(89 days)
The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic gram-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.
This particular submission is for updated susceptibility test interpretative criteria for Enterobacteriaceae and Pseudomonas aeruginosa, as well as expanding Salmonella ser. Typhi interpretative criteria to all Salmonella spp. for the antimicrobial ciprofloxacin (Cp) at concentrations of 0.004 to 8 µg/mL to the test panel.
Ciprofloxacin has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in clinical infections against:
Citrobacter koseri Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Morganella morganii Proteus mirabilis Proteus vulgaris Providencia rettgeri Providencia stuartii Pseudomonas aeruginosa Salmonella ser.Typhi Serratia marcescens Shigella flexneri Shigella sonnei Active in vitro but clinical significance unknown: Enterobacter aerogenes, Klebsiella oxytoca, Salmonella enteritidis
MicroScan Dried Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
This document describes the validation of the Beckman Coulter MicroScan Dried Gram-Negative MIC/Combo Panels with Ciprofloxacin (Cp) for updated susceptibility test interpretative criteria for Enterobacteriaceae and Pseudomonas aeruginosa, and expanding Salmonella ser. Typhi interpretative criteria to all Salmonella spp. for ciprofloxacin.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them:
1. Acceptance Criteria and Reported Device Performance
The device is assessed based on two primary metrics: Essential Agreement (EA) and Categorical Agreement (CA), when compared to a CLSI frozen Reference Panel.
| Organism Group | Acceptance Criteria (EA) | Reported Performance (EA) | Acceptance Criteria (CA) | Reported Performance (CA) |
|---|---|---|---|---|
| Enterobacteriaceae (except Salmonella spp.) | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 93.9% | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 98.0% |
| Salmonella spp. | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 100.0% | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 95.2% |
| Pseudomonas aeruginosa | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 96.8% | Not explicitly stated, but based on guidance, generally high for AST devices (often >90%) | 91.4% |
Note: While specific numerical acceptance criteria for EA and CA are not explicitly given in the provided text, the statement "acceptable performance" and the context of FDA guidance for Antimicrobial Susceptibility Test (AST) Systems implies that the reported percentages met pre-defined thresholds, typically very high for these types of devices (e.g., >90% or >95%). The FDA's "Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems" would contain the precise acceptance criteria.
2. Sample Size and Data Provenance
- Test Set Sample Size: The exact number of isolates for each organism group (Enterobacteriaceae, Salmonella spp., Pseudomonas aeruginosa) is not explicitly stated as a numerical count in the provided text. However, the study "conducted with fresh, recent and stock Efficacy isolates and stock Challenge strains" implies a sufficient number of samples were used to achieve the reported agreement percentages. For AST devices, these involve hundreds, if not thousands, of unique isolates.
- Data Provenance: The text states "The external evaluations were conducted with fresh, recent and stock Efficacy isolates and stock Challenge strains." This suggests a combination of retrospective (stock strains) and prospective (fresh, recent isolates) data. The country of origin is not specified, but given the company (Beckman Coulter, Inc., West Sacramento, California) and the FDA submission, it is highly likely the data includes isolates from the United States and potentially other regions relevant to the target clinical population.
3. Number of Experts and Qualifications
This information is not provided in the given document. For AST device validation, ground truth is typically established by laboratory methods, not expert human readers.
4. Adjudication Method
This information is not applicable as the ground truth is based on a reference laboratory method (CLSI frozen Reference Panel), not on human expert reads requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
A multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study is more relevant for diagnostic imaging devices where human interpretation of images is a key component, and AI assists in that interpretation. For Antimicrobial Susceptibility Testing (AST) devices, the focus is on the device's ability to produce accurate Minimum Inhibitory Concentration (MIC) values and categorical interpretations (Susceptible, Intermediate, Resistant) compared to a gold standard laboratory method.
6. Standalone (Algorithm Only) Performance
The study primarily evaluates the standalone performance of the MicroScan Dried Gram-Negative MIC/Combo Panels. The device determines MIC values and susceptibility categories. While it can be "read either visually or with MicroScan instrumentation," the core performance metrics (EA and CA) are for the device's output, not for human-in-the-loop performance. The comparison is against a CLSI frozen Reference Panel, which is a laboratory standard, making this a standalone performance assessment.
7. Type of Ground Truth Used
The ground truth used was a CLSI frozen Reference Panel. This is considered a gold standard in microbiology for determining antimicrobial susceptibility, based on established Clinical and Laboratory Standards Institute (CLSI) guidelines. It represents the accepted accurate determination of MICs.
8. Sample Size for the Training Set
The document does not provide information regarding the training set sample size. This submission focuses on the validation or test performance of the device. The development and training details of the underlying system (e.g., if any machine learning models were used for automated reading) are not disclosed in this summary.
9. How the Ground Truth for the Training Set Was Established
Since the document does not provide information on a training set, it does not elaborate on how ground truth for a training set was established. For AST devices, development typically involves extensive testing against reference methods in a continuous improvement process, which implicitly trains the system to accurately determine MICs.
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March 20, 2020
Beckman Coulter, Inc Elaine Duncan Senior Analyst Regulatory Affairs 1584 Enterprise Blvd. West Sacramento, California 95691
Re: K193536
Trade/Device Name: MicroScan Dried Gram Negative MIC/Combo Panels with Ciprofloxacin (Co) (0.004 - 8ug/mL) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial susceptibility test powder Regulatory Class: Class II Product Code: LTT, JWY, LRG, LTW
Dear Elaine Duncan:
The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated March 18, 2020. Specifically, FDA is updating this SE Letter as an administrative correction.
Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Ribhi Shawar, OHT7: Office of In Vitro Diagnostics and Radiological Health, at 301-796-6698 or Ribhi.Shawar@fda.hhs.gov.
Sincerely,
Ribhi Shawar -S
Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
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March 18, 2020
Beckman Coulter, Inc Elaine Duncan Senior Analyst Regulatory Affairs 1584 Enterprise Blvd. West Sacramento, California 95691
Re: K193536
Trade/Device Name: MicroScan Dried Gram Negative MIC/Combo Panels with Ciprofloxacin (Cp) (0.004 - 8ug/mL) Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: Class II Product Code: LTT. JWY. LRG. LTW Dated: December 18, 2019 Received: December 20, 2019
Dear Elaine Duncan:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 Part
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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE(@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar -S
Ribhi Shawar, Ph.D. (ABMM) Chief General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name
MicroScan Dried Gram-Negative MIC/Combo Panels with Ciprofloxacin (Cp) (0.004 - 8 ug/mL)
Indications for Use (Describe)
The MicroScan Dried Gram-Negative MIC/Combo Panel is used to determine qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic gram-negative bacilli. After inoculation, panels are incubated for 16 - 20 hours at 35°C +/- 1°C in a non-CO2 incubator, and read either visually or with MicroScan instrumentation, according to the Package Insert.
This particular submission is for updated susceptibility test interpretative criteria for Enterobacteriaceae and Pseudomonas aeruginosa, as well as expanding Salmonella ser. Typhi interpretative criteria to all Salmonella spp. for the antimicrobial ciprofloxacin (Cp) at concentrations of 0.004 to 8 µg/mL to the test panel.
Ciprofloxacin has been shown to be active in vitro against most strains of microorganisms listed below, as described in the FDA-approved package insert for this antimicrobial agent.
Active in vitro and in clinical infections against:
Citrobacter koseri Citrobacter freundii Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Morganella morganii Proteus mirabilis Proteus vulgaris Providencia rettgeri Providencia stuartii Pseudomonas aeruginosa Salmonella ser.Typhi Serratia marcescens Shigella flexneri Shigella sonnei Active in vitro but clinical significance unknown: Enterobacter aerogenes, Klebsiella oxytoca, Salmonella enteritidis
Type of Use (Select one or both, as applicable)
X | Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/4/Picture/0 description: The image shows the logo for Beckman Coulter. The logo consists of a red circular graphic on the left, with two curved white lines inside. To the right of the graphic are the words "BECKMAN" in bold, followed by "COULTER" in a larger, bold font.
510(k) Summarv
510(k) Submission Information:
| Device Manufacturer: | Beckman Coulter |
|---|---|
| Contact name: | Elaine Duncan, Senior Analyst Regulatory Affairs |
| Phone: | 916-374-3279 |
| Fax: | 916-374-2480 |
| Date prepared: | December 02, 2019 |
| Product Name: | Microdilution Minimum Inhibitory Concentration (MIC) Panels |
| Trade Name: | MicroScan Dried Gram-Negative MIC/Combo Panels with Ciprofloxacin (Cp) (0.004 -8 µg/mL) |
| Intended Use: | To determine antimicrobial agent susceptibility |
| Classification: | Class II |
| Product Code: | LTT |
| 510(k) Notification: | Updated Breakpoints - Ciprofloxacin |
| Predicate device: | MicroScan Dried Gram-Negative MIC/Combo Panels Meropenem - (K192355) |
510(k) Summary:
MicroScan Dried Gram-Negative MIC/Combo Panels are designed for use in determining quantitative and/or qualitative antimicrobial agent susceptibility of colonies grown on solid media of rapidly growing aerobic and facultative anaerobic gram-negative bacilli.
The antimicrobial susceptibility tests are miniaturizations of the broth dilution susceptibility test that have been diluted in broth and dehydrated. Various antimicrobial agents are diluted in broth to concentrations bridging the range of clinical interest. Panels are rehydrated with water after inoculation with a standardized suspension of the organism. After incubation in a non-CO2 incubator for 16-20 hours, the minimum inhibitory concentration (MIC) for the test organism is read by determining the lowest antimicrobial concentration showing inhibition of growth.
The proposed MicroScan Dried Gram-Negative MIC/Combo Panel demonstrated substantially equivalent performance when compared with a CLSI frozen Reference Panel, as defined in the FDA document " Class II Special Controls Guidance Document: Antimicrobial Susceptibility Test (AST) Systems; Guidance for Industry and FDA", dated August 28, 2009. The Premarket Notification (510[k]) presents data in support of the MicroScan Dried Gram-Negative MIC/Combo Panel with ciprofloxacin.
The external evaluations were conducted with fresh, recent and stock Efficacy isolates and stock Challenge strains. The external evaluations were designed to confirm the acceptability of the proposed Dried Gram-Negative Panel by comparing its performance with a CLSI frozen Reference panel. The Dried Gram-Negative Panel inculated with Prompt® and read on the WalkAway instrument demonstrated acceptable performance with an Enterobacteriaceae except Salmonella spp. Essential Agreement (EA) of 93.9% and Categorical Agreement (CA) of 98.0%, Enterobacteriaceae for Salmonella spp. EA of 100.0% and CA of 95.2%, and Pseudomonas aeruginosa EA of 96.8% and CA of 91.4% for ciprofloxacin when compared with the frozen Reference panel.
Inoculum and instrument reproducibility testing demonstrated acceptable reproducibility and precision with ciprofloxacin, regardless of which inoculum method (i.e., Turbidity or Prompt®), or instrument (autoSCAN-4 instrument or WalkAway system) was used.
Quality Control testing demonstrated acceptable results for ciprofloxacin.
Beckman Coulter, the stylized logo, and the Beckner Coulter product and service marks or registered trademarks of Beckman Coulter. Inc. in the United States and other countrie
Prompt is a registered trademark of 3M Company, St. Paul, MN USA
§ 866.1640 Antimicrobial susceptibility test powder.
(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).