(218 days)
Not Found
No
The device description details a standard immunochromatographic assay (lateral flow test) that relies on antibody-antigen binding and visual line development for results. There is no mention of computational analysis, algorithms, or learning processes.
No
The device is an immunochromatographic test system used to detect cryptococcal antigens, aiding in diagnosis. It does not provide any treatment or prevention of disease.
Yes
The device is explicitly stated to "aid in the diagnosis of cryptococcosis" by detecting specific antigens in patient samples.
No
The device is a lateral flow assay, which is a physical test strip that uses immunochromatography to detect antigens. This involves physical components and chemical reactions, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's a "test system for the qualitative or semi-quantitative detection of capsular polysaccharide antigens of Cryptococcus species complex... in serum and cerebral spinal fluid (CSF)." This describes a test performed in vitro (outside the body) on biological specimens to aid in diagnosis.
- Device Description: The description details a "dipstick sandwich immunochromatographic assay" that detects antigens in "serum and CSF." This further confirms it's a laboratory test performed on biological samples.
- Performance Studies: The document describes performance studies conducted on "CSF specimens" and "serum specimens," which are biological samples. The studies evaluate the device's ability to detect the target analyte in these samples.
- Key Metrics: The document provides metrics like Sensitivity and Specificity, which are standard performance indicators for diagnostic tests.
- Predicate Device: The mention of a "Predicate Device" with a K number (K102286) indicates that this device is being compared to a previously cleared device, which is a common process for IVDs seeking regulatory approval.
All these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Cryptococcal Antigen Lateral Flow Assay (CrAg LFA) is an immunochromatographic test system for the qualitative or semi-quantitative detection of capsular polysaccharide antigens of Cryptococcus species complex (Cryptococcus neoformans and Cryptococcus gattii) in serum and cerebral spinal fluid (CSF).
The CrAg Lateral Flow Assay is a prescription-use laboratory assay, which can aid in the diagnosis of cryptococcosis.
Product codes
GMD
Device Description
The CrAg Lateral Flow Assay is a dipstick sandwich immunochromatographic assay, which detects cryptococcal antigen in serum and CSF. For the qualitative procedure, specimens are diluted 1:2 in 1x Specimen Diluent and analyzed. For the semi-quantitative procedure, specimens are diluted 1:5 in 1x Specimen Diluent followed by 1:2 serial dilutions. All dilutions are then analyzed as in the qualitative procedure. Specimens are placed into an appropriate reservoir, such as a test tube or microtiter plate, and the lateral flow device is then placed into the reservoir allowing the specimen to come into contact with the test membrane. The test uses specimen wicking to capture gold-conjugated, anti-cryptococcal monoclonal antibodies and gold-conjugated control antibodies that are deposited onto a membrane. If cryptococcal antigen is present in the specimen, it binds to the gold-conjugated, anti-cryptococcal antibodies. The gold-labeled antibody-antigen complex will continue to wick up the membrane where it will interact with the Test Line (T). The Test Line is immobilized anti-cryptococcal monoclonal antibodies. If the specimen contains cryptococcal antigen, a sandwich is created with the gold-labeled antibodies and the immobilized antibodies, causing a visible line to develop at the test line site (T). If proper flow occurs and the reagents are reactive at the time of use, the wicking of any specimen, positive or negative, will cause the gold-conjugated control goat IgG antibody to move to the Control Line (C) which is immobilized bovine anti-goat IgG antibody. The immobilized anti-goat antibody will bind to the gold-conjugated goat IgG Control antibody and will cause a visible line to develop (C). A positive test result will create two lines, while a negative test result will create one line (Figure 1). If the control line fails to develop a line, then the test is not valid.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription-use laboratory assay
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Precision Studies (Repeatability & Reproducibility):
CSF specimens were spiked with cryptococcal antigen at four concentrations (Negative, high negative, low positive, and medium positive). Samples were analyzed on the CrAg Lateral Flow Assay in triplicate on five different days, at three different sites (one internal, two external US laboratories) with a total of five different operators, on one lot. For repeatability, percent positive and percent negative detected were calculated for each site. For reproducibility, overall percent positive and percent negative detected were calculated by combining data from all three sites.
Analytical Sensitivity:
Estimated by running 24 replicates of varying concentrations of cryptococcal antigen diluted in mock CSF on one lot of kits. The analytical cut-off was defined as the concentration where 50% of the results were positive and 50% of the results were negative. The analytical cut-off is 1.25ng/ml.
Analytical Specificity (cross-reactivity):
No information provided on the test set for analytical specificity; instead, it is stated that "Due to specimen availability, the following CSF conditions were not tested in the CrAg Lateral Flow Assay: S. pneumonia, Enterovirus, Enterobacteriaceae, Streptococcus spp., Staphylococcus spp., diphtheroid, H. influenzae type B, N. meningitidis, Enterococcus spp., Epstein Barr, Herpes simplex virus Type 1 and 2, Listeria monocytogenes, Trichosporon beigelii, and samples with syneresis fluid condensation." And "This assay was not evaluated for potential interference related to specimen pretreatment with 2-mercaptoethanol or with specimens including the following subastances or conditions: bloody CSF, cloudy CSF, white blood cells, xanthochromic CSF, bilirubin, protein, systemic lupus erythmatosus (SLE), sarcoidosis, or N. memingitides."
High Dose Hook Effect:
High dose hook effect concentrations were determined by spiking negative serum (previously negative by IMMY Latex-Cryptococcus Antigen Detection System and CrAg Lateral Flow Assay) with cryptococcal antigen at various concentrations between 20 and 500ug/ml. Each concentration was tested in triplicate on one lot of CrAg Lateral Flow Assay. It was determined that serum specimens with a cryptococcal antigen concentration higher than 200ug/ml can produce a high dose hook effect and therefore may produce a false negative result.
Other Method Comparison - Culture/India Ink (Gold Standards):
The CrAg Lateral Flow Assay was compared to the gold standard for the diagnosis of cryptococcosis (culture and/or India Ink) using CSF specimens. These studies contained a mix of both prospective and retrospective specimens.
Sample Size: Not explicitly stated for each category, but from the 2x2 table, 65 positive culture/India Ink samples and 99 negative culture/India Ink samples were tested.
Key Results:
Sensitivity: 100% (95% CI: 94.4-100.0%)
Specificity: 100% (95% CI: 96.3-100%)
Key Metrics
Analytical sensitivity cut-off: 1.25 ng/ml.
Repeatability/Reproducibility CSF:
High Negative: Site 1: 90% negative, 10% positive; Site 2: 100% negative, 0% positive; Site 3: 100% negative, 0% positive. Overall: 96% negative, 4% positive.
Medium Positive: Site 1: 100% positive; Site 2: 100% positive; Site 3: 100% positive. Overall: 100% positive.
Low Positive: Site 1: 100% positive; Site 2: 100% positive; Site 3: 100% positive. Overall: 100% positive.
Negative: Site 1: 100% negative; Site 2: 100% negative; Site 3: 100% negative. Overall: 100% negative.
Method Comparison (CrAg LFA vs. Culture/India Ink for CSF):
Sensitivity: 100% (95% CI: 94.4-100.0%)
Specificity: 100% (95% CI: 96.3-100%)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 866.3165
Cryptococcus neoformans serological reagents.(a)
Identification. Cryptococcus neoformans serological reagents are devices that consist of antigens used in serological tests to identify antibodies toCryptococcus neoformans in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) and are used to identifyCryptococcus neoformans directly from clinical specimens or from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of cryptococcosis and provides epidemiological information on this type of disease. Cryptococcosis infections are found most often as chronic meningitis (inflammation of brain membranes) and, if not treated, are usually fatal.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.
0
KII2Y22
MAR 2 8 2012
10(k) Sumi CrAg Lateral Flow Assav
This 510(k) summary is submitted in accordance with 21 CFR §807.92
| Owner: | Immuno-Mycologics, Inc.
2700 Technology Place
Norman, OK 73071
Tel: 405-360-4669
Fax: 405-364-1058
Contact: Dr. Sean K. Bauman, President & CEO
Sean-Bauman@immy.com |
|-------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Prepared: | March 26, 2012 |
| Trade Name: | CrAg Lateral Flow Assay |
| Common Name: | Cryptococcal Antigen Lateral Flow Immunoassay |
| Regulation: | 866.3165 |
| Predicate Device: | Immuno-Mycologics' CrAg Lateral Flow Assay (K102286) |
| Intended Use: | The CrAg Lateral Flow Assay is an immunochromatographic test system
for the qualitative or semi-quantitative detection of capsular
polysaccharide antigens of Cryptococcus species complex (Cryptococcus
neoformans and Cryptococcus gatti) in serum and cerebral spinal fluid
(CSF). |
The CrAg Lateral Flow Assay is a prescription-use laboratory assay, which can aid in the diagnosis of Cryptococcosis.
Device Description:
Explanation:
Detection of cryptococcal antigen in serum and CSF has been used for over forty years to aid in the diagnosis of cryptococcosis with very high sensitivity and specificity (9,14,15). Current guidelines for the management of cryptococcal disease partially base treatment recommendations on cryptococcal antigen presence and more specifically on cryptococcal antigen titers (16).
Cryptococcosis is caused by both species of the Cryptococcus species complex (Cryptococcus neoformans and Cryptococcus gatti) (5,6,12,13). Individuals with impaired cell-mediated
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1
immune (CMI) function due to acquired immunodeficiency syndrome (AIDS) (19), lymphoproliferative disorders (18), steroid therapy (8), and organ transplantation (7) are at increased risk of cryptococcosis. AIDS accounts for 80-90% of cryptococcal infections (11). The incidence of cryptococcosis in AIDS patients in the United States is estimated to be 5-10% (11), while the incidence of cryptococcosis in other parts of the world, such as Africa, is as high as 30% (3). Cryptococcosis is the fourth most common opportunistic, life-threatening infection among AIDS patients (10).
Description:
The CrAg Lateral Flow Assay is a dipstick sandwich immunochromatographic assay, which detects cryptococcal antigen in serum and CSF. For the qualitative procedure, specimens are diluted 1:2 in 1x Specimen Diluent and analyzed. For the semi-quantitative procedure, specimens are diluted 1:5 in 1x Specimen Diluent followed by 1:2 serial dilutions. All dilutions are then analyzed as in the qualitative procedure. Specimens are placed into an appropriate reservoir, such as a test tube or microtiter plate, and the lateral flow device is then placed into the reservoir allowing the specimen to come into contact with the test membrane. The test uses specimen wicking to capture gold-conjugated, anti-cryptococcal monoclonal antibodies and gold-conjugated control antibodies that are deposited onto a membrane. If cryptococcal antigen is present in the specimen, it binds to the gold-conjugated, anti-cryptococcal antibodies. The gold-labeled antibody-antigen complex will continue to wick up the membrane where it will interact with the Test Line (T). The Test Line is immobilized anti-cryptococcal monoclonal antibodies. If the specimen contains cryptococcal antigen, a sandwich is created with the gold-labeled antibodies and the immobilized antibodies, causing a visible line to develop at the test line site (T). If proper flow occurs and the reagents are reactive at the time of use, the wicking of any specimen, positive or negative, will cause the gold-conjugated control goat IgG antibody to move to the Control Line (C) which is immobilized bovine anti-goat IgG antibody. The immobilized anti-goat antibody will bind to the gold-conjugated goat IgG Control antibody and will cause a visible line to develop (C). A positive test result will create two lines, while a negative test result will create one line (Figure 1). If the control line fails to develop a line, then the test is not valid.
Image /page/1/Figure/3 description: The image shows a diagram of a cryptococcal antigen test. The diagram illustrates the components of the test, including the plastic overlay, backer card, sample application area, gold-conjugated antibodies, test line, and control line. It also shows the results of a positive and negative test. The positive test result shows two lines, while the negative test result shows only one line.
Figure 1. CrAg Lateral Flow Assay Schematic
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2
Technological Characteristics Summary
A comparison between the CrAg LFA and the CrAg LFA (K102286 - Serum only) is presented in Table 1.
Table 1. Comparison with Predicate Device
| SIMILARITIES | ||
|---|---|---|
| Feature | CrAg LFA (New Device) | CrAg LFA (Serum Only) (K102286) |
| Intended Use | Immunochromatographic test system for the | |
| qualitative or semi-quantitative detection of the | ||
| capsular polysaccharide antigens of Cryptococcus | ||
| species complex (Cryptococcus neoformans and | ||
| Cryptococcus gattii) in serum | Immunochromatographic test system for the | |
| qualitative or semi-quantitative detection of the | ||
| capsular polysaccharide antigens of Cryptococcus | ||
| species complex (Cryptococcus neoformans and | ||
| Cryptococcus gattii) in serum | ||
| Indication For | ||
| Use | Prescription-use laboratory assay, which can aid in | |
| the diagnosis of cryptococcosis | Prescription-use laboratory assay, which can aid in | |
| the diagnosis of cryptococcosis | ||
| Technology | Lateral Flow Assay | Lateral Flow Assay |
| Sample Matrix | Serum | Serum |
| Instruments | None | None |
| Assay | ||
| Components | Specimen diluent, lateral flow strips, built-in control, | |
| gold conjugated antibodies | Positive control, negative control, latex cards, latex | |
| conjugated antibodies | ||
| Specimen Pre- | ||
| Treatment | Dilution | Dilution |
| Detection | ||
| Antibody | Anti-cryptococcal monoclonal antibody | Anti-cryptococcal monoclonal antibody |
| Storage | ||
| Requirements | 20-25°C | 20-25°C |
| DIFFERENCES | ||
| Feature | Cryptococcal Antigen Lateral Flow Assay | Latex-Cryptococcus Antigen Detection |
| System | ||
| Intended Use | Test for the qualitative or semi-quantitative | |
| detection of capsular polysaccharide antigens of | ||
| Cryptococcus in serum | Test for the qualitative or semi-quantitative | |
| detection of capsular polysaccharide antigens of | ||
| Cryptococcus in serum and CSF | ||
| Indication For | ||
| Use | No differences | No differences |
Performance Summary
A. Precision Studies (Repeatability & Reproducibility)
Serum repeatability and reproducibility results can be found in the predicate device 510(k) (K102286)
3
Repeatability and reproducibility with CSF specimens were determined by spiking a mock CSF that was negative by the IMMY Latex-Cryptococcus Antigen Detection System with cryptococcal antigen at four concentrations: Negative, high negative (CJ), low positive (near C95), and medium positive. The samples were analyzed on the CrAg Lateral Flow Assay in triplicate on five different days, at three different sites with a total of five different operators, on one lot, according to EP5-A2. One site was internal (Site 1) and the remaining two were a US reference laboratory (Site 2) and a US hospital laboratory (Site 3). For repeatability, percent positive and percent negative detected were calculated for each site (Table 2). For reproducibility, overall percent positive and percent negative detected were calculated by combining the data from all three sites (last two rows of Table 2).
| CSF | ||||||||
|---|---|---|---|---|---|---|---|---|
| Sample | 1 | |||||||
| Med. Pos | 2 | |||||||
| Low Pos | 3 | |||||||
| High Neg | 4 | |||||||
| Neg | ||||||||
| Neg/Pos | - | + | - | + | - | + | - | + |
| Site 1 | 0 | 30 | 0 | 30 | 27 | 3 | 30 | 0 |
| Percent % | 0 | 100 | 0 | 100 | 90 | 10 | 100 | 0 |
| Site 2 | 0 | 30 | 0 | 30 | 30 | 0 | 30 | 0 |
| Percent % | 0 | 100 | 0 | 100 | 100 | 0 | 100 | 0 |
| Site 3 | 0 | 15 | 0 | 15 | 15 | 0 | 15 | 0 |
| Percent % | 0 | 100 | 0 | 100 | 100 | 0 | 100 | 0 |
| Total No. | 0 | 75 | 0 | 75 | 72 | 3 | 75 | 0 |
| Percent % | 0 | 100 | 0 | 100 | 96 | 4 | 100 | 0 |
| Table 2. Repeatability at 3 Different Sites | ||||
|---|---|---|---|---|
| -- | --------------------------------------------- | -- | -- | -- |
- B. Analytical Sensitivity (lower limits of the assay/analytical cut-off)
Serum analytical sensitivity can be found in the predicate device 510(k) (K102286)
Analytical sensitivity for the CrAg Lateral Flow Assay was estimated by running 24 replicates of varying concentrations of cryptococcal antigen diluted in mock CSF on one lot of kits, according to EP12-A2. The analytical cut-off was defined as the concentration where 50% of the results were positive and 50% of the results were negative. The analytical cut-off is 1.25ng/ml.
- C. Analytical Specificity (cross-reactivity)
Serum analytical specificity can be found in the predicate device 510(k) (K102286)
Due to specimen availability, the following CSF conditions were not tested in the CrAg Lateral Flow Assay: S. pneumonia, Enterovirus, Enterobacteriaceae, Streptococcus spp., Staphylococcus spp., diphtheroid, H. influenzae type B, N. meningitidis, Enterococcus spp., Epstein Barr, Herpes simplex virus Type 1 and 2, Listeria monocytogenes, Trichosporon beigelii, and samples with syneresis fluid condensation.
4
This assay was not evaluated for potential interference related to specimen pretreatment with 2-mercaptoethanol or with specimens including the following subastances or conditions: bloody CSF, cloudy CSF, white blood cells, xanthochromic CSF, bilirubin, protein, systemic lupus erythmatosus (SLE), sarcoidosis, or N. memingitides.
-
D. Linearity
N/A -
E. High Dose Hook Effect
High dose hook effect concentrations with specimens were determined by spiking negative serum that was negative by the IMMY Latex-Cryptococcus Antigen Detection System and CrAg Lateral Flow Assay, with cryptococcal antigen at various concentrations between 20 and 500ug/ml. Each concentration was tested in triplicate at IMMY on one lot of CrAg Lateral Flow Assay, according to the package insert. It was determined that serum specimens with a cryptococcal antigen concentration higher than 200ug/ml can produce a high dose hook effect and therefore may produce a false negative result. -
F. Method Comparisons
Predicate Device Method Comparison
Not Applicable
Other Method Comparison - Culture/India Ink (Gold Standards)
Serum method comparison to gold standards can be found in the predicate device 510(k) (K102286)
The CrAg Lateral Flow Assay was compared to the gold standard for the diagnosis of cryptococcosis (culture and/or India Ink) to evaluate the sensitivity and specificity of the assay in CSF. These studies contained a mix of both prospective and retrospective specimens. A summary of the data collected is included in Tables 3 and 4 below:
| Culture/India Ink | |||
|---|---|---|---|
| Positive | Negative | ||
| CrAg LFA | |||
| Assay | Positive | 65 | 0 |
| Negative | 0 | 99 | |
| Table 4. CSF Statistical Analysis: Culture/India Ink | |||
| Calculated | 95% CI | ||
| Sensitivity | 100% | 94.4-100.0% | |
| Specificity | 100% | 96.3-100% |
CSF 2x2 Contingency Table: Culture/India Ink
5
Conclusion
.
The information submitted in this premarket notification is complete and supports a substantial equivalence decision.
.
6
Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three stripes forming its body and wing. The eagle's head is facing left. Encircling the eagle is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.
10903 New Hampshire Avenue Silver Spring, MD 20993
MAR 2 8 2012
Immuno-Mycologics, Inc. c/o Sean K. Bauman, Ph.D. President and CEO 2700 Technology PL Norman, OK 73071
Re: K112422
Trade/Device Name: CrAg Lateral Flow Assay (CrAg LFA) Regulation Number: 21 CFR § 866.3165 Regulation Name: Cryptococcal antigen lateral flow assay Regulatory Class: II Product Code: GMD Dated: March 26, 2012 Received: March 27, 2012
Dear Dr. Bauman:
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 commence 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 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
7
Page 2 - Sean K. Bauman, Ph.D.
requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter requirences as be form arketing your device as described in your Section 510(k) premarket with anow you to organ mading 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 11 you don't up 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 yours,
Vayathra
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
8
Indications for Use Sta
510{k} Number (if known): K112422
Device Name: CrAg Lateral Flow Assay
Indications for Use:
The Cryptococcal Antigen Lateral Flow Assay (CrAg LFA) is an immunochromatographic test system for the qualitative or semi-quantitative detection of capsular polysaccharide antigens of Cryptococcus species complex (Cryptococcus neoformans and Cryptococcus gattii) in serum and cerebral spinal fluid (CSF).
The CrAg Lateral Flow Assay is a prescription-use laboratory assay, which can aid in the diagnosis of cryptococcosis.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR Over-The-Counter Use (21 CFR 801 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)
Freddie lu. Poole
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k): K112422
www.immy.com | 2700 Technology Pl Norman, OK 73071 USA | 405.360.4669
Rev. 03/28/2012
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