(116 days)
Not Found
No
The device description details a fixed algorithm based on comparing absorbance ratios to pre-defined cut-off values. There is no mention of learning, adaptation, or complex pattern recognition characteristic of AI/ML.
No
This device is an in vitro diagnostic test for detecting Bordetella pertussis, which aids in diagnosis and does not provide therapeutic treatment.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that the device "is a qualitative in vitro diagnostic test for the direct detection of Bordetella pertussis" and its results "should be used ... as an aid in diagnosis of Bordetella pertussis infection".
No
The device description explicitly states that the system is comprised of a test kit, an external control kit, and an automated isothermal amplification and detection system (illumipro-10™), which is a piece of hardware.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states it is a "qualitative in vitro diagnostic test". It is designed to detect the presence of Bordetella pertussis in human samples (nasopharyngeal swabs) to aid in the diagnosis of respiratory tract infection. This aligns perfectly with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
- Device Description: The description details the components of the system, including the test kit, controls, and the automated system. It explains how the assay works by detecting DNA from the pathogen in the sample, which is a typical function of an IVD.
- Clinical Performance Studies: The document describes clinical trials where the device was tested against a comparator method using human specimens to evaluate its performance (sensitivity, specificity, etc.) in a clinical setting. This is a standard requirement for demonstrating the effectiveness of an IVD.
- Key Metrics: The reporting of metrics like Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) are standard performance measures for IVDs.
- Predicate Device(s): The listing of predicate devices with K numbers indicates that this device is being compared to other legally marketed IVDs.
In summary, the intended use, the nature of the test (analyzing human samples for diagnostic information), the performance studies, and the comparison to predicate devices all confirm that the illumigene® Pertussis DNA Amplification Assay is an In Vitro Diagnostic device.
N/A
# Intended Use / Indications for Use
The illumigene® Pertussis DNA Amplification Assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of Bordetello pertussis in human nasopharyngeal swab samples taken from patients suspected of having respiratory tract infection attributable to Bordetella pertussis.
The illumigene Pertussis assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Bordetella pertussis by targeting the IS481 insertional element of the Bordetella pertussis genome. The IS481 insertional element can also be found in Bordetello holmesii and Bordetello bronchiseptica strains. Respiratory infection with Bordetella pertussis, Bordetella bronchiseptica may yield positive test results in 19481 assays. B. holmesii infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the illumigene Pertussis DNA Amplification Assay do not preclude Bordetella pertussis infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the illumigene Pertussis assay should be used in conjunction obtained during the patient's clinical evaluation as an aid in diagnosis of Bordetella pertussis infection and should not be used as for treatment or other patient management decisions.
illumigene Pertussis is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
# Product codes (comma separated list FDA assigned to the subject device)
OZZ
# Device Description
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Pertussis DNA Amplification Assay Test Kit, the illumigene® Pertussis External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Pertussis assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Bordetella pertussis in human nasopharyngeal swab specimens. Each illumigene Pertussis assay is completed using an illumigene Assay Control Reagent containing Control material, an illumigene Sample Buffer, an illumigene Pertussis Test Device and Mineral Oil. Nasopharyngeal swab specimens are eluted with illumigene Sample Buffer. The illumigene Assay Control Reagent is added to the eluted sample and heat-treated. Target and Control DNA are made available for isothermal amplification via heat-treatment. The heat-treated Specimen/Control sample is added to the illumigene Test Device. Mineral oil is added to the illumigene Test Device to prevent evaporation. DNA amplification occurs in the illumigene Test Device.
The illumipro-10 heats each illumigene Pertussis Test Device containing prepared Sample and Control material, facilitating amplification of target DNA. When B. pertussis is present in the specimen, a 198 base pair sequence located within the IS481 insertional element of the B. pertussis genome is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture.
The illumipro-10 monitors the absorbance characteristics of the reaction solutions at the assay Run Start (Signalmore) S.) and at the assay Run End (Signalman Sp). The illumipro-10™ catio of the Run End (Signal final or Sy) reads with the Run Start (Signal Initial or S) reads and compares the ratio to an established cut-off value. The illumipro-10 performs this ratio calculation to both the TEST chamber and the CONTROL chamber.
Fixed cut-off values for the CONTROL chamber are used to determine validity. CONTROL chamber Sp. S ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE, NEGATIVE). CONTROL chamber S; S; ratios greater than or equal to 90% are considered invalid. Results are reported as 'INVALID'; Test chamber results are not reported. More stringent cut-off criteria are applied to the Control chamber reaction to ensure amplification is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
Fixed cut-off values for the TEST chamber are used to report sample results. TEST chamber Sy:S, ratios less than 82% are reported as 'POSITIVE'; TEST chamber S;:S, ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.
The illumigene Pertussis External Control Kit contains a Positive Control Reagent. The illumigene Assay Control/Negative Control Reagent provided in the illumigene Pertussis kit serves as the External Negative Control Reagent. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. External Control reagents are provided for use in routine Quality Control testing.
# Mentions image processing
Not Found
# Mentions AI, DNN, or ML
Not Found
# Input Imaging Modality
Not Found
# Anatomical Site
human nasopharyngeal swab samples
# Indicated Patient Age Range
Patient age ranged from 1 month to 88 years.
# Intended User / Care Setting
illumigene Pertussis is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
# Description of the training set, sample size, data source, and annotation protocol
Not Found
# Description of the test set, sample size, data source, and annotation protocol
A total of 729 qualified nasopharyngeal (NP) swab specimens collected from patients suspected of having Bordetella pertussis infection were evaluated with the test. All specimens were leftover and de-identified. Performance characteristics of the assay were determined by comparison to a Composite Comparator Reference Method that included two manufacturer validated, real-time PCR Assays (PCR1 and PCR2) followed by bi-directional sequencing. Both comparator PCR assays targeted unique sequences within the IS481 insertional element; neither of the comparator target sequences overlaps with the illumigene Pertussis assay target sequence. Specimens producing positive Bordetella pertussis results from either comparator PCR assay were sent for bi-directional sequencing. Only samples that matched sequences within the Bordetella pertussis genome with pre-defined quality scores (PHRED20 and E-values) were considered true positives. Samples were considered negative when neither comparator PCR assay returned positive Bordetella pertussis results. The clinical study population included retrospective and prospective specimens. A total of 508 (69.7%) prospective and 221 (30.3%) retrospective specimens were tested and included in final performance calculations. The retrospective sample population included non-selected specimens (all comers) and selected specimens.
# Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
**Clinical Performance:**
Clinical trials for the illumigene Pertussis DNA Amplification Assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted from December 2012 to July 2013.
A total of 729 qualified nasopharyngeal (NP) swab specimens were evaluated.
Performance was determined by comparison to a Composite Comparator Reference Method (two real-time PCR assays followed by bi-directional sequencing).
**Overall Performance Characteristics (Composite Method Comparator, All Comers):**
* **Prospective:**
* Positive Percent Agreement (PPA): 39/45 (86.7%) [95% CI: 73.8 - 93.7%]
* Negative Percent Agreement (NPA): 447/459 (97.4%) [95.5 – 98.5%]
* Invalid Results: 2 (13)
* **Retrospective:**
* Positive Percent Agreement (PPA): 4/4 (100.0%) [95% CI: 51.0 - 100.0%]
* Negative Percent Agreement (NPA): 176/178 (98.9%) [96.0 - 99.7%]
* Invalid Results: 0
* **Total (All Comers):**
* Positive Percent Agreement (PPA): 43/49 (87.8%) [95% CI: 75.8 - 94.3%]
* Negative Percent Agreement (NPA): 623/637 (97.8%) [96.3 - 98.7%]
* Invalid Results: 2 (13)
**Composite Method Comparator, Selected Specimens (Retrospective):**
* Positive Percent Agreement (PPA): 19/21 (90.5%) [95% CI: 71.1 - 97.3%]
* Negative Percent Agreement (NPA): 14/16 (87.5%) [95% CI: 64.0 - 96.5%]
* Invalid Results: 0
**Key Results:**
* Eight specimens produced false-negative illumigene results compared to the Composite Comparator Method. Six of these had detectable DNA at high Ct values (between 35 and 40) in comparator amplification cycles and were confirmed by bi-directional sequencing, suggesting low levels of DNA.
* 11 of 13 initial invalid specimens produced valid results upon repeat testing.
**Analytical Performance:**
**Precision/Reproducibility Study:**
* **Method:** Blind coded panels of 10 samples (moderately positive (n=3), low positive (n=3), high negative (n=3), and negative (n=1)) were supplied to three independent laboratories. Samples were contrived.
* **Testing:** Performed by at least two different operators at each site for five days. Three lots of illumigene Pertussis and six illumipro-10 instruments were used.
* **Results (Total 90 replicates for each sample type except Negative with 30):**
* **Moderate Positive:** 90/90 (100.0%) agreement; Average S:S: 57.51, SD 4.14, %CV 7.20%, 95% CI 95.9-100.0
* **Low Positive:** 86/90 (95.6%) agreement; Average S:S: 58.16, SD 10.02, %CV 17.23%, 95% CI 89.1-98.3
* **High Negative:** 78/90 (86.7%) agreement; Average S:S: 96.19, SD 11.47, %CV 11.92%, 95% CI 78.1-92.2
* **Negative:** 29/30 (96.7%) agreement; Average S:S: 100.29, SD 4.75, %CV 4.73%, 95% CI 83.3-99.4
* **Positive Control:** 30/30 (100.0%) agreement; Average S:S: 56.83, SD 4.83, %CV 8.50%, 95% CI 88.6-100.0
* **Negative Control:** 30/30 (100.0%) agreement; Average S:S: 100.70, SD 3.04, %CV 3.01%, 95% CI 88.6-100.0
**Detection Limit (Analytical Sensitivity):**
* **Method:** Evaluated Bordetella pertussis strain BAA-589 through serial dilutions in sterile saline combined with simulated negative matrix. Preliminary LoD was identified as the lowest dilution producing positive results in at least 19 of 20 replicates. Confirmed with an additional 60 replicates by two technicians.
* **Limit of Detection:** 1.48 CFU/Test (3265 CFU/mL).
* **Strains Tested and Reacted Positively at 1.48 CFU/Test (3265 CFU/mL):** ATCC 12743, ATCC 8478, ATCC 8467, ATCC 9797, ATCC 53894, ATCC 10380, ATCC 12742, and A639.
* **Strains Tested and Reacted Positively at 1.59 CFU/Test (3500 CFU/mL):** ATCC 51445 and ATCC BAA-1335.
**Analytical Specificity (Interference Testing):**
* **Method:** Potentially interfering substances were added to simulated negative and contrived positive (B. pertussis strain BAA-589) nasopharyngeal swab samples.
* **No Interference:** Mucin (1% w/v), Human DNA (200 ng/μL), Whole blood (1% w/v).
* **No Interference (Chemical Substances):** Acetaminophen (10 mg/ml), Advil® [Ibuprofen (10 mg/mL)], Afrin® Decongestant Nasal Spray [Oxymetazoline hydrochloride (0.0005% w/v)], Albuterol Sulfate [Salbutamol sulfate (1% w/v)], Aspirin (5 mg/mL), Coricidin® HBP Cold/Flu tablets, Diphenhydramine HCl (0.25 mg/mL), Erythromycin (2% w/v), Mupirocin (2% w/v), Petroleum Jelly [White Petrolatum (1% w/v)], Robitussin® Cough+Chest Congestion DM Cough Syrup, Suphedrine PE [Phenylephrine HCl (0.3 mg/mL)], Saline Nasal Spray [Sodium chloride (0.0065% w/v)], Smokeless Tobacco (snuff) (1% w/v), Tobramycin (0.6 mg/mL), Vicks® VaporRub®.
* **Interference Found:** Aspirin at concentrations above 5 mg/mL.
**Cross-Reactivity Study:**
* **Method:** Potentially cross-reacting microorganisms were added to negative and contrived positive samples (Bordetella pertussis strain BAA-589 at or around LoD). Tested in triplicate.
* **No Cross-reactivity:** Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter lwoffii, Acinetobacter odontolyticus, Arcanobacterium haemolyticum, Bacillus subtilis, Actinomyces Bacteroides fragilis, Bordetella avium, Bordetella hinzii (not confirmed as cross-reactive after retesting), Bordetella parapertussis, Bordetella petrii, Bordetella trematum, Burkholderia cepacia, Candida albicans, Candida glabrata, Chlamydia pneumoniae, Chlamydia trachomatis, Citrobacter freundii, Clostridium difficile, Corynebacterium diphtheriae, Corynebacterium pseudodiphtheriticum, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Escherichia coli (ESBL), Fusobacterium nucleatum, Haemophilus influenzae, Haemophilus parainfluenzae (not confirmed as cross-reactive after retesting), Klebsiella oxytoca, Klebsiella pneumoniae (KPC), Lactobacillus acidophilus, Lactobacillus plantarum, Legionella jordanis, Legionella longbeachae, Legionella micdadei, Legionella pneumophila, Listeria monocytogenes, Moraxella catarrhalis, Mycobacterium tuberculosis, Mycoplasma genitalium (not confirmed as cross-reactive after retesting), Mycoplasma hominis, Mycoplasma pneumoniae, Neisseria cinerea, Neisseria elongata, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Peptostreptococcus anaerobius, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia liquefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Stenotrophomonas maltophilia, Streptococcus anginosus (Group F), Streptococcus bovis (Group D), Streptococcus canis (Group G), Streptococcus dysgalactiae ssp. dysgalactiae, Streptococcus dysgalactiae ssp. equisimilis, Streptoccus intermedius, Streptococcus mitis, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus salivarius, Streptoccus suis, Ureaplasma urealyticum, Adenovirus, Coronavirus, Coxsackievirus, Cytomegalovirus, Epstein Barr Virus, Herpes Simplex Virus 1, Herpes Simplex Virus 2, Human Metapneumovirus, Influenza A, Influenza B, Measles virus, Mumps virus, Parainfluenza virus 1, Parainfluenza virus 2, Parainfluenza virus 3, Respiratory syncytial virus A, Respiratory syncytial virus B, Rhinovirus.
* **Cross-reactivity observed due to IS481 element:** Bordetella holmesii and Bordetella bronchiseptica (both tested at 1.0 x 10^8 CFU/mL).
# Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement (PPA)
Negative Percent Agreement (NPA)
**Overall Performance (Composite Method Comparator, All Comers, Total):**
PPA: 87.8% (43/49)
NPA: 97.8% (623/637)
# Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
[K123620](https://510k.innolitics.com/search/K123620). [K120267](https://510k.innolitics.com/search/K120267). [K110764](https://510k.innolitics.com/search/K110764) and [K103175](https://510k.innolitics.com/search/K103175).
# Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
# Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.
(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.
0
mar 2 5 2014
Image /page/0/Picture/1 description: The image contains the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is "Bioscience, Inc." with "Inc." in a smaller font and a trademark symbol. The tagline "Inspired Science. Trusted Solutions." is located beneath the company name.
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
ー.
·
510(k) Summary
| 510(k) number: | K133673 | Date of Preparation: March 19, 2014 |
|---|---|---|
| Owner: | Meridian Bioscience, Inc. | |
| 3471 River Hills Drive | ||
| Cincinnati, Ohio 45244 USA | ||
| Phone: (513) 271-3700 | ||
| Fax: (513) 272-5213 | ||
| Contact: | Primary Contact: | |
| Michelle L. Smith | ||
| Sr. Director, Regulatory Affairs & Design Assurance |
Secondary Contact:
Susan D. Rolih
Executive Vice President, Regulatory and Quality Systems | |
| Trade Name: | illumigene® Pertussis DNA Amplification Assay
illumigene® Pertussis External Controls | |
| Common Name: | Respiratory Viral Panel Multiplex Nucleic Acid Assay | |
| Classification Name: | Bordetella Pertussis DNA Assay System
(21 CFR 866.3980, Product Code OZZ) | |
| Predicate Device: | FilmArray® Respiratory Panel (RP), Catalog RFIT-ASY-001
K123620. K120267. K110764 and K103175. | |
.
1
Image /page/1/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is "Bioscience, Inc." in a smaller, also bolded, font. The tagline "Inspired Science. Trusted Solutions." is located beneath the company name.
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
Device Description:
The illumigene Molecular Diagnostic Test System is comprised of the illumigene® Pertussis DNA Amplification Assay Test Kit, the illumigene® Pertussis External Control Kit and the illumipro-10™ Automated Isothermal Amplification and Detection System.
The illumigene Pertussis assay utilizes loop-mediated isothermal amplification (LAMP) technology to detect the presence of Bordetella pertussis in human nasopharyngeal swab specimens. Each illumigene Pertussis assay is completed using an illumigene Assay Control Reagent containing Control material, an illumigene Sample Buffer, an illumigene Pertussis Test Device and Mineral Oil. Nasopharyngeal swab specimens are eluted with illumigene Sample Buffer. The illumigene Assay Control Reagent is added to the eluted sample and heat-treated. Target and Control DNA are made available for isothermal amplification via heat-treatment. The heat-treated Specimen/Control sample is added to the illumigene Test Device. Mineral oil is added to the illumigene Test Device to prevent evaporation. DNA amplification occurs in the illumigene Test Device.
The illumipro-10 heats each illumigene Pertussis Test Device containing prepared Sample and Control material, facilitating amplification of target DNA. When B. pertussis is present in the specimen, a 198 base pair sequence located within the IS481 insertional element of the B. pertussis genome is amplified and magnesium pyrophosphate is generated. Magnesium pyrophosphate forms a precipitate in the reaction mixture.
The illumipro-10 monitors the absorbance characteristics of the reaction solutions at the assay Run Start (Signalmore) S.) and at the assay Run End (Signalman Sp). The illumipro-10™ catio of the Run End (Signal final or Sy) reads with the Run Start (Signal Initial or S) reads and compares the ratio to an established cut-off value. The illumipro-10 performs this ratio calculation to both the TEST chamber and the CONTROL chamber.
Fixed cut-off values for the CONTROL chamber are used to determine validity. CONTROL chamber Sp. S ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE, NEGATIVE). CONTROL chamber S; S; ratios greater than or equal to 90% are considered invalid. Results are reported as 'INVALID'; Test chamber results are not reported. More stringent cut-off criteria are applied to the Control chamber reaction to ensure amplification is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
Fixed cut-off values for the TEST chamber are used to report sample results. TEST chamber Sy:S, ratios less than 82% are reported as 'POSITIVE'; TEST chamber S;:S, ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.
The illumigene Pertussis External Control Kit contains a Positive Control Reagent. The illumigene Assay Control/Negative Control Reagent provided in the illumigene Pertussis kit serves as the External Negative Control Reagent. External Control reagents are provided to aid the user in detection of reagent deterioration, adverse environmental or test conditions, or variance in operator performance that may lead to test errors. External Control reagents are provided for use in routine Quality Control testing.
2
Image /page/2/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a stylized globe on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is the word "Bioscience, Inc." and the tagline "Inspired Science. Trusted Solutions."
| illumigene® Pertussis DNA Amplification Assay | ||
|---|---|---|
| Application Reference: | K133673 | |
| Attachment Description: | Additional Information Request (January 13, 2014) | |
| 510(k) Summary | ||
| Application Date: | March 19, 2014 |
Intended Use:
The illumigene® Pertussis DNA Amplification Assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direct detection of Bordetello pertussis in human nasopharyngeal swab samples taken from patients suspected of having respiratory tract infection attributable to Bordetella pertussis.
The illumigene Pertussis assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Bordetella pertussis by targeting the IS481 insertional element of the Bordetella pertussis genome. The IS481 insertional element can also be found in Bordetello holmesii and Bordetello bronchiseptica strains. Respiratory infection with Bordetella pertussis, Bordetella bronchiseptica may yield positive test results in 19481 assays. 8. holmesii infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both B. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the illumigene Pertussis DNA Amplification Assay do not preclude Bordetella pertussis infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the illumigene Pertussis assay should be used in conjunction obtained during the patient's clinical evaluation as an aid in diagnosis of Bordetella pertussis infection and should not be used as for treatment or other patient management decisions.
illumigene Pertussis is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.
| Similarities | ||
|---|---|---|
| DEVICE | ||
| illumigene® Pertussis | PREDICATE | |
| FilmArray® Respiratory Panel (RP) System | ||
| Package Insert: RFIT-PRT-0011-02, May 2012 | ||
| Intended Use | Qualitative | Qualitative |
| Indications for Use | Professional Use | Professional Use |
| Assay Target | Bordetella pertussis IS481 Insertional Element | Bordetella pertussis DNA, promoter region of |
| Toxin gene | ||
| Specimen Types | Nasopharyngeal Swab | Nasopharyngeal Swab |
| Detection | Self contained and automated | Self contained and automated |
Predicate Device Comparison:
3
Image /page/3/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a stylized globe on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is the text "Bioscience, Inc." and the tagline "Inspired Science. Trusted Solutions."
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
| Differences | ||
|---|---|---|
| DEVICE | PREDICATE | |
| illumigene® Pertussis | FilmArray® Respiratory Panel (RP) System | |
| Test Format | DNA Amplification Assay; Loop-Mediated | |
| Isothermal Amplification (LAMP) | Multiplex PCR Amplification Assay | |
| Reagents/Components | The illumigene Pertussis DNA Amplification | |
| Assay Kit contains illumigene Assay | ||
| Control/Negative Control, illumigene Sample | ||
| Buffer, illumigene Pertussis Test Device and | ||
| Mineral Oil. | ||
| External Positive Control materials are | ||
| provided separately in the illumigene | ||
| Pertussis External Control Kit. The | ||
| illumigene Assay Control/Negative Control | ||
| functions as the External Negative Control. | ||
| The illumipro-10 is provided separately. | The FilmArray Respiratory Panel (RP) Assay | |
| Kit contains FilmArray RP pouch, Sample | ||
| Buffer, Hydration Solution, transfer pipettes | ||
| and Sample Loading Syringes (with attached | ||
| cannula). The FilmArray Instrument with | ||
| Loading Station is provided separately. | ||
| External Controls | External Positive Control for the illumigene | |
| Pertussis Assay is provided in the illumigene | ||
| Pertussis External Control Kit. | ||
| The External Positive Control Reagent | ||
| contains tris-buffered solution containing | ||
| non-infectious Plasmid DNA ( B. pertussis | ||
| target DNA inserts) with azide (0.09%) as a | ||
| preservative. | ||
| The illumigene Assay Control/Negative | ||
| Control provided in the illumigene Pertussis | ||
| DNA Amplification Assay Kit functions as the | ||
| External Negative Control. | ||
| The Assay Control/Negative Control Reagent | ||
| contains tris-buffered solution containing | ||
| formalin-treated E. coli harboring non- | ||
| infectious Plasmid DNA ( S. aureus insert) with | ||
| azide (0.09%) as a preservative. | The FilmArray Respiratory Panel (RP) Assay | |
| does not require external controls. External | ||
| Controls are not providedfor the FilmArray | ||
| Respiratory Panel (RP) Assay. | ||
| Amplification | ||
| Technology and Target | ||
| Sequence Detected | Assay performed with the illumipro-10™ | |
| instrument, utilizes loop-mediated isothermal | ||
| amplification (LAMP) technology for the | ||
| detection of 198 base pair (bp) sequence of | ||
| found in the IS481 Insertional Element of the | ||
| the Bordetella pertussis genomeThe | ||
| illumipro-10™ detects changes in reaction | ||
| solution absorbance by visible light | Assay performed with the FilmArray | |
| Instrument, utilizes freeze-dried reagents to | ||
| perform nucleic acid purification reverse | ||
| transcription, and nested multiplex PCR with | ||
| DNA melt analysis for the detection of | ||
| multiple respiratory pathogens along with a | ||
| specific B. pertussis toxin DNA sequence. |
4
Image /page/4/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is "Bioscience, Inc." and the tagline "Inspired Science. Trusted Solutions."
| illumigene ® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
| Differences (continued) | ||
|---|---|---|
| DEVICE | PREDICATE | |
| illumigene® Pertussis | FilmArray® Respiratory Panel (RP) System | |
| Instrumentation | illumipro-10™ Automated Isothermal | |
| Amplification and Detection System | FilmArray® Instrument | |
| Reading Method | Visible Light Transmission | Fluorescence Emissions |
| Interpretation of | ||
| Results | Results of the illumigene Pertussis Assay are | |
| interpreted by the illumipro-10 and reported | ||
| as INVALID, POSITIVE and NEGATIVE based on | ||
| change in light transmission of the reaction | ||
| mixtures. EMPTY WELL is reported when an | ||
| illumigene Test Device is not detected by the | ||
| illumipro-10 or when questionable Signal | ||
| Initial (Si) transmission is detected. | Results of the FilmArray Respiratory Panel | |
| (RP) Assay report are interpreted by the | ||
| FilmArray Instrument for B. pertussis and | ||
| reported as Detected, Not Detected or | ||
| Invalid. | ||
| Performance | ||
| Characteristics | Prospective and Retrospective, All Comers | |
| Positive Percent Agreement (PPA): | ||
| 87.8 % [95% CI: 75.8 - 94.3%] | ||
| Negative Percent Agreement (NPA): | ||
| 97.8% [95% CI: 96.3 - 98.7%] |
Retrospective Samples, Selected
Positive Percent Agreement (PPA):
90.5 % [95% CI: 71.1 - 97.3%]
Negative Percent Agreement (NPA):
87.5% [95% CI: 64.0 - 96.5%] | Prospective Samples
PPA: 100.0% [95% CI:54.1 - 100%]
NPA: 99.9% [95% CI: 99.5 - 100%]
Retrospective Samples
PPA: 94.6% [95% CI: 85.1 - 98.9%]
NPA: 96.5% [95% CI: 88.1 - 99.6%] |
NON-CLINICAL PERFORMANCE DATA
Analytical Performance:
Precision/Reproducibility:
Blind coded panels of 10 samples were supplied to three independent laboratories. Samples were randomly sorted consisting of moderately positive (n=3), low positive (n=3), high negative (n=3) and negative (n=1) samples. Contrived moderately positive, low positive and high negative samples were prepared by inoculating simulated negative matrix (flocked nylon nasopharyngeal swabs inoculated with nasal wash) with Bordetella pertussis strain BAA-589, Tahoma I. A negative specimen containing no Bordetella pertussis was included in the study. Panel specimens were qualified for study use by replicate testing (n=20) for each of three production lots of illumigene Pertussis.
5
Image /page/5/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, sans-serif font. Below "Meridian" is "Bioscience, Inc." and the tagline "Inspired Science. Trusted Solutions."
| illumigene® Pertussis DNA Amplification Assay | ||||
|---|---|---|---|---|
| Application Reference: | K133673 | |||
| Attachment Description: | Additional Information Request (January 13, 2014) | |||
| 510(k) Summary | ||||
| Application Date: | March 19, 2014 |
Testing was performed by at least two different operators at each site on the same day (intra-assay variability) for five days (inter-assay variability). Three lots of illumigene Pertussis and six illumipro-10 instruments were used in this study. Positive and Negative Controls were tested with each panel. The results are given in the table below:
| Sample Type | Clinical Site 1
Percent
Agreement | Clinical Site 2
Percent
Agreement | Clinical Site 4
Percent
Agreement | Total | | | | |
|-------------------|-----------------------------------------|-----------------------------------------|-----------------------------------------|----------------------|------------------|-------|--------|------------|
| | | | | Percent
Agreement | Average
S₁:S₁ | SD | %CV | 95% CI |
| Moderate Positive | 30/30 100.0 | 30/30 100.0 | 30/30 100.00 | 90/90 100.0 | 57.51 | 4.14 | 7.20% | 95.9-100.0 |
| Low Positive. | 27/30 90.0 | 29/30 96.7 | 30/30 100.0 | 86/90 95.6 | 58.16 | 10.02 | 17.23% | 89.1-98.3 |
| High Negative | 26/30 86.7 | 23/30 76.7 | 29/30 96.7 | 78/90 86.7 | 96.19 | 11.47 | 11.92% | 78.1-92.2 |
| Negative | 10/10 100.0 | 9/10 90.0 | 10/10 100.0 | 29/30 96.7 | 100.29 | 4.75 | 4.73% | 83.3-99.4 |
| Positive Control | 10/10 100.0 | 10/10 100.0 | 10/10 100.0 | 30/30 100.0 | 56.83 | 4.83 | 8.50% | 88.6-100.0 |
| Negative Control | 10/10 100.0 | 10/10 100.0 | 10/10 100.0 | 30/30 100.0 | 100.70 | 3.04 | 3.01% | 88.6-100.0 |
Detection limit:
Analytical Sensitivity studies were designed to determine, within 95% confidence intervals, the analytical limit of detection (LoD) of Bordetella pertussis. The LoD is the lowest number of colony-forming units (CFUs) per test aliquot that can be distinguished from negative samples with a high degree of probability (95%). Bordetella pertussis strain BAA-589 was evaluated for analytical Limit of Detection. Culture confirmed stock concentrations were standardized and subsequently diluted serially into sterile saline. Dilutions were combined with simulated negative matrix {flocked nylon swabs inoculated with nasal wash screened negative for B. pertussis) prior to test; Meridian utilized a simulated negative matrix for all analytical studies.
Each dilution evaluated in the illumigene Pertussis assay used individually prepared replicates. Not all prepared dilutions were tested in the illumigene Pertussis assay; testing for select dilutions was discontinued when replicate testing did not meet criteria established for limit of detection (e.g. more than 1 negative replicate obtained). The lowest dilution producing positive results in at least 19 of 20 replicates was identified as the preliminary assay limit of detection. Once a preliminary LoD concentration was established, an additional 60 replicates were evaluated by two different technicians to confirm the final LoD concentration for each kit lot.
6
Image /page/6/Picture/12 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, stylized font. Below the word "Meridian" is the text "Bioscience, Inc." in a smaller, bolder font. Underneath that, the text "Inspired Science. Trusted Solutions." is displayed in a smaller font.
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
Testing was performed using three lots of illumigene Pertussis and six illumipro-10 instruments. External Positive and Negative Controls were tested daily. The Limit of Detection for the assay was reported as 1.48 CFU/Test or 3265 CFU/mL).
The following B. pertussis strains were tested and produced positive reactions at the stated assay limit of detect of 1.48 CFU/Test (3265 CFU/mL) with illumigene Pertussis: ATCC 12743, ATCC 8478, ATCC 8467, ATCC 9797, ATCC 53894, ATCC 10380, ATCC 12742, and A639. The following B. pertussis strains were tested and produced positive reactions at 1.59 CFU/Test or 3500 CFU/mL) with illumigene Pertussis: ATCC 51445 and ATCC BAA-1335.
Analytical specificity:
Interference Testing:
Interfering substance testing was performed to assess the potential impact of nonmicrobial contaminants expected to be present in samples collected for Bordetella pertussis testing on illumigene Pertussis test results. Potentially interfering substances were tested with simulated negative and contrived positive (B. pertussis strain BAA-589) nasopharyngeal swab samples. Potentially interfering substances were added to eluted simulated negative and contrived positive swab samples in Tris EDTA at final concentrations of 0.1 mg/mL, 1% v/v, 1% w/v, or greater and tested. Dilution Controls were prepared by adding a sterile saline solution in place of the potentially interfering substance.
The following biological substances, at the saturated solvent/diluents concentrations indicated do not interfere with the illumigene Pertussis test results: Mucin (1% w/v), Human DNA (200 ng/μL), Whole blood (1% w/v).
The following chemical substances, at the saturated solvent/diluents concentrations indicated do not interfere with test results: Acetaminophen (10 mg/ml), Advil® [Ibuprofen (10 mg/mL)], Afrin® Decongestant Nasal Spray [Oxymetazoline hydrochloride (0.0005% w/v)], Albuterol Sulfate [Salbutamol sulfate (1% w/v)], Aspirin (5 Coricidin® HBP Cold/Flu tablets [Acetominophen (3.26 mg/mL), mg/mL), Chlorpheniramine maleate (0.02 mg/mL)], Diphenhydramine HCl (0.25 mg/mL) , Erythromycin (2% w/v), Mupirocin (2% w/v), Petroleum Jelly |White Petrolatum (1% w/v)], Robitussin® Cough+Chest Congestion DM Cough Syrup [Dextromethorphan HBr (0.1 mg/mL), Guaifenesin (1.0 mg/mL)}, Suphedrine PE {Phenylephrine HCl (0.3 mg/mL)], Saline Nasal Spray [Sodium chloride (0.0065% w/v)], Smokeless Tobacco (snuff) (1% w/v), Tobramycin (0.6 mg/mL), Vicks® VaporRub® [Camphor (0.48% w/v), Eucalyptus oil (0.12% w/v), Menthol (0.26% w/v)].
Ibuprofen (10 mg/mL) produced invalid results (3/6 replicates) during original testing of contrived B. pertussis specimens. All repeat testing produced positive results (10/10
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Image /page/7/Picture/0 description: The image contains the logo for Meridian Bioscience, Inc. The logo features a stylized globe graphic to the left of the word "Meridian" in a bold, sans-serif font. Below "Meridian" is the text "Bioscience, Inc." in a smaller, also bolded, sans-serif font. Underneath that, the text "Inspired Science. Trusted Solutions." is displayed in an even smaller font size.
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
replicates). As the original results were not confirmed, Ibuprofen (10 mg/ml.) is not considered an interfering substance.
Aspirin was found to interfere with illumigene Pertussis testing at concentrations above 5 mg/mL.
Cross-Reactivity Study:
Potentially cross-reacting microorganisms expected to be present in nasopharyngeal swab specimens were added to negative and contrived positive samples. Negative samples were prepared with flocked nylon nasopharyngeal swabs inoculated with confirmed negative nasal wash. The contrived positive sample was prepared by spiking confirmed negative sample matrix (flocked nylon nasopharyngeal swabs inoculated with nasal wash) with Bordetella pertussis strain BAA-589, at concentrations at or around the determined limit of detection. Dilution Controls were prepared by adding a sterile saline solution in place of the potentially cross-reactive organisms. Each inoculated sample was tested in triplicate.
Potentially cross-reactive microorganisms were at minimum concentrations of 1.0 x 10 CFU/mL for bacteria/fungi or concentrations greater than 1.0 x 10° TCIDs//mL for viruses.
None of the following organisms reacted with illumigene Pertussis:
baumannii, Acinetobacter calcoaceticus, Acinetobacter lwoffii. Acinetobacter odontolyticus, Arcanobacterium haemolyticum, Bacillus subtilis. Actinomyces Bacteroides fragilis, Bordetella avium, Bordetella hinzii, Bordetella parapertussis, Bordetella petrii, Bordetella trematum, Burkholderia cepacia, Candida albicans, Candida glabrata, Chlamydia pneumoniae, Chlamydia trachomatis, Citrobacter freundii, difficile, Corynebacterium diphtheriae, Corynebacterium Clostridium pseudodiphtheriticum, Enterobacter cloacae, Enterococcus faecalis, Escherichia coli, Escherichia coli (ESBL), Fusobacterium nucleatum, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae (KPC), Lactobacillus acidophilus, Lactobacillus plantarum, Legionella jordanis, Legionella longbeachae, Leaionella micdadei. Leaionella pneumophila, Listeria monocytogenes, Moraxella catarrhalis, Mycobacterium tuberculosis, Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma pneumoniae, Neisseria cinerea, Neisseria elongata, Neisseria gonorrhoeae, Neisseria meningitidis, Nocardia asteroides, Peptostreptococcus anaerobius, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia liquefaciens, Staphylococcus aureus, Staphylococcus epidermidis, Stenotrophomonas maltophilia, Streptococcus anginosus (Group F), Streptococcus bovis (Group D), Streptococcus canis (Group G), Streptococcus dysgalactiae ssp. dysgalactiae, Streptococcus dysgalactiae ssp. equisimilis Streptoccus intermedius, Streptococcus mitis, Streptococcus mutans, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus salivarius, Streptoccus suis, Ureaplasma urealyticum, Adenovirus,
8
| Meridian
Bioscience, Inc.
| Inspired Science. Trusted Solutions." | illumigene® Pertussis DNA Amplification Assay | |
|---|---|---|
| Application Reference: | K133673 | |
| Attachment Description: | Additional Information Request (January 13, 2014) | |
| 510(k) Summary | ||
| Application Date: | March 19, 2014 |
Coronavirus, Coxsackievirus, Cytomegalovirus, Epstein Barr Virus, Herpes Simplex Virus 1, Herpes Simplex Virus 2, Human Metapneumovirus, Influenza A, Influenza B, Measles virus, Mumps virus, Parainfluenza virus 1, Parainfluenza virus 2, Parainfluenza virus 3, Respiratory syncytial virus A, Respiratory syncytial virus B, Rhinovirus.
Bordetella holmesii and Bordetella bronchiseptica also contain the IS481 insertional element. Bordetella bronchiseptica ATCC® Strain 4617 and Bordetella holmesii were tested at 1.0 x 108 CFU/mL and found to react with the illumigene Pertussis assay.
Unexpected results were observed during original testing of specimens containing B. hinzii, H. parainfluenzae and M. genitalium. One of three negative sample replicates containing B. hinzii produced a false-positive result that was not confirmed with further testing (20/20 replicates). Three of three negative sample replicates containing H. parainfluenzae produced false-positive results that were not confirmed with further testing (20/20 replicates). Three of three B. pertussis positive sample replicates produced invalid results that were not confirmed with further testing (10/10 replicates). Three of three negative sample replicates containing M. genitolium produced invalid results that were not confirmed with further testing (10/10 replicates). As repeat testing using a heightened number of replicates did not confirm original results, B. hinzii, H. parainfluenzae and M. genitalium are not considered cross-reactive or interferents in illumigene Pertussis testing.
Assay cut-off:
The illumigene Pertussis assay is manufactured with fixed cut-off values. The product is designed around a pre-selected cut-off value and amplification reagent concentrations are optimized to ensure appropriate reactions are obtained. Development optimization includes evaluation of characterized positive and negative clinical specimens. Amplification reagent concentrations are adjusted during design as needed to ensure illumigene results are aligned with clinical specimen reported results.
Cut-off values applied in the following manner:
- . The illumipro-10™ calculates the ratio of the Run End (Signal final or S;) reads with the Run Start (Signal Initial or S;) reads and compares the ratio to an established cut-off value. The illumipro-10 performs this ratio calculation to both the TEST chamber and the CONTROL chamber.
- . Fixed cut-off values for the CONTROL chamber are used to determine validity. CONTROL chamber S;:S; ratios less than 90% are considered valid and allow for reporting of TEST chamber results (POSITIVE, NEGATIVE). CONTROL chamber S :S, ratios greater than or equal to 90% are considered invalid. Results are reported as 'INVALID'; Test chamber results are not reported. More stringent cut-off criteria are applied to the Control chamber reaction to ensure amplification is not inhibited, reagents are performing as intended and that sample processing was performed appropriately.
9
Image /page/9/Picture/0 description: The image is a logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, italicized font. Below that is "Bioscience, Inc." and the tagline "Inspired Science. Trusted Solutions."
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
Fixed cut-off values for the TEST chamber are used to report sample results. TEST chamber S;:S; ratios less than 82% are reported as 'POSITIVE'; TEST chamber S;:S; ratios greater than or equal to 82% are reported as 'NEGATIVE'. Numerical values are not reported.
CLINICAL PERFORMANCE DATA:
Clinical Studies:
Clinical Performance:
Clinical trials for the illumigene Pertussis DNA Amplification Assay, including the illumipro-10 Automated Isothermal amplification and detection system, were conducted from December 2012 to July 2013. A total of 729 qualified nasopharyngeal (NP) swab specimens collected from patients suspected of having Bordetella pertussis infection were evaluated with the test. All specimens were leftover and de-identified.
Performance characteristics of the assay were determined by comparison to a Composite Comparator Reference Method that included two manufacturer validated, real-time PCR Assays (PCR1 and PCR2) followed by bi-directional sequencing. Both comparator PCR assays targeted unique sequences within the IS481 insertional element; neither of the comparator target sequences overlaps with the illumigene Pertussis assay target sequence. Specimens producing positive Bordetella pertussis results from either comparator PCR assay were sent for bi-directional sequencing. Only samples that matched sequences within the Bordetella pertussis genome with pre-defined quality scores (PHRED20 and E-values) were considered true positives. Samples were considered negative when neither comparator PCR assay returned positive Bordetella pertussis results.
The clinical study population included retrospective and prospective specimens. A total of 508 (69.7%) prospective and 221 (30.3%) retrospective specimens were tested and included in final performance calculations. The retrospective sample population included non-selected specimens (all comers) and selected specimens. Overall performance characteristics of illumigene Pertussis Assay are summarized in Table 1.
10
Image /page/10/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the word "Meridian" in a bold, stylized font. Below "Meridian" is the text "Bioscience, Inc." and the tagline "Inspired Science. Trusted Solutions."
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
Table 1. illumigene Assay Performance
| Positive Specimens | Negative Specimens | ||||||
|---|---|---|---|---|---|---|---|
| Specimen | |||||||
| Description | illumigene | ||||||
| vs. | |||||||
| Comparator | PPAa | 95% CI | illumigene | ||||
| vs. | |||||||
| Comparator | NPA | 95% CI | Invalid | ||||
| Resultsb | |||||||
| Composite Method Comparator, All Comers | |||||||
| Prospective | 39/45 | 86.7% | 73.8 - 93.7% | 447/459 | 97.4% | 95.5 – 98.5% | 2 (13) |
| Retrospective | 4/4 | 100.0% | 51.0 - 100.0% | 176/178 | 98.9% | 96.0 - 99.7% | 0 |
| Total: | 43/49 | 87.8% | 75.8 - 94.3% | 623/637 | 97.8% | 96.3 - 98.7% | 2 (13) |
| Composite Method Comparator, Selected Specimens | |||||||
| Retrospective | 19/21 | 90.5% | 71.1 - 97.3% | 14/16 | 87.5% | 64.0 - 96.5% | 0 |
° Eight specimens produced false-negative illumigene results when composite Comparator Method. Six of the eight specimens produced detectable levels of DNA between 35 and 40 comparator assay amplification cycles and were confirmed positive by bi-directional sequencing. Three of these six specimens gave positive results in only one of the two comparator PCR/Sequencing assays.
b 11/13 initial invalid specimens produced valid results upon repeat testing.
False-negative illumigene results were individually evaluated at the conclusion of clinical testing. The Cycle threshold (Ct) values produced during comparator assay testing were above 35 for one or both PCR/Bi-directional sequencing assays for six of the eight specimens evaluated. High Ct values in PCR assays may indicate that low levels of DNA are present. False-negative illumigene results and corresponding Composite Comparator data are shown in Table 2.
Table 2. False-Negative illumigene Specimens, Comparator Assay Results
| Specimen
Designation | Specimen
Status | PCR1 | | PCR2 | |
|-------------------------|--------------------|----------|----------------------------------------|----------|----------------------------------------|
| | | Ct Value | Bi-Directional
Sequencing
Result | Ct Value | Bi-Directional
Sequencing
Result |
| 1-19 | Prospective | 34.90 | + | 33.85 | + |
| 1-29 | Prospective | Negative | N/A | 37.69 | + |
| 1-259 | Prospective | 34.07 | + | 35.09 | + |
| 1-269 | Prospective | 35.72 | + | Negative | N/A |
| 1-275 | Prospective | Negative | N/A | 39.13 | + |
| 3-33 | Prospective | 39.28 | + | 35.80 | + |
| 4-710 | Retrospective | 36.87 | + | 36.06 | + |
| 4-712 | Retrospective | 37.44 | + | 38.41 | + |
Four independent clinical test sites located in the Midwestern, Northern, and Eastern regions of the United States participated in the device evaluation All samples included in the study were submitted to the testing laboratory by an ordering physician
11
| Image: Globe logo | Meridian |
|---|---|
| Bioscience, Inc. | |
| Inspired Science. Trusted Solutions. |
| illumigene® Pertussis DNA Amplification Assay | |||||
|---|---|---|---|---|---|
| Application Reference: | K133673 | ||||
| Attachment Description: | Additional Information Request (January 13, 2014) | ||||
| 510(k) Summary | |||||
| Application Date: | March 19, 2014 |
for Bordetella pertussis testing and were presumed from symptomatic patients. No restrictions were placed on age, gender, medications or known pharmaceutical therapies.
Clinical studies were conducted with multiple nasopharyngeal swab and sample elution buffer types. Sample buffers tested during clinical studies included 0.85 % Saline (n=30 or 4.1%), Tris EDTA (n=8 or 1.1%) and Molecular Grade Water (n=687 or 94.2%). All sample buffers were used in 0.5 mL volumes. Analytical studies were performed with 0.85% Saline, Tris EDTA, Phosphate Buffered Saline (PBS) and Molecular Grade Water. Analytical studies established equivalence between all sample elution buffer types.
Clinical performance data was evaluated by patient age and gender. Age information was known for 723 (99.2%) of the patients from whom samples were tested. Patient age ranged from 1 month to 88 years. Thirty-eight (5.2%) patients were less than 1 year of age; 13 (1.8%) were between 1 and 2 years old; 296 (40.6%) were between 2 and up . to 12 years, 157 (21.5%) were between 12 and up to 21 years, 190 (26.0%) were above 21 but below 65 years, and the remaining 29 (4.0%) patients were above 65 years of age. The study population included 413 (56.7%) female and 308 (42.2%) male patients. Gender was unknown for 8 (1/1%) patients included in the study. There is no expectation that the illumigene Pertussis assay performance characteristics are influenced by patient gender.
Performance data by Clinical Test Site, analyzed based on the Composite Reference Method, is shown in Table 3. Statistical analysis of Site performance data was performed with no significant difference among Sites identified.
| Positive Specimens | Negative Specimens | ||||||
|---|---|---|---|---|---|---|---|
| Specimen Description | illumigene | ||||||
| vs. | |||||||
| Comparator | PPA | 95% CI | illumigene | ||||
| vs. | |||||||
| Comparator | NPA | 95% CI | Invalid | ||||
| Results | |||||||
| Composite Method Comparator, All Comers | |||||||
| Site 1 | 35/40 | 87.5% | 73.9 - 94.5% | 440/450 | 97.8% | 96.0 - 98.8% | 2 (13) |
| Site 2 | 4/4 | 100.0% | 51.0 - 100.0% | 67/69 | 97.1% | 90.0 - 99.2% | 0 (2) |
| Site 3 | 0/1 | 0.0% | 0.0 - 79.3% | 7/7 | 100.0% | 64.6 - 100.0% | 0 (0) |
| Site 4 | 4/4 | 100.0 | 51.0 - 100.0% | 109/111 | 98.2% | 93.7 - 99.5% | 0 (0) |
| Composite Method Comparator, Selected Specimens | |||||||
| Site 1 | 15/15 | 100.0% | 79.6 - 100.0% | 6/8 | 75.0% | 40.9 - 92.9% | 0 (0) |
| Site 4 | 4/6 | 66.7% | 30.0 - 90.3% | 8/8 | 100.0% | 67.6 - 100.0% | 0 (0) |
Table 3. illumigene Pertussis Assay Performance by Clinical Test Site, Composite Reference Method (CRM)
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Image /page/12/Picture/0 description: The image shows the logo for Meridian Bioscience, Inc. The logo features a globe graphic on the left, followed by the company name in bold, black font. Below the name is the tagline "Inspired Science. Trusted Solutions."
| illumigene® Pertussis DNA Amplification Assay | |
|---|---|
| Application Reference: | K133673 |
| Attachment Description: | Additional Information Request (January 13, 2014) |
| 510(k) Summary | |
| Application Date: | March 19, 2014 |
Expected values/Reference Range:
Overall incidence of B. pertussis as detected by the illumigene Pertussis Assay in prospectively and retrospectively collected, non-selected specimens (all comers) during the period of this study was 8.2% (57/692).
CONCLUSIONS
The illumigene® Pertussis DNA amplification assay, performed on the illumipro-10™, can be used to detect Bordetello pertussis in human nasopharyngeal swabs obtained from patients suspected of having respiratory infection attributable to Bordetella pertussis.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WObb-Cition Silver Spring, MD 20993-00012
March 25, 2014
MERIDIAN BIOSCIENCE, INC. MICHELLE SMITH SR. DIRECTOR REGULATORY AFFAIRS AND DESIGN ASSURANCE 3471 RIVER HILLS DRIVE CINCINNATI, OH 45244
Re: K133673
్రా
Trade/Device Name: illumigene Pertussis DNA Amplification Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: II Product Code: OZZ Dated: March 13, 2014 Received: March 19, 2014
Dear Ms. Smith:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA). it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the clectronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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Page 2-Ms. Smith
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely yours,
John Hobson -S for
Sally Hojvat, M.Sc., Ph.D Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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| DEPARTMENT OF HEALTH AND HUMAN SERVICES |
|---|
| Food and Drug Administration |
Indications for Use
510(k) Number (if known)
K133673 Device Name
illumigene® Pertussis DNA Amplification Assay
Indications for Use (Describe)
The illumigene® Pertussis DNA Amplification Assay, performed on the illumipro-10™, is a qualitative in vitro diagnostic test for the direction of Bordetella pertussis in human nasopharyngeal swab samples taken from patients suspected of having respiratory tract infection attributable to Bordetello pertussis.
The illumigene Pertussis assay utilizes loop-mediated isothermal DNA amplification (LAMP) technology to detect Bordetella pertussis by targeting the IS481 insertional element of the Bordetella pertussis genome. The IS481 insertional element can also be found in Bordetella holmesii and Bordetella bronchiseptica strains. Respiratory infection with Bordetella pertussis Bardetella bronchiseptica may yield positive test results in IS481 assays. B. holmesii infection may cause clinical illness similar to B. pertussis, and mixed outbreaks involving both 8. pertussis and B. holmesii infection have been reported. Additional testing should be performed if necessary to differentiate B. holmesii and B. pertussis. B. bronchiseptica is a rare cause of infection in humans. When clinical factors suggest that B. pertussis may not be the cause of respiratory infection, other clinically appropriate investigation(s) should be carried out in accordance with published guidelines.
Negative results for the illumigene Pertussis DNA Amplification Assay do not preclude Bordetello pertussis infection and positive results do not rule out co-infection with other respiratory pathogens. Results from the illumigene Pertussis assay should be used in conjunction with information obtained during the patient's clinical evaluation as an aid in diagnosis of Bordetella pertussis infection and should not be used as the sole basis for treatment or other patient management decisions.
illumigene Pertussis is intended for use in hospital, reference or state laboratory settings. The intended for point-of-care use.
Type of Use (Select one or both, as applicable) Over-The-Counter Use (21 CFR 801 Subpart C) X Prescription Use (Part 21 CFR 801 Subpart D)
PLEASE DO NOT WRITE BELOW THIS LINE -- CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
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