- | --- | | 0 mg/L | 0.0322 mg/L | 0.2463mg/L | e. Analytical specificity: **Endogenous interference:** Interference by endogenous substances was evaluated by using one CSF sample base pool at the medical decision point (1.3 mg/L) spiked with hemoglobin and bilirubin. The negative samples were prepared by spiking the same volume of commercially obtained blanks reagents into the CSF pool. The resulting samples were tested in triplicate and the mean values were used to calculate % interference. No significant interference was noted for sample containing hemoglobin at 2.5 g/L and bilirubin at 100 mg/L. **Drug interference:** Interference by drugs was evaluated by using one CSF sample base pool (at concentration of $1.3\mathrm{mg / L}$) spiked with acetaminophen and aspirin dissolved in distilled water. The negative samples were prepared by spiking the CSF pool with the same volume of distilled water. All samples were tested in triplicate and the mean values were used to calculate % interference. No significant interference was observed for sample containing acetaminophen at $200\mathrm{mg / L}$ and aspirin at $600\mathrm{mg / L}$. **Bacterial interference:** No bacterial interference study was performed. In the labeling, the following statement is added in section of Limitations of the package insert: "Bacterial interference has not been assessed. CSF samples should be as fresh as possible to limit bacterial growth and all samples must be centrifuged prior to testing (see section 7)". f. Assay cut-off: The cut-off is the same as the predicate and is defined as the upper limit of the {6} reference range (established from literature). The reference range for IgM in CSF is $< 1.3\mathrm{mg / L}$ ## 2. Comparison studies: a. Method comparison with predicate device: A method comparison study was performed to compare the IgM CSF kit on $\mathrm{SPA}_{\mathrm{PLUS}}$ (y) and the predicate device on BNII system (x) using CSF samples. Total 58 samples including 32 normal and 26 clinical CSF samples were tested. Samples covered the measuring range for both proposed and predicate devices. The comparison analysis showed the following equation (Passing/Bablok): | N= | Sample range (mg/L) | Comparison (Passing/Bablok) | | --- | --- | --- | | 58 | 0.32 – 4.05 | y =1.08x – 0.02 Slope (95% CI): 1.00 – 1.15 Intercept (95% CI): -0.07 – 0.04 | b. Matrix comparison: Not applicable, assay use CSF sample only ## 3. Clinical studies: a. Clinical Sensitivity: Not applicable b. Clinical specificity: Not applicable c. Other clinical supportive data (when a. and b. are not applicable): Not applicable ## 4. Clinical cut-off: See assay cut-off ## 5. Expected values/Reference range: The reference range for IgM in CSF is $< 1.3\mathrm{mg / L}$ according to the literature. It is strongly recommended that each facility should determine its own reference intervals. The reference values in the true sense only exist to the CSF/serum ratio. 7 {7} N. Proposed Labeling: The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. 8 --- **Source:** [https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/CFN/K120750](https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/CFN/K120750) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com