ASTORIA-PACIFIC SPOTCHECK G6PD KIT 50 HR, MODEL 80-3000-13K

{0}------------------------------------------------ MAY 1 1 1999 ## 000016 Astoria-Pacific, Inc G6PD 50-Hour Reagent Kit ### 510(K) SUMMARY - Name, address, telephone number, contact person and 1. date of preparation of summary. Applicant's Name and Address Astoria-Pacific, Inc. FDA Establishment No. 3050015 14600 S. E. 82nd Drive Post Office Box 830 Clackamas, OR 97015-0830 USA 1-503-657-3010 TEL 1-503-655-7367 FAX Raymond. L. Pavitt, President Official Correspondent Signature of Applicant: Date: March 18, 1999 : Lesterd Blannion Garrison, Diagnostics Manager Submission Correspondent - Name of the device, including trade or proprietary 2. name, and classification name. ### Product Classification Product Code Requlation Number 510(k) Number Classification Panel Device Classification 81 JBL 21 CFR 864.7360 K Hematology Kits and Packages Class II ### Product Nomenclature | Common Name | G6PD Test | |---------------------|----------------------------------------------------------------------| | Classification Name | Erythrocytic glucose-6-phosphate<br>dehydrogenase assay, qantitative | | Proprietary Name | Astoria-Pacific SPOTCHECK<br>G6PD 50 Hour Reagent Kit | | Model Number | Astoria-Pacific<br>Part No. 80-3000-13K | {1}------------------------------------------------ ### 510(K) SUMMARY - Identification of the legally marketed device for which 3. substantial equivalence is claimed. ### Product Classification | Product Code | 81 JBL | |-----------------------|------------------------------| | Regulation Number | 21 CFR 864.7360 | | 510(k) Number | K790211 | | S/E Decision Date | March 15, 1979 | | Classification Panel | Hematology Kits and Packages | | Device Classification | Class II | ### Product Nomenclature | Common Name | G6PD Test | |---------------------|-----------------------------------------------------------------------| | Classification Name | Erythrocytic glucose-6-phosphate<br>dehydrogenase assay, quantitative | | Proprietary Name | Glucose Phosphate Dehydrogenase | | Model Number | SIGMA Chemical Company<br>Preocedure No. 345-UV | - 4 . Description of the device as found in the labeling ### G6PD 50 HOUR REAGENT KIT API Part No. 80-3000-13K Glucose-6-Phosphate Dehydrogenase Test System ### INTENDED USE The Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit is intended for the semi-quantitative determination of glucose-6phosphate dehydrogenase activity in erythrocytes using the Astoria-Pacific SPOTCHECK Analyzer. Measurements of glucose-6-phosphate dehydrogenase activity are used primarily in the diagnosis and treatment of disease states associated with a G6PD deficiency. This method is intended for in vitro diagnostic use primarily as an aid in screening for decreased levels of G6PD enzyme activity. This device is intended for use by trained, qualified laboratory personnel. {2}------------------------------------------------ ### 510(K) SUMMARY #### Description of the device as found in the labeling (cont.) 4. ### SUMMARY AND EXPLANATION OF THE METHOD G6PD deficiency occurs in many forms. A genetic variant resulting in enzyme instability and mild enzyme deficiency, designated G6PD A, occurs among American blacks at a frequency of about 11%. A mutation that also results in enzyme lability and a much more severe deficiency, designated G6PD Mediterranean, exists in frequencies ranging from <1 to >50% in various Mediterranean populations. Other common variants exist among Asian populations. Such polymorphic enzyme deficiencies are associated with hemolytic anemia during drug administration, infection, and certain other stresses. Less common, functionally more severe mutations result in a chronic hemolytic state even when no abnormal stress is present. The Astoria-Pacific method is based on the established spectrophotometric methods. Maleimide, an inhibitor of 6phosphoqluconate dehydrogenase (6-PGD) activity, is added to inhibit the production of NADPH by 6-phosphogluconate dehydrogenase. ### CHEMICAL PRINCIPLES OF THE PROCEDURE Enzyme activity is measured by observing NADP+ reduction to NADPH when glucose-6-phosphate is present as a substrate. G6PD catalyzes the conversion of glucose -6-phosphate (Glu-6-P) to 6-phosphogluconate (6-PG) and, concurrently, the reduction of NADP+ to NADPH. G6PD Glu-6-P + NADP+ ----------> 6-PG + NADPH + H+ Ma++ The fluorescent NADPH produced is proportional to the G6PD enzyme activity. {3}------------------------------------------------ # 510(K) SUMMARY #### Description of the device as found in the labeling (cont.) 4. Further conversion of 6-PG to ribulose-5'-phosphate (R-5-P) by 6phosphogluconate dehydrogenase (6-PGD) is inhibited by the addition of maleimide. | | 6-PGD | | |--------------|----------------|--------------------------| | 6-PG + NADP+ | ---BLOCKED---> | R-5-P + NADPH + H+ + CO2 | ### REAGENTS | Reagent<br>Name | Reactive<br>Ingredient | Final<br>Concentration | |-------------------|-----------------------------------------------------------------------------------|-----------------------------------------------------------| | Extraction Buffer | Succinate Buffer<br>pH 5.2 | 6 mM | | Tris Buffer | Tris, pH 7.8<br>Triton X-100 | 50 mM<br>0.5 ml/L | | G6PD Substrate | Tris, pH 7.8<br>Maleimide<br>NADP<br>Magnesium<br>Glu-6-phosphate<br>TRITON X-100 | 100 mM<br>13 mM<br>1.3 mM<br>1.2 mM<br>1.0 mM<br>0.5 ml/L | | NADH Stock Std | TEA Buffer pH 9<br>NADH | 50 mM<br>2 mM | {4}------------------------------------------------ ### 510(K) SUMMARY Statement of intended use. 5. ### Intended Use The Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit is intended for the semi-quantitative determination of glucose-6-phosphate dehydrogenase activity in erythrocytes using the Astoria-Pacific SPOTCHECK Analyzer. Measurements of glucose-6-phosphate dehydrogenase activity are used primarily in the diagnosis and treatment of nonspherocytic congenital hemolytic anemia or drug-induced hemolytic anemia associated with a G6PD deficiency. It is for in vitro diagnostic use primarily as an aid in screening for decreased levels of G6PD enzyme activity. This device is for use by trained, qualified laboratory personnel. {5}------------------------------------------------ ### 510(K) SUMMARY A summary of the technological characteristics of the device 6. compared to the predicate device, including chemical composition. Both devices respond quantitatively to G6PD Activity. The subject device has the same technological characteristics as the legally marketed predicate device. Specifically, the features, specifications, materials and mode of action are equivalent. There are no significant differences in technology characteristics between the proposed device and the legally marketed predicate device. The proposed device has the same indications for use as the legally marketed predicate device. The propose device has the same chemical composition and reaction mechanism as the legally marketed predicate device. There are no new reagents. The proposed device uses a similar temperature, time and ratio of reagents to sample as the predicate device. The proposed device uses fluorescence of NADPH to measure G6PD activity in the sample; the predicate device uses UV absorbance of NADPH to measure G6PD activity. The proposed device is used as an element in a screening strategy that includes other tests and observations and requires confirmation testing and follow-up clinical assesment, as is the predicate device. {6}------------------------------------------------ G6PD 50-Hour Reagent Kit # 510(K) SUMMARY A summary of the technological characteristics of the device 6. compared to the predicate device, continued ### Comparison Table | Feature | Predicate Device<br>Sigma Diagnostics | Proposed Device<br>Astoria-Pacific Inc | |---------------------|---------------------------------------------------------------------------------|--------------------------------------------------------------------------------------| | Intended User | Clinical laboratory<br>professionals | Clinical laboratory<br>professionals | | Intended Use | Quan titative<br>determination of G6PD<br>activity in blood<br>red blood cells) | Semi-quan titative<br>determination of G6PD<br>activity in blood<br>red blood cells) | | Indications for use | Screening for<br>decreased levels of<br>G6PD activity | Screening for<br>decreased levels of<br>G6PD activity | | Chemical Principle | NADP+ Reduction to<br>NADPH | NADP+ Reduction to<br>NADPH | | Temperature | 30° C or 37° C | 37° C | | Stability | 8 hours | 8 hours | | Expected Value | 4.6-13.5 U/g Hb | 40-224 µM NADPH | | Sensitivity | 0.4 U/g Hb | 2 µM NADPH | | Detection Limit | 1.0 U/g Hb | 9 µM NADPH | | Detection Method | UV absorbance<br>of NADPH | fluorescence of<br>NADPH | | Wavelength | 340 nm | λ excit. =350 nm<br>λ emiss.=450 nm | {7}------------------------------------------------ ### Astoria-Pacific, Inc ### G6PD 50-Hour Reagent Kit ### 510(K) SUMMARY 7. Performance characteristics of the device, including: > Expected values Interfering substances Specific performance characteristics carryover specificity sensitivity within-run precision total precision correlation ### EXPECTED VALUES We have studied a normal population of neonates and these were the values: > 17 Number of observations Average Value observed 54 µM Sample Standard Deviation Range of the data >42 µM 95% Confidence interval 150 µM NADPH 40 - 224 μM We studied a G6PD deficient population, and these were the values: | Number of observations | 10 | |---------------------------|---------------| | Average Value observed | 18 μM NADPH | | Sample Standard Deviation | 12 μM | | Range of the data | 4 - 40 μM | | 95% Confidence interval | 0 - 42 μM | We also studied a population with intermediate G6PD activity. These were the values: | Number of observations | 4 | |---------------------------|---------------| | Average Value observed | 49 µM NADPH | | Sample Standard Deviation | 22 µM | | Range of the data | 28 - 69 µM | | 95% Confidence interval | 5 - 93 µM | {8}------------------------------------------------ ### 510(K) SUMMARY - Performance characteristics of the device (continued) 7. These studies indicate: 1. Samples exhibiting activity less than about 40 µM NADPH, the lowest observed value of the normal population range, are outside the normal range for G6PD activity and require follow-up and/or additional testing. 2. There is an overlap in the range for persons with intermediate G6PD activity and the normal population. When that occurs, those samples require follow-up and additional testing. Each laboratory must determine its own range of normal, intermediate, and deficient levels of G6PD activity, based on its population and analytical variables. The activity of normal samples varies widely, and the activity of all samples decreases with time under any conditions of storage. Samples showing sufficient activity can be classified as in the normal range. However, the G6PD 50 Hour Reagent Kit can not be used to classify a particular genotype. Specimens producing abnormal or non-expected responses require confirmation/follow-up testing according to local, state and federal requirements. Low activity may represent a deteriorated sample. If a sample has deteriorated, or was incorrectly collected, stored or handled, inaccurate results may be obtained. {9}------------------------------------------------ ### 510(K) SUMMARY - Performance characteristics of the device (continued) 7. ### INTERFERING SUBSTANCES G6PD is inhibited by NADPH with a K; of 0.02 mM, and by ATP with a Ki of 2 mM 7. Sulfate at 5 mM in vitro causes a decrease of G6PD activity8. G6PD is increased in cases of pernicious anemia, folic acid deficiency and sickle cell disease; it isn't affected by hairy cell leukemia or multiple sclerosis 9. Copper strongly inhibits this enzyme10. Neither smoking nor physical training have an effect on the level of enzyme activity10. In one study in the literature, the interindividual variability of G6PD was observed to be 32%, and the intraindividual variation was observed to be 33%. Hemoglobin may minimally decrease G6PD activity by quenching fluorescence; in this procedure hemoglobin is removed from the reagent stream by dialysis. Bilirubin to 25 mg/dl and lipemia to 1000 mg/dl do not interfere with this test. {10}------------------------------------------------ ### G6PD 50-Hour Reagent Kit ### 510(K) SUMMARY - Performance characteristics of the device. (continued) 7. ### SPECIFIC PERFORMANCE CHARACTERISTICS Carryover from sample-to-sample is less than 2% and is corrected when a CARRYOVER cup is entered in the sample table. Specificity for G6PD is achieved by using the specific substrate for the enzyme, glucose-6-phosphate. A small amount of NADPH may be produced by samples in the absence of the substrate. As little as 2 µM NADPH is discernable from no Sensitivity. response. The response standards from 0 to 75 µm NADH gave a correlation coefficient r > .999 linearity. Within-run and total precision were evaluated for this Precision. method. Samples with three levels of activity were assayed in duplicate, in 2 runs per day over 5 days to estimate the within-run and total precision. The data is summarized below: WITHIN-RUN PRECISION (SWR) | | G6PD<br>Deficient | Intermediate | G6PD<br>Normal | |---------|-------------------|--------------|----------------| | Average | 7.80 μM | 43.0 μM | 158 μM | | S.D | 0.25 μM | 1.9 μM | 7.34.9 μM | | C.V. | 3.2 % | 4.4 % | 3.1 % | TOTAL PRECISION (ST) | | G6PD<br>Deficient | Intermediate | |---------|-------------------|--------------| | Average | 7.80 μM | 43.0 μM | | S.D | 0.42 μM | 2.6 μM | | C.V. | 5.4 % | 6.0 % | {11}------------------------------------------------ Astoria-Pacific, Inc G6PD 50-Hour Reagent Kit ### 510(K) SUMMARY - 7. Performance characteristics of the device (continued) Correlation. The performance of the G6PD 50-Hour Reagent Kit and a competitive device were evaluated by analyzing samples known to be normal (16), intermediate (4), and G6PD deficient (10). Based upon the evaluation of these 30 samples, a comparison of the performance is presented below: | | False<br>Positives | False<br>Negatives | |----------------------|--------------------|--------------------| | API G6PD 50 Hour Kit | 0 of 20 | 0 of 10 | | Competitive Device | 0 of 20 | 0 of 10 | ### END ### 510(K) SUMMARY This 510(k) summary is submitted in accordance with the requirements of 21 CFR § 807.92, as revised April 1, 1998. {12}------------------------------------------------ Image /page/12/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle with three lines representing its wings and three wavy lines representing its body. Food and Drug Administration 2098 Gaither Road Rockville MD 20850 ### MAY 1 1 1999 Mr. Raymond L. Pavitt President Astoria-Pacific, Inc. 14600 S. E. 82nd Drive Post Office Box 830 Clackamas, Origan 97015-0830 K990957 Re: Trade Name: Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit Regulatory Class: II Product Code: JBL Dated: March 18, 1999 Received: March 22, 1999 Dear Mr. Pavitt: We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations. {13}------------------------------------------------ Page 2 Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655. This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification"(21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597, or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html". Sincerely yours, Steven Sutman Steven I. Gutman, M.D. M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health Enclosure {14}------------------------------------------------ Page / of / | <strong>Labels</strong> | <strong>Values</strong> | |---------------------------|-------------------------| | 510(k) Number (if known): | K990957 | | Device Name: | Spotcheck G6PD | | | Kit, so hour. | Indications For Use: Astoria-Pacific, Inc G6PD 50-Hour Reagent Kit ### INDICATIONS FOR USE ### Intended Use The Astoria-Pacific SPOTCHECK G6PD 50 Hour Reagent Kit is intended for the semi-quantitative determination of glucose-6-phosphate dehydrogenase activity in erythrocytes using the Astoria-Pacific SPOTCHECK Analyzer. Measurements of glucose-6-phosphate dehydrogenase activity are used primarily in the diagnosis and treatment of nonspherocytic congenital hemolytic anemia or drug-induced hemolytic anemia associated with a G6PD deficiency. It is for in vitro diagnostic use primarily as an aid in screening for decreased levels of G6PD enzyme activity. This device is for use by trained, qualified laboratory personnel. (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE) Situe. Maker (Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number K990957 **Prescription Use** (Per 21 CFR 801.109) OR Over-The-Counter Use_ (Optional Format 1-2-96)