Mueller Hinton Agar is a standard basal medium intended for in vitro antimicrobial disk diffusion susceptibility testing of isolated colonies of common, rapidly growing bacteria by the Bauer-Kirby method as standardized by the Clinical and Laboratory Standards Institute (CLSI). This product has not been evaluated for gradient diffusion testing.

Device Description

Mueller Hinton Agar is a standard basal medium intended for in vitro antimicrobial disk diffusion susceptibility testing of isolated colonies of common, rapidly growing bacteria by the Bauer-Kirby method standardized by the Clinical and Laboratory Standards Institute (CLSI). This product has not been evaluated for gradient diffusion testing.

The Bauer-Kirby procedure is based on the diffusion through an agar gel of antimicrobial substances which are impregnated on sterile paper disks. This method employs disks with a sinqle concentration of antimicrobial agent and zone sizes are correlated with minimum inhibitory concentrations. In the test procedure, a standardized suspension of the organism is swabbed over the entire surface of the agar medium. Sterile paper disks impregnated with specified amounts of antibiotic or other antimicrobial agents are then placed on the surface of the inoculated agar medium. The agar medium is incubated at 35+ 2°C for 16-18 hours. The organism will grow as a solid "lawn". The antimicrobial will diffuse outward (in a circle). If the antimicrobial agent has activity against the organism, a circular zone of growth inhibition will result. The zone of inhibition around the paper disk is measured. A determination as to whether the organism is susceptible, intermediate or resistant to the antimicrobial agent is determined by comparing the size of the zone of inhibition to the zone diameter interpretive criteria in the CLSI M100 Standard.

AI/ML Overview

Here's an analysis of the provided information regarding the Mueller Hinton Agar device, structured according to your request:

Acceptance Criteria and Device Performance Study

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Acceptable performance for each organism-antimicrobial combination: test results falling within the acceptable range ≥95% of the time, as indicated by the antimicrobial-specific FDA drug label or CLSI Standards M100-S24 or M02-A11.	Escherichia coli ATCC 25922: 99.7% of results within expected range (969/972). Staphylococcus aureus ATCC 25923: 99.4% of results within expected range (644/648). Pseudomonas aeruginosa ATCC 27853: 99.8% of results within expected range (467/468). Enterococcus faecalis ATCC 29212: 100% of results within expected range (72/72). Enterococcus faecalis ATCC 51299: 100% of results within expected range (144/144). Escherichia coli ATCC 35218: 100% of results within expected range (360/360).
Adequate levels of thymine and thymidine (indicated by results for Enterococcus faecalis ATCC 29212 with trimethoprim/sulfamethoxazole being within range).	The results of the testing for Enterococcus faecalis ATCC 29212 with trimethoprim/sulfamethoxazole were within range.
Adequate levels of calcium and magnesium (indicated by results for Pseudomonas aeruginosa ATCC 27853 with gentamicin and tobramycin being within range).	The results of the testing for Pseudomonas aeruginosa ATCC 27853 with gentamicin and tobramycin were within range.

2. Sample size used for the test set and the data provenance

Test Set Sample Size: The sample size varies per organism-antimicrobial combination.
- For most organism-antimicrobial combinations, a total of 72 results were generated (3 sites x 3 separate days x 2 duplicate tests x 2 lots of Mueller Hinton Agar x 2 different manufacturers of antimicrobial disks).
- For Ceftaroline, High Level Gentamicin, and High Level Streptomycin, a total of 36 results were generated (only one manufacturer of antimicrobial disks available).
- The total number of individual test results presented are:
  - Escherichia coli ATCC 25922: 972
  - Staphylococcus aureus ATCC 25923: 648
  - Pseudomonas aeruginosa ATCC 27853: 468
  - Enterococcus faecalis ATCC 29212: 72
  - Enterococcus faecalis ATCC 51299: 144
  - Escherichia coli ATCC 35218: 360
Data Provenance: The study was a "multi-site reproducibility study" conducted with "CLSI recommended quality control organisms from American Type Culture Collection (ATCC)". The document implies it was a prospective study specifically designed for the 510(k) submission. The country of origin for the data is not explicitly stated, but given the submission to the FDA and reference to CLSI standards, it is highly likely to be the USA.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This type of study (in vitro diagnostic for microbial susceptibility) does not typically involve human experts establishing a "ground truth" for each individual test result in the same way an imaging study would. The ground truth (acceptable range) is established by:

Antimicrobial-specific FDA drug label: These labels are based on extensive clinical trials and regulatory review, involving many experts in microbiology, pharmacology, and clinical medicine.
CLSI Standards M100-S24 or M02-A11: These standards are developed by consensus of numerous international experts in clinical microbiology, including microbiologists, infectious disease physicians, and laboratory scientists.
Therefore, the "ground truth" is derived from a consensus of a large, unnamed group of highly qualified experts in the field of clinical microbiology and infectious diseases, codified in widely accepted standards.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Not applicable. This study measures the zone of inhibition, which is a quantitative measurement compared against predefined interpretive criteria (acceptable range). There is no subjective interpretation requiring adjudication by multiple readers for individual test results.

5. 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

Not applicable. This is an in vitro diagnostic device for antimicrobial susceptibility testing, not an AI-based diagnostic platform for human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, this was a standalone performance study of the Mueller Hinton Agar medium itself. The performance was evaluated based on the quantitative measurement of inhibition zones, with the interpretation of these zones determined by established CLSI standards and FDA drug labels, not by a human interpreting a visual output from an AI algorithm.

7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)

The ground truth used is expert consensus and regulatory/scientific standards. Specifically, the acceptable ranges for zone of inhibition measurements are derived from:

Antimicrobial-specific FDA drug labels.
CLSI Standards M100-S24 (Performance Standards for Antimicrobial Susceptibility Testing) or M02-A11 (Performance Standards for Antimicrobial Disk Susceptibility Tests). These standards represent the consensus of experts in clinical microbiology.

8. The sample size for the training set

Not applicable. This is not an AI/machine learning device that requires a training set. The study evaluated the intrinsic performance of the agar medium itself.

9. 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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K132491

JUN 3 0 2014

Mueller Hinton Agar

Traditional 510(k) Submission

Edge Biologicals, Inc.

510 (k) SUMMARY

This summary of 510(k) safety and effectiveness is submitted in accordance with the requirements of 21 CRF 807.92

510(k) Number:	K132491
Submitter:	Edge Biologicals, Inc.598 N 2nd StreetMemphis, Tennessee 38105
Contact Person:	Ted Pearson
	Telephone: 901-523-0034
	Fax: 901-527-3343
	E-mail: pearson@edgebiological.com
Date Prepared:	May 30, 2014
Trade Name:	Mueller Hinton Agar
Common Name:	Mueller Hinton Agar
Device Class:	II
Classification Name:	21 CFR 866.1700Culture Medium for Antimicrobial Susceptibility TestsProduct Code - JTZ
Predicate Device:	Mueller Hinton Agar with 5% Sheep BloodBecton Dickinson (K960420)

510(k) Summary:

Mueller Hinton Agar is a standard basal medium intended for in vitro antimicrobial disk diffusion susceptibility testing of isolated colonies of common, rapidly growing bacteria

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by the Bauer-Kirby method standardized by the Clinical and Laboratory Standards Institute (CLSI). This product has not been evaluated for gradient diffusion testing.

Summary of Substantial Equivalence Testing:

Mueller Hinton Agar was evaluated in a multi-site reproducibility study. Antimicrobial disk diffusion susceptibility testing was conducted, according to the CLSI Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard, M02-A11. Vol. 32, No. 1 at three sites, on three separate days. Six bacterial strains representing Gram negative and Gram positive rapidly growing (non-fastidious) CLSI recommended quality control organisms from American Type Culture Collection (ATCC) were included in the study (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853. Enterococcus faecalis ATCC 29212. Enterococcus faecalis ATCC 51299, and Escherichia coli ATCC 35218). Antimicrobials representing the major drug classes relevant to each organism were included in the study. Testing was conducted in duplicate using two different lots of Mueller Hinton Agar, and antimicrobial disks from two different manufacturers, resulting in a total of 72 results for most orqanism-antimicrobial combinations. Antimicrobial disks from only one manufacturer were available at the time of testing for Ceftaroline, High Level Gentamicin, High Level Streptomycin, resulting in a total of 36 results for each of these antimicrobials.

The performance of Mueller Hinton Agar was evaluated relative to the acceptable range as indicated in the antimicrobial specific FDA drug label, or CLSI Standards M100-S24 or M02-A11. Acceptable performance for each organism-antimicrobial combination was determined as test results falling within the acceptable range ≥95% of the time.

Escherichia coli ATCC 25922 was tested against 14 antimicrobials. A total of three results were out of expected range. The percent of results within expected range was 99.7% (969/972).

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Staphylococcus aureus ATCC 25923 was tested against 10 antimicrobials. A total of four results were out of expected range. The percent of results within expected range was 99.4% (644/648).

Pseudomonas aeruginosa ATCC 27853 was tested against seven antimicrobials. One result was out of expected range. The percent of results within expected range was 99.8% (467/468).

Enterococcus faecalis ATCC 29212 was tested aqainst one antimicrobial. The percent of results within expected range was 100%(72/72).

Enterococcus faecalis ATCC 51299 was tested against three antimicrobials. The percent of results within expected range was 100% (144/144).

Escherichia coli ATCC 35218 was tested against five antimicrobials. The percent of results within expected range was 100% (360/360).

The levels of thymine and thymidine in Mueller Hinton Agar were evaluated by testing Enterococcus faecalis ATCC 29212 with trimethoprim/sulfamethoxazole. Excess amounts of thymine and thymidine can reverse the inhibitory effect of sulfonamides and trimethoprim, resulting in smaller, less distinct zones of inhibition or no zones at all. The results of the testing of this organism-antimicrobial combination were within range, indicating adequate levels of thymine and thymidine.

The levels of the cations calcium and magnesium in Mueller Hinton Agar were evaluated by testing Pseudomonas aeruginosa ATCC 27853 with the aminoglycosides gentamicin and tobramycin. Excess cation content results in reduced zone sizes, whereas low cation content results in unacceptably large zone sizes. The results of the testing of these antimicrobials were within range, indicating adequate levels of calcium and magnesium.

The results of the study for each organism-antimicrobial combination, were within acceptable range ≥95% of the time. This demonstrates that Mueller Hinton Agar is substantially equivalent to similar medium already in commercial distribution.

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Image /page/3/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three legs, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged in a circular fashion around the eagle. The eagle is black, and the text is also black.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

EDGE BIOLOGICALS, INCORPORATED TED PEARSON QUALITY ASSURANCE DIRECTOR 589 N 2ND STREET MEMPHIS TN 38105

June 30, 2014

Re: K132491

Trade/Device Name: Mueller Hinton Agar Regulation Number: 21 CFR 866.1700 Regulation Name: Culture medium for antimicrobial susceptibility tests Regulatory Class: II Product Code: JTZ Dated: June 12, 2014 Received: June 13, 2014

Dear Mr. Pearson:

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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 1000-1050.

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Page 2-Mr. Pearson

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Uwe Scherf -S for

Sally A. Hojvat Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K132491

Device Name: Mueller Hinton Agar

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 Center for Devices and Radiological Health (CDRH)

Image /page/5/Picture/10 description: The image shows the words "Ribhi Shawar-S" and "2014.06.26 16:11:42 -04'00'". The words are printed in black ink on a white background. The letters are large and easy to read. The image is likely a scan or photograph of a document.

Regulation Number and Section

§ 866.1700 Culture medium for antimicrobial susceptibility tests.

(a)
Identification. A culture medium for antimicrobial susceptibility tests is a device intended for medical purposes that consists of any medium capable of supporting the growth of many of the bacterial pathogens that are subject to antimicrobial susceptibility tests. The medium should be free of components known to be antagonistic to the common agents for which susceptibility tests are performed in the treatment of disease.(b)
Classification. Class II (performance standards).