TRIAGE,PARASITE PANEL, TRIAGE CRYPTOSPORIDIUM AND ENTAMOEBA HISTOLYTICA, TRIAGE CRYPTOSPORIDIUM AND GIARDIA LAMBLIA

• K Number: K982245
• Device Name: TRIAGE,PARASITE PANEL, TRIAGE CRYPTOSPORIDIUM AND ENTAMOEBA HISTOLYTICA, TRIAGE CRYPTOSPORIDIUM AND GIARDIA LAMBLIA
• Manufacturer: BIOSITE INCORPORATED
• Date Cleared: 1998-10-06 ( 102 days)
• Product Code: MHI , GMO , MHJ
• Regulation Number: 866.3220
• Type: Traditional
• Panel: Microbiology
• Age Range: All
• Reference & Predicate Devices: N/A
• Predicate For: N/A

Intended Use

The Triage® Parasite Panel is an enzyme immunoassay used for the detection of antigens for Entamoeba histolyticaldispar, Cryptosporidium parvum and Giardia lamblia in human fecal specimens. The test will be offered as singular tests for each protein, combinations of two organisms per panel and a panel consisting of all three tests. This test is used as an aid in the diagnosis of intestinal parasitic diseases.

Device Description

The Triage® Parasite Panel is an enzyme immunoassay used to detect the presence of parasite specific antigens in human fecal specimens. It is a membrane based immunoassay that depends on the detection of the antigen using antibodies with specificities to at least two distinct antigenic sites on the molecule.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Triage® Parasite Panel, based on the provided text:

Acceptance Criteria and Reported Device Performance

For Giardia lamblia:

Metric	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Comparable to O&P	95.1%
Specificity	Comparable to O&P	88.4%
Positive Predictive Value	Not specified	79.4%
Negative Predictive Value	Not specified	97.4%
Agreement (95% CI)	Not specified	87.8% - 93.3%

For Entamoeba histolytica/dispar:

Metric	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Comparable to O&P	90.5%
Specificity	Comparable to O&P	85.0%
Positive Predictive Value	Not specified	38.8%
Negative Predictive Value	Not specified	98.8%
Agreement (95% CI)	Not specified	82.3% - 88.8%

For Cryptosporidium parvum:

Metric	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Comparable to O&P	91.4%
Specificity	Comparable to O&P	98.2%
Positive Predictive Value	Not specified	88.3%
Negative Predictive Value	Not specified	98.7%
Agreement (95% CI)	Not specified	95.8% - 98.8%

General Acceptance Criteria (Implied):
The primary implied acceptance criteria are that the Triage® Parasite Panel produce "essentially the same results" as:

1. Recognized standard methods for parasite identification in stool specimens (i.e., traditional O&P examination).
2. Other commercially available immunoassays.

The document specifically states that "statistical analysis of the data showed that the sensitivity of the three tests contained in the Triage® Parasite Panel was not statistically different from those of commercially available immunoassays" reported to have similar sensitivities when compared to microscopic techniques. Similarly, "there was not a statistical difference in the specificity of the Triage® G. lamblia or the C. parvum tests" compared to commercial tests with reported 98% specificity. The specificity of the Triage® E. histolytica test was even "significantly greater" than a commercially available immunoassay.

Study Details:

1. Sample Size Used for the Test Set and Data Provenance:

   • Giardia lamblia: 444 fecal specimens
   • Entamoeba histolytica/dispar: 443 fecal specimens
   • Cryptosporidium parvum: 444 fecal specimens
   • Data Provenance: Not explicitly stated regarding country of origin. The study was conducted using both "positive and negative stool specimens," implying they were clinical samples, though whether retrospective or prospective is not specified.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:

   • Not explicitly stated. The ground truth was established by "standard ova and parasite examination using Modified Acid Fast Staining and Trichrome Staining procedures." This implies trained laboratory personnel, but the specific number or qualifications are not provided.

3. Adjudication Method for the Test Set:

   • Not explicitly stated. The document describes comparison to "standard ova and parasite examination." For discrepancies, specimens producing apparent false positive results with the Triage® Parasite Panel were "evaluated using other commercially available enzyme immunoassays." This suggests a form of secondary evaluation or adjudication for discrepant results.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

   • No, an MRMC comparative effectiveness study was not done. This study compares the device's performance to traditional laboratory methods and other immunoassays, not human reader performance with or without AI assistance.

5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

   • Yes, this was a standalone study. The Triage® Parasite Panel is an enzyme immunoassay, which is a laboratory test and not an AI algorithm. Its performance was evaluated independently against the ground truth.

6. The Type of Ground Truth Used:

   • Expert Consensus / Reference Method: The ground truth was established by "standard ova and parasite examination using Modified Acid Fast Staining and Trichrome Staining procedures." This is considered a reference laboratory method for detecting parasites. However, the document acknowledges that "Conventional microscopic examination of fecal specimens has been demonstrated to be less sensitive than other scientifically valid techniques," and refers to it as not "ideal for the detection of the organisms."

7. Sample Size for the Training Set:

   • Not applicable. This is an immunoassay, not a machine learning model, so there is no "training set" in the context of AI.

8. How the Ground Truth for the Training Set Was Established:

   • Not applicable, as there is no training set for this type of device.

Summary

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OCT 6 1998

982a345

510(k) Summary of Safety and Effectiveness

Triage® Parasite Panel

• Name and Address of Submitter A.
• Company Name and Address: t

Biosite Diagnostics, Inc. 11030 Roselle St. San Diego, CA 92121 Telephone: [phone] FAX: [phone] John F. Bruni, Ph.D. 09/02/98

Contact Person Date Summary Prepared

• Device Names B.
  • 1. Trade Name

Triage® Parasite Panel

• 2. Common Names
     An immunoassay for the detection of the antigens for Entamoeba. histolytica, Giardia lamblia and Cryptosporidium parvum in human fecal specimens.
• 3. Classification Name
     Entamoeba histolytica serological reagents

• C. Legally Marketed Devices
  Single Test Kits Manufactured by Alexon, TechLabs, Meridian Diagnostics for the same parasites using enzyme immunoassay technology.

• D. Device Description
  The Triage® Parasite Panel is an enzyme immunoassay used to detect the presence of parasite specific antigens in human fecal specimens. It is a membrane based immunoassay that depends on the detection of the antigen using antibodies with specificities to at least two distinct antigenic sites on the molecule.

• ய் Intended Use

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The Triage® Parasite Panel is an enzyme immunoassay used for the detection of antigens for Entamoeba histolytica. Giardia lamblia and Cryptosporidium parvum in human fecal specimens. This test is used as an aid in the diagnosis of intestinal parasitic disease.

• ய Comparison of the Methods with Predicate Devices
  The Triage® Parasite Panel provides a qualitative determination of the presence of parasite specific antigens in human fecal specimens. Other tests manufactured by Alexon, Trend, LMD laboratories. TechLabs are all enzyme immunoassays that have been cleared through the 510(k) process. These tests have been shown to provide essentially the same clinical results as traditional O&P examination using microscopic visualization of various phases of the life cycle of the parasite.

• Summary of Analytical Data G.
  Analytical Sensitivity

The analytical sensitivity of the Triage® Parasite Panel is 3 ng of alpha-1giardin (G. lamblia), 4 ng of 29 kDa surface antigen (E. histolytica/dispar) and 6 ng of protein disulfide isomerase (C. parvum) per milliliter of fecal specimen.

Reproducibility

The precision and reproducibility of this product has been demonstrated to be comparable to other products of this nature.

• H. Summary of Clinical Data
  The performance of the Triage® Parasite Panel was evaluated using both positive and negative stool specimens. All specimens were examined using standard ova and parasite examination using Modified Acid Fast Staining and Trichrome Staining procedures. The results of the Triage® Parasite Panel were compared to standard ova and parasite examination for the presence of G. lamblia, E. histolytica/dispar, and C. parvum. The clinical sensitivity and specificity, the positive and negative predictive value, the 95% confidence intervals and the prevalence of the disease in the population tested are presented.

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Triage G. lamblia

O & P Evaluation
	+	-	Total
+	135	35	170
-	7	267	274
Total	142	302	444

Sensitivity		95.1%
Specificity		88.4%
		LOWERLIMIT	UPPERLIMIT
95% Confidence Limits Sensitivity		91.5%	98.6%
95% Confidence Limits Specificity		84.8%	92.0%
95% Confidence Limits Agreement		87.8%	93.3%
Positive Predictive Value		79.4%
Negative Predictive Value		97.4%
Prevalence		32.0%

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Triage E. + histolytica/ dispar

O & P Evaluation
+	-	Total
38	60	98
4	341	345
42	401	443

Sensitivity	90.5%
Specificity	85.0%
	LOWERLIMIT	UPPERLIMIT
95% Confidence Limits Sensitivity	81.6%	99.4%
95% Confidence Limits Specificity	81.5%	88.5%
95% Confidence Limits Agreement	82.3%	88.8%
Positive Predictive Value	38.8%
Negative Predictive Value	98.8%
Prevalence	9.5%

Total

The large number of "apparent false positive results" using the Triage® Parasite Panel is primarily attributed the overall lack of sensitivity of microscopic examination as compared to culture. The sensitivity of microscopic examination has been reported to be 62% as compared to culture techniques.

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O & P Examination

Triage C. parvum

+	-	Total
53	7	60
5	379	384
58	386	444

Total

에

Sensitivity	91.4%
Specificity	98.2%
		LOWER LIMIT	UPPER LIMIT
95% Confidence Limits Sensitivity		84.2%	98.6%
95% Confidence Limits Specificity		96.9%	99.5%
95% Confidence Limits Agreement		95.8%	98.8%
Positive Predictive Value		88.3%
Negative Predictive Value		98.7%
Prevalence		13.1%

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:

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All specimens were tested using commercially available immunoassays. Those specimens that produced a positive result were evaluated using the "gold standard" of microscopic examination. - Statistical analysis of the data showed that the sensitivity of the three tests contained in the Triage® Parasite Panel was not statistically different from those of commercially available immunoassays for Giardia lamblia, Entamoeba histolytica/dispar. and Cryptosporidium parvum that have reported sensitivities of 96%. 87% and 95% when compared to microscopic techniques. Additionally, there was not a statistical difference in the specificity of the Triage® G. lamblia or the C. parvum tests when compared to commercially available tests, each having a reported specificity of 98% for both organisms. The specificity of the Triage® E. histolytica test was significantly greater than a commercially available immunoassay having a reported specificity of 99%.

Conventional microscopic examination of fecal specimens has been demonstrated to be less sensitive than other scientifically valid techniques for the identification of the presence of parasites, including immunoassays and the detection of parasite-specific nucleic acid. In addition, the presence of disease as determined by collection and analysis of multiple specimens from the same patient provides evidence for the lack of clinical sensitivity of conventional microscopic examination . Inasmuch as the "gold standard" is not ideal for the detection of the organisms, the likelihood of observing false positive results using a comparative method is increased. Therefore, those specimens producing apparent false positive results in the Triage® Parasite Panel were evaluated using other commercially available enzyme immunoassays. Twenty-eight of the 35 apparent false positive results for G. lamblia, 57 of the 60 apparent false positive results for the E. histolytica/dispar and, 6 of the 7 apparent false positive results for the C. parvum test also were positive using other commercial immunoassays for these same organisms. These results support the studies stating that the sensitivity of conventional microscopic examination is less than desired.

1. Conclusion

The Triage® Parasite Panel is an enzyme immunoassay used for the detection of antigens for Entamoeba histolytica, Giardia lamblia and Cryptosporidium parvum in human fecal specimens. This test is used as an aid in the diagnosis of intestinal parasitic disease. The summarized data provided demonstrate that the Triage® Parasite Panel produces essentially the same results as the recognized standard methods for the identification of parasites in stool specimens. Additionally, the Triage® Parasite Panel produces essentially the same results as other commercially available products.

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OCT 6 1998

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

John F. Bruni. Ph.D. Director, Clinical and Regulatory Affairs Biosite Diagnostics 11030 Roselle Street San Diego, CA 92121

Re: K982245

Trade Name: Triage® Parasite Panel, Triage Cryptosporidium, Giardia and Entamoeba

Regulatory Class: II Product Code: MHI: MHJ: GMO Dated: September 2, 1998 Received: September 8, 1998

Dear Dr. Bruni:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at [phone].

This letter will allow you to begin marketing your device as described in your 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 Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at [phone]. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number [phone] or at [phone] or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours.

Steven Autman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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5 IO(k) Number if known) K982245

Jevice Name: Triage® Parasite Panel

Indications for Use:

The Triage® Parasite Panel is an enzyme immunoassay used for the detection of antigens for Entamoeba histolyticaldispar, Cryptosporidium parvum and Giardia lamblia in human fecal specimens. The test will be offered as singular tests for each protein, combinations of two organisms per panel and a panel consisting of all three tests. This test is used as an aid in the diagnosis of intestinal parasitic diseases.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Woody Dubois

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K982245

Prescription Use X

Regulation Number and Section

§ 866.3220

Entamoeba histolytica serological reagents.(a)
Identification. Entamoeba histolytica serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toEntamoeba histolytica in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyEntamoeba histolytica directly from clinical specimens. The identification aids in the diagnosis of amebiasis caused by the microscopic protozoan parasiteEntamoeba histolytica and provides epidemiological information on diseases caused by this parasite. The parasite may invade the skin, liver, intestines, lungs, and diaphragm, causing disease conditions such as indolent ulcers, an amebic hepatitis, amebic dysentery, and pulmonary lesions.(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.