INVERNESS MEDICAL TESTPACK + PLUS STREP A WITH OBC

K051638 · Unipath , Ltd. · GTY · Dec 6, 2005 · Microbiology

Device Facts

• Record ID: K051638
• Device Name: INVERNESS MEDICAL TESTPACK + PLUS STREP A WITH OBC
• Applicant: Unipath , Ltd.
• Product Code: GTY · Microbiology
• Decision Date: Dec 6, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3740
• Device Class: Class 1
• Attributes: Pediatric

Indications for Use

The Inverness Medical TestPack + Plus Strep A with OBC Test is intended for the qualitative detection of Group A Streptococcal (Group A Strep) antigen in throat swab specimens from patients with suspected Group A Strep associated pharyngitis and for confirmation of presumptive Group A Strep colonies isolated on culture plates. The test is intended for Professional and Laboratory Use only.

Device Story

Lateral-flow enzyme immunoassay for qualitative detection of Group A Streptococcal antigen. Input: throat swab specimens or isolated culture colonies. Operation: specimen extraction using reagents; mixture applied to chromatography strip membrane; Group A Strep antigen binds to colloidal gold-labeled polyclonal antibodies; complex migrates to result window; captured by immobilized antibodies; visual readout (pink/red plus sign for positive, minus sign for negative). Includes on-board positive/negative controls and end-of-assay indicator. Used in clinical/laboratory settings by professional staff. Output: visual qualitative result. Benefits: rapid identification of Group A Strep to guide clinical management of pharyngitis.

Clinical Evidence

Multi-center clinical study evaluated performance against established culture techniques. Physician office studies demonstrated that personnel with diverse backgrounds could correctly perform and interpret the test. Interference studies confirmed common bacterial organisms and OTC sore throat products do not interfere with performance.

Technological Characteristics

Lateral-flow immunochromatographic assay. Components: chromatography strip membrane, plastic frame, polyclonal anti-Strep A antibodies, colloidal gold dye particles. Extraction reagents (3). Visual readout. No electronic components or software. Standalone point-of-care test.

Indications for Use

Indicated for qualitative detection of Group A Streptococcal antigen in throat swab specimens from patients with suspected pharyngitis and for confirmation of presumptive Group A Strep colonies from culture plates. For professional and laboratory use.

Regulatory Classification

Identification

Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identify Streptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Streptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.

Predicate Devices

• Quidel QuickVue® Dipstick Strep A Test (K011097)

Submission Summary (Full Text)

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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
DEVICE ONLY TEMPLATE

A. 510(k) Number:
K051638

B. Purpose of Submission:
To obtain clearance for the Inverness Medical TestPack + Plus
Strep Test

C. Analyte:
Group A Streptococcal antigen

D. Type of Test:
Horizontal-flow enzyme immunoassay

E. Applicant:
Unipath Limited

F. Proprietary and Established Names:
Inverness Medical TestPack + Plus Strep A with OBC

G. Regulatory Information:
1. Regulation section:
21 CFR Part 866.3740 Streptococcus spp. serological reagents
Limitation: 21 CFR 866.9 (6)
2. Classification:
I
3. Product Code:
GTY – Streptococcus spp.
4. Panel:
83 Microbiology

H. Intended Use:
1. Intended use(s):
INVERNESS MEDICAL TESTPACK PLUS STREP A with On Board
Controls (OBC) (TESTPACK STREP A) is a rapid immunoassay for
the qualitative detection of Group A Streptococcal (Group A Strep)
antigen in throat swab specimens from patients with suspected
Group A Strep associated pharyngitis and for confirmation of
presumptive Group A Strep colonies isolated on culture plates. For
Professional and Laboratory use only.
2. Indication(s) for use:
INVERNESS MEDICAL TESTPACK PLUS STREP A with (OBC) TEST is
intended for the qualitative detection of Group A Streptococcal (Group A
Strep) antigen in throat swab specimens from patients with suspected
Group A Strep associated pharyngitis and for confirmation of
presumptive Group A Strep colonies isolated on culture plates. The test is
intended for Professional and Laboratory use only.
3. Special condition for use statement(s):
For Prescription Use Only

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4. Special instrument Requirements:
Not applicable

I. Device Description:
The device consists of a chromatography strip membrane housed in a plastic frame. The membrane carries immobilized polyclonal anti-Strep A antibody coupled to colloidal gold dye particles. The test line contains sheep and rabbit anti-group A streptococcus antibody. The control line consists of an immobilized antibody to the anti-Strep A indicator antibody. At the control line, anti-Strep A indicator antibody-unbound/bound colloidal gold complexes form a control line in the control window which indicates that the device is functioning properly. Additionally, the test device consists of negative and positive on board controls that also serve as indicators that the test reagents are working correctly.

J. Substantial Equivalence Information:
1. Predicate device name(s):
Quidel QuickVue® Dipstick Strep A Test
2. Predicate K number(s):
K011097
3. Comparison with predicate(s):

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended use | For the qualitative detection of group A streptococcal antigen directly from throat swabs. | same |
| Specimen type | Throat swab or culture colonies | same |
| technology | Immunochromatographic | same |
| antibodies | Polyclonal anti-Strep A | same |
| Limit of detection | 1.5x10^5 CFU mL | same |
| | Difference | |
| Item | Device | Predicate |
| Extraction method | Extraction applied to device test well | Dipstick placed in tube of extract |
| Clinical sensitivity | 97.6% CI (93.1-99.5%) | 92% CI (86-96%) |
| Clinical specificity | 98.4% CI (95.9-99.6%) | 98% CI (95-99%) |
| Positive and negative on board controls | Yes | No |
| End of assay control | Yes | No |
| Extraction reagents | 3 | 2 |

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# K. Standard/Guidance Document referenced (if applicable):

Not applicable

# L. Test Principle:

The test device is a lateral flow immunoassay consisting of a chromatography strip membrane housed in a plastic frame. The membrane carries immobilized sheep and rabbit polyclonal antibodies bound to colloidal gold dye particles. The Streptococcal Group A specific antigen is extracted from the throat swab using Reagent 1 and Reagent 2. Following this, Reagent 3 is added to neutralize the acid formed by Reagents 1 and 2. The mixture is then dropped into the Sample Well of the reaction disc and allowed to migrate through the membrane until it reaches the End of Assay Window. As the specimen extract migrates through the membrane, it mobilizes the Group A Strep antibody-coated colloid. If Group A Streptococcal antigen is present in the specimen it will form a complex with the antibody-colloid. The antibody colloid complex migrates through the membrane and is then captured by the Group A Strep antibody in the result window, providing a visual indication of the presence of antigen. The test can be read when the End of Assay Window has turned pink/red. A pink/red Plus Sign (+) appearing in the Result Window indicates the presence of the Group A Strep antigen. A Minus Sign (–) indicates no antigen was detected.

# M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Within lot, between lot and between operator reproducibility were tested over a 3 day period. Five replicates of a negative, weak positive and positive control were tested by 3 operators on each occasion. No differences were seen between runs, and all controls produced the expected results.

b. Linearity/assay reportable range:

Not applicable

c. Traceability (controls, calibrators, or method):

Not applicable

d. Detection limit:

The test device has a minimum limit of detection of $1.5 \times 10^{5}$ CFU/mL.

e. Analytical specificity:

The analytical specificity was determined by testing organisms expected to be found in the respiratory tract at $1 \times 10^{8}$ organisms per mL, with the exception of Staphylococcus aureus, which was tested at $1 \times 10^{9}$ organisms per mL. No cross reactivity was found when TESTPACK STREP A was tested with the bacteria listed below:

Arcanobacterium haemolyticum

Bordetella pertussis

Candida albicans

Corynebacterium diphtheria

Escherichia coli

Fusobacterium necrophorum

Klebsiella pneumoniae

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Haemophilus influenzae

Haemophilus parahaemolyticus

Moraxella catarrhalis

Moraxella lacunata

Neisseria gonorrhoeae

Neisseria lactamica

Neisseria meningitidis

Neisseria sicca

Neisseria subflava

Proteus vulgaris

Pseudomonas aeruginosa

Serratia marcescens

Staphylococcus aureus (Cowan's serotype I)

Staphylococcus aureus

Staphylococcus epidermidis

Staphylococcus haemolyticus

Staphylococcus saprophyticus

Streptococcus groups B, C, D, F, G

Streptococcus oralis

Streptococcus salivarius

Streptococcus sanguis

Streptococcus mitis

Streptococcus mutans

Streptococcus pneumoniae

Yersinia enterocolitica

TESTPACK STREP A was found to perform as expected with both positive and negative samples in the presence of benzocaine and lidocaine, which are active ingredients found in a number of commercially available sore throat treatments.

f. Assay cut-off

Using ATCC strain 12344, the limit of detection of TESTPACK STREP A (at which Streptococci were detected $100\%$ of the time) was shown to be $1.05 \times 105$ CFU/swab.

2. Comparison studies:

a. Method comparison with gold standard:

For visually positive SBA (Sheep Blood agar) plates, clinicians recorded the density and growth of presumptive group A Streptococcus colonies. The results from SBA culture and the corresponding TESTPACK STREP A rapid results are compared below:

| | | SBA plates | | |
| --- | --- | --- | --- | --- |
| | | Pos | Neg | Total |
| Testpack Strep A (+) | | 122 | 4 | 126 |
| Testpack Strep A (-) | | 3 | 240 | 243 |
| Total | | 125 | 244 | 369 |
| | | | | 95% CI |
| Clinical sensitivity | 122/125 (97.6%) | | | 93.1-99.5% |

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| Clinical specificity | 240/244 (95.9%) | 95.9-99.6% |
| --- | --- | --- |

b. Matrix comparison:
Not applicable

3. Clinical studies:

a. Clinical sensitivity:
The clinical performance of TESTPACK STREP A was compared with standard sheep blood agar culture. In a multi-center field evaluation, two throat swabs were collected simultaneously from children and adults presenting to clinics with symptoms of pharyngitis. One swab was tested by clinic staff according to each clinic's normal standard of care. The remaining swab was retained for evaluation of TESTPACK STREP A and was either tested immediately or stored at 2-8°C in transport tubes prior to testing. All swabs were tested on the day of collection. Swabs retained for evaluation of TESTPACK STREP A were used to inoculate a sheep blood agar (SBA) plate, prior to being tested using the TESTPACK STREP A test. Plates were incubated for 24-48 hours at 35°C with 5-10% CO2. Presumptive group A Streptococcus colonies on SBA culture plates were confirmed using a commercially available Streptococcal latex grouping test. Results were obtained for 369 (335 pediatric and 34 adult) patients, of which 125 were found positive by standard SBA culture and 244 were found negative. The sensitivity of the TESTPACK STREP A test was 97.6% when compared to standard SBA culture (95% confidence interval [CI]: (93.1-99.5%). The specificity of the TESTPACK STREP A test was 98.4% when compared to standard SBA culture (95% Confidence Interval [CI]: (95.9-99.6%).

b. Clinical specificity:
Refer to (e.) above

c. Other clinical supportive data (when a and b is not applicable):
Not applicable

4. Clinical cut-off:
The lower limit of detection of this assay is 1.5 x 10⁵ cfu/ml.

5. Expected values/Reference range: (Interpretive Criteria)
It is believed that approximately 19% of all upper respiratory tracts infections are caused by Group A Streptococcus. A prevalence of 33.7% was observed in the clinical performance evaluation of TESTPACK STREP A. Group A Strep associated pharyngitis displays a seasonal variation and is most prevalent during the Winter and early Spring. Certain populations are at higher risk of infection, for example, schools, nursing homes and hospitals. Clustering of cases occurs.

N. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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