(67 days)
Use of BBL Trovafloxacin Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Trovafloxacin has been shown to be active against most strains of microorganisms listed below, as described in the Roerig package insert for this antimicrobic.
Trovafloxacin Susceptibility Test Discs are prepared by impregnating high guality paper with accurately determined amounts of Trovafloxacin supplied by the manufacturer, Roerig. Each Trovafloxacin disc is clearly marked on both sides with the agent and content. Trovafloxacin discs are furnished in cartridges of 50 discs each. Trovafloxacin cartridges are packed as either a single cartridge in a single box, or in a package containing ten cartridges.
Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940's. In order to eliminate or minimize variability in the testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.
Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO). The procedure was adopted as a consensus standard by the National Committee for Clinical Laboratory Standards (NCCLS) and is periodically updated. The latest NCCLS documents are M2-A6 (1/97) and M100-S7 (1/97).
Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar plates {or Haemophilus Test Medium Agar for Haemophilus influenzae or Mueller Hinton Aqar with 5% Sheep Blood for Streptococcus pneumoniae] inoculated with pure cultures of clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the discs are measured and compared with established zone size ranges for individual antimicrobial agents in order to determine the agent(s) most suitable for use in antimicrobial therapy. The determination as to whether the organism in question is susceptible (S), intermediate (I), or resistant (R) to an antimicrobial agent is made by comparing zone sizes to those found in the respective organism tables of National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Sixth Edition, Approved Standard", 1/97) and of NCCLS Document M100-S8 ("Performance Standards for Antimicrobial Susceptibility Testing", Eighth Informational Supplement, 1/98).
Based on the provided text, here's an analysis of the acceptance criteria and study information for the Trovafloxacin Sensi-Discs:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" in a quantitative, pass/fail table format that is typical for modern device submissions. Instead, it relies on alignment with established industry standards for antimicrobial susceptibility testing. The accepted performance is essentially defined by adherence to these standards and the established zone size ranges for Trovafloxacin.
| Performance Metric/Criteria | Reported Device Performance |
|---|---|
| Zone Sizes for Interpretation | Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Roerig, a Division of Pfizer Inc., and received FDA approval under NDA Nos. 20-759 and 20-760. The determination as to whether the organism in question is susceptible (S), intermediate (I), or resistant (R) is made by comparing zone sizes to those found in the respective organism tables of National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Sixth Edition, Approved Standard", 1/97) and NCCLS Document M100-S8 ("Performance Standards for Antimicrobial Susceptibility Testing", Eighth Informational Supplement, 1/98). |
| Standardized Test Procedure Adherence | The device performance implicitly meets the acceptance criteria by conforming to standardized agar diffusion test procedures, specifically those based on the Bauer-Kirby method as adopted by the National Committee for Clinical Laboratory Standards (NCCLS), and documented in M2-A6 (1/97) and M100-S7 (1/97) and M100-S8 (1/98). |
| Activity against specified microorganisms (In Vitro and In Clinical Infections) | Demonstrated activity against the list of microorganisms provided (e.g., Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Haemophilus influenzae, Bacteroides fragilis, Chlamydia pneumoniae, etc.) as described in the Roerig package insert for Trovafloxacin. |
| Activity against specified microorganisms (In Vitro Only) | Demonstrated activity against the list of microorganisms provided for in vitro only (e.g., penicillin-resistant Streptococcus pneumoniae, Citrobacter freundii, Bacteroides distasonis, Mycoplasma hominis, etc.) as described in the Roerig package insert for Trovafloxacin. |
| Product Manufacturing Quality (e.g., accurate amounts of Trovafloxacin, clear marking) | "Trovafloxacin Susceptibility Test Discs are prepared by impregnating high quality paper with accurately determined amounts of Trovafloxacin supplied by the manufacturer, Roerig. Each Trovafloxacin disc is clearly marked on both sides with the agent and content." (This is a description of the product and implicitly a quality criterion). |
2. Sample Size Used for the Test Set and Data Provenance:
The document refers to "Performance Data: See attached Roerig product insert section on Susceptibility Tests - Diffusion Techniques for TROVAN™ Tablets (trovafloxacin mesylate tablets) and TROVAN™ I.V. (alatrofloxacin mesylate injection) for intravenous infusion."
- Sample Size: The specific sample size for the test set is not provided in the excerpt. It defers to the Roerig product insert, which is not included.
- Data Provenance: The document does not specify the country of origin of the data. It seems to refer to data generated by Roerig (a division of Pfizer Inc.), which is a pharmaceutical company. The type of data would be related to clinical trials and in vitro susceptibility testing that formed the basis for the drug's FDA approval (NDA Nos. 20-759 and 20-760). This would implicitly be prospective data collected during the drug's development.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts:
This information is not explicitly provided in the excerpt. The ground truth for antimicrobial susceptibility testing, especially for establishing zone size breakpoints, is typically determined through extensive in vitro and in vivo correlation studies, pharmacokinetic/pharmacodynamic modeling, and epidemiological cutoff values. This process involves numerous clinical microbiologists, pharmacologists, and infectious disease specialists, but their specific number and qualifications are not detailed for this submission. The document states that the zone sizes and control organism limits "were determined by the antimicrobic manufacturer, Roerig... and received FDA approval." This implies expert consensus and rigorous review by regulatory bodies.
4. Adjudication Method for the Test Set:
The document does not describe any adjudication method. For antimicrobial susceptibility testing, the "ground truth" (i.e., whether an organism is S, I, or R to an agent) is established by comparing measured zone sizes to predetermined interpretive criteria (breakpoints) set by standardized bodies like the NCCLS, which are themselves derived from extensive studies. It's not a subjective interpretation requiring adjudication in the way medical imaging might.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done:
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done or described. This type of study is highly relevant for subjective diagnostic interpretations (e.g., AI in radiology). Here, the device is a disc for in vitro laboratory testing, not a diagnostic imaging AI. The "readers" are laboratory technicians measuring zone diameters, which is a relatively objective measurement compared to interpreting complex clinical images.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done:
The device itself (Trovafloxacin Sensi-Discs) is not an "algorithm" in the AI sense. It's a consumable product used in a manual laboratory procedure.
However, the "performance data" referred to in the Roerig product insert would represent the standalone performance of the antimicrobial agent (Trovafloxacin) in determining susceptibility, based on the established zone size breakpoints. This is a form of standalone performance in that it evaluates the accuracy of the drug's activity and the interpretive criteria, independent of the specific disc manufacturer, as long as the disc meets quality standards (e.g., accurate drug concentration).
7. The Type of Ground Truth Used:
The ground truth used is primarily expert consensus based on extensive in vitro (microbiological) and in vivo (clinical outcomes) correlation data, pharmacokinetic/pharmacodynamic studies, and epidemiological cutoff values. This is distilled into the standardized interpretive criteria (zone size breakpoints) published by organizations like the NCCLS and approved by the FDA (as indicated by the references to NDA approvals for the drug itself). The product relies on the established validity of these breakpoints.
8. The Sample Size for the Training Set:
This information is not provided in the excerpt. The concept of a "training set" in the context of machine learning doesn't directly apply to this device. For the drug itself (Trovafloxacin), the data used to establish its activity profile and breakpoints would have involved a very large number of microbial isolates tested in vitro and patients treated in vivo.
9. How the Ground Truth for the Training Set Was Established:
Similar to point 8, the concept of a "training set" ground truth is not directly applicable. However, for the underlying interpretive breakpoints, the ground truth was established through:
- Clinical Efficacy Studies: For the drug Trovafloxacin, its efficacy against various microorganisms would have been established through clinical trials (human outcomes data).
- Microbiological Studies: Extensive in vitro testing of thousands of bacterial isolates to determine Minimum Inhibitory Concentrations (MICs) and correlate them with zone diameters.
- Pharmacokinetic/Pharmacodynamic (PK/PD) Modeling: Studies to understand how the drug behaves in the human body and how its concentration correlates with bacterial killing.
- Expert Panels: Review and approval by expert committees (e.g., NCCLS, FDA) who synthesize all available data to set the final interpretive criteria (susceptible, intermediate, resistant breakpoints).
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1 MAY
Date 2/20/98
SUMMARY OF SAFETY AND EFFECTIVENESS
SUBMITTED BY:
Virginia C. Weinknecht Requlatory Affairs Specialist Becton Dickinson Microbiology Systems 7 Loveton Circle Sparks, MD 21152-0999
NAME OF DEVICE:
| Trade Name: | Trovafloxacin, 10 µg, Sensi-Discs Catalog Numbers 4331715 and 4331716 |
|---|---|
| Common Name/Description: | Antimicrobial Susceptibility Test Discs |
| Classification Name: | Antimicrobial Susceptibility Test Discs |
| INDICATE DEVICE: | Other BBL® Sensi-Discs® such as Ciprofloxacin, 5 mcg, Sensi-Disc® |
DEVICE DESCRIPTION:
PRE
INTENDED USE:
Antimicrobial Susceptibility Test Discs are used for semi-quantitative in vitro susceptibility testing by standardized agar diffusion test procedures. Trovafloxacin Sensi-Discs® are intended for use in determining the susceptibility to Trovafloxacin of a wide range of bacteria, as described under Indications For Use below. Zone sizes used for interpretation of tests, including control organism limits, were determined by the antimicrobic manufacturer, Roerig, a Division of Pfizer Inc., and received FDA approval under NDA Nos. 20-759 and 20-760.
INDICATIONS FOR USE:
Use of BBL® Trovafloxacin Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Trovafloxacin. Trovafloxacin has been shown to
{1}------------------------------------------------
be active against most strains of microorganisms listed below, as described in the Roerig package insert for this antimicrobic.
Active In Vitro and In Clinical Infections Against:
Aerobic Gram-Positive Microorganisms Enterococcus faecalis (many strains are only moderately susceptible Staphylococcus aureus (methicillin-susceptible strains) Staphylococcus epidermidis (methicillin-susceptible strains) Streptococcus agalactiae Streptococcus pneumoniae (penicillin-susceptible strains) Streptococcus pyogenes Viridans group streptococci Aerobic Gram-Negative Microorganisms Escherichia coli Gardnerella vaginalis Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Moraxella catarrhalis Neisseria gonorrhoeae Proteus mirabilis Pseudomonas aeruginosa Anaerobic Microorganisms Bacteroides fragilis Peptostreptococcus species Prevotella species Other Microorganisms: Chlamydia pneumoniae Chlamvdia trachomatis Legionella pneumophila Mycoplasma pneumoniae
Active In Vitro Only Aqainst:
Aerobic Gram-Positive Microorganisms Streptococcus pneumoniae (penicillin-resistant strains) Aerobic Gram-Negative Microorganisms Citrobacter freundii Enterobacter aerogenes Morganella morganii Proteus vulgaris Anaerobic Microorganisms Bacteroides distasonis Bacteroides ovatus Clostridium perfringens
{2}------------------------------------------------
Active In Vitro Only Against (continued): Other Microorganisms: Mvcoplasma hominis Ureaplasma urealyticum
PRODUCT DESCRIPTION:
Trovafloxacin Susceptibility Test Discs are prepared by impregnating high guality paper with accurately determined amounts of Trovafloxacin supplied by the manufacturer, Roerig. Each Trovafloxacin disc is clearly marked on both sides with the agent and content. Trovafloxacin discs are furnished in cartridges of 50 discs each. Trovafloxacin cartridges are packed as either a single cartridge in a single box, or in a package containing ten cartridges.
Agar diffusion methods employing dried filter paper discs impregnated with specific concentrations of antimicrobial agents were developed in the 1940's. In order to eliminate or minimize variability in the testing, Bauer et al. developed a standardized procedure in which Mueller Hinton Agar was selected as the test medium.
Various regulatory agencies and standards-writing organizations subsequently published standardized reference procedures based on the Bauer-Kirby method. Among the earliest and most widely accepted of these standardized procedures were those published by the U.S. Food and Drug Administration (FDA) and the World Health Organization (WHO). The procedure was adopted as a consensus standard by the National Committee for Clinical Laboratory Standards (NCCLS) and is periodically updated. The latest NCCLS documents are M2-A6 (1/97) and M100-S7 (1/97).
Discs containing a wide variety of antimicrobial agents are applied to the surface of Mueller Hinton Agar plates {or Haemophilus Test Medium Agar for Haemophilus influenzae or Mueller Hinton Aqar with 5% Sheep Blood for Streptococcus pneumoniae] inoculated with pure cultures of clinical isolates. Following incubation, the plates are examined and the zones of inhibition surrounding the discs are measured and compared with established zone size ranges for individual antimicrobial agents in order to determine the agent(s) most suitable for use in antimicrobial therapy. The determination as to whether the organism in question is susceptible (S), intermediate (I), or resistant (R) to an antimicrobial agent is made by comparing zone sizes to those found in the respective organism tables of National Committee for Clinical Laboratory Standards (NCCLS) Document M2-A6 ("Performance Standards for Antimicrobial Disk Susceptibility tests - Sixth Edition, Approved Standard", 1/97) and of NCCLS Document M100-S8
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("Performance Standards for Antimicrobial Susceptibility Testing", Eighth Informational Supplement, 1/98).
PERFORMANCE DATA:
See attached Roerig product insert section on Susceptibility Tests - Diffusion Techniques for TROVAN™ Tablets (trovafloxacin mesylate tablets) and TROVAN™ I.V. (alatrofloxacin mesylate injection) for intravenous infusion.
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Image /page/4/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features a stylized caduceus, a symbol often associated with medicine and healthcare, with three intertwined snakes and a staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the caduceus. The seal is black and white.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAY 1 1998
1998
Virginia C. Weinknecht Regulatory Affairs Specialist Becton Dickinson Microbiology Systems 7 Loveton Circle Sparks, Maryland 21152-0999
Re: K980683 Trade Name: Trovafloxacin 10μg, Sensi-Disc® Regulatory Class: II Product Code: JTN Dated: February 20, 1998 Received: February 23, 1998
Dear Ms. Weinknecht:
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 requirement, as set forth in the Ouality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (OS) 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 (770)488-7655.
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 (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. 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 (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Sutman
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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Page 1 of 2 510(k) Number (if known):
Device Name: Trovafloxacin, 10 ug, Sensi-Disc®
Indications For Use:
Use of BBL Trovafloxacin Sensi-Discs® for in vitro agar diffusion susceptibility testing is indicated when there is a need to determine the susceptibility of bacteria to Trovafloxacin has been shown to be active against most strains of microorganisms listed below, as described in the Roerig package insert for this antimicrobic.
Active In Vitro and In Clinical Infections Against:
Aerobic Gram-Positive Microorganisms
Enterococcus faecalis (many only mod. suscept.) Streptococcus agalactiae Staphylococcus aureus (meth. suscept.) Streptococcus pneumoniae (pen. suscept.) Staphylococcus epidermidis (meth. suscept.) Streptococcus pyogenes Viridans group streptococci
Aerobic Gram-Negative Microorganisms
| Escherichia coli | Moraxella catarrhalis |
|---|---|
| Gardnerella vaginalis | Neisseria gonorrhoeae |
| Haemophilus influenzae | Proteus mirabilis |
| Haemophilus parainfluenzae | Pseudomonas aeruginosa |
| Klebsiella pneumoniae | |
| Anaerobic Microorganisms | |
| Bacteroides fragilis | Prevotella species |
| Peptostreptococcus species | |
| Other Microorganisms | |
| Chlamydia pneumoniae | Legionella pneumophila |
| Chlamydia trachomotis | Mycoplasma pneumoniae |
Active In Vitro Only Against:
| Aerobic Gram-Positive Microorganisms | |
|---|---|
| Streptococcus pneumoniae (penicillin-resistant strains) | |
| Aerobic Gram-Negative Microorganism | |
| Citrobacter freundii | Morganella morganii |
| Enterobacter aerogenes | Proteus vulgaris |
| Anaerobic Microorganisms | |
| Bacteroides distasonis | Clostridium perfringens |
| Bacteroides ovatus | |
| Other Microorganisms | |
| Mycoplasma hominis | Ureaplasma urealyticum |
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
| (Division Sign-Off) | |
|---|---|
| Division of Clinical Laboratory Devices | |
| 510(k) Number | K980683 |
OR
| Prescription Use Per 21 CFR 801.109 | Over-The-Counter Use Optional Format 1-2-96 |
|---|---|
| ------------------------------------- | --------------------------------------------- |
§ 866.1620 Antimicrobial susceptibility test disc.
(a)
Identification. An antimicrobial susceptibility test disc is a device that consists of antimicrobic-impregnated paper discs used to measure by a disc-agar diffusion technique or a disc-broth elution technique the in vitro susceptibility of most clinically important bacterial pathogens to antimicrobial agents. In the disc-agar diffusion technique, bacterial susceptibility is ascertained by directly measuring the magnitude of a zone of bacterial inhibition around the disc on an agar surface. The disc-broth elution technique is associated with an automated rapid susceptibility test system and employs a fluid medium in which susceptibility is ascertained by photometrically measuring changes in bacterial growth resulting when antimicrobial material is eluted from the disc into the fluid medium. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).