(223 days)
Accuwell Thyroid Stimulating Hormone (TSH) ELISA
Not Found
No
The device description and performance studies detail a standard enzyme immunoassay (ELISA) method for measuring TSH. There is no mention of AI, ML, or any computational methods beyond standard data analysis for generating a standard curve and performing linear regression.
No.
This device is designed for diagnostic screening by measuring TSH concentrations to identify congenital hypothyroidism, not for treating or preventing a disease or condition.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states that "The results are used to screen newborns for congenital hypothyroidism," which is a diagnostic purpose. The device measures TSH concentrations to identify a specific medical condition.
No
The device description clearly outlines a physical kit containing microplates, antibodies, enzymes, and reagents used in an enzyme immunoassay. This involves significant hardware and chemical components, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of Thyroid Stimulating Hormone (TSH) concentrations in neonatal blood samples" and that the "results are used to screen newborns for congenital hypothyroidism." This clearly indicates it's used to analyze a biological sample (blood) in vitro (outside the body) to provide information for a medical purpose (screening for a condition).
- Device Description: The description details an "enzyme immunoassay" performed on "neonatal blood samples that have been collected onto Whatman 903 specimen collection paper." This describes a laboratory test conducted on a biological specimen.
- Performance Studies: The performance studies describe analytical evaluations of the device's ability to measure TSH in blood samples, including precision, sensitivity, linearity, specificity, and method comparison with a predicate device. These are all characteristics evaluated for IVD devices.
- Predicate Device: The mention of a "Predicate Device(s)" which is another "Thyroid Stimulating Hormone (TSH) ELISA" further confirms that this device falls within the category of IVDs used for TSH testing.
The device meets the definition of an In Vitro Diagnostic device as it is intended for use in the examination of specimens derived from the human body to provide information for diagnostic purposes.
N/A
Intended Use / Indications for Use
The GBI TSH Neonatal Screening Kit is designed for the quantitative determination of Thyroid Stimulating Hormone (TSH) concentrations in neonatal blood samples that have been collected onto Whatman 903 specimen collection paper. The results are used to screen newborns for congenital hypothyroidism.
Product codes
JLW
Device Description
The GBI TSH Neonatal Screening Kit is an enzyme immunoassay. A highly specific polyclonal goat antihTSH (human) antibody has been immobilized onto each well of the 96-well microplates provided. To begin the assay, sample discs punched from dried whole blood spot standards, controls and neonate specimens are added to the coated wells. An elution buffer is also added. The plate is incubated to elute TSH from the sample disc and to allow capture of the eluted TSH by the antibody immobilized onto the microplate wells. Following incubation the plates are washed to remove the sample discs as well as the eluate.
A second antibody, a D-specific anti-hTSH monoclonal that has been conjugated to the enzyme horseradishperoxidase (HRP), is then added to the wells and incubated. The eluted TSH of the sample already captured by the microplate-bound antibody is now also bound by the enzyme-conjugated monoclonal antibody added. An antibody-TSH-antibody bridge, or "sandwich", forms that is bound to the surface of the microplate wells. Any unbound complexes are removed with subsequent plate washings.
The final stage of the assay is the detection of the microwell-bound complexes by the addition of a color developing reagent. The enzyme (HRP) portion of the bound "sandwich" reacts with the color developer, 3, 3', 5, 5'-Tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). The TMB/ H2O2 liquid is converted from colorless to blue. The degree of color change is directly proportional to the amount of TSH antigen that is bound in the well. The color development is terminated with the addition of a color stopper that converts the blue to yellow.
The results are measured with a microplate reader at a wavelength of 450 mm. The absorbance measured is directly proportional to the concentration of TSH in the sample. A standard curve is generated by plotting the light absorbance of each standard versus its known TSH concentrations of TSH in the unknown samples are determined by interpolation from this standard curve.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
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Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Neonatal
Intended User / Care Setting
Clinical Laboratory Professionals
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies
Precision studies were conducted in accordance with NCCLS EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition. Testing included two sample aliquots per run, one run per day, performed on 20 different days using the GBI published assay procedure. The resulting data were used to estimate repeatability, between-day and withindevice precision.
Analytical Sensitivity: The Analytical Limit at Low Levels (limit of sensitivity) for the GBI TSH EIA Kit was determined by testing the zero standard multiple times (N=20) within a single assay. The resulting data were used to calculate the analytical limit at low levels. The analytical sensitivity is defined as the calculated concentration that corresponds to the mean of the absorbance values of the zero standard (N=20) plus two times the standard deviation derived from those same (N=20) absorbance values.
Linearity, Recovery and Assay Measurable (Reportable) Range: The GBI TSH EIA Kit linear range was assessed according to the NCCLS Guideline EP6-A: Evaluation of the Linearity of Quantitative Analytical Methods, 2003. A series of dried whole blood spot samples was prepared to provide the desired range of TSH concentrations for the study (N=19). Two one-eighth inch punches from each concentration level were tested in each of two runs. The mean of the total number of results for a level (n=4) was compared to the expected value.
Specificity (Cross Reactivity): Compounds (FSH, LH, HCG) were tested for cross-reactivity. Each compound was added at several concentrations to TSH-free whole blood which had been adjusted to a hematocrit of 55%. The samples were spotted onto Whatman 903 specimen collection paper, air-dried and assayed.
Interfering Substances: Assay interference due to the presence of hemoglobin, conjugated bilirubin, and lipids was studied using methods described in NCCLS EP7A: Interference Testing in Clinical Chemistry as guidance. Testing was performed to evaluate the effects of interfering substances at the medical decision(s) concentrations using fresh whole blood.
Method Comparison: A total of 995 neonatal blood spot specimens, 980 randomly selected from a presumed normal population and 15 from patients confirmed as positive for hypothyroidism, were analyzed in-house with the GBI TSH EIA. Results were compared to those obtained using a commercially available neonatal TSH assay (Predicate). Of the 995 total blood spot samples tested, 163 results produced non-numeric values (either "less than the limit of sensitivity", n=153; or "greater than the highest standard", n=10) for one or both assays, and were therefore not included in statistical analysis for the N=832 population.
Key Metrics
Precision:
| Parameter | Sample ID C1 | Sample ID C2 | Sample ID C3 | Sample ID C4 | Sample ID C5 |
|---|---|---|---|---|---|
| Mean | 14.6 | 28.3 | 30.6 | 46.3 | 86.8 |
| SD | 1.2 | 2.5 | 3.7 | 4.4 | 12.1 |
| %CV | 7.9 | 8.7 | 11.9 | 9.4 | 13.9 |
| Sr (Within-Run SD) | 0.9 | 1.3 | 2.6 | 4.2 | 6.5 |
| Sdd (Between-Day SD) | 1.0 | 2.3 | 2.6 | 1.2 | 10.3 |
| ST (Within Device SD) | 1.2 | 2.5 | 3.7 | 4.4 | 12.2 |
Analytical Sensitivity: 2.4 uIU/ml
Linearity and Recovery:
Average Recovery-Overall %: 95.2
Minimum %: 88.1
Maximum %: 114
Linear Regression Analysis: y = 0.8997x + 0.6036, R^2 = 0.999
Method Comparison (N=995):
| GBI Results | Normal ( 40) | Row Totals |
|---|---|---|---|---|
| Predicate Normal (N=974) | 967 | 7 | 0 | 974 |
| Predicate Borderline (N=6) | 2 | 4 | 0 | 6 |
| Predicate Positive (N=15) | 0 | 0 | 15 | 15 |
| Column Totals | 969 | 11 | 15 | 995 |
Method Comparison (Subset N=832):
GBI TSH Mean = 8.9 uIU/ml, range 2.4 to 114 uIU/ml
Predicate TSH Mean = 8.1 uIU/ml, range 2.9 to 104 uIU/ml
Linear regression: y (GBI TSH EIA) = 1.0695x (Predicate) + 0.2671, R2 = 0.9185
Predicate Device(s)
Accuwell Thyroid Stimulating Hormone (TSH) ELISA
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1690 Thyroid stimulating hormone test system.
(a)
Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as thyrotrophin and thyrotrophic hormone, in serum and plasma. Measurements of thyroid stimulating hormone produced by the anterior pituitary are used in the diagnosis of thyroid or pituitary disorders.(b)
Classification. Class II.
0
Golden Bridge International, Inc. Mukilteo, WA 98275 USA
APR 1 0 2008
| 1) | Submitter Name: | Golden Bridge International, Inc. |
|---|---|---|
| Address: | 9700 Harbour Place, Suite 129 | |
| Mukilteo, WA 98725 USA | ||
| Telephone Number: | 425-493-1801 | |
| Contact Person: | Xiaoping Zhang, Vice President | |
| Date Prepared: | 03/27/08 | |
| 2) | Device Trade or | |
| Proprietary Name: | GBI TSH Neonatal Screening Kit | |
| Device Common or | ||
| Usual Name: | Thyroid stimulating hormone (TSH) neonatal screening enzyme | |
| immunoassay (EIA) | ||
| Device Classification Name: | Radioimmunoassay, Thyroid Stimulating Hormone | |
| Product Code: | JLW | |
| 3) | Legally Marketed | |
| Predicate Device: | Accuwell Thyroid Stimulating Hormone (TSH) ELISA |
GBI Thyroid Stimulating Hormone (TSH) EIA 510(k) Summary
4) Device Description:
Summary and Explanation of the Test
Congenital hypothyroidism (CH) is one of the most common metabolic disorders resulting in permanent mental retardation if undetected or left untreated soon after birth. Newborns that have been identified and treated for CH within two weeks of birth can be expected to have normal cognitive development.
Screening programs for the disorder were developed early in 1974 and have now been established in Western Europe, North America, Japan and parts of Eastern Europe, Asia, South and Central American Academy of Pediatrics first published recommendations for CH in 1993. Advances in screening methods and expanded knowledge of the physiology of thyroid hormones has lead to new recommendations by the Academy in 2006.2 In North America more than five million newborns are screened annually with over 1400 hypothyroid cases detected each year. The incidence of hypothyroidism varies among different populations and ranges from 1 in 3000 to 1 in 4000. The incidence of CH is higher in Hispanics and lower in black individuals. Females have a 2:1 greater incidence of CH than males. A higher frequency of the CH disorder has been observed in individuals with Downs Syndrome.
Thyroid stimulating hormone (TSH) is a pituitary-derived glycoprotein with a molecular weight of approximately 28 kDa. TSH is produced by the anterior lobe of the pituitary gland under the control of thyrotropin releasing hormone (TRH) which is secreted by the hypothalamus. TSH acts on the thyroid gland to release the thyroid hormones triiodothyronine (T)) and thyroxine (T). Under normal thyroid function, the level of the thyroid hormones T3 and T4 is inversely related to the concentrations of TSH and TRH in the bloodstream via a negative feedback mechanism. As a result of this negative feedback mechanism between the thyroid gland and the pituitary, TSH is always elevated in cases of primary hypothyroidism and often to very high levels. It is
1
for this reason that the measurement of TSH concentration is a valuable diagnostic tool for the detection of hypothyroidism.
Thyroid hormone (TH) levels of the fetus are low during the first half of pregnancy. Maternal status of TH hormones is entirely responsible for the regulation of fetal TH, transmitted through the placenta. The fetal hypothalamic-pituitary-thyroid axis develops during the second half of gestation and is mature at time of birth. A surge of TSH concentration occurs at birth and then declines rapidly within the first few days of life, and continues to decrease more slowly to adult levels. It is recommended to perform screening for CH ideally within the 2nd to 4th days after birth or at time of discharge.
Blood samples collected before 24 hours of age, from low birth weight or ill infants can lead to elevated TSH and thus false positive results. Hypothyroid infants may be partially protected by maternal TH levels and so most infants will appear normal at birth. There have also been reported cases of transient hypothyroidism due to maternal hypothyroidism and other maternal abnormalities. Hypothyroidism can develop after birth, and in such cases will yield a normal newborn screening result.
Since the incidence of hypothyroidism and the concentrations of TSH have been shown to a variety of factors (e.g., demographics, ethnicity, the sex and age of the infant, low birth weights and premature births) it is important that each newborn screening laboratory examine its test population and determine its own normal range and cut-off values with these factors taken into consideration.
Screening algorithms vary among centers from initial TSH with confirmation via T4 initial screen with confirmation via TSH measurements, to both tests (174 and TSH) being performed simultaneously. Regardless of method, repeated positive results on a neonate should be cause for referral for additional confirmation testing.
Principle of the Assay
The GBI TSH Neonatal Screening Kit is an enzyme immunoassay. A highly specific polyclonal goat antihTSH (human) antibody has been immobilized onto each well of the 96-well microplates provided. To begin the assay, sample discs punched from dried whole blood spot standards, controls and neonate specimens are added to the coated wells. An elution buffer is also added. The plate is incubated to elute TSH from the sample disc and to allow capture of the eluted TSH by the antibody immobilized onto the microplate wells. Following incubation the plates are washed to remove the sample discs as well as the eluate.
A second antibody, a D-specific anti-hTSH monoclonal that has been conjugated to the enzyme horseradishperoxidase (HRP), is then added to the wells and incubated. The eluted TSH of the sample already captured by the microplate-bound antibody is now also bound by the enzyme-conjugated monoclonal antibody added. An antibody-TSH-antibody bridge, or "sandwich", forms that is bound to the surface of the microplate wells. Any unbound complexes are removed with subsequent plate washings.
The final stage of the assay is the detection of the microwell-bound complexes by the addition of a color developing reagent. The enzyme (HRP) portion of the bound "sandwich" reacts with the color developer, 3, 3', 5, 5'-Tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2). The TMB/ H2O2 liquid is converted from colorless to blue. The degree of color change is directly proportional to the amount of TSH antigen that is bound in the well. The color development is terminated with the addition of a color stopper that converts the blue to yellow.
The results are measured with a microplate reader at a wavelength of 450 mm. The absorbance measured is directly proportional to the concentration of TSH in the sample. A standard curve is generated by plotting the light absorbance of each standard versus its known TSH concentrations of TSH in the unknown samples are determined by interpolation from this standard curve.
2
Kit Contents
Materials Supplied
| Quantity per Kit | |
|---|---|
| Total Tests: | 576 |
| TSH Capture Microplate | 6 X 96 wells |
| TSH Elution Buffer | 1 x 70 ml |
| Anti-TSH PO Conjugate | 1 x 1.4 ml |
| TSH Diluent Buffer | 1 x 70 ml |
| PO Wash Buffer (20X) | 1 x 100 ml |
| PO Color Reagent* | 1 x 70 ml |
| PO Color Stopper | 1 x 70 ml |
| TSH Dried Blood Standards and Controls | 1 Set |
* This reagent is light sensitive. Avoid prolonged exposure to light.
NOTE: Do NOT use reagents that are cloudy or discolored as these conditions indicate deterioration. Reagents should be stored in their original containers with the exception of the diluted wash buffer.
Do NOT exchange reagents from one kit with those of another kit.
Reagent Descriptions
TSH Capture Microplate
Goat polyclonal anti-alpha hTSH antibody coated 96-well microplates. The microplates are packaged in zipper-lock bags containing a desiccant. Store the unused microplates in zipper-lock bags with desiccant. Storage: Dry at 2-25° C.
Expiration: Refer to the expiration date printed on the label
TSH Elution Buffer
A borate buffer containing bovine albumin, surfactant and preservatives. This buffer contains sodium azide as a preservative.
Storage: 2-8° C Refer to the expiration date printed on the label. Expiration:
Anti-TSH PO Conjugate
A mouse monoclonal p-specific antibody conjugated to horseradish peroxidase (HRP) in borate buffer containing bovine albumin, surfactant, and preservatives. This buffer contains thimerosal as a preservative; refer to "Warnings and Precautions", below. Store in the original brown container. This conjugate is concentrated and must be diluted before use.
Storage: 2-8° C
Refer to the expiration date printed on the label. Expiration:
TSH Diluent Buffer
A borate buffer containing bovine albumin, surfactant, and preservatives. This buffer contains thimerosal as a preservative.
2-8° C Storage:
Refer to the expiration date printed on the label. Expiration:
3
PO Wash Buffer (20X)
A concentrated solution of phosphate buffered saline containing a surfactant and preservatives. Wash Buffer Concentrate must be diluted with deionized or distilled water before use. Storage: 2-25° C
Expiration:
Concentrate: Refer to the expiration date printed on the label. Diluted wash buffer is stable for 1 month when stored at 2-25° C.
PO Color Reagent*
hydrogen coloriess solution of 3,3', 5,5'-Tetramethylbenzidine (TMB) and peroxide. A *This reagent is light sensitive. Store in the original brown container. Do not pour any of the unused Color Developer back into the original container. This reagent should remain colorless. If it has discolored, discard it.
2-8° C Protected from light. Storage:
Refer to the expiration date printed on the label. Expiration:
PQ Color Stopper
、
A solution containing 40 uIU/ml serum equivalent | From American Academy of Pediatrics:
Normal 40 uIU/ml serum equivalent |
| 17 | Expected Values -
Normal Neonate
Population | N=1040:
Mean = 9.9 ulU/ml
S.D. = 5.8 uIU/ml | N=902:
Mean = 8.1 uIU/ml
S.D. = 4.0 uIU/ml |
| 18 | Analytical Sensitivity | 2.9 uIU/ml | 2.4 uIU/ml |
| 19 | Precision³ | Within Run Precision:
NA
NA
24.0 uIU/ml cv = 10.0 %
51.1 uIU/ml cv = 7.8 %
159.2 uIU/ml cv = 4.3 %
Between Run Precision:
NA
NA
27.3 uIU/ml cv = 6.1 %
40.8 uIU/ml cv = 8.4 %
78.5 uIU/ml cv = 6.5 %
Over-All (Within-Device) Precision:
NA - Not published | Within-Run Standard Deviation (Sr):
15 uIU/ml Sr = 0.9 ulU/ml cv= 6.2%
30 uIU/ml Sr = 1.3 " cv= 4.6%
25+uIU/ml Sr = 2.6 " cv= 8.5%
40+ ulU/ml Sr = 4.2 " cv= 9.1%
80+ ulU/ml Sr = 6.5 " cv=7.5%
Between-Day Standard Deviation (Sdd):
15 uIU/ml Sdd = 1.0 ulU/ml cv= 6.8%
30 uIU/ml Sdd = 2.3 " cv= 8.1%
25+uIU/ml Sdd = 2.6 " cv= 8.5%
40+uIU/ml Sdd = 1.2 " cv= 2.6%
80+uIU/ml Sdd = 10.3 " cv= 11.9%
Within-Device Standard Deviation (ST):
15 ulU/ml ST = 1.2 ulU/ml cv= 8.2%
30 ulU/ml ST = 2.5 " cv= 8.8%
25+ ulU/ml ST = 3.7 " cv= 12.1%
40+uIU/ml ST = 4.4 " cv= 9.5%
80+uIU/ml ST = 12.2 " cv= 14.1% |
| 20 | Interfering Substances | No Interference observed at the highest
concentration tested*:
Bilirubin - no interference up to 60 mg/dl*
Lipids - no interference up to 1000 mg/dl*
Hemoglobin - no interference up to 78 g/dl* | No Interference observed at the highest
concentration tested*:
Bilirubin - no interference up to 20 mg/dl*
Lipids - no interference up to 1350 mg/dl*
Hemoglobin - no interference up to 80 g/dl* |
| 21 | Cross Reacting
Substances | No interference found at the highest
concentration tested:
FSH- no interference up to 500 mIU/ml
LH- no interference up to 500 mIU/ml
HCG- no interference up to 100,000 mIU/ml | No interference found at the highest
concentration tested:
FSH- no interference up to 500 mIU/ml
LH- no interference up to 500 mIU/ml
HCG- no interference up to 100,000 mIU/ml |
| 22 | Method Comparison | For N=995:
Normal = 974/995 (97.9%)
Borderline = 6/995 (0.6%)
Positive = 15/995 (1.5%)
For (subset) N=832:
Mean = 8.1 uIU/ml;
Range = 2.9 to 104 uIU/ml. | For N=995:
Normal = 969/995 (97.4%)
Borderline = 11/995 (1.1%)
Positive = 15/995 (1.5%)
For (subset) N=832:
Mean = 8.9 ulU/ml;
Range = 2.4 to 114 uIU/ml
y (GBI TSH EIA) = 1.0695x (Predicate) +
0.2671. R² = 0.9185 |
| | CDC Controls
(Enrichment Values in
serum equivalents) | N = 294
intercept = 0.1505
slope = 1.0231 | N = 405
intercept = 5.2083
slope = 1.0208 |
| 23 | CDC Lot 611 –
25 uIU/ml | 26.0 uIU/ml serum equivalent | 30.6 uIU/ml serum equivalent |
| | CDC Lot 612 –
40 uIU/ml | 40.7 uIU/ml serum equivalent | 46.3 uIU/ml serum equivalent |
| | CDC Lot 613 –
80 uIU/ml | 82.1 uIU/ml serum equivalent | 86.8 uIU/ml serum equivalent |
5
:
:
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6
Golden Bridge International, Inc. Mukilteo, WA 98275 USA
l
Predicate data and descriptive text were obtained from the Accuwell TSH ELISA Directions For Use (DFU) unless otherwise indicated.
2 The predicate DFU declares the use of "Schleicher & Schuell (S&S) 903™" filter paper as the sample substrate. S&S has since been purchased by Whatman and the name of the 903 filter paper has been changed to "Whatman 903". For this reason, table references throughout use the Whatman 903" designation only, even though the predicate DFU actually refers to the paper as S&S 903™
3 Precision data were not generated in the same way nor reported in precisely the same terms for the predicate vs the new device. The new (GBI TSH) device precision was established and reported according to NCCLS EP5-A2, "Evaluation of Precision Performance of Quantitative Measurement Methods"; Approved Guideline-Second Edition.
4 Predicate values were obtained from the CDC's Newborn Screening Quality Assurance Program (NSQAP) 2006 Annual Summary Report; Volume 24, January 2007.
5 GBI values were obtained from the same data sct that was used to establish assay precision values.
7
7) Clinical and Non-Clinical Data:
Precision
Precision studies were conducted in accordance with NCCLS EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition.
Testing included two sample aliquots per run, one run per day, performed on 20 different days using the GBI published assay procedure. The resulting data were used to estimate repeatability, between-day and withindevice precision as described by the standard. Refer to the table below.
Sources of variability included the use of different: operators, days and reagent lot numbers.
| Summary Results and Estimates of Precision for GBP TSH EIA Kit | ||||||
|---|---|---|---|---|---|---|
| Sample ID: | C1 | C2 | C3 | C4 | C5 | |
| Precision Parameter | Count | 40 | 40 | 40 | 40 | 40 |
| Mean | 14.6 | 28.3 | 30.6 | 46.3 | 86.8 | |
| SD | 1.2 | 2.5 | 3.7 | 4.4 | 12.1 | |
| %CV | 7.9 | 8.7 | 11.9 | 9.4 | 13.9 | |
| Min | 12.5 | 23.5 | 23.3 | 37.5 | 71.4 | |
| Max | 18.0 | 34.0 | 40.4 | 59.1 | 122.5 | |
| Within-Run Standard Deviation: | Sr = | 0.9 | 1.3 | 2.6 | 4.2 | 6.5 |
| Between-Day Standard Deviation: | Sdd = | 1.0 | 2.3 | 2.6 | 1.2 | 10.3 |
| Within Device Standard Deviation: | ST = | 1.2 | 2.5 | 3.7 | 4.4 | 12.2 |
Summary Results and Estimates of Precision for GBI TSH EIA Kit
Analytical Sensitivity
The Analytical Limit at Low Levels (limit of sensitivity) for the GBI TSH EIA Kit was determined by testing the zero standard multiple times (N=20) within a single assay. The resulting data were used to calculate the analytical limit at low levels. Refer to the table below.
The analytical sensitivity is defined as the calculated concentration that corresponds to the mean of the absorbance values of the zero standard (N=20) plus two times the standard deviation derived from those same (N=20) absorbance values.
These data are provided for example only. Each laboratory should establish appropriate working limits based upon their own patient population and/or data.
| Summary Results and Analytical Limits at Low Levels for GBI TSH EL | |
|---|---|
| GBI TSH | |
| Count | 20 |
| Mean ABS | 0.0354 |
| SD | 0.0063 |
| %CV | 18 |
| Min | 0.0289 |
| Max | 0.0570 |
| Mean + (2 *S.D.) ABS: | 0.0480 |
| Analytical Limit (uIU/ml) | 2.4 |
Posults and Analytical Limits of Low Levels for CBI TSH FIA ﮯ
8
Linearity, Recovery and Assay Measurable (Reportable) Range
The GBI TSH EIA Kit linear range was assessed according to the NCCLS Guideline EP6-A: Evaluation of the Linearity of Quantitative Analytical Methods, 2003.
A series of dried whole blood spot samples was prepared to provide the desired range of TSH concentrations for the study (N=19; see table column "Expected Value", below).
Two one-eighth inch punches from each concentration level were tested in each of two runs. The mean of the total number of results for a level (n=4) was compared to the expected value. Results are described in the table below.
| Linear Regression Analysis | $y = 0.8997x + 0.6036, R^2 = 0.999$ | ||
|---|---|---|---|
| Linearity Sample # | Expected Value | ||
| (uIU/ml) | GBI Assay Result | ||
| (Mean uIU/ml; N=4) | Recovery (%) | ||
| 1 | 1.5 | 1.6 | 107 |
| 2 | 2.7 | 3.1 | 114 |
| 3 | 3.9 | 4.1 | 105 |
| 4 | 6.2 | 6.0 | 96.8 |
| 5 | 8.6 | 8.1 | 93.6 |
| 6 | 10.0 | 10.6 | 106 |
| 7 | 10.9 | 9.8 | 89.4 |
| 8 | 13.3 | 12.4 | 93.0 |
| 9 | 15.6 | 14.9 | 95.4 |
| 10 | 18.0 | 16.1 | 89.2 |
| 11 | 20.3 | 17.9 | 88.1 |
| 12 | 22.7 | 20.1 | 88.3 |
| 13 | 24.5 | 21.9 | 89.4 |
| 14 | 25.0 | 22.8 | 91.1 |
| 15 | 39.0 | 37.2 | 95.3 |
| 16 | 68.0 | 65.4 | 96.2 |
| 17 | 97.0 | 89.5 | 92.3 |
| 18 | 126.0 | 113.5 | 90.1 |
| 19 | 155.0 | 138.0 | 89.0 |
| Average Recovery-Overall % | 95.2 | ||
| Minimum % | 88.1 | ||
| Maximum % | 114 |
Results of Assay Linearity and % Recovery Study for GBI TSH ELA Kit
The GBI TSH EIA Kit reportable range is approximately 2.4 uIU/ml. The lower limit is the concentration calculated from the analytical sensitivity study (above) and the upper limit is the concentration of the highest standard of the calibration curve.
Assay results obtained outside the measuring (reportable) range should be reported as either "less than" or "greater than" the established low or high limit, respectively, as applicable to the individual result.
9
Specificity
Cross Reactivity
The following compounds were tested for cross-reactivity. Each compound was added at several concentrations to TSH-free whole blood which had been adjusted to a hematocrit of 55%. The samples were spotted onto Whatman 903 specimen collection paper, air-dried and assayed. Refer to the table below.
| Results of a Cross-Reactivity Study of the GBI TSH EIA Screening Assay | ||
|---|---|---|
| Peptide Hormone | Cross-Reactant | |
| Concentration Added | ||
| (µIU/ml) | TSH Concentration | |
| Measured | ||
| (µIU/ml) | ||
| FSH | ||
| (WHO 2nd IRP HMG) | 125 | None Detected* |
| 250 | None Detected* | |
| 500 | None Detected* | |
| LH | ||
| (WHO 1st IRP 68/40) | 125 | None Detected* |
| 250 | None Detected* | |
| 500 | None Detected* | |
| HCG | ||
| (WHO 2nd I.S. 61/6) | 10,000 | None Detected* |
| 50,000 | None Detected* | |
| 100,000 | None Detected* |
- "None Detected" represents values obtained that were below the limit of detection for the assay (i.e., 40 | (Row) Totals: | |
| Predicate Results | Normal | (40) N=15 | 0 | 0 | 15 | 15 |
| (Column) Totals: | | | 969 | 11 | 15 | 995 |
Of the 995 total blood spot samples tested, 163 results produced non-numeric values (either "less than the limit of sensitivity", n=153; or "greater than the highest standard", n=10) for one or both assays. These samples could not therefore be included in statistical analysis presented below and account for the observed difference in method comparison population "N" (995 - 163 = 832),
The method comparison results for the N=832 population were:
GBI TSH Mean = 8.9 uIU/ml, with a range of 2.4 to 114 uIU/ml, Predicate TSH Mean = 8.1 uTU/ml, with a range of 2.9 to 104 uIU/ml.
The results of linear regression analysis were:
y (GBI TSH EIA) = 1.0695x (Predicate) + 0.2671, R2 = 0.9185
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Image /page/12/Picture/1 description: The image shows the seal of the Department of Health & Human Services - USA. The seal features a stylized eagle-like symbol with flowing lines, representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol. The seal is presented in black and white.
Public Health Service
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Golden Bridge International, Inc. c/o Dr. Xiaoping Zhang 9700 Harbour Place, Suite 129 Mukilteo, WA 98275
APR 1 0 2008
Re: K072458
Trade/Device Name: GBI TSH Neonatal Screening Kit Regulation Number: 21 CFR 862.1690 Regulation Name: Thyroid Stimulating Hormone Test System Regulatory Class: II Product Code: JLW Dated: March 10, 2008 Received: March 12, 2008
Dear Dr. Zhang:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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 (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours.
Jean M. Cooper, M.S., D.V.M.
Yean M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known): K072458
Device Name: GBI TSH Neonatal Screening Kit
Indication For Use:
The GBI TSH Neonatal Screening Kit is designed for the quantitative determination of Thyroid Stimulating Hormone (TSH) concentrations in neonatal blood samples that have been collected onto Whatman 903 specimen collection paper. The results are used to screen newborns for congenital hypothyroidism.
Prescription Use X (21 CFR Part 801 Subpart D) And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
Signature Off.
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K072458 = ==