The AVL OPTI Critical Care Analyzer is intended to be used for the measurement of pH, PCO2, PO2, sodium, potassium, ionized calcium, chloride, glucose, urea (BUN), total hemoglobin content and oxygen saturation in samples of whole blood, serum, plasma or dialysate in either a traditional blood gas, clinical laboratory setting or point-of-care locations by personnel minimally qualified to perform and report these results.

Device Description

The AVL OPTI Critical Care Analyzer is a small [4.9 x 14.3 x 9.8 in, 10 lbs], instrument using optical fluorescence for the measurement of pH, PCO2, sodium, potassium, ionized calcium, choride. glucose and urea (BUN) of whole blood, plasma, serum or dialysate as appropriate. In addition, it uses scattering for the measurement of total hemoglobin and oxygen saturation. A disposable, single-use cassette containing six optical fluorescence sensors is packaged in a sealed foil pouch which bears a bar-coded label with calibration and identification information. The OPTI can perform up to 8 tests on a single sample, determined by the type of disposable cassette used.

AI/ML Overview

The provided text describes the AVL OPTI Critical Care Analyzer, focusing on its substantial equivalence to other marketed devices and its technological characteristics. However, it does not explicitly state specific acceptance criteria (e.g., performance thresholds like "accuracy must be within X%") in a table format, nor does it provide a detailed study that proves the device meets such criteria with quantitative results in the way you've requested.

Instead, the document focuses on:

Demonstrating substantial equivalence: By comparing the AVL OPTI to existing devices and stating that there was "no significant difference in mean values (P<0.05) obtained on measurement by the AVL OPTI from those of the predicate devices."
Confirming compliance with standards: Mentioning EN 50081-1, FCC Class B, EN 50081-2, and IEC 1010-1.
General testing methods: Describing how precision, linearity, and interferences were evaluated.

Given this, I cannot fully complete all sections of your request as the specific quantitative acceptance criteria and detailed study results (like sample sizes for test sets, experts, adjudication methods, effect sizes, standalone performance, and training set details) are not explicitly present in the provided text.

However, I can extract the available information and structure it as per your request, indicating where information is missing.

1. Table of Acceptance Criteria and Reported Device Performance

Parameter / Metric	Acceptance Criteria (Explicitly Stated in Document)	Reported Device Performance (Summary from Document)
Comparative Performance	Not explicitly stated as a quantitative threshold.	"no significant difference in mean values (P<0.05) obtained on measurement by the AVL OPTI from those of the predicate devices."
Precision	Not explicitly stated as a quantitative threshold.	"Typical Within-Run (Swr), Between-Day (Sdd) and Total (ST) precision were determined..." (Specific values for Swr, Sdd, ST are not provided in this summary)
Linearity	Not explicitly stated as a quantitative threshold.	"Linearity for the OPTI measurement has been established against reference materials or methods." (Specific range or R-squared values are not provided in this summary)
Interference	Not explicitly stated as a quantitative threshold.	"Representative samples taken the published guidelines for evaluation of interference substances and identified from literature were evaluated." (Specific findings are not provided)
Regulatory Compliance	Compliance with relevant standards.	"The AVL OPTI Critical Care Analyzer has been tested and found to comply with EN 50081-1, FCC Class B, EN 50081-2 and IEC 1010-1."
Safety and Effectiveness	Demonstrated equivalence to predicate devices.	"safe, effective, and equivalent to those predicate devices to which it is compared."

2. Sample size used for the test set and the data provenance

Sample Size (Test Set): Not explicitly stated. The document mentions "Specimens analyzed in these tests were remnant from patient specimens of both whole blood and plasma collected for routine analysis on existing instrumentation." It does not provide the number of patient specimens or samples.
Data Provenance: Retrospective, using "remnant from patient specimens... collected for routine analysis on existing instrumentation." Country of origin is not specified, but the submission is to the US FDA, implying clinical relevance to the US.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Number of Experts: Not specified.
Qualifications of Experts: Not specified. The document states "operated by personnel trained to perform and report these analyses," which refers to the clinical personnel using the device, not experts establishing ground truth for comparisons. Ground truth seems to be established by comparison to predicate devices, not by expert review of complex images or interpretations.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Adjudication Method: Not specified. The comparison relies on statistical analysis of mean values against predicate devices rather than human adjudication of agreement.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

MRMC Study: No, this device is a standalone analyzer, not an AI-assisted diagnostic tool requiring human reader interpretation in the context of an MRMC study.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Standalone Performance: Yes, the device itself is a standalone analyzer. The performance described (precision, linearity, comparisons to predicate devices) represents the device's standalone analytical capabilities.

7. The type of ground truth used

Ground Truth Type: Comparison to predicate devices (other commercially available and legally marketed 'Combi Analyzers' and 'Point of Care' analyzers) served as the primary "ground truth" for demonstrating substantial equivalence. Additionally, "reference materials or methods" were used for linearity, and "N.I.S.T. traceable pH buffers" for pH standardization.

8. The sample size for the training set

Training Set Sample Size: Not applicable/not specified. The document describes a "new device" that is an "improved design" of an existing AVL OPTI 1 pH/Blood Gas Analyzer. The testing described focuses on verification and validation of the new device's performance, not the training of a machine learning model.

9. How the ground truth for the training set was established

Ground Truth for Training Set: Not applicable/not specified, as this is not an AI/ML device that requires a training set in the conventional sense. The device's operation is based on established fluorescence optode technology and optical scattering, calibrated against known standards and verified through traditional analytic methods.

Summary

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DEC I 6 1999

K993837

Image /page/0/Picture/2 description: The image shows a logo with the letters "AVL" in a stylized, bold, sans-serif font. The letters are interconnected, forming a single, unified shape. The logo is black against a white background, creating a high-contrast visual. The overall design is modern and geometric.

510(k) Summary

Submitter's name, address (a) (1) AVL Scientific Corporation 235 Hembree Park Drive Roswell, GA 30076

Date of preparation of this summary:

Contact Person Randy Byrd Director, Quality Assurance 770.576.5000 x 631

11 November 1999

Device trade or proprietary name:

AVL OPTI Critical Care Analyzer

Device common or usual name or classification name

pH, Blood Gas, Electrolyte, hemoglobin and oxygen saturation analyzer

PRODUCT NOMENCLATURE	REGULATION	NUMBER	CLASS	PANEL
ELECTRODE, ION-SPECIFIC, POTASSIUM	862.1600	75 CEM	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, CALCIUM	862.1145	75 JFP	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, SODIUM	862.1665	75 JGS	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, CHLORIDE	862.1170	75 CGZ	II	CHEMISTRY
ELECTRODE, BLOOD GASES (PCO2, PO2) AND pH	862.1120	75 CHL	II	CHEMISTRY
SYSTEM, HEMOGLOBIN, AUTOMATED	864.5620	81 GKR	II	HEMATOLOGY
OXIMETER, WHOLE BLOOD	864.7500	81 GLY	II	HEMATOLOGY
ACID, LACTIC ENZYMATIC METHOD	862.1450	75 KHP	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, UREA NITROGEN	862.1770	75 CDS	II	CHEMISTRY
GLUCOSE OXIDASE, GLUCOSE	862.1345	75 CGA	II	CHEMISTRY

Substantial Equivalence (3)

The AVL OPTI is substantially equivalent in function, safety and efficacy to a number of currently marketed devices known as 'Combi Analyzers' and 'Point of Care' analyzers, Specifically: NOVA Biomedical STAT Profile [K981426], Chiron 865 [K946206], AVL OMNI [K990092], SenDx 100 [954482], Diametrics IRMA [981270], I-STAT 200 [940918], as well as electrolyte analyzers such as AVL 9181 [972763] and IL 943 Flame Photometer JK8234801. The OPTI Critical Care Analyzer is an improved design of the AVL OPTI 1 pH/Blood Gas Analyzer [K944089, K961161, K974784, 984299].

Description of the new device (4)

(2)

000019

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(5) Intended use of the device

(6) Technological characteristics of the device.

Principles of Measurement

The OPTI Critical Analyzer uses fluorescence optode technology similar to that used in commercially available products since late 1983 and is unchanged in principle of operation from the originally submitted 510(k) for this device. Additional parameters, sodium and potassium, ionized calcium, chloride, glucose and urea (BUN) are measured by fluorescence intensity and measurement of total Hemoglobin (ctHb) and oxygen saturation (SO2) is accomplished by optical scattering.

Calibration

A disposable, single-use cassette contains all the elements needed for calibration, QC sample measurement, patient sample measurement and waste containment. Calibration verification is performed with each cassette immediately prior to use. No other calibration is required for the usual operation of this device for the measurement of pH, PCO2, PO2, Na , K , Ca , Cl , Glucose, Urea (BUN). Total hemoglobin and SO2 are calibrated at 6month intervals.

(b) (1) Summary of non-clinical tests submitted with the premarket notification for the device.

The AVL OPTI Critical Care Analyzer has been tested and found to comply with EN 50081-1, FCC Class B, EN 50081-2 and IEC 1010-1.

Precision

Typical Within-Run (Swr), Between-Day (Sdd) and Total (ST) precision were determined from two runs per day with 2 replicates per run for 20 days on two AVL OPTI instruments using samples: serum, reduced bovine hemoglobin solution and three levels of aqueous quality control solution.

Linearity

Wherever possible, linearity for the OPTI measurement has been established against reference materials or methods. Linearity for pH of whole blood is established by measurement of blood specimens which were tonometered to various CO2 values, and measured on an AVL 995 pH/Blood Gas Analyzer standardized to N.I.S.T. traceable pH buffers, and on OPTI Critical Care Analyzers.

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Interferences1

Representative samples taken the published guidelines for evaluation of interference substances and identified from literature were evaluated.

(b) (2) Summary of clinical tests submitted with the premarket notification for the device.

Clinical testing was conducted to demonstrate the correlation of AVL OPTI Critical Care Analyzer to predicate devices in a clinical setting, operated by personnel trained to perform and report these analyses. Specimens analyzed in these tests were remnant from patient specimens of both whole blood and plasma collected for routine analysis on existing instrumentation.

In all evaluations, there was no significant difference in mean values (P<0.05) obtained on measurement by the AVL OPTI from those of the predicate devices.

(b) (3) Conclusions drawn from the clinical and non-clinical trials.

Analysis of the comparative measurement presented in the 510(k) for this device, together with the linearity and precision data collected during these clinical and non-clinical trials demonstrates that the AVL OPTI Critical Care Analyzer with the additional analytes: glucose and urea (BUN), is safe, effective, and equivalent to those predicate devices to which it is compared.

000021

1 NCCLS. Interference Testing in Clinical Chemistry; Proposed Guideline. NCCLS Document EP7-P. NCCLS, 771 East Lancaster Avenue, Villanova, Pennsylvania 19085, 1986,

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States of America. The seal features a stylized eagle with three lines representing the three levels of health services: prevention, treatment, and rehabilitation. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the eagle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC I 6 1999

Mr. Randy Byrd Director, Quality Assurance AVL Scientific Corporation 235 Hembree Park Drive Roswell, Georgia 30076

K993837 Re:

Trade Name: AVL OPTI Critical Care Analyzer Regulatory Class: II Product Code: CGA, CDS Dated: November 11, 1999 Received: November 12, 1999

Dear Mr. Byrd:

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 OS 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.

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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

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510(k) Number: K993837

Device Name:

The AVL OPTI Critical Care Analyzer intended to be used for the measurement of pH, PCO2, PO2, ctHb, SO2, Na*, K*, Cl*, Cl*, glucose and BUN in whole blood, serum, plasma and aqueous dialysate solutions as appropriate by minimally trained personnel qualified to perform and to report these values in either a traditional blood gas, clinical laboratory setting or point-of-care locations by personnel minimally qualified to perform and report these results.

For Professional Use Only For In Vitro Diagnostic Use

Indications for Use1,2

The pH value of the blood may be the single most valuable factor in the evaluation of the acid-base status of a patient. The pH value is an indicator of the balance between the buffer (blood), renal (kidnev) and respiratory (lung) systems, and one of the most tightly controlled parameters in the body. The causes of abnormal blood pH values are generally classified as:

· primary bicarbonate deficit metabolic acidosis
primary bicarbonate excess . metabolic alkalosis · primary hypoventilation respiratory acidosis
· primary hyperventilation respiratorv alkalosis

An increase in blood, serum or plasma pH (alkalemia) may be due to increased plasma bicarbonate, or a feature of respiratory alkalosis due to an increased elimination of CO2 due to hyperventilation.

A decrease of pH value (acidemia) in blood, serum or plasma may occur due to an increased formation of organic acids, an increased excretion of H -ions in certain renal disorders, an increased acid intake such as in salicylate poisoning or loss of alkaline body fluids. Respiratory acidosis is the result of a decreased alveolar ventilation and may be acute, as the result of pulmonary edema, airway obstruction or medication, or maybe be chronic, as the result of obstructive or restrictive respiratory diseases.

The composition of serous body fluids: pleural, pericardial, ascitic and cerebrospinal fluid, is similar to serum and plasma in electrolyte content and pH. The AVL OPTI may be used for the analysis of these fluids, limited to a pH in the

1 Tietz, Norbert W., Ed., Clinical Guide to Laboratory Tests, 2nd Ed., (Philadelphia: W.B.Saunders, Co., 1990) p.436.

2 Burtis C, Ashwood E (Eds.), Tietz Textbook of Clinical Chemistry, 2nd Ed., (Philadelphia: W.B.Saunders, Co., 1994) pp.1354-1360,2180-2206.

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range between 6.8 and 7.7, as long as care is taken to ensure the specimen to be analyzed is clear of fibrin clots or other debris which may block the sample transport in the cassette.

Pleural fluid3

The pH measurement of pleural fluid can be a clinically useful tool in the management of patients with parapneumonic effusions. Patients with pneumonia may develop effusions when the infectious process extends to the visceral pleura, causing exudation of fluid into the pleural space. Fluids are divided into potentially benign and complicated effusions on the basis of pH. Fluids with a pH greater than 7.30 resolve spontaneously, whereas a pH less than 7.20 is an indication of tube drainage.

PCO2

The PCO2 value of arterial blood is used to assess how well the body eliminates carbon dioxide in relation to the metabolic rate of CO2 production.

An arterial PCO2 below the normal range is termed respiratory alkalosis and indicates hypocapnia, a condition caused by increased alveolar ventilation such as hyperventilation. An arterial PCO2 above the normal range is termed respiratory acidosis and indicates hypercapnia, a sign of hypoventilation and failure, resulting from cardiac arrest, chronic obstructive lung disease, drug overdose, or chronic metabolic acid-base disturbances.

PCO2

The PO2 value of arterial blood has become the primary tool for the evaluation of arterial oxygenation status. Values below the normal arterial PO2 (arterial hypoxemia) are usually caused by pulmonary, circulatory, or respiratory abnormalities (e.g. bronchial obstruction, vascular problems, decrease in cardiac output, increased oxygen demand, anatomical heart defect, low inspired O2 content). Generally, PO2 levels above 100 mmHg do not contribute significantly to the oxygen content since, with normal hemoglobin concentrations, 80 - 100 mmHg, PO2 provides a 97 % saturation level, and a level greater than 100 % cannot be achieved.

Sodium

Sodium is the major cation of extracellular fluid. Its primary functions in the body are to chemically maintain osmotic pressure and acid-base balance and to transmit nerve impulses. Sodium functions at the cell membrane level by creating an electrical potential between different cell membranes causing the transmission of nerve impulses and neuromuscular excitability to be maintained. Sodium is involved in some enzyme catalyzed reactions as a cofactor. The body has a strong tendency to maintain a total base

3 Kaplan LA. Pesce AJ. Clinical Chemistry: Theory, analysis and correlation. 2nd Ed. (St.Louis: C.V.Mosby Co. 1989) p 590-591.

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content, and only slight changes are found even under pathologic conditions.

Low sodium values, hyponatremia, usually reflect a relative excess of body water rather than a low total body sodium. Reduced sodium levels may be associated with: low sodium intake; sodium losses due to vomiting or diarrhea with adequate water and inadequate salt replacement, diuretics abuse, or salt-losing nephropathy; osmotic diuresis, metabolic acidosis; adreocortical insufficiency; congenital adrenal hyperplasia; dilution type due to edema, cardiac failure, hepatic failure; and hypothyroidism.

Elevated sodium values, hypernatremia, are associated with conditions with water loss in excess of salt loss through profuse sweating, prolonged hyperpnea, severe vomiting or diarrhea. diabetes insipidus or diabetic acidosis; increased renal sodium conservation in hyperaldosteronism, Cushing's syndrome; inadequate water intake because of coma or hypothalamic diseases; dehydration; or excessive saline therapy.

The sodium value obtained may be used in the diagnosis or monitoring of all disturbances of the water balance, infusion therapies, vomiting, diarrhea, burns, heart and kidney insufficiencies, central or renal diabetes insipidus, endocrine disturbances and primary or secondary cortex insufficiency of the adrenal gland or other diseases involving electrolyte imbalance.

Potassium

Potassium is the major cation in the intracellular fluid and functions as the primary buffer within the cell itself. Ninety percent of potassium is concentrated within the cell, and damaged cells release potassium into the blood. Potassium plays an important role in nerve conduction, muscle function, and helps maintain acid-base balance and osmotic pressure.

Elevated potassium levels, hyperkalemia, can be found in oligouria, anemia, urinary obstruction, renal failure due to nephritis or shock, metabolic or respiratory acidosis. renal tubular acidosis with the K /H exchange and hemolysis of the blood. Low potassium levels, hypokalemia, can be found in excessive loss of potassium through diarrhea or vomiting, inadequate intake of potassium, malabsorption, severe burns and increased secretion of aldosterone. High or low potassium levels may cause changes in muscle irritability, respiration and myocardial function.

The potassium value obtained may be used to monitor electrolyte imbalance in the diagnosis and treatment of infusion therapies, shock, heart or circulatory insufficiency, acid-base imbalance, therapy with diuretics, all kinds of kidney problems, diarrhea and hyper- and hypo-function of adrenal cortex and other diseases involving electrolyte imbalance.

lonized Calcium

Calcium in blood is distributed as free calcium ions (50%) bound to protein, mostly albumin (40%) and 10% bound to anions such as bicarbonate, citrate, phosphate

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and lactate. However, only ionized calcium can be used by the body in such vital processes as muscular contraction, cardiac function, transmission of nerve impulses and blood clotting. The OPTI CCA measures the ionized portion of the total calcium. In certain disorders such as pancreatitis and hyperparathyroidism, ionized calcium is a better indicator for diagnosis than total calcium.

Elevated calcium, hypercalcemia, may be present in various types of malienancy. and calcium measurements may serve as biochemical markers. In general, while ionized calcium may be slightly more sensitive, either ionized or total calcium measurements have about equal utility in the detection of occult malignancy. Hypercalcemia occurs commonly in critically ill patients with abnormalities in acidbase regulation and losses of protein and albumin, which gives a clear advantage to monitoring calcium status by ionized calcium measurements.

Patients with renal disese caused by glomular failure often have altered concentrations of calcium, phosphate, albumin, magnesium and pH. Since these conditions tend to change ionized calcium independently of total calcium, ionized calcium is the preferred method of accurately monitoring calcium status in renal disease 19.

Ionized calcium is important for diagnOosis or monitoring of: hypertension management, parathyroidism, renal diseases, malnutrition, kidney stoes, multiple myeloma and diabetes mellitus.

Chloride

Chloride is an anion that exists predominantly in extracellular spaces. It maintains cellular integrity through its influence on osmotic pressure. It is also significant in monitoring acid-base balance and water balance. In metabolic acidosis, there is a reciprocal rise in chloride concentration when the bicarbonate concentration drops.

Decreased levels are found in severe vomiting, severe diarrahea, ulcerative colitis, pyloric obstruction, severe burns, heat exhaustion, diabetic acidosis, Addison's disease, fever and acute infections such as pneumonia.

Increased levels are found in dehydration, Cushing's syndrome, hyperventilation, eclampsia, anemia, cardiac decompensation.

Glucose

Hyperglycemia can be due to a number of causes which can be sub-divided into those due to diabetes mellitus or those due to non-diabetic causes. Diabetes mellitus is a syndrome of chronic hyperglycemia which is due to either absolute insulin deficiency or reduced tissue response to insulin, or both. It is a common condition which is diagnosed according to strict criteria that rely upon measurement of the blood glucose level. Nondiabetic causes of hyperglycaemia include

19 Burritt MF, Pierides AM, Offord KP: Comparative studies of total and ionized scrum calcium values in normal subjects and in patients with renal disorders. Mayo Clinic Proc. 55:606. 1980.

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postprandial (occurs immediately after a carbohydrate-containing meal), factitious (blood taken from an arm where glucose is being infused), drugs (produce a tissue insensitivity to insulin), non-pancreatic endocrine disease (excessive production of anti-insulin hormones), pancreatic disorders (secondary diabetes mellitus), and stress (physical and psychogenic types causing excess secretion of cortisol and catecholamines.

Hypoglycemia is an acute medical condition with a number of characteristic signs and symptoms which are accompanied by biochemical hypoglycamia and which are relieved by the administration of glucose. The causes of hypoglycaemia can be divided into three groups: Medication/Toxins, Reactive Hypoglycemia; Fasting Hypoglycemia. Hypoglycemia due to excessive amounts of certain Medications or Toxins include insulin (insulin overdose is the commonest cause of hypoglycemia), oral hypoglycaemics or suphonylureas, ethanol and other drugs such as salicylate and propanalol. Reactive Hypoglycemia occur, within 5-hours of a carbohydrate meal in otherwise normal subjects, in patients with early adult-onset diabetes mellitus and in patients who have had gastric surgery. Fasting Hypoglycemia can be due to insulinomas, non-pancreatic tumors, endocrine disorders, liver failure, sepsis, renal failure or autoimmune disorders.

Urea Nitrogen

Urea is produced in the liver as a by-product from the breakdown of amino acids. These are transaminated and deaminated to ammonia which is a toxin. Detoxification of ammonia occurs in the urea cycle where two molecules of ammonia are joined to a molecule of carbon dioxide to form urea. Approximately 1120-1680 mg/dL of urea nitrogen are produced per day but the production depends upon protein intake and liver function. A wide variety of renal diseases with different permutations of glomerlular, tubular, interstitial or vascular damage can effect azotemia (increased urea concentration).

total Hemoglobin concentration (ctHb)

The hemoglobin is the main component of erythrocytes. It serves as the vehicle for transportation of oxygen within the bloodstream and each gram/dL of hemoglobin can carry 1.39 mL of oxygen. The oxygen combining capacity of the blood is directly proportional to the hemoglobin concentration rather than to the number of red blood cells (RBC), because some red cells contain more hemoglobin than the others.

Although oxygen transport is the main function of hemoglobin, it also serves as an important buffer in the extracellular fluid. Decreases in the amount of hemoglobin can come about as a result of a decreased concentration of hemoglobin in the erythrocytes, or a decreased number of erythrocytes that contain a normal concentration of hemoglobin.

Decreased levels are found in anemia states, hyperthyroidism, severe hemorrhage and hemolytic reactions due to transfusions of incompatible blood, reaction to

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chemical, infectious and physical agents as well as various systemic diseases. Increased levels are found in hemoconcentration of the blood, chronic obstructive pulmonary disease and congestive heart failure.

CtHb gives valuable information in an emergency situation if interpreted not in an isolated fashion but in conjunction with other pertinent laboratory data.

ctHb is used to screen for disease associated with anemia, to determine the severity of anemia, to follow the response to treatment for anemia and to evaluate polycythemia.

Oxygen Saturation (SO2%)

When each heme group of the hemoglobin molecule is associated with one molecule of oxygen, the hemoglobin is referred to as oxyhemoglobin (O2Hb). The amount of oxyhemoglobin, expressed as a fraction of the total available hemoglobin is termed, hemoglobin oxygen saturation (SO2). The largest portion (about 98%) of blood oxygen content is the oxygen bound to hemoglobin. The reference interval for arterial blood from healthy adults is typically 94 to 98%. Decrease in SO2 below the critical level necessary for tissue oxygen saturation is a grave clinical situation. Low oxygen saturation may be caused by many of the same factors responsible for arterial hypoxemia, as well as from unusually large amounts of non-functional hemoglobins, high concentrations of deoxyhemoglobin, chemically altered hemoglobin or factors affecting the affinity of hemoglobin for oxygen, including: temperature, pH, PCO2, 2,3-DPG concentration and type of hemoglobin. 3

4 Siggaard-Andersen O. Durst RA. Maas AHJ. IFCC/IUPAC approved recommendation (1984) on physicochemical quantities and units in clinical chemistry. J Clin Chem Clin Biochem. 25:369-391. 1987.

5 Burtis C, Ashwood E (Eds.), Tietz Textbook of Clinical Chemistry, 2nd Ed., (Philadelphia: W.B.Saunders, Co., 1994) pp.1354-1360,2180-2206.

Qian Cooper

I Laborator

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use \ (Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Format 1-2-96)

000017

Regulation Number and Section

§ 862.1345 Glucose test system.

(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.