← Product Code [OSK](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/OSK) · K100017 # EUROIMMUN HIPPOCAMPUS/CEREBELLUM/GLUTAMATE RECEPTOR/IFA BIOCHIP MOSAIC TEST SYSTEM (K100017) _Euroimmun Us, Inc. · OSK · Sep 13, 2010 · Immunology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/OSK/K100017 ## Device Facts - **Applicant:** Euroimmun Us, Inc. - **Product Code:** [OSK](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/OSK.md) - **Decision Date:** Sep 13, 2010 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.5660 - **Device Class:** Class 2 - **Review Panel:** Immunology ## Intended Use The EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA is intended for the qualitative determination of autoantibodies against glutamate receptor (type NMDA) in human serum. It is used as an aid in the diagnosis of anti-glutamate receptor (type NMDA) autoimmune encephalitis in conjunction with other laboratory and clinical findings. ## Device Story The EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA is an indirect immunofluorescence assay (IFA) used in clinical laboratories. The device utilizes BIOCHIP slides coated with NMDA receptor-transfected cells and non-transfected control cells. Patient serum is incubated on the slides; if autoantibodies are present, they bind to the NMDA receptors. A fluorescein-labelled anti-human IgG conjugate is then applied. After washing, the slides are examined using a fluorescence microscope. The presence of fluorescence indicates the presence of anti-NMDA receptor antibodies. The test is performed by laboratory personnel to assist clinicians in diagnosing autoimmune encephalitis. The TITERPLANE technique is used to standardize the immunological analysis by allowing simultaneous reactions in a reagent tray, eliminating the need for a humidity chamber. The output is a qualitative determination of antibody presence, which clinicians use alongside other laboratory and clinical findings to support a diagnosis. ## Clinical Evidence Clinical performance evaluated across four studies (n=183 total). Combined sensitivity 98.1% (51/52 positive) and specificity 100% (131/131 negative) in cohorts of patients with anti-NMDA receptor encephalitis, other encephalopathies, and healthy donors. Study 2 screened 2,990 patients with encephalitis of unknown origin, identifying 5/6 positive cases. Analytical precision showed variation within ±1 intensity level unit. ## Technological Characteristics Semi-quantitative IFA using BIOCHIP TITERPLANE technology. Substrates include NMDA receptor-transfected and non-transfected cells. Reagents include fluorescein-labelled anti-human IgG, PBS-Tween, and embedding medium. Requires fluorescence microscope for visualization. Standardized reaction tray system (TITERPLANE) used for incubation. No automated software algorithm; manual visual interpretation of fluorescence. ## Regulatory Identification A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies). ## Predicate Devices - EUROIMMUN ANCA IFA Granulocyte BIOCHIP Mosaic™ Test System (k083850) ## 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}------------------------------------------------ # EUROIMMUN US INC. Image /page/0/Picture/1 description: The image shows the text 'K100017' written in black ink. The text is positioned above a black graphic consisting of two horizontal lines with four black circles placed between them. The circles are evenly spaced along the lines, creating a visual pattern. ## PREMARKET NOTIFICATION 510(K) SAFETY AND EFFECTIVENESS SUMMARY (as required by 21 CFR § 807.92) - A. 510(k)Number: K010017 - Purpose for Submission: B. - New device C. Measurand: - Autoantibodies against glutamate receptor (type NMDA) - D. Type of Test: - Semi-quantitative indirect immunofluorescent antibody assay - E. Applicant: - EUROIMMUN US INC. - Proprietary and Established Names: E. EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA - G. Regulatory Information: - 1. Requlation: - 21 CFR 866.5660 Multiple autoantibodies immunological test system - 2. Classification: Class II - 3. Product code: ેટાર - 4. Panel: Immunology #### H. Intended Use: - Intended use(s): 1. The EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA is intended for the qualitative determination of autoantibodies against glutamate receptor (type NMDA) in human serum. It is used as an aid in the diagnosis of anti-glutamate receptor (type NMDA) autoimmune encephalitis in conjunction with other laboratory and clinical findings. - 2. Indication(s) for use: Same as intended use. - Special conditions for the use statement(s): 3. - For prescription use only. - Special instrument requirements: 4. Fluorescence microscope. #### Device Description: l. The EUROIMMUN IFA is an assay for standardized detection of anti-glutamate receptor (type NMDA) antibodies utilized in each laboratories familiar with indirect immunofluorescence. The non-transfected cells are used as a control to simplify differentiation of potential co-existing and non-specific reactivity such as ANA. The test kit consists of slides, which contain BIOCHIPs coated with glutamate receptor (type NMDA) transfected cells and non-transfected cells, fluorescein-labelled anti-human IgG (goat), a positive control for transforced volle and non new and of a negative control, a salt for preparation of PBS, Tween 20, embedding medium, cover glasses and an instruction booklet. # SEP 1 8 2010 {1}------------------------------------------------ Image /page/1/Picture/1 description: The image shows a black and white illustration of a ladder. The ladder has two long, horizontal rails on the top and bottom. There are four rungs connecting the two rails. #### J. Substantial Equivalence Information: - Predicate device name (s): 1. EUROIMMUN ANCA IFA Granulocyte BIOCHIP Mosaic™ Test System. - Predicate 510(k) number(s): 2. - K083850 - 3. Comparison with predicate: The EUROIMMUN ANCA IFA Granulocyte BIOCHIP Mosaic™ Test System was choosen as a device of equivalent method and technology. There is no exact predicate device available for the detection of antibodies against glutamate receptor (type NMDA). | Similarities | | | | | | | |-----------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------|--|--|--|--| | Item | New device | Predicate device | | | | | | Intended Use | Semi-quantitative detection of antibodies
in human serum. | Same | | | | | | Technology | IFA
BIOCHIP TITERPLANE technology
using multiple substrates | Same | | | | | | Procedure | Standard IFA technique; serum
incubation with tissues/cells, followed by
a wash step, incubation with fluorescein-
labelled anti-human globulin, wash step,
embedding and reading fluorescence
with a fluorescence microscope. | Same | | | | | | Reagent | Fluorescein | Same | | | | | | Sample type and
dilution | Serum
1:10 dilution | Same | | | | | | Controls | Positive control
Negative control | Same | | | | | | Cut Off Level | 1:10 dilution | Same | | | | | | Differences | | | | | | | | Intended Use | Detection of antibodies against
glutamate receptor (type NMDA) | Detection of anti-neutrophil cytoplasmic
antibodies (ANCA) | | | | | #### Standard/Guidance Document Referenced (if applicable): K. cells Glutamate receptor (type NMDA) transfected cells and non-transfected ## None referenced. #### L. Test Principle: Substrates The procedure follows the TITERPLANE Technique developed by EUROIMMUN as an aid in standardize immunological analyses. The TITERPLANE Technique of EUROIMMUN was cleared previously via the FDA 510(k) processes under 510(k) No. K051489, K061408, K070763 and K083850. Human granulocytes native antigen Patient samples, controls and in separate steps conjugate and embedding medium are applied to the reaction fields of a reagent tray. The BIOCHIP slides are then placed into the recesses of the reagent tray, where all nold of a reagen the slide comact with the fluids, and the individual reactions commence simultaneously. The fluids are confined to the recessed wells eliminating the need to use a conventional "humidity chamber". Patient samples are diluted 1:10 in PBS-Tween, 25 µl of each diluted patient sample are added to each reaction field of the reagent tray. Reactions are started by fitting the BIOCHIP slides containing the substrates reachion hold of the reagon traym rype NMDA transfected cells and non-transfected cells) into the corresponding recesses of the reagent tray and incubated for 30 minutes at room temperature. into the other antigens. After incubation the BIOCHIP slides are washed with PBS-Tween to opecific antibodies. In the meantime, 20 ul of fluorescein-labelled anti-human globulin are added to remove unbodne antibodios. In the means, the BIOCHIP slides placed into the recesses of the tray. After a {2}------------------------------------------------ 30 minutes incubation at room temperature, the BIOCHIPs are again washed with PBS-Tween to remove any unbound fluorescein-labelled reagent. 10 ul of Embedding medium are placed for each reaction field on a cover glass and the BIOCHIP slides, with the BIOCHIPs facing downwards, placed onto the prepared cover glass. Fluorescence is read with a fluorescence microscope. #### M. Performance Characteristics (where applicable): #### Analytical performance: 1. - a. Precision/Reproducibility: - Intra-assay reproducibility The intra-assay reproducibility was determined by 10fold repeated measurements of 6 characterized positive and negative serum samples. The results did not exceed the acceptable deviation of fluorescence intensity of +/- 1 intensity level. Inter-assay reproducibility The inter-assay reproducibility was determined by repeated measurements of 6 characterized positive and negative serum samples at 5 different times. 2 slides were tested with each run. The results did not exceed the acceptable deviation of fluorescence intensity of +/- 1 intensity level. Lot to lot reproducibility The inter-lot reproducibility was determined by measurements of 3 characterized positive and negative serum samples using 3 different kit lots. The results did not exceed the acceptable deviation of fluorescence intensity of +/- 1 intensity level. - b. Linearity/assay reportable range: Not applicable. - Traceability, Stability, Expected values (controls, calibrators or methods): C. There is no recognized standard or reference material for autoantibodies against glutamate receptor (type NMDA). - d. Detection limit: Not applicable. - Analytical specificity: e. Cross-reactivity: Cross reactivity was investigated using 31 samples from patients with infectious and autoimmune encephalitis other than anti-qlutamate receptor (type NMDA) encephalitis. Samples positive for anti-GluR2, anti-VGKC and anti-zic4 (cerebellar degeneration) do not react with the qlutamate receptor (type NMDA). Interference: Three different samples are spiked with potential interfering substances in 3 different concentrations and are incubated with the test system. The recovery in relation to the original sample (not spiked) is calculated. The deviation in fluorescence intensity level did not exceed +/- 1. No interference was observed with hemolytic, lipemic or icteric samples for concentrations of up to 500 mg/dl for hemoglobin, 2000 mg/dl for triglyceride and 40 mg/dl for bilirubin. - f. Assay cut-off: Not applicable. - 2. Comparison studies: - Method comparison with predicate device: a. Not applicable. - b. Matrix comparison: Not applicable. {3}------------------------------------------------ Image /page/3/Picture/1 description: The image shows a pattern of alternating black and white shapes. There are four black shapes that are separated by white spaces. The black shapes are connected by two horizontal black lines at the top and bottom of the image. #### 3. Clinical studies: #### Prevalence and specificity: a. Study 1: 47 serum samples from the US from patients diagnosed with anti-gluatamate receptor (type NMDA) encephalitis and controls with other encephalopathies, including anti-VGKC and AMPA receptor encephalitis, were examined. The panel comprised samples from 7 men and 40 women with an average age of 17 years (age range: 5 to 42 years; 1 unknown). In addition, sera of 100 adult healthy blood donors of mixed age and sex from Germany were analyzed. All samples from patients with anti-qlutamate receptor (type NMDA) encephalitis (29 sera) were tested positive with the transfected cells, while all disease control samples (18 sera) and healthy blood donors (100 sera) were negative. Study 2: In a retrospective study, 2990 patients were screened for clinical symptoms of encephalitis of unknown origin. 5 of 6 samples fulfilling the criteria (6 women with an average age of 23 years, age range: 18 to 31 years; origin: Germany) were found positive for antibodies against glutamate receptor (type NMDA). The results support the fact that anti-glutamate receptor (type NMDA) encephalitis is a very frequent cause among these patients. Study 3: 8 samples from patients with anti-glutamate receptor (type NMDA) encephalitis (origin: Germany) were investigated. The panel comprised samples from 3 men and 5 women with an average age of 25 years (age range: 16 to 39 years). All samples were found positive for antiqlutamate receptor (tpye NMDA). Study 4: 9 samples from patients with anti-glutamate receptor (type NMDA) encephalitis and 13 samples from patients with other encephalopathies (origin: Italy) were investigated. The panel comprised samples from 8 men and 14 women with an average age of 47 years (age range: 9 to 89 years). All samples from patients with anti-glutamate receptor (type NMDA) encephalitis (9 sera) were tested positive with the transfected cells, while all disease control samples (13 sera) were negative. | Panel | | n | EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA | | | |---------------------|-------------------------------------------------------------------|-----|---------------------------------------------------|------------|---------------| | | | | positive | % positive | 95% C.I. | | Study 1 | Patients with anti-glutamate receptor
(type NMDA) encephalitis | 29 | 29 | 100.0% | 88.1 - 100.0% | | | Patients with other encephalopathies | 18 | 0 | 0.0% | 0.0 - 18.5% | | | Healthy blood donors | 100 | 0 | 0.0% | 0.0 - 3.6% | | Study 2 | Patients with encephalitis of unknown
origin | 6 | 5 | 83.3% | 35.9 - 99.6% | | Study 3 | Patients with anti-glutamate receptor
(type NMDA) encephalitis | 8 | 8 | 100.0% | 63.1 - 100.0% | | Study 4 | Patients with anti-glutamate receptor
(type NMDA) encephalitis | 9 | 9 | 100.0% | 66.4 - 100.0% | | | Patients with other encephalopathies | 13 | 0 | 0.0% | 0.0 - 24.7% | | Overall sensitivity | | 52 | 51 positive | 98.1% | 89.7 - 100.0% | | Overall specificity | | 131 | 131 negative | 100.0% | 97.2 - 100.0% | Other clinical supportive data (when a. and b. are not applicable): b. Not applicable. - Clinical cut-off: 4. See Assay cut-off. Expected values/Reference range: 5. The levels of the anti-glutamate receptor (type NMDA) antibodies (IgG) were analyzed with the EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA in a panel of 120 sera from normal healthy adult blood donors of mixed age and gender. All samples were found negative. The reference range was determined as titer 1: < 10. #### Proposed Labeling: N. The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10. {4}------------------------------------------------ Image /page/4/Picture/1 description: The image shows a pattern of alternating black and white shapes. The black shapes are arranged in a row and are separated by white spaces. The black shapes are rounded and symmetrical. The white spaces are rectangular and evenly spaced. ### O. Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision. Date Signature Kathryn Kohl, Managing Director Typed Name, Title {5}------------------------------------------------ ### DEPARTMENT OF HEALTH & HUMAN SERVICES Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus, which is a symbol of medicine, with three lines representing the serpent and staff. The logo is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" in a circular arrangement. ### Public Health Service Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993 EUROIMMUN US INC. c/o Ms. Kathryn Kohl Managing Director . 429 Rockaway Valley Road Unit 1200 Boonton Township, NJ 07005 SEP 1 3 2010 Re: k100017 Trade/Device Name: EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA Regulation Number: 21 CFR§866.5660 Regulation Name: Multiple Autoantibodies Immunological Test System Regulatory Class: Class II. Product Code: OSK Dated: August 4, 2010 Received: August 9, 2010 Dear Ms. Kohl: 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 {6}------------------------------------------------ Page 2 - Ms. Kathryn Kohl comply with all the Act's requirements, including, but not limited to: registration and listing (21 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 (OS) 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/ReportaProblem/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 vours. e m Chan Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health Enclosure {7}------------------------------------------------ # EUROIMMUN US INC. 510(k) Number (if known): K100017 Device Name: Anti-Glutamate receptor (type NMDA) IFA Indications For Use: The EUROIMMUN Anti-Glutamate receptor (type NMDA) IFA is intended for the qualitative determination of autoantibodies against glutamate receptor (type NMDA) in human serum. It is used as an aid in the diagnosis of anti-glutamate receptor (type NMDA) autoimmune encephalitis in conjunction with other laboratory and clinical findings. INDICATIONS FOR USE STATEMENT Prescription Use X (Part 21 CFR 801 Subpart D) (PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (OIVD) AND/OR Leena Division Sign-Off 510 Office of In Vitro Diagnost Device Evaluation an • Image /page/7/Picture/13 description: The image shows the text 'K100017' written in black ink. Below the text, there is a design consisting of two horizontal lines with four black circles placed between them. The circles are evenly spaced and appear to be solid black. ### ATTACHMENT 2 SEP 1 3 2010 Over-The-Counter Use (21 CFR 801 Subpart C) --- **Source:** [https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/OSK/K100017](https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/OSK/K100017) **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