The OSOM C. difficile Toxin A/B Test is an immunochromatographic assay intended for the qualitative detection of Clostridium difficile toxins A and/or B in human stool samples. This test is intended as an aid in the diagnosis of C. difficile-associated disease (CDAD) in patients with symptoms of CDAD.

Device Description

The OSOM C. difficile Toxin A/B Test is a rapid test which can detect the presence of Clostridium difficile toxins A and B in human stool samples. A test kit contains 25 OSOM test stick devices and 25 disposable pipettes. The OSOM C. difficile Toxin A/B Test is a qualitative assay that employs immunochromatographic, dipstick technology. The test format is a sandwich immunoassay, with a single test zone on the nitrocellulose dipstick to detect Toxin A and/or Toxin B ("blue/gray" line) and a single control line zone to indicate proper sample flow ("red" line). The test procedure involves binding of C. difficile Toxin A and/or Toxin B from a patient stool sample to blue colored latex particles conjugated to a monoclonal antibody against Toxin B or a polyclonal antibody against Toxin A. When Toxin A and/or B is present in the sample, it will form a partial immune complex with the antibody-conjugated colored particles. The OSOM C. difficile Toxin A/B Test stick, when placed in the sample mixture, initiates sample migration along the nitrocellulose membrane. If C. difficile toxin A or toxin B is present, a blue/gray line will appear in the test line region indicating a positive result. A red control line must appear for the results to be valid. If C. difficile toxins are not present, only the red control line will appear. An invalid test occurs when no control line appears.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Clinical Study 1 (Overall)	Adequate sensitivity, specificity, and agreement compared to cytotoxicity assay for diagnostic aid.
Sensitivity	Sufficiently high to detect positive cases.	88.2% (95% CI, 80.5 - 93.1%)
Specificity	Sufficiently high to correctly identify negative cases.	96.8% (95% CI, 95.7 - 97.7%)
Agreement	Overall high agreement with the reference method.	96.2% (95% CI, 95.1 - 96.9%)
Clinical Study 2 (Comparison to Predicate)	Performance of the new device should be comparable to or better than the predicate device.
OSOM Sensitivity	Comparable to predicate.	87.5% (95% CI, 75.3 - 94.1%)
OSOM Specificity	Comparable to predicate.	90.1% (95% CI, 85.2 - 93.5%)
Predicate Sensitivity	Baseline for comparison.	70.8% (95% CI, 56.8 - 81.8%)
Predicate Specificity	Baseline for comparison.	97.5% (95% Cl, 94.3 - 98.9%)
Analytical Sensitivity	Ability to detect C. difficile toxins at specified concentrations.	Detected 15 ng/mL for Toxin A and 40 ng/mL for Toxin B.
Cross-Reactivity	No false positives with common bacteria and viruses typically found in clinical samples.	All listed bacteria and viruses gave negative responses.
Interfering Substances	No effect on performance from common substances found in stool or used by patients.	No effect from the 11 tested substances.
Reproducibility	Consistent results across different operators, sites, and testing days.	Expected result 99.2% (357/360) of the time.

Study Details

Sample sizes used for the test set and the data provenance:
- Clinical Study 1 (Overall performance): 1274 de-identified excess loose or watery stool specimens.
  - Provenanc: Obtained from patients at five sites in the United States.
  - Nature: Retrospective (specimens submitted for CDAD testing).
- Clinical Study 2 (Comparison to Predicate): 250 paired sample results (OSOM and Predicate Device).
  - Provenance: Not explicitly stated, but implies from a clinical trial site, likely within the US given the overall study context.
  - Nature: Retrospective (using existing clinical trial samples).
- Analytical Sensitivity: Not reported as a sample size, but involved serial dilutions prepared from purified toxins.
- Cross-Reactivity: Not reported as a numerical sample size, but tested against a panel of 28 bacterial isolates and 6 viral isolates.
- Interfering Substances: Not reported as a numerical sample size, but tested against 11 potential interferents.
- Reproducibility: 360 total test results (12 samples x 2 operators/day x 5 days x 3 sites = 360)
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for the clinical studies was established using a cytotoxicity assay. The text does not specify the number of experts or their qualifications for performing this assay, beyond stating it was "performed at Genzyme using a standard C. difficile toxin cytotoxicity assay." It notes that "Those performing the cytotoxicity assay testing were blinded to the OSOM test results," which indicates an effort to reduce bias.
Adjudication method for the test set:
- No explicit adjudication method is described for the primary clinical study. The cytotoxicity assay served as the direct reference standard.
- Discrepant testing was performed for some cases:
  - 12 cytotoxin positive, OSOM negative cases were tested with PCR for tcdB gene.
  - 37 cytotoxin negative, OSOM positive cases were tested with PCR for tcdB gene (one sample not available).
  - This suggests a form of post-hoc analysis for discordant results, but not a formal adjudication process to establish the initial ground truth for all samples.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This study is not an MRMC comparative effectiveness study involving human readers and AI. It is a study comparing an immunoassay device (OSOM C. difficile Toxin A/B Test) to a laboratory reference method (cytotoxicity assay) and a predicate device.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, for the OSOM C. difficile Toxin A/B Test. The study evaluates the performance of the OSOM C. difficile Toxin A/B Test, which is a rapid immunochromatographic assay device, as a standalone diagnostic tool. Its performance is assessed directly against the ground truth (cytotoxicity assay) without human interpretation in a human-in-the-loop scenario. The device itself produces the qualitative "positive" or "negative" result.
The type of ground truth used:
- The primary ground truth used for the clinical studies was a cytotoxicity assay, which detects biologically active C. difficile toxins.
- For discrepant analysis, a PCR-based molecular method (tcdB gene detection) was used as a secondary reference.
The sample size for the training set:
- The document does not report a separate training set size. This is common for traditional in vitro diagnostic (IVD) devices like this immunochromatographic assay, which are based on biochemical reactions and antibody binding, rather than machine learning algorithms that typically require extensive training data. The "training" in this context would be the development and optimization of the assay itself.
How the ground truth for the training set was established:
- As there is no explicit "training set" in the context of machine learning, there's no ground truth established for it. The assay's performance characteristics (e.g., analytical sensitivity, cross-reactivity) are established using purified toxins or cultured microorganisms, which serve as known positive and negative controls during the assay development and validation phases.

Summary

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510(k) Summary of Safety and Effectiveness Section 5.

This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is:K102242

Sponsor/Applicant Name and Address 1.

Company Name:	Genzyme Diagnostics
Address:	31 New York AvenueFramingham, MA 01701-9322
Telephone:	508-661-1154
Contact Person:	Carol C. RyersonDirector, Regulatory Affairs
Date Summary Prepared:	08/05/2010

Device Name and Classification

Trade Name:	OSOM C. difficile Toxin A/B Test
Classification of Device:	21 CFR 866.2660 Microorganismdifferentiation and identification device;reagents, Clostridium difficile toxin
Product Code:	LLH
Classification:	Class I

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3. Predicate Device

K041951 – Remel Xpect® Clostridium difficile Toxin A/B

Device Description 4.

5. Intended Use

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Comparison to Predicate Device 6.

The Table below provides a summary of the device characteristics for the OSOM C. difficile Toxin A/B Test and the predicate device.

Device Characteristics	OSOM C. difficileToxin A/B Test[New Device]	Remel Xpect C. difficileToxin A/B test[Predicate/ K041951]
Intended Use	An immunochromatographicassay intended for the qualitativedetection of Clostridium difficiletoxins A and/or B in human stoolsamples. Intended as an aid inthe diagnosis of Clostridiumdifficile-associated disease(CDAD) in patients withsymptoms of CDAD.	A rapid in vitroimmunochromatographic test forthe direct, qualitative detectionof Clostridium difficile Toxin Aand/or B in human fecalspecimens from patientssuspected of having Clostridiumdifficile-associated disease(CDAD). Intended for use as anaid in diagnosis of CDAD.
Specifically detecting:	Qualitative C. DifficileToxin A/B	Qualitative - C. DifficileToxin A/B
Specimen	Human fecal specimen	Human fecal specimen
Assay Method	Immunochromatographicdipstick technology	Immunochromatographicmembrane assay
Antibodies	Capture: goat polyclonal anti-Toxin A and rabbit polyclonalanti-Toxin BDetection: goat polyclonal anti-Toxin A and mouse monoclonalanti-Toxin B	Capture: mouse anti-Toxin A andrabbit anti-Toxin BDetection: Biotinylated goat anti-Toxin A and rabbit anti-Toxin B
Sample Volume	Solid stool: pea-sized portionusing applicator stick providedLiquid stool: 0.05 mL	Solid stool: 0.2gLiquid stool: 0.2 mL
Assay Time	20 minutes	20 minutes

Table 1: Comparison of Technological Characteristics of Genzyme OSOM C. difficile Toxin A/B Test with Legally Marketed Device

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7. Summary of Performance Data

Clinical Performance. A clinical trial was conducted at five sites in the United States to establish the clinical sensitivity and clinical specificity of the OSOM C. difficile Toxin A/B Test in detecting Clostridium difficile toxins A and/or B in human stool samples. Qualitative results obtained using the OSOM C. difficile Toxin A/B Test were compared with those determined by cytotoxicity assay.

De-identified excess loose or watery stool specimens were obtained from patients at or over the age of 18 years whose stool specimen had been submitted to the laboratory for C. difficileassociated disease (CDAD) testing. Specimens were tested with the OSOM C. difficile Toxin A/B Test within 72 hours of receipt. The cytotoxicity assay was performed at Genzyme using a standard C. difficile toxin cytotoxicity assay. Those performing the cytotoxicity assay testing were blinded to the OSOM test results.

The total incidence rate observed in this study for C. difficile associated disease (CDAD) based on the cytotoxicity assay results was 8.0% (102/ 1274). The overall sensitivity, specificity and accuracy of the OSOM test compared to cytotoxicity assay are shown in the table below.

		Cytotoxin
		+	-	Total
OSOM®C. difficileToxin A/BTest	+	90	37	127
	-	12	1135	1147
Total		102	1172	1274
Sensitivity: $90/102 = 88.2%$ (95% CI, 80.5 - 93.1%)
Specificity: $1135/1172 = 96.8%$ (95% CI, 95.7 - 97.7%)
Agreement: $1225/1274 = 96.2%$ (95% CI, 95.1 - 96.9%)

Table 2: OSOM C. difficile Toxin A/B Test Performance vs. Cytotoxicity Assay
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Discrepant testing was performed with a commercially available PCR-based molecular method which detects the tcdB gene. Note this PCR method does not detect biologically active protein or Toxin A gene. Twelve of twelve specimens that were cytotoxin positive and OSOM C. difficile

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Toxin A/B negative were positive for the presence of tcdB gene. Of the 37 specimens that were cytotoxin negative and OSOM C. difficile Toxin A/B positive, 30 of 36 were negative for the tcdB gene, 6 were positive for the tcdB gene, 1 specimen was not available for testing by PCR.

Performance of OSOM C. difficile Toxin A/B Test and the Predicate Device Compared to Cytotoxicity Assay .

The performance of the OSOM C. difficile Toxin A/B Test and a commercially available predicate device were compared to cytotoxicity assay results (see Table 3). All immunoassay device testing was performed at a clinical trial site. A total of 250 paired sample results (OSOM and Predicate Device) were included in this comparison. The performance of the Predicate Device and OSOM tests were compared to the results from the cytotoxicity assay.

Table 3: Performance of OSOM C. difficile Toxin A/B Test and a Commercially Available Lateral Flow Assay Compared to Cytotoxicity Assay (CTA)

		Cytotoxin		Total
		+	-
OSOM C.difficile ToxinA/B Test	+	42	20	62
	-	6	182	188
	Total	48*	202	250

1 sample gave an invalid OSOM test result with the frozen sample - no internal control line appeared even on repeat; included in the analysis as an incorrect result for purposes of comparison.

		Cytotoxin		Total
ﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤ		+
Predicate	+	34	5	રૂત્વે
Device		14	197	211
	Total	48	202	250

Sensitivity: 87.5% (42/48; 95% CI, 75.3 - 94.1%) Specificity: 90.1% (182/202; 95% CI, 85.2 - 93.5%)

Sensitivity: 70.8% (34/48; 95% Cl, 56.8 - 81.8%) tal Specificity: 97.5% (197/202; 95% Cl, 94.3 - 98.9%)

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Analytical Sensitivity. The OSOM C. difficile Toxin A/B Test detected 15 ng/mL for Toxin A and 40 ng/mL Toxin B. These studies were conducted with three representative lots of the OSOM C. difficile Toxin A/B Test using a serial dilution series prepared from purified C. difficile toxin A and toxin B in a buffer matrix.

Cross-Reactivity. The OSOM C. difficile Toxin A/B Test was evaluated with bacterial and viral isolates. All testing was performed in a diarrhea matrix except where noted. Cross-reactivity testing was performed with materials obtained from ATCC. Bacterial isolates were tested at a concentration of 10° cfu/mL except where noted. All viruses were cultured to ensure viability and tested at the specified concentrations. All bacteria listed gave negative responses. All viruses listed produced negative responses.

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Aeromonas hydrophila	Escherichia coli
Bacillus cereus	Escherichia coli sero:0157
Bacillus subtilis	Escherichia coli type 0124:NM (ETEC)
Bacteroides fragilis	Escherichia coli type o78:k80:h12 (EIEC)
Campylobacter coli	Giardia lamblia2
Campylobacter fetus	Helicobacter pylori
Campylobacter jejuni	Klebsiella pneumoniae
Candida albicans	Peptostreptococuss anaerobius
Clostridium difficile (non-toxigenic)	Porphyromonas asaccharolytica
Clostridium beijerinckii	Proteus vulgaris
Clostridium haemolyticum	Pseudomonas aeruginosa
Clostridium histolyticum	Salmonella typhimurium
Clostridium novyi	Serratia liquefaciens
Clostridium perfringens3	Shigella dysenteriae2
Clostridium septicum	Shigella flexneri
Clostridium sordellii	Shigella sonnei
Clostridium sporogenes	Staphylococcus aureus (Cowan's serotype 1)
Clostridium tetani	Staphylococcus aureus
Cryptosporidium parvum1	Staphylococcus epidermidis
Enterobacter aerogenes	Vibrio cholerae3
Enterobacter cloacae	Vibrio parahaemolyticus
Enterococcus faecalis	Yersinia enterocolitica

Table 3: Organisms tested at 10° cfu/mL except where noted

l Tested at 0.91x106 cfu/mL

² Tested at 1 x 10⁶ cfu /mL

2 Tested at 1x10* cfu /mL
3 Tested 1x10* cfu /mL in a buffer matrix

	TCID50/mL
Human adenovirus 40 (strain Dugan)	5.25x104
Human coxsackievirus B4 (strain J.V.B)	2.34x104
Human cytomegalovirus (strain Towne)	1.86x102
Human echovirus 22 (strain Harris)	4.79x106
Human enterovirus 69 (strain Toluca – 1)	9.55x104
Human rotavirus (strain HRV-408)	1.62x102

Table 4: Viruses tested at specified concentrations
-----------------------------------------------------

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Interfering Substances. The following potential interferents were tested and were found to have no effect on the performance of the OSOM C. difficile Toxin A/B Test.

Potential Interferent	Concentration
Barium sulfate	5% w/v
Fecal fat	5% w/v
Hemorrhoidal Cooling Gel	5% v/v
Imodium® AD caplets	5% w/v
Kaopectate®	5% v/v
KY Jelly	5% v/v
Metronidazole	0.25% w/v
Mucin	3.5% w/v
Pepto Bismol®	5% v/v
Vancomycin	0.25% w/v
Whole blood	40% v/v

Table 5: Exogenous Substances

Reproducibility. Reproducibility studies were performed by two laboratory personnel per day at two external clinical laboratories and one internal site, on a coded panel that contained synthetic stool samples representing both negative and positive C. difficile Toxin A and Toxin B samples. Testing occurred twice per day over a period of 5 days for 120 total test results for each of the three sites. Each operator tested a coded panel of 12 samples: 3 negative samples, 3 high negative samples, 3 low positive samples and 3 moderate positive samples. The OSOM C. difficile Toxin A/B Test gave the expected result 99.2% (357/360) of the time.

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8. Conclusion

The information presented in this Premarket Notification demonstrates the performance of the OSOM C. difficile Toxin A/B Test for use with human stool samples is substantially equivalent in intended use, technological characteristics, and performance to the predicate device, thereby supporting 510(k) clearance.

Equivalence was demonstrated using manufactured reagents along with patient and quality control samples containing C. difficile toxins A and B.

The studies in this submission demonstrate the substantial equivalence of the OSOM C. difficile Toxin A/B Test to products already marketed for the qualitative detection of Clostridium difficile in human stool specimens.

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Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993

Genzyme Diagnostics c/o Ms. Carol C. Ryerson Director, Regulatory Affairs 31 New York Avenue Framingham, MA 01701-9322

DEC 2 1 250

Re: K102242

Trade/Device Name: OSOM C. difficile Toxin A/B Test Regulation Number: 21 CFR 866.2660 Regulation Name: Microorganism differentiation and identification device Regulatory Class: Class I Product Code: LLH Dated: December 8, 2010 Received: December 9, 2010

Dear Ms. Ryerson:

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 ffor 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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000

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Page 2 - Carol C. Ryerson

electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. 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 Part 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 yours,

Valla, aAr

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

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Indications for Use

DEC 2 1 2010

510(k) Number (if known): _ K102242

OSOM C. difficile Toxin A/B Test Device Name:

Indications For Use:

Prescription Use X (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)

Raguel Peat acting Associate Director
Division Sign-Off for Freddie Poole

Office of In Vitro Diagnostic Device Evaluation and Safety

Page 1 of 1

K102242 ﺔ ﺍﻟﻤﺮﺍﺟﻊ

Regulation Number and Section

§ 866.2660 Microorganism differentiation and identification device.

(a)
Identification. A microorganism differentiation and identification device is a device intended for medical purposes that consists of one or more components, such as differential culture media, biochemical reagents, and paper discs or paper strips impregnated with test reagents, that are usually contained in individual compartments and used to differentiate and identify selected microorganisms. The device aids in the diagnosis of disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.