(156 days)
MDx-Chex for BCID2 is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of yeast, Gram positive and Gram negative bacteria, as vell as snciated antimicrobial resistance genes, by the BioFire FilmArray Blood Culture Identification 2 (BCID2) Panel on FilmArray systems. Control 1 - GN: Gram negative bacteria: Acinetobacter colcacer in complex, Baceronides fragilis, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella oxytoca, Klebsiella pneumats Jray, Proteus spp., Salmonella spp., Serratia marcescens, Heisseria vivoca, Neisseria meningitides, Poeudnonas aeruginosa, Stenotrophomonas matophilia; antimicrobial resistance genes: KPC, CTX-M, IMP, NDM, OXA-Ike, VIM, mcr- 1. Control 2 - GPY: Gram positive bacteria: Enterococcus face: 11, 27712-10, nr., iUDM, U.Steria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdumsis, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes; yeast: Candida dhicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans/gatit; animicrobial resistance genes mecA/C and MREJ, vanA/B. This product is not intended to replace manufacturer controls provided with the device.
MDx-Chex for BCID2 Control 1 - GN is positive for certain pathogens and antimicrobial resistance genes in the FilmArray BCID 2 panel and negative for those contained in MDx-Chex for BCID2 Control 2 - GPY. MDx-Chex for BCID2 Control 2 - GPY is positive for the remaining pathogen and antimicrobial resistance genes and negative for those present in MDx-Chex for BCID2 Control 1 - GN (see Table 1 below). Each control mix also contains and controls for blood and blood culture media components that have been identified as PCR inhibitors namely hemoglobin, leukocyte DNA, and anticoagulants. MDx-Chex for BCID2 is a quality control containing stabilized blood components, blood culture media components, and inactivated microorganisms resulting in a full-process, cellular-based control for the BioFire BCID2 Panel. Use of full-process cellular controls are necessary to evaluate the entire analytical process, including sample lysis, nucleic acid isolation and purification, amplification, detection, and analysis, as well as the impact of PCR inhibitors and preanalytical variables. Routine use of full process quality controls can help identify variations in the test system that can lead to incorrect results.
This document describes the performance of a quality control material (MDx-Chex for BCID2) for a qualitative detection assay (BioFire FilmArray Blood Culture Identification 2 (BCID2) Panel). Therefore, the "acceptance criteria" and "device performance" are related to the ability of this quality control material to consistently produce expected positive and negative results when tested with the BCID2 panel, along with its stability under various conditions.
The provided document describes a series of performance studies for the MDx-Chex for BCID2 device. Since this is a quality control material and not a diagnostic device that interprets clinical images or data, many of the typical acceptance criteria and study design elements of AI/ML-based diagnostic devices (e.g., number of experts, adjudication methods, MRMC studies) are not applicable here.
Here's an analysis based on the information provided, focusing on the relevant criteria for a quality control material:
1. Table of Acceptance Criteria and the Reported Device Performance:
The acceptance criterion across all relevant studies (Multi-Site Precision, Single-Site Precision, Lot-to-Lot Reproducibility, Closed-Vial Stability, Open-Vial Stability, Shipping Stability) is "overall positive and negative percent agreement of ≥ 95%" (except for Lot-to-Lot Reproducibility which states "≥ 90%").
| Test Study | Acceptance Criteria (Positive & Negative Percent Agreement) | Reported Device Performance (Combined PPA & NPA) |
|---|---|---|
| Multi-Site Precision (Reproducibility) | ≥ 95% | Positive: 95.8% (230/240) Negative: 99.6% (239/240) |
| Single-Site Precision (Repeatability) | ≥ 95% | Positive: 95% (114/120) Negative: 100% (120/120) |
| Lot-to-Lot Reproducibility | ≥ 90% (Note: Document states 90% for this test) | Positive: Lot 20363: 91.7%, Lot 20366: 100%, Lot 21129: 100% Negative: All Lots: 100% |
| Within-run Reproducibility | Not explicitly stated, but implies high agreement | Positive: 100% (12/12) Negative: 100% (12/12) |
| Closed-Vial Stability (Day 61+) | ≥ 95% | Positive: 2-8°C: 96.7%, 20-25°C: 100% Negative: 2-8°C: 98.3%, 20-25°C: 98.3% |
| Open-Vial Stability (Day 61+) | ≥ 95% | Positive: 2-8°C: 100%, 20-25°C: 95% Negative: 2-8°C: 100%, 20-25°C: 100% |
| Matrix Effect | 100% Agreement (for the specific findings) | MDx-Chex, Positive Matrix: 100% (3/3) Clinical, Positive Matrix: 100% (3/3) MDx-Chex, Negative Matrix: 100% (3/3) Clinical, Negative Matrix: 100% (3/3) |
| Shipping Stability | ≥ 95% | Positive: Summer: 95%, Winter: 100% Negative: Summer: 95%, Winter: 100% |
2. Sample size used for the test set and the data provenance:
- Multi-Site Precision (Reproducibility):
- Sample Size: 10 samples per control level (20 samples total per lot) were tested over 10 days at each of 4 sites. Three lots were used, totaling 240 expected results for positive agreement (4 sites * 20 samples/lot * 3 lots). The narrative indicates "230/240" for observed positive results and "239/240" for negative results (which means 240 expected negative results reported).
- Data Provenance: Prospective. Collected internally at Streck (La Vista, NE) and externally at UNMC (Omaha, NE), Children's Hospital and Medical Center (Omaha, NE), and Mary Lanning Healthcare (Hastings, NE). All locations are in the USA.
- Single-Site Precision (Repeatability):
- Sample Size: 20 samples per lot per level were tested by four operators over 20 non-consecutive days. Three lots were used. This totals 120 expected results for positive agreement (20 samples/lot/level * 2 levels * 3 lots, if pooling levels/lots for the single site precision table, or 2023 = 120 positive AND 120 negative). The table shows 114/120 for positive and 120/120 for negative.
- Data Provenance: Prospective. Collected at Streck (La Vista, NE), USA.
- Lot-to-Lot Reproducibility:
- Sample Size: 6 samples per control lot and level (12 total samples per lot). Three lots were tested. A total of 36 complete runs were generated. The tables show 12 expected results per lot for positive and negative agreements (12 expected positive results + 12 expected negative results, repeated for 3 lots).
- Data Provenance: Prospective. Likely collected at Streck (La Vista, NE), USA, as it states "Data from the first 6 timepoints in the repeatability study above were also used".
- Closed-Vial Stability:
- Sample Size: 10 samples per control lot and level. Three lots. Tested at Day 0 (baseline) and at least Day 61. For Day 0, 120 tubes were completed. For Day 61+, 60 tubes per storage condition (2-8°C and 20-25°C) across the three lots were tested.
- Data Provenance: Prospective. Likely collected at Streck (La Vista, NE), USA.
- Open-Vial Stability:
- Sample Size: Same as Closed-Vial Stability, 10 samples per lot per level, three lots, same time points.
- Data Provenance: Prospective. Likely collected at Streck (La Vista, NE), USA.
- Matrix Effect:
- Sample Size: Triplicate tests (3/3) for each matrix type (MDx-Chex positive, Clinical positive, MDx-Chex negative, Clinical negative).
- Data Provenance: Prospective. Likely collected at Streck (La Vista, NE), USA.
- Shipping Stability:
- Sample Size: Two sets of samples from one control lot were used. Ten samples of Control 1 and Control 2 were tested for each temperature profile (Summer, Winter). This results in 20 expected positive results and 20 expected negative results per temperature profile.
- Data Provenance: Prospective. Likely collected at Streck (La Vista, NE), USA.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
Not applicable. This is a quality control material where the "ground truth" is the expected positive or negative result for the specific analytes contained or not contained within the control sample, based on its formulation. The performance is assessed by how consistently the QC material produces these known results when run on the target diagnostic system (BioFire FilmArray BCID2 Panel).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. As noted above, the "ground truth" is inherent to the formulation of the quality control material itself (i.e., it is designed to be positive for certain targets and negative for others). Where initial false results occurred, the "correct results upon a single retest" are noted, which implies a re-run of the test and confirms the expected outcome for the control. This is a standard practice in QC testing to ensure an isolated error vs. a systemic issue.
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 not an AI/ML diagnostic device for human interpretation. It's a quality control material for an automated molecular diagnostic assay.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
The device (MDx-Chex for BCID2) is a physical control material. Its "standalone" performance is assessed by how accurately the BioFire FilmArray BCID2 Panel (the primary device it controls) identifies the known positive and negative components within the MDx-Chex material. The studies listed demonstrate this "standalone" performance of the control material with the primary diagnostic system. There is no "algorithm" per se being evaluated in terms of its diagnostic accuracy on clinical cases.
7. The type of ground truth used:
- Formulation-based Ground Truth: The ground truth for this quality control material is established by its known composition. The MDx-Chex for BCID2 Controls are manufactured to contain specific inactivated microorganisms and antimicrobial resistance genes (for positive results) or to be free of certain targets (for negative results), as detailed in Table 1 (pages 4-5).
- For the "Matrix Effect" study, "inactivated Streptococcus pneumoniae was spiked into the control matrix" and "into a BD BACTEC Plus Aerobic/F culture bottle with negative whole blood to simulate a clinical samples". The expected results are thus inherently known based on the spiking.
8. The sample size for the training set:
Not applicable in the conventional sense of training an AI/ML model for diagnostic purposes. This is a manufactured chemical/biological control product. Its "training" equivalent would be the R&D and manufacturing processes to ensure its consistent composition and stability. However, if looking for manufacturing lots/batches rather than a statistical training set: Most studies used three separately manufactured lots of the control material (Lot 20363, Lot 20366, Lot 21129) to demonstrate reproducibility and stability.
9. How the ground truth for the training set was established:
Not applicable as it's not an AI/ML model with a discrete training set. The "ground truth" for the characteristics of the product itself would be established through its design specifications, formulation, and in-house characterization during manufacturing.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
January 19, 2022
Streck, Inc Deborah Kipp Regulatory Affairs Manager 7002 S. 109th Street La Vista, Nebraska 68128
Re: K212576
Trade/Device Name: MDx-Chex for BCID2 Regulation Number: 21 CFR 866.3920 Regulation Name: Assayed Quality Control Material For Clinical Microbiology Assays Regulatory Class: Class II Product Code: PMN Dated: August 13, 2021 Received: August 16, 2021
Dear Deborah Kipp:
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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
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- 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 mediation-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, 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) K212576
Device Name MDx-Chex for BCID2
Indications for Use (Describe)
MDx-Chex for BCID2 is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of yeast, Gram positive and Gram negative bacteria, as vell as snciated antimicrobial resistance genes, by the BioFire FilmArray Blood Culture Identification 2 (BCID2) Panel on FilmArray systems. Control 1 - GN: Gram negative bacteria: Acinetobacter colcacer in complex, Baceronides fragilis, Enterobacter cloacae complex, Escherichia coli, Klebsiella oxytoca, Klebsiella oxytoca, Klebsiella pneumats Jray, Proteus spp., Salmonella spp., Serratia marcescens, Heisseria vivoca, Neisseria meningitides, Poeudnonas aeruginosa, Stenotrophomonas matophilia; antimicrobial resistance genes: KPC, CTX-M, IMP, NDM, OXA-Ike, VIM, mcr- 1. Control 2 - GPY: Gram positive bacteria: Enterococcus face: 11, 27712-10, nr., iUDM, U.Steria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdumsis, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes; yeast: Candida dhicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans/gatit; animicrobial resistance genes mecA/C and MREJ, vanA/B. This product is not intended to replace manufacturer controls provided with the device.
| 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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510(k) Summary
| 510(k) Submitter | Streck, Inc.7002 S. 109th StreetLa Vista, NE 68128 |
|---|---|
| Official Correspondent:Address: | Deborah Kipp, Regulatory Affairs Manager7002 S. 109th StreetLa Vista, NE 68128 |
| Phone | 402-537-5215 |
| Fax | 402-537-5317 |
| dkipp@streck.com | |
| Date Prepared | August 6, 2021 |
| Trade Name: | MDx-Chex™ for BCID2 |
| Common Name: | Quality Control Material for MicrobiologyAssays |
| Device Type | Assayed external control material formicrobiology nucleic acid amplification (NAT)assays |
| Product Code: | PMN (866.3920) |
| Panel | Microbiology |
Predicate Device:
K200010-Maine Molecular FilmArray BCID2 Control Panel M416
Device Description
MDx-Chex for BCID2 Control 1 - GN is positive for certain pathogens and antimicrobial resistance genes in the FilmArray BCID 2 panel and negative for those contained in MDx-Chex for BCID2 Control 2 - GPY. MDx-Chex for BCID2 Control 2 - GPY is positive for the remaining pathogen and antimicrobial resistance genes and negative for those present in MDx-Chex for BCID2 Control 1 - GN (see Table 1 below). Each control mix also contains and controls for blood and blood culture media components that have been identified as PCR inhibitors namely hemoglobin, leukocyte DNA, and anticoagulants.
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| Gram-Negative Bacteria | ||
|---|---|---|
| Pathogen | MDx-Chex for BCID2 Control 1 - GN | MDx-Chex for BCID2 Control 2 - GPY |
| Acinetobacter colcoaceticus-baumannii complex | Detected | Not Detected |
| Bacteroides fragilis | Detected | Not Detected |
| Enterobacter cloacae complex | Detected | Not Detected |
| Escherichia coli | Detected | Not Detected |
| Klebsiella aerogenes | Detected | Not Detected |
| Klebsiella oxytoca | Detected | Not Detected |
| Klebsiella pneumoniae group | Detected | Not Detected |
| Proteus spp. | Detected | Not Detected |
| Salmonella spp. | Detected | Not Detected |
| Serratia marcescens | Detected | Not Detected |
| Haemophilus influenzae | Detected | Not Detected |
| Neisseria meningitides | Detected | Not Detected |
| Pseudomonas aeruginosa | Detected | Not Detected |
| Stenotrophomonas maltophilia | Detected | Not Detected |
| Gram-Positive Bacteria | ||
| Pathogen | MDx-Chex for BCID2 Control 1 - GN | MDx-Chex for BCID2 Control 2 - GPY |
| Enterococcus faecalis | Not Detected | Detected |
| Enterococcus faecium | Not Detected | Detected |
| Listeria monocytogenes | Not Detected | Detected |
| Staphylococcus aureus | Not Detected | Detected |
| Staphylococcus epidermidis | Not Detected | Detected |
| Staphylococcus lugdunesis | Not Detected | Detected |
| Streptococcus agalactiae | Not Detected | Detected |
| Streptococcus pneumoniae | Not Detected | Detected |
| Streptococcus pyogenes | Not Detected | Detected |
| Yeast | ||
| Pathogen | MDx-Chex for BCID2 Control 1 - GN | MDx-Chex for BCID2 Control 2 - GPY |
| Candida albicans | Not Detected | Detected |
| Candida auris | Not Detected | Detected |
| Candida glabrata | Not Detected | Detected |
| Candida krusei | Not Detected | Detected |
| Candida parapsilosis | Not Detected | Detected |
| Candida tropicalis | Not Detected | Detected |
| Cryptococcus neoformans/gatti | Not Detected | Detected |
Table 1 – Pathogens and antimicrobial resistance genes detected by MDx-Chex for BCID2 Control
MDx-Chex for BCID2 is a quality control containing stabilized blood components, blood culture media components, and inactivated microorganisms resulting in a full-process, cellular-based control for the BioFire BCID2 Panel. Use of full-process cellular controls are necessary to evaluate the entire analytical process, including sample lysis, nucleic acid isolation and purification, amplification, detection, and analysis, as well as the impact of PCR inhibitors and preanalytical variables. Routine use of full process quality controls can help identify variations in the test system that can lead to incorrect results.
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Intended Use
MDx-Chex for BCID2 is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of yeast. Gram positive and Gram negative bacteria, as well as associated antimicrobial resistance genes, by the BioFire® FilmArray® Blood Culture Identification 2 (BCID2) Panel on FilmArray® systems. Control 1 - GN: Gram negative bacteria: Acinetobacter colcoaceticus-baumannii complex, Bacteroides fragilis, Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus spp., Salmonella spp., Serratia marcescens, Haemophilus influenza, Neisseria meningitides, Pseudomonas aeruginosa, Stenotrophomonas maltophilia; antimicrobial resistance genes: KPC, CTX-M, IMP, NDM, OXA-48-like, VIM, mcr-1. Control 2 -GPY: Gram positive bacteria: Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus lugdunesis, Streptococcus agalactiae, Streptococcus pneumonia, Streptococcus pyogenes; yeast: Candida albicans, Candida auris, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans/gatti, antimicrobial resistance genes: mecA/C and MREJ, vanA/B. This product is not intended to replace manufacturer controls provided with the device.
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Comparison to Predicate Device
| Device &PredicateDevice(s): | K212576 | K200010 |
|---|---|---|
| Device TradeName | MDx-Chex for BCID2 | FilmArray BCID2 ControlPanel M416 |
| General DeviceCharacteristicSimilarities | ||
| IntendedUse/IndicationsFor Use | MDx-Chex for BCID2 is intended for useas an external positive and negativeassayed control to monitor theperformance of the qualitative detectionof yeast, Gram positive and Gramnegative bacteria, as well as associatedantimicrobial resistance genes, by theBioFire FilmArray Blood CultureIdentification 2 (BCID2) Panel onFilmArray systems. Control 1 - GN:Gram negative bacteria: Acinetobactercolcoaceticus-baumannii complex,Bacteroides fragilis, Enterobactercloacae complex, Escherichia coli,Klebsiella aerogenes, Klebsiella oxytoca,Klebsiella pneumoniae group, Proteusspp., Salmonella spp., Serratiamarcescens, Haemophilus influenza,Neisseria meningitides, Pseudomonasaeruginosa, Stenotrophomonasmaltophilia; antimicrobial resistancegenes: KPC, CTX-M, IMP, NDM, OXA-48-like, VIM, mcr-1. Control 2 - GPY:Gram positive bacteria: Enterococcusfaecalis, Enterococcus faecium, Listeriamonocytogenes, Staphylococcusaureus, Staphylococcus epidermidis,Staphylococcus lugdunesis,Streptococcus agalactiae, Streptococcuspneumonia, Streptococcus pyogenes;yeast: Candida albicans, Candida auris,Candida glabrata, Candida krusei,Candida parapsilosis, Candida tropicalis,Cryptococcus neoformans/gatti;antimicrobial resistance genes: mecA/Cand MREJ, vanA/B. This product is notintended to replace manufacturercontrols provided with the device. | FilmArray BCID2 Control Panel M416is intended for use as an externalpositive and negativeassayed quality control to monitor theperformance of in vitro laboratorynucleic acid testingprocedures for the qualitative detectionof antimicrobial resistance genes:CTX-M, IMP, KPC,mcr-1, mecA/C, mecA/C and MREJ(MRSA), NDM, OXA-48-like, vanA/B,VIM; Gram positiveand Gram-negative bacteria:Enterococcus faecalis, Enterococcusfaecium, Listeriamonocytogenes, Staphylococcus spp.,Staphylococcus aureus,Staphylococcus epidermidis,Staphylococcus lugdunensis,Streptococcus spp., Streptococcusagalactiae (Group B),Streptococcus pneumoniae,Streptococcus pyogenes (Group A),Acinetobacter calcoaceticusbaumannii complex, Bacteroidesfragilis, Enteric bacteria, Enterobactercloacae complex,Escherichia coli, Klebsiella aerogenes,Klebsiella oxytoca, Klebsiellapneumoniae group, Proteus spp.,Salmonella spp., Serratia marcescens,Haemophilus influenzae, Neisseriameningitidis, Pseudomonasaeruginosa and Stenotrophomonasmaltophilia; and yeast pathogens:Candida albicans, Candida auris,Candida glabrata, Candida krusei,Candida parapsilosis,Candida tropicalis, and Cryptococcusneoformans/gattii on the BioFire BloodCultureIdentification 2 (BCID2) Panel assayon FilmArray systems.FilmArray BCID2 Control Panel M416is composed of synthetic DNAspecifically designed for and intendedto be used solelywith the BioFire BCID2 Panel assay.This product is not intended to replace |
| manufacturer controls provided withthe device. | ||
| Physical Format | Ready-to-Use Liquid | Same |
| Direction for Use | Process like patient sample | Same |
| Number oftargets monitoredin one assay | Multiple, >30 targets | Same |
| General DeviceCharacteristicDifferences | ||
| Composition | Intact inactivated bacteria, humanerythrocytes and leukocytes, andrelevant components of blood culturemedia | Synthetic DNA |
| Assay StepsMonitored | Lysis, nucleic acidisolation/purification/PCR inhibitorremoval, amplification, detection,identification/data reporting | Reverse transcription, amplification,detection |
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Discussion of Tests and Test Results
To substantiate the product performance claims for BCID2, Streck collected product performance data for the following studies. Results of studies are summarized below ::
- Multi-Site Precision (Reproducibility)
- Single-Site Precision (Repeatability)
- Lot-to-Lot Reproducibility ●
- . Closed-Vial Stability
- Open-Vial Stability .
- . Matrix Effect
- Shipping Stability ●
Multi-Site Precision (Reproducibility)
Ten samples per control level (20 samples total per lot) were tested using the BCID2 panel by users at each site over a 10-day period. Three lots were used for this study. All samples were prepared and analyzed on the BioFire FilmArray Instrument per the control and BCID2 Instructions for Use. Samples were analyzed internally at Streck (La Vista, NE). External studies were conducted at UNMC (Omaha, NE), Children's Hospital and Medical Center (Omaha, NE), and Mary Lanning Healthcare (Hastings, NE). All MDx-Chex lots passed with an overall positive and negative percent agreement of ≥ 95%. The results therefore support the conclusion that MDx-Chex for BCID2 shows reproducibility across three separately manufactured control lots between sites, days, and operators when used with the BioFire FlimArray BCID2 panel on the BioFire Film Array Torch and 2.0 Systems.
| Category | Site #1# ObservedResults/#ExpectedResults1 | Site #1PositivePercentAgreement | Site #2# ObservedResults/#ExpectedResults1 | Site #2PositivePercentAgreement | Site #3# ObservedResults/#ExpectedResults1 | Site #3PositivePercentAgreement | Site #4# ObservedResults/#ExpectedResults1 | Site #4PositivePercentAgreement | PercentAgreement(all sitescombined) |
|---|---|---|---|---|---|---|---|---|---|
| SMCLevel 1(GN) andLevel 2(GPY),Combined | 59/60* | 98.3% | 57/60* | 95% | 58/60* | 96.7% | 56/60* | 93.3% | 95.8%(230/240) |
Multi-site Precision (Reproducibility) Positive Percent Agreement
- 10 Positive controls gave initial false negative results; all produced the correct results upon a single retest.
1 Expected result for the Positive. Denominator = total # of results for Level 1-GN and Level 2-GPY controls. GPY = Gram-positive and yeast control, GN = Gram-negative control.
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Multi-site Precision (Reproducibility) Negative Percent Agreement
| Category | Site #1 | Site #2 | Site #3 | Site #4 | Percent | ||||
|---|---|---|---|---|---|---|---|---|---|
| #ObservedResults/#ExpectedResults 1 | NegativePercentAgreement | #ObservedResults/#ExpectedResults 1 | NegativePercentAgreement | #ObservedResults/#ExpectedResults 1 | NegativePercentAgreement | #ObservedResults/#ExpectedResults 1 | NegativePercentAgreement | Agreement(all sitescombined) | |
| SMCLevel 1(GN) andLevel 2(GPY),Combined | 60/60 | 100% | 60/60 | 100% | 60/60 | 100% | 59/60* | 98.3% | 99.6%(239/240) |
- 1 Negative control gave initial false positive result and produced correct result upon a single retest.
1 Expected result for the Negative. Denominator = total # of results for Level 1-GN and Level 2-GPY controls. GPY = Gram-positive and yeast control, GN = Gram-negative control.
Single-Site Precision (Repeatability)
The repeatability of MD-Chex for BCID2 was evaluated using three separately manufactured lots of control. Each lot was tested across two BioFire FilmArray Torch instruments (2 modules per instrument). A minimum of three BCID2 pouch lots were used.
Twenty samples per lot per level were tested by four operators over a period of 20 non-consecutive days at Streck. The first time point was also used as the Day 0, replicate 1 for the closed-vial stability testing summarized below. The remainder of the data points were independently run and analyzed. Samples and pouches were prepared according to BCID2 and control instructions. Samples were analyzed on the BioFire FilmArray Torch per the BioFire BCID2 Panel Instructions for Use. All MDx-Chex lots passed with an overall positive and negative percent agreement of ≥ 95%. The data supports that there are no significant differences between operators on different days when testing different SMC lots. The results support the conclusion that MDx-Chex for BCID2 shows repeatability across three separately manufactured control lots when used with the BioFire FilmArrav BCID2 panel.
Single-site Precision (Repeatability) Positive Percent Agreement
| Category | # Observed Results/# Expected Results 1 | Positive PercentAgreement |
|---|---|---|
| SMC Level 1-GN andLevel 2-GPY,Combined | 114/120* | 95% |
6 Positive controls gave initial false negative results: all produced the correct results upon a single retest.
1 Expected to the Positive Control is positive. Denominator = total # of results for GN (Level 2) controls. GPY = gram-positive and yeast control, GN = gram negative control.
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Single-site Precision (Repeatability) Negative Percent Agreement
| Category | # Observed Results/# Expected Results 1 | Negative PercentAgreement |
|---|---|---|
| SMC Level 1- GN andLevel 2-GPY,Combined | 120/120 | 100% |
1 Expected result for the Negative. Denominator = total # of results for GN (Level 1) and GPY (Level 2) controls. GPY = gram-positive and yeast control, GN = gram negative control.
Lot-to-Lot Reproducibility
The reproducibility of MDx-Chex for BCID2 was evaluated using three separately manufactured lots of control. Each lot was removed from 2-8 °C storage and allowed to warm to room temperature per the control Instructions for Use (IFU) prior to testing with the BCID2 panel. Multiple lots of BCID2 pouches were used for testing. Pouches were prepared according to the BCID2 assay instructions. Samples were prepared in accordance with the control IFU.
Testing consisted of 6 samples per control lot and level (12 total samples per lot). A total of 36 complete runs were generated for the data analysis from all control lots. Data from the first 6 timeooints in the repeatability study above were also used for the lot-to-lot precision analysis. For within-run precision analysis, data from the first 6 control vials tested, per control level, for closed-vial stability below were used for analysis of one control lot collected on the same day. All MDx-Chex lots passed with an overall positive and negative percent agreement of ≥ 90%. The results support that MDx-Chex for BCID2 is reproducible across three separately manufactured lots when used with the BioFire FilmArray BCID2 panel. The results also demonstrate that there are no significant differences in results within-run and between different control lots.
Lot-to-Lot Reproducibility Positive Percent Agreement
| Category | SMC Lot | # Observed Results/#Expected Results 1 | Positive PercentAgreement |
|---|---|---|---|
| SMC Level 1(GN)and Level 2 (GPY),Combined | 20363 | 11/12* | 91.7% |
| 20366 | 12/12 | 100% | |
| 21129 | 12/12 | 100% |
- 1 Positive control gave an initial false negative result; it produced the correct result upon a single retest.
1 Expected result for the Positive. Denominator = total # of expected positive result sets for Level 1-GN and Level 2-GPY controls. GN = gram negative control, GPY = gram-positive and yeast control.
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Lot-to-Lot Reproducibility Negative Percent Agreement
| Category | SMC Lot | # Observed Results/# Expected Results 1 | NegativePercentAgreement |
|---|---|---|---|
| SMC Level 1(GN)and Level 2 (GPY),Combined | 20363 | 12/12 | 100% |
| 20366 | 12/12 | 100% | |
| 21129 | 12/12 | 100% |
1 Expected result for the Negative. Denominator = total # of expected negative result sets for Level 1-3N and Level 2-GPY controls. GN = gram negative control, GPY = gram-positive and yeast control.
Within-run Reproducibility Positive Percent Agreement
| Category | SMC Lot | # Observed Results/# Expected Results 1 | Positive PercentAgreement |
|---|---|---|---|
| SMC Level 1(GN)and Level 2 (GPY),Combined | 21129 | 12/12 | 100% |
1 Expected result for the Positive. Denominator = total # of expected positive result sets for Level 1-GN and Level 2-GPY controls. GN = gram negative control, GPY = gram-positive and yeast control.
Within-run Reproducibility Negative Percent Agreement
| Category | SMC Lot | # Observed Results/# Expected Results 1 | Negative PercentAgreement |
|---|---|---|---|
| SMC Level 1(GN)and Level 2 (GPY),Combined | 21129 | 12/12 | 100% |
1 Expected result for the Negative. Denominator = total # of expected negative result sets for Level 1-GN and Level 2-GPY controls. GN = gram negative control, GPY = gram-positive and yeast control.
Closed-Vial Stability
The closed-vial stability study assessed the real-time stability of MDx-Chex for BCD2 using the FilmArray Torch system. Three separately manufactured lots were stored at 2-8°C (refrigerated) and 20-25°C (room temperature). Ten samples per control lot and level were tested with the BCID2 panel at Day 0 and a minimum of 61 days per each lot and storage condition. Prior to sample analysis, BCID2 pouches were prepared according to the BCID2 assay instructions. Samples were prepared and analyzed on the BioFire FilmArray Torch per MDx-Chex for BCID2 and BCID2 assay Instructions for Use. This summary contains results that support a 60 day closed-vial stability claim for MDx-Chex for BCID2 when stored at 2-25℃. All MDx-Chex lots passed with an overall positive and negative percent agreement of ≥ 95%.
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Closed-Vial Stability Positive Percent Agreement
| Shelf-Life | StorageTemperature | #Observed Results/#Expected Results 1 | PositivePercentAgreement | PPA ≥ 90%Acceptance |
|---|---|---|---|---|
| Day 0* | NA | 115/120** | 95.8% | Pass |
| Day 61+ | 2-8°C | 58/60*** | 96.7% | Pass |
| Day 61+ | 20-25°C | 60/60 | 100% | Pass |
1 Expected result for the Positive. Denominator = total combined # of expected positive results for Level 1-GN and Level 2-GPY controls. GPY = gram-positive and yeast control, GN = gram negative control.
- 120 tubes were completed for Day 0 (baseline). Tubes were divided in half for storage.
** 5 Positive controls gave false negative results on the first test; all reruns produced correct results upon a single retest.
** 2 Positive controls gave false negative results on the first test; all reruns produced correct results upon a single retest.
-
- Indicates that each lot was tested for at least 61 days. Lot 20263 (75 days); and Lot 21129 (63 days).
Closed-Vial Stability Negative Percent Agreement
| Shelf-Life | StorageTemperature | #Observed Results/#Expected Results 1 | NegativePercentAgreement | NPA ≥ 90%Acceptance |
|---|---|---|---|---|
| Day 0* | NA | 117/120** | 97.5% | Pass |
| Day 61+ | 2-8°C | 59/60*** | 98.3% | Pass |
| Day 61+ | 20-25°C | 59/60**** | 98.3% | Pass |
1 Expected result for the Negative. Denominator = total combined # of expected negative results for Level 1-GN and Level 2-GPY controls. GPY = Gram-positive and yeast control, GN = Gram-negative control.
- 120 tubes were completed for Day 0 (baseline). Tubes were divided in half for storage.
** 3 negative controls gave false positive results on the first test, all reruns produced correct results upon a single retest.
** 1 negative control gave a false positive result on the first test; all reruns produced correct results upon a single retest.
*** 1 negative control gave false positive result on the first test; rerun produced correct result upon a single retest.
- Indicates that each lot was tested for at least 61 days. Lot 20263 (75 days); and Lot 21129 (63 days).
Open-Vial Stability
The open-vial stability study assessed the real-time stability of MDx-Chex for BCD2 using the BioFire FilmArray Torch system. Three separately manufactured lots were stored at 2-8°C (refrigerated) and 20-25°C (room temperature). Ten samples per lot per level were tested with the BCID2 panel at Day 0 (baseline) and a minimum of 61 days for each lot and storage condition. At baseline, 120 total tubes were tested then divided in half for storage. The same data set collected for closed-vial stability at Day 0 was used for analysis of opened-vial stability at Day 0 for each respective temperature. This summary contains results that support a 60 day open-vial stability claim for MDx-Chex for BCID2 when stored at 2-25°C. All MDx-Chex lots passed with an overall positive and negative percent agreement of ≥ 95%.
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Open-Vial Stability Positive Percent Agreement
| Shelf-Life | StorageTemperature | #Observed Results/#Expected Results 1 | PositivePercentAgreement | PPA ≥ 90%Acceptance |
|---|---|---|---|---|
| Day 0* | NA | 115/120** | 95.8% | Pass |
| Day 61+ | 2-8°C | 60/60 | 100% | Pass |
| Day 61+ | 20-25°C | 57/60*** | 95% | Pass |
1 Expected result for the Positive. Denominator = total combined # of expected positive results for Level 1-GN and Level 2-GPY controls. GPY = gram-positive and yeast control, GN = gram negative control.
- 120 tubes were completed for Day 0 (baseline). Tubes were divided in half for storage.
** 5 Positive controls gave false negative results on the first test; all reruns produced correct results upon a single retest.
** 3 positive controls gave false negative results on the first test; all reruns produced correct results upon a single retest.
-
- Indicates that each lot was tested for at least 61 days. Lot 20263 (75 days); and Lot 21129 (63 days).
Open-Vial Stability Negative Percent Agreement
| Shelf-Life | StorageTemperature | #Observed Results/#Expected Results 1 | NegativePercentAgreement | NPA ≥ 90%Acceptance |
|---|---|---|---|---|
| Day 0* | NA | 117/120** | 97.5% | Pass |
| Day 61+ | 2-8°C | 60/60 | 100% | Pass |
| Day 61+ | 20-25°C | 60/60 | 100% | Pass |
1 Expected result for the Negative. Denominator = total combined # of expected negative results for Level 1-GN and Level 2-GPY controls. GPY = Gram-positive and yeast control, GN = Gram-negative control.
- 120 tubes were completed for Day 0 (baseline). Tubes were divided in half for storage.
** 3 negative controls gave false positive results on the first test, all reruns produced correct results upon a single retest.
- Indicates that each lot was tested for at least 61 days. Lot 20263 (77 days); and Lot 21129 (63 days).
Matrix Effect
To assess the MDx-Chex matrix effect on the BioFire FilmArray BCID2 panel, inactivated Streptococus pneumoniae was spiked into the control matrix (containing RBCs, WBCs, and simulated blood culture media). Streptococcus pneumoniae was also spiked into a BD BACTEC Plus Aerobic/F culture bottle with negative whole blood to simulate a clinical samples were tested in triplicate using the BCID2 Panel. Three replicates of each simulated matrix with no spike-in organism were also tested to serve as negative controls. BCID2 pouches were prepared according to the BCID2 assay instruction. Samples were prepared and analyzed on the BioFire FilmArray Torch per the control and BCID2 Instructions for Use. The MDx-Chex matrix passed with an overall positive and negative percent agreement of 100% to the analytes tested. The results demonstrated that samples prepared with the MDx-Chex matrix showed no inhibition and/or false negative results when used with the FilmArray BCID2 panel. The data therefore support the conclusion that MDx-Chex performs identically to a clinical BCID2 panel sample, positive blood culture sample.
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Matrix Effect of MDx-Chex and Clinical Samples Spiked with S. pneumonia, Tested on BCID-2 panel
| Matrix type | # Expected results / # tested 1 | Percent Agreement | |
|---|---|---|---|
| MDx-Chex, Positive Matrix | 3/3 | 100% | |
| Clinical, Matrix | Positive | 3/3 | 100% |
1 Expected result for the Positive Matrix is positive.
Matrix Effect of Negative MDx-Chex and Negative Clinical Samples, Tested on BCID-2 panel
| Matrix type | # Expected results /#tested 1 | Percent Agreement |
|---|---|---|
| MDx-Chex,NegativeMatrix | 3/3 | 100% |
| Clinical,NegativeMatrix | 3/3 | 100% |
1 Expected result for Negative Matrix is negative.
Shipping Stability
The purpose of this study was to validate the stability of MDx-Chex for BCID2 after shipment during simulated summer and winter shipping conditions. Two sets of samples from one control lot were exposed to summer and winter temperature profiles using an environmental chamber.
Samples exposed to Winter and Summer profiles were then stored at 2 -8 °C prior to being tested on the BioFire FilmArray Torch. For each temperature profile, ten samples of control (Control 1 and Control 2) from the same lot were tested using BCID2 pouches according to the BCID2 assay instruction. All pouches were prepared according to the BCID2 assay instructions before analysis. All samples were prepared and analyzed on the BioFire FilmArray Torch per MDx-Chex for BCID2 and BCID2 assay Instructions for Use. All summer and winter shipping conditions passed with ≥ 95% positive and negative agreement. The claim that MDx-Chex for BCID2 remains functional after exposure to extreme temperature (winter, summer) shipping conditions.
Shipping Stability Study Positive Percent Agreement
| Category | # Expected results / #Tested 1 | Positive PercentAgreement |
|---|---|---|
| Summer | 19/20* | 95% |
| Winter | 20/20 | 100% |
1 Expected result for the Positive Control is positive.
- 1 Positive control gave initial false negative result; it produced the correct result upon a single retest.
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Shipping Stability Study Negative Percent Agreement
| Category | # Expected results / #Tested 1 | Negative PercentAgreement |
|---|---|---|
| Summer | 19/20* | 95% |
| Winter | 20/20 | 100% |
1 Expected result for the Negative Control is negative.
- 1 Negative control gave initial false positive result; it produced correct result upon a single retest.
Conclusions of Performance Tests
Study results show MDx-Chex for BCID2 to be consistently reproducible, substantially equivalent to the predicate product, and stable for the product dating. MDx-Chex for BCID2 is a safe and effective product, which fulfills its intended use when used as instructed in the Instructions for Use.
§ 866.3920 Assayed quality control material for clinical microbiology assays.
(a)
Identification. An assayed quality control material for clinical microbiology assays is a device indicated for use in a test system to estimate test precision or to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. This type of device consists of single or multiple microbiological analytes intended for use with either qualitative or quantitative assays.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate:
(i) Analyte concentration;
(ii) Expected values;
(iii) Analyte source;
(iv) Base matrix;
(v) Added components;
(vi) Safety and handling information; and
(vii) Detailed instructions for use.
(2) Premarket notification submissions must include detailed documentation, including line data as well as detailed study protocols and a statistical analysis plan used to establish performance, including:
(i) Description of the process for value assignment and validation.
(ii) Description of the protocol(s) used to establish stability.
(iii) Line data establishing precision/reproducibility.
(iv) Where applicable, assessment of matrix effects and any significant differences between the quality control material and typical patient samples in terms of conditions known to cause analytical error or affect assay performance.
(v) Where applicable, identify or define traceability or relationship to a domestic or international standard reference material and/or method.
(vi) Where applicable, detailed documentation related to studies for surrogate controls.
(3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling.
(4) Your 21 CFR 809.10 compliant labeling must include the following:
(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:
(A) Assayed control material analyte(s);
(B) Whether the material is intended for quantitative or qualitative assays;
(C) Stating if the material is a surrogate control; and
(D) The system(s), instrument(s), or test(s) for which the quality control material is intended.
(ii) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following statement: “This product is not intended to replace manufacturer controls provided with the device.”
(iii) A limiting statement that reads “Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.”