Diazyme Vitamin B12 Assay, Diazyme Vitamin B12 Calibrators Set, Diazyme Vitamin B12 Controls Set
Device Facts
| Record ID | K161721 |
|---|---|
| Device Name | Diazyme Vitamin B12 Assay, Diazyme Vitamin B12 Calibrators Set, Diazyme Vitamin B12 Controls Set |
| Applicant | Diazyme Laboratories |
| Product Code | CDD · Clinical Chemistry |
| Decision Date | Sep 20, 2016 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.1810 |
| Device Class | Class 2 |
Indications for Use
The Diazyme Vitamin B12 Assay is for the quantitative determination of Vitamin B12 levels in human serum. Measurements of vitamin B12 may be used in the diagnosis of Vitamin B12 deficiency. For in vitro diagnostic use only. The Diazyme Vitamin B12 Calibrator Set is intended for use in the calibration of the Diazyme Vitamin B12 Assay. For in vitro diagnostic use only. The Diazyme Vitamin B12 Control Set is intended for use as quality controls for the Diazyme Vitamin B12 Assay. For in vitro diagnostic use only.
Device Story
Diazyme Vitamin B12 Assay is an in vitro diagnostic test for quantitative measurement of Vitamin B12 in human serum. Used in clinical laboratory settings by trained personnel to assist in diagnosing Vitamin B12 deficiency. The system includes a calibrator set and control set for quality assurance. Operates via standard laboratory instrumentation for biochemical analysis. Provides numerical concentration values to clinicians to support diagnostic decision-making regarding patient nutritional status and deficiency-related conditions.
Clinical Evidence
Bench testing only. Precision evaluated per CLSI EP5-A2 (N=80 per sample). Linearity established from 96.7 to 2000 pg/mL (R^2=0.9985). Method comparison with predicate (k121994) using 99 samples yielded Y = 0.969x - 5.77 (R=0.9847). Reference range established using 211 healthy individuals (213.7–908.9 pg/mL). No clinical diagnostic studies performed.
Technological Characteristics
In vitro diagnostic assay for serum Vitamin B12; includes calibrator and control sets; intended for use on clinical chemistry analyzers.
Indications for Use
Indicated for the quantitative determination of Vitamin B12 levels in human serum to aid in the diagnosis of Vitamin B12 deficiency. For prescription use only.
Regulatory Classification
Identification
A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.
Related Devices
- K965186 — AXSYM B12 · Abbott Laboratories · Mar 24, 1997
- K051327 — ABBOTT AXSYM B12 · Abbott Laboratories · Aug 3, 2005
- K984321 — VITROS IMMUNODIAGNOSTIC PRODUCTS VITAMIN B12, REAGENT PACK 1/2, FOLATE REAGENT PACK 3, ANF CALIBRATORS · Ortho-Clinical Diagnostics, Inc. · Jan 22, 1999
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k161721
B. Purpose for Submission:
New Device
C. Measurand:
Vitamin B12
D. Type of Test:
Quantitative, competitive enzymatic method
E. Applicant:
Diazyme Laboratories
F. Proprietary and Established Names:
Diazyme Vitamin B12 Assay, Diazyme Vitamin B12 calibrator Set, Diazyme Vitamin B12 Control Set
G. Regulatory Information:
| Product Code | Regulation Name | Classification | Regulation Section | Panel |
| --- | --- | --- | --- | --- |
| CDD | Diazyme Vitamin B12 Assay | II | 21 CFR 862.1810, | Chemistry 75 |
| JIT | Diazyme Vitamin B12 Calibrator set | II | 21 CFR 862.1150 | Chemistry 75 |
| JJX | Diazyme Vitamin B12 Control set | I, reserved | 21 CFR 862.1660 | Chemistry 75 |
H. Intended Use:
1. Intended use(s):
Refer to indications for use below
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2. Indication(s) for use:
The Diazyme Vitamin B12 Assay is for the quantitative determination of Vitamin B12 levels in human serum. Measurements of vitamin B12 may be used in the diagnosis of Vitamin B12 deficiency. For in vitro diagnostic use only.
The Diazyme Vitamin B12 Calibrator Set is intended for use in the calibration of the Diazyme Vitamin B12 Assay. For in vitro diagnostic use only.
The Diazyme Vitamin B12 Control Set is intended for use as quality controls for the Diazyme Vitamin B12 Assay. For in vitro diagnostic use only.
3. Special conditions for use statement(s):
For prescription use only.
4. Special instrument requirements:
The assay can be run on a chemistry analyzer that can measure absorbance at 415 nm. The performance characteristics of the candidate assay was established on Roche Modular P Chemistry Analyzer
I. Device Description:
The Diazyme Vitamin B12 Assay contains four reagents and their ingredients are shown below:
| REAGENT 1 (R1a) | 1x4.5 mL of Sodium hydroxide < 5%, Potassium cyanide < 0.01%, Potassium ferricyanide < 0.01% |
| --- | --- |
| REAGENT 1 (R1b) | 1x0.5 mL Reducing agent <5% |
| REAGENT 2 (R2) | 1x15 mL Phosphate buffer < 5%, Nitro-phenyl-β-galactoside (NPG) substrate <1%, Porcine Intrinsic Factor: <0.1% |
| REAGENT 3 (R3) | 1x8.5 N-Cyclohexyl-2-aminoethanesulfonic acid (CHES) buffer 1%, Enzyme donor-B12 conjugate:Trace, Sodium dodecyl sulfate (SDS) < 0.1% |
| REAGENT 4 (R4) | 1x8.5 mL Enzyme acceptor:<0.1%, Tris-HCl < 2%, NaCl < 3%, Sodium Azide 0.1% |
The following are required but not provided with the reagent kit:
Diazyme Vitamin B12 Calibrator set is in liquid form with human serum and additives as the reactive components with the following five concentrations values: 0, 299.7, 659.0, 1327.8, and 2343.8 pg/mL.
Diazyme vitamin B12 control set is in liquid form with human serum albumin and additives as the active components with target values of 350 pg/mL for level 1, and 650 pg/mL for level 2.
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Each donor unit of serum used in the preparation of this Calibrator Set and Control Set was tested by FDA-approved methods and found negative for the Human Immunodeficiency Virus Antibody (HIV I/II Ab), Hepatitis B Surface Antigen (HBsAg), and Hepatitis C Virus Antibody (HCV).
## J. Substantial Equivalence Information:
1. Predicate device name(s):
Siemens Vitamin B12 Assay and Calibrator
Bio-Rad Liquichek Immunoassay plus controls
2. Predicate 510(k) number(s):
k121994
k961941
3. Comparison with predicate:
Reagent
| Similarities/Differences | | |
| --- | --- | --- |
| Item | Predicate Device Siemens vitamin B12 Assay (k121994) | Candidate Device Diazyme Vitamin B12 Assay (k161721) |
| Intended Use | The Vitamin B12 method is an in vitro diagnostic test for the quantitative measurement of vitamin B12 (B12) in human serum. Measurements of vitamin B12 may be used in the diagnosis of vitamin B12 deficiency. | Same |
| Specimen Type | Human serum and plasma | Human serum only |
| Sample volume | 12μL | 25 μL |
| Unit of measure | pg/mL | Same |
| Principle | Competitive Chemiluminescent Immunoassay | Competitive enzymatic |
| Assay Range | Assay Range: 60 – 2000 pg/mL | Assay Range: 96.7 – 2000 pg/mL |
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| Similarities/Differences | | |
| --- | --- | --- |
| Item | Predicate Device Siemens vitamin B12 Assay (k121994) | Candidate Device Diazyme Vitamin B12 Assay (k161721) |
| Reagent stability | Opened well vial stability 3 days Sealed reagent onboard is stable for 30 days. | Onboard and Opened vial stability is 4 days. Unopened vial is stable until expiration date on the vial. |
| Detection Limit | LoB = 18.0 pg/mL LoD = 28.0 pg/mL LoQ = 52 pg/mL | LoB = 30.6 pg/mL LoD = 63.3 pg/mL LoQ = 96.7 pg/mL |
Calibrator:
| Similarities/Differences | | |
| --- | --- | --- |
| Item | Predicate device Siemens Calibrator (k121994) | Candidate Device Diazyme Vitamin B12 calibrator Set (k161712) |
| Intended Use | Vitamin B12 Calibrator Set is intended for use in the calibration of the Vitamin B12 Assay. | Same |
| Traceability | Traceable to Vitamin B12 United States Pharmacopeia Grade Vitamin B12 | Same |
| Form | Liquid ready to use | Same |
| Matrix | Hepes Buffer Level A 2% BSA based matrix | Base buffer of 7% human serum albumin |
| Target concentrations Vitamin B12 (pg/mL) | Level A: 4
Level B: 200
Level C: 500
Level D: 1000
Level E: 2200 | Level 1 = 0
Level 2 = 299.7
Level 3 = 659.0
Level 4 = 1327
Level 5 = 2343.8 |
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Controls:
| Similarities/Differences | | |
| --- | --- | --- |
| Item | Predicate Device Bio-Rad Liquichek Immunoassay plus controls (k961941) | Candidate Device Diazyme Vitamin B12 controls (k161712) |
| Intended Use | Intended for use as quality controls for the vitamin B12 assay | Same |
| Form | Liquid | Same |
| Concentration levels | level 1= mean value of 275 pg/mL, level 2 = mean value of 518 pg/mL, level 3= mean value of 682 pg/mL | level 1 mean value = 249 pg/mL, level 2 mean value = 488pg/mL |
# K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods
- CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures
- CLSI EP07-A2: Interference Testing in Clinical Chemistry
- CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples
- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures
- CLSI C28-A3: Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory
# L. Test Principle:
The test is based on the principle of $\alpha$ -complementation of the enzyme $\beta$ -galactosidase and the competition between an enzyme do-nor-vitamin B12 conjugate, an anti-vitamin B12 protein (Intrinsic Factor) and the vitamin B12 content of a serum sample. Samples with higher vitamin B12 concentrations produce higher $\beta$ -galactosidase activities and vice versa. A nitro-phenyl- $\beta$ -galactoside derivative (NPG) is used as the enzyme substrate. The reaction's product has maximum absorbance at $415~\mathrm{nm}$ . The vitamin B12 concentration of a sample is proportional to the measured $\beta$ -galactosidase activity.
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M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision of the Diazyme vitamin B12 assay was evaluated according to the CLSI EP5-A2 guideline. This study comprised assessment of the following elements:
- Repeatability (within-run precision).
- Within-laboratory (total precision based on between-day, between-run and within-run precision).
Precision assessment was performed on the Roche Modular P chemistry analyzer. In the study, three lots of reagents were used. For each reagent lot, 12 specimens were tested: 2 vitamin B12 controls and 10 vitamin B12 human serum samples. All precision samples were tested in duplicates per run and two runs per day over 20 working days. 80 data points were obtained per specimen and per reagent lot. All 3 lots of reagents yielded similar results. One representative lot is summarized below.
| Sample | Mean pg/mL (N=80) | Within-Run | | Total | |
| --- | --- | --- | --- | --- | --- |
| | | SD | %CV | SD | %CV |
| Control 1 | 248.4 | 17.1 | 6.9 | 21.1 | 8.5 |
| Control 2 | 488.1 | 16.0 | 3.3 | 22.9 | 4.7 |
| Sample 1 | 244.4 | 18.8 | 7.7 | 22.3 | 9.1 |
| Sample 2 | 346.2 | 18.4 | 5.3 | 22.5 | 6.5 |
| Sample 3 | 539.5 | 30.3 | 5.6 | 2.6 | 6.1 |
| Sample 4 | 740.6 | 28.2 | 3.8 | 47.9 | 6.5 |
| Sample 5 | 961.5 | 36.5 | 3.8 | 48.6 | 5.0 |
| Sample 6 | 1168.4 | 31.7 | 2.7 | 46.2 | 4.0 |
| Sample 7 | 1390.2 | 41.6 | 3.0 | 55.5 | 4.0 |
| Sample 8 | 1582.3 | 42.2 | 2.7 | 66.5 | 4.2 |
| Sample 9 | 1743.8 | 37.9 | 2.2 | 59.8 | 3.4 |
| Sample 10 | 1881.8 | 45.7 | 2.4 | 59.0 | 3.1 |
b. Linearity/assay reportable range:
The sponsor conducted a linearity study according to the CLSI EP6-A guideline. A human serum sample was spiked with a vitamin B12 stock solution to a concentration of 2017 pg/mL. A diluted low serum sample was prepared with a concentration of 69.8 pg/mL. The prepared high sample was diluted with the prepared low sample to create 10 intermediate levels of vitamin B12 concentrations. The linearity set prepared with 12 different sample concentrations were tested with the Diazyme vitamin B12 assay in triplicate using one lot of reagent. Samples tested covered concentration between 69.8
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pg/mL to 2017.9 pg/mL. The linear regression was determined by plotting the observed values against the expected values generated the following equation:
Linear regression equation: $y = 1.0249x + 6.9387$, $R^2 = 0.9985$
The obtained results supports the claim that Diazyme vitamin B12 assay is linear from 96.7 pg/mL to 2000 pg/mL.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability: The calibrators for Diazyme Vitamin B12 Assay are traceable to WHO reference material 03/178.
Value assignment:
Vitamin B12 was purchased from commercial vendor and was used in the preparation of both calibrators and control. Vitamin B12 stock solutions were prepared according to the vendor certificate of analysis. 5 levels of master calibrators were prepared by spiking Vitamin B12 into pooled a base buffer consisting of 7% human serum albumin and values assigned by internal procedure.
Vitamin B12 Calibrator Set:
Vitamin B12 calibrator set were prepared by spiking Vitamin B12 into a base buffer containing 7% human serum albumin, except for calibrator level 1 which was automatically assigned a value of 0 pg/mL. The other four calibrators have values covering the entire measuring range. The four spiked calibrators were initially assigned by running them as samples using the master calibrators and released Vitamin B12 reagents. The production calibrators value assignment were verified and adjusted using controls and patient samples in which Vitamin B12 values were determined by reference lot of Vitamin B12 reagent and calibrators. Below are the target values of one lot of calibrators in pg/mL:
Level 1 = 0 pg/mL
Level 2 = 299.7 pg/mL
Level 3 = 659.0 pg/mL
Level 4 = 1327.8 pg/mL
Level 5 = 2343.8 pg/mL
Vitamin B12 Control Set:
Vitamin B12 controls were prepared by spiking Vitamin B12 into a base buffer consisting of 7% human serum albumin. Two Vitamin B12 target concentrations were prepared one below 400 pg/mL with target value of about 350 pg/mL and one above the cut-off of 400 pg/mL with target value of about 650 pg/mL. Lot specific values will differ.
Value assignment of Vitamin B12 Controls was performed by replicate analysis. The Diazyme Vitamin B12 Assay and calibrators are used in replicate analysis to determine the mean value of the prepared controls. Final value is the mean of the replicate value and
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the expected range is calculated $\pm 25\%$ from the mean value for the respective controls. Control ranges are lot specific, an example of one lot of QC ranges are provided below.
Control mean and ranges:
Level 1: mean $= 362.1\mathrm{pg / mL}$ range $= 271.6 - 452.6\mathrm{pg / mL}$
Level 2: mean $= 662.9\mathrm{pg / mL}$ range $= 497.1 - 828.6\mathrm{pg / mL}$
# Stability:
Vitamin B12 calibrator and control stability:
Accelerated study was performed at $37^{\circ}\mathrm{C}$ for 7 days to simulate real time storage at $2 - 8^{\circ}\mathrm{C}$ for one year. The study results support a shelf-life of 12 months for both the calibrator and the control at $2 - 8^{\circ}\mathrm{C}$ . Real time study is on-going. Open-vial stored at $2 - 8^{\circ}\mathrm{C}$ is stable for 4 days. Protocols and acceptance criteria for the stability study were reviewed and found acceptable.
# d. Detection limit:
# Limit of Blank (LoB)
To calculate the LoB of the Diazyme vitamin B12 assay, a $10\%$ BSA solution in physiological saline was run as a sample, in 60 replicates with three lots of the reagents, on the Roche Modular P analyzer. LoB was calculated as the mean of the $57^{\circ}$ and $58^{\circ}$ highest obtained values and was determined to be $30.6~\mathrm{pg / mL}$ .
# Limit of Detection (LoD)
Five serum samples were obtained commercially, diluted with $10\%$ BSA and then tested with three lots of the vitamin B12 reagents on the Roche Modular P analyzer (12 replicates per sample obtained from three independent runs). LoD was calculated from the following formula and determined to be $63.3~\mathrm{pg / mL}$ .
$\mathrm{LoD} = \mathrm{LoB} + (1.645 * \mathrm{SD}$ of LoD samples)
# Limit of Quantitation (LoQ)
The LOQ of the Diazyme vitamin B12 assay was determined following CLSI EP17-A2 Approved Guideline. Five serum samples were diluted with $10\%$ BSA to concentrations ranging from 1 to 20 times the claimed LOB. The diluted serum samples were then tested in 40 replicates from 5 independent runs. Data was processed using EP Evaluator software (version 11.0) was used to estimate the LOQ. The lowest concentration that demonstrated $\mathrm{CV}\leq 20\%$ is the LoQ, which was determined to be $96.7~\mathrm{pg / mL}$ .
| Analyte | LoB | LoD | LoQ |
| --- | --- | --- | --- |
| Vitamin B12 | 30.6 pg/mL | 63.3 pg/mL | 96.7 pg/mL |
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Based on the detection limit studies, sponsor claimed that the measuring range of the candidate device is $96.7~\mathrm{pg / mL}$ to $2000~\mathrm{pg / mL}$ .
# e. Analytical specificity:
Endogenous Interferences/ therapeutic drugs:
An interference study was performed according to the CLSI guideline EP7-A2. To determine the levels of interference of substances present in human serum, the Diazyme vitamin B12 assay was used to test three serum samples, containing "low", "medium", and "high" vitamin B12 concentrations. These samples were spiked with various concentrations of interfering substances. Human serum pools from individual serum samples purchased from a commercial source were used. To ensure precision, each level serum sample spiked with an interference substance was tested in triplicates.
The common interfering endogenous substances of ascorbic acid, bilirubin, conjugated bilirubin, triglycerides, glucose, uric acid, and urea showed no significant interference $(\leq 10\%)$ bias up to the concentrations summarized below.
| Endogenous Substances | Highest concentration at which no significant interference (≤10% bias) was observed. | Units |
| --- | --- | --- |
| Ascorbic acid | 176 | mg/dL |
| Free bilirubin | 20 | mg/dL |
| Conjugated bilirubin | 20 | mg/dL |
| Hemoglobin | 200 | mg/dL |
| Total Protein | 8.5 | g/dL |
| Triglycerides | 450 | mg/dL |
| Biotin | 100.0 | ng/mL |
Based on hemoglobin testing a falsely depressed results from hemoglobin of $>250\mathrm{mg/dL}$ was observe; therefore the sponsor has the following limitation in the specimen collection and preparation section of the package insert:
"Avoid using hemolyzed samples."
In addition the sponsor states the following limitation in the interference section of the package insert:
Hemoglobin at $250\mathrm{mg / dL}$ [0.155 mmol/L] decreases VB12 results by $12.4\%$ at 257.3 pg/mL and $12.1\%$ at 544.4 pg/mL.
The exogenous substances listed in the table below do not significantly interfere with the Diazyme vitamin B12 assay, when present at concentrations listed.
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| Interference Substances | Concentration Tested |
| --- | --- |
| Acetaminophen | 20.0 mg/dL |
| Ampicillin | 5.3 mg/dL |
| Creatinine | 30.0 mg/dL |
| Ethanol | 400.0 mg/dL |
| Flurosemide | 6.0 mg/dL |
| Heparin | 3.0 U/mL |
| Ibuprofin | 50.0 mg/dL |
| Acety Salicylic Acid | 60.0 mg/dL |
| Digoxin | 6. ng/ml |
| Lidocaine | 1.2 mg/dL |
| Chloramphenicol | 5.0 mg/dL |
| Lithium Acetate | 2.2 mg/dL |
| Carbamazepine | 3.0 mg/dL |
| Ethosuximide | 25.0 mg/dL |
| Valproic Acid | 50.0 mg/dL |
| Urea | 300.0 mg/dL |
| Uric Acid | 20.0 mg/dL |
| Vancomycin | 10.0 mg/dL |
| Rifampicin | 5.0 mg/dL |
| Theophylline | 4.0 mg/dL |
| Cefotaxime | 180.0 mg/dL |
| Noradrenalin | 4.0 mg/mL |
## Anti-Intrinsic Factor Antibody Interference:
Interference study was performed to access the effects of (Intrinsic Factor Blocking antibody, IFBA) on Vitamin B12 measurement. Purified antibodies were spiked, at various concentrations, in to three vitamin B12 serum samples. The tested IFBA concentrations (0.0, 0.1, 1.0, 10.0 and 100.0 µg/mL) covered a four orders of magnitude of its normal range. Spiked samples were then tested with the Diazyme vitamin B12 assay and their recovery compared to that of non-spiked samples. Sponsor defined non-significant interference if the spiked result is ≤ 10% bias against the unspiked sample. Three lots of reagents were used in this study. Results show that human antibodies directed against human intrinsic factor do not significantly interfere with the Diazyme vitamin B12 assay, even when present at extremely high concentrations (100 µg/mL).
## Cross reactivity:
To test the cross-reaction between vitamin B12 and cobinamide (a metabolism precursor of vitamin B12 a serum pool averaging 250-300 pg/mL of vitamin B12 was spiked with vitamin B12 or cobinamide at the concentrations of 0, 200, 500, 1000 or 2000 pg/mL. Spiked and un-spiked samples were then tested with the Diazyme vitamin B12 assay in triplicates. Three lots of reagents were used in this study. Sponsor defined no significant cross reactivity if the spiked recovery is ≤ 10% of the unspiked sample. The percent cross-reactivity was calculated and the sponsor concluded that Diazyme vitamin B12
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does not significantly cross-react with cobinamide when present at concentrations as high as 2000 pg/mL.
| Cross reactant tested (Cobinamide) | Concentration tested | %cross reactivity |
| --- | --- | --- |
| Cobinamide | 200 pg/mL | 2.2% |
| Cobinamide | 500 pg/mL | 1.9% |
| Cobinamide | 1000 pg/mL | 0.6% |
| Cobinamide | 2000 pg/mL | 0.2% |
f. Assay cut-off:
Not applicable
2. Comparison studies:
a. Method comparison with predicate device:
For method comparison study, individual serum samples were tested with the Diazyme vitamin B12 assay and compared to the predicate device (k121994). The serum samples were obtained from a commercial source. Samples that had values outside the intended assay range were excluded. A total of 99 unaltered samples spanning the intended assay range were used in the assessment of accuracy. Sample range tested from 123 to 1969 pg/mL. The Linear regression results between Diazyme values and the predicate values are shown below:
$$
\mathrm {Y} = 0. 9 6 9 \mathrm {x} - 5. 7 7, \mathrm {R} = 0. 9 8 4 7
$$
b. Matrix comparison:
Not applicable.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not Applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
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4. Clinical cut-off:
Not applicable
5. Expected values/Reference range:
To determine a reference range for the Diazyme vitamin B12 assay, the vitamin B12 levels of a total of 211 samples from healthy individuals were measured. The range was established with one lot of reagents. The age of the individuals ranged between 21 and 64 years old (average age = 37.5 years). The population was composed of 55% females and 45% males. Data was processed with the EP Evaluator statistical software.
The reference range interval was calculated using non-parametric statistics representing the central 95% of the population. Results indicated the reference range is from 213.7 pg/mL to 908.9 pg/mL.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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