IDkit HP ONE

1 INDICATIONS AND USAGE IDkit Hp ® One and IDkit Hp ® Two are indicated for use as a diagnostic aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori (H. pylori) infection in adults and pediatric patients 3 years of age and older. IDkit Hp One and IDkit Hp Two are to be administered only by trained personnel as ordered by a licensed healthcare practitioner using the BreathID ® system device as identified in the BreathID ® system device labeling. IDkit Hp One and IDkit Hp Two are indicated for use as a diagnostic aid in the initial diagnosis and post-treatment monitoring of Helicobacter pylori (H. pylori) infection in adults and pediatric patients 3 years of age and older. ( 1 ) IDkit Hp One and IDkit Hp Two are to be administered only by trained personnel as ordered by a licensed healthcare practitioner using the BreathID ® system device as identified in the BreathID ® system device labeling. ( 1 )

2 DOSAGE AND ADMINISTRATION IDkit Hp One and IDkit Hp Two each contain a 75 mg 13 C-urea tablet for oral solution, and 4 g Citrica (citric acid) for oral solution along with other materials for use with the BreathID system device ( 2.1 , 16 ) o IDkit Hp One is co-packaged with a nasal canula to be used with the BreathID system device as identified in the BreathID system device labeling. ( 2.1 ) o IDkit Hp Two is co-packaged with breath sample bags to be used with the BreathID system device as identified in the BreathID system device labeling. ( 2.1 ) To prepare the oral solution for either kit, dissolve the 13 C-urea tablet and the Citrica (citric acid) for oral solution in 150 to 200 mL of water to provide a clear, colorless solution for oral administration. The resulting solution is ingested by the patient. ( 2.3 ) See full prescribing information for detailed important instructions concerning preparation, administration, and disposal of IDkit Hp One and IDkit Hp Two. ( 2.3 - 2.6 ) See BreathID ® system device manual for additional details for use of IDkit Hp One and IDkit Hp Two with the BreathID system device, including troubleshooting device malfunction. ( 2.2 ) 2.1 Dosage and Administration Overview IDkit Hp One or IDkit Hp Two contain the same drug product, 75 mg 13 C-urea tablet and 4 g Citrica (citric acid) for oral solution and follow the same drug preparation and administration instructions. IDkit Hp One and IDkit Hp Two are to be administered only by trained personnel as ordered by a licensed healthcare practitioner, using the BreathID system device that as identified in the BreathID system device labeling, is intended for use with IDkit Hp One and IDkit Hp Two. For in vitro diagnostic use only. Inform the patient that each 4 g packet of Citrica (citric acid) for oral solution contains 84 mg of phenylalanine per dose. Phenylketonurics restrict dietary phenylalanine [see Warnings and Precautions ( 5.2 )] . The patient should have fasted for at least one hour before administering the test drink. The patient should not have taken antimicrobials, proton pump inhibitors (PPI), or bismuth preparations within two weeks prior to administering the test. If PPIs are used within two weeks of breath testing, false negative test results may occur, and the test should be repeated two weeks after discontinuation of PPI treatment. A positive result for a patient on PPI could be considered as indicative of the presence of urease enzyme associated with H. pylori . Before opening the kit (IDkit Hp One or IDkit Hp Two), verify that the entire package is intact [see How Supplied/Storage and Handling ( 16 )] . 2.2 Recommended Dosage for Adults and Pediatric Patients 3 Years of Age and Older IDkit Hp One Single-use Kit or IDkit Hp Two Single-use Kit A 75 mg 13 C-urea tablet for oral solution and 4 g Citrica (citric acid) for oral solution are dissolved in 150 to 200 mL of water for oral consumption, and the resulting solution is ingested by the patient. 2.3 Preparation of IDkit Hp One Single-use kit or IDkit Hp Two Single-use Kit Preparation Instructions with IDkit Hp One single-use kit or IDkit Hp Two single-use kit Dissolve the 13 C-urea tablet and Citrica (citric acid) for oral solution in 150 mL to 200 mL of tap water in a single drinking cup of at least eight ounces (236 mL) in capacity. In the IDkit Hp Two kit a drinking cup is provided. Stir thoroughly with the provided straw until the 13 C-urea tablet and Citrica (citric acid) for oral solution are completely dissolved. Tiny particles may remain visible after thorough mixing. However, if more substantial particulate matter is still present after five minutes of stirring, discard the solution and repeat the procedure with a new kit. Use the test drink within two hours of preparation, as this is the maximal time for maintaining solution stability. 2.4 IDkit Hp One Single-use Kit: Instruction for Performing the BreathID H. pylori Test Preparing the BreathID System Device Refer to the BreathID system device labeling for additional details. Ensure that the BreathID system device is activated, and the status is Ready . The status appears on the top right of the screen. Follow the screen instructions Connecting the IDcircuit ® : Take the IDcircuit ® out of its bag and slide the tubing sleeve down as far as it will go. Gently place the cannula tips into the patient’s nostrils, and place the cannula tubing over the ears, as shown in Figure 1. Figure 1 Slide the tubing sleeve up towards the neck to fit comfortably under the chin. Connect the IDcircuit to the BreathID system device by twisting the orange connector at the free end of the cannula clockwise until it is secured into the dedicated socket of the BreathID system device. Verify that the IDcircuit is not twisted or kinked and that the cannula tips are in the nostrils. Ensure that the IDcircuit cannula tips moldings are positioned inwards. Press the START button on the touch screen to proceed. The baseline values will be measured by the BreathID system device, and the results will be shown on the screen. Administering the Test Drink and Starting Measurement Do not administer the test drink until prompted by the screen instructions on the device (this makes certain that the baseline sample has been collected properly). Ensure that the patient drinks the solution through the straw. The patient, including pediatric patients 3 years of age and older, regardless of age and body weight, must drink the solution within two minutes and consume the entire amount. After the patient finishes drinking the solution, press the Continue button on the touch screen to proceed. Measurement with the BreathID System Device The BreathID system device continually analyzes the trend of measured results. When the device determines that the final value will be positive or negative, i.e., greater or less than 5 Delta Over Baseline, it will automatically end the test and print out the results. The breath sample is analyzed in real-time by the BreathID system device; therefore, the stability of the final breath sample will not affect the outcome of the results. Removing and Discarding the IDcircuit: When the measurement is complete, disconnect the IDcircuit from both the patient and the device. Dispose of the IDcircuit and all other used components of the kit according to standard operating procedures or local regulations for the disposal of used medical waste. If you do not disconnect the IDcircuit, instructions will appear on the device screen reminding you to do so. The device will not proceed to the next screen until the IDcircuit is disconnected. Printing Results: After the measurement is complete, the device will automatically print the test results. The printout contains the graph as seen on the screen, including the Patient ID (if entered), date, time, test number, and Delta Over Baseline value of the last point measured. Tear off the printed results and fill in additional patient data as required. Figure 1 2.5 IDkit Hp Two Single-use Kit: Instructions for Performing the BreathID H. pylori Test Identify the two Breath Sample Bags (the blue BASELINE bag and the gray POST INGESTION bag). Prior to sampling the patient’s breath, label each bag with the supplied barcode labels or write the necessary identification information in the appropriate fields on each bag. Collection of the BASELINE breath sample: Remove the cap from the mouthpiece of the blue BASELINE bag. Instruct the patient to take a deep breath, hold their breath for 4 to 5 seconds and then exhale directly into the mouthpiece of the blue BASELINE breath bag until completely full. If the bag is not full, repeat step b. If the patient has not held their breath for 4-5 seconds or does not fill the bag completely, there is a possibility that a test result will not be obtainable. Replace the cap on the bag mouthpiece and firmly press until it clicks and is securely locked into place. The bag is not fully closed if the cap does not click into place. Not fully closing the bag may cause the breath sample to slowly leak out. Administering the test drink: Give the prepared test drink to the patient. Ensure that the patient drinks the solution through the provided straw. The patient, including pediatric patients 3 years of age and older, regardless of age and body weight, must drink the solution within two minutes and consume the entire amount. Start the timer for 15 minutes. After the patient finishes drinking the solution, record the present time plus (+) another 15 minutes in the Time to Fill field on the gray POST INGESTION bag. Collection of the POST INGESTION breath sample: Fifteen minutes after the administration of the test drink (but not later than 20 minutes after administration) remove the cap from the mouthpiece of the gray POST INGESTION bag. Instruct the patient to take a deep breath, hold their breath for 4 to 5 seconds, and then exhale directly into the mouthpiece of the gray POST INGESTION bag until it is full. If the bag is not full, repeat step b. Note: If the patient has not held their breath for 4-5 seconds or does not fill the bag completely, there is a possibility that a test result will not be obtainable Replace the cap on the bag mouthpiece and firmly press until it clicks and is securely locked into place. Note: The bag is not fully closed if the cap does not click into place. Not fully closing the bag may cause the breath sample to slowly leak out. Storage of Breath Sample Bags for future measurement: Assure both filled Breath Sample Bags are correctly labeled, and all fields are complete for future identification. Place both filled Breath Sample Bags (the blue BASELINE bag and the gray POST INGESTION bag) into the provided sample transport bag. Until analyzed, Breath Sample Bags should be stored at room temperature (15°C to 30°C, 59°F to 86°F), protected from direct sunlight and sharp objects. Refrain from applying any external pressure on the Breath Sample Bags. 2.6 Interpretation of Results and Retesting Refer to the BreathID system device labeling for additional details. A negative result does not rule out the possibility of H. pylori infection. False negative results can occur with this procedure. If clinical signs suggest H. pylori infection, retest with a new sample or an alternate method. A false positive test may occur due to urease associated with other gastric spiral organisms observed in humans, such as Helicobacter heilmanni . A false positive test could occur in patients who have achlorhydria. False negative test results may be caused by: Ingestion of antimicrobials or bismuth preparations within two weeks prior to performing the breath test. Ingestion of proton pump inhibitors (PPIs) within two weeks prior to performing the breath test. If a negative result is obtained from a patient ingesting a PPI within two weeks prior to the breath test, the results cannot be considered indicative of the absence of urease associated with H. pylori, and the test should be repeated two weeks after discontinuing the PPI treatment. A positive result for a patient on a PPI could be considered as indicative of the presence of urease associated with H. pylori. Post-treatment monitoring of H. pylori should be performed after at least six weeks of treatment for H. pylori infection. An earlier assessment may give false results. 2.1 Dosage and Administration Overview IDkit Hp One or IDkit Hp Two contain the same drug product, 75 mg 13 C-urea tablet and 4 g Citrica (citric acid) for oral solution and follow the same drug preparation and administration instructions. IDkit Hp One and IDkit Hp Two are to be administered only by trained personnel as ordered by a licensed healthcare practitioner, using the BreathID system device that as identified in the BreathID system device labeling, is intended for use with IDkit Hp One and IDkit Hp Two. For in vitro diagnostic use only. Inform the patient that each 4 g packet of Citrica (citric acid) for oral solution contains 84 mg of phenylalanine per dose. Phenylketonurics restrict dietary phenylalanine [see Warnings and Precautions ( 5.2 )] . The patient should have fasted for at least one hour before administering the test drink. The patient should not have taken antimicrobials, proton pump inhibitors (PPI), or bismuth preparations within two weeks prior to administering the test. If PPIs are used within two weeks of breath testing, false negative test results may occur, and the test should be repeated two weeks after discontinuation of PPI treatment. A positive result for a patient on PPI could be considered as indicative of the presence of urease enzyme associated with H. pylori . Before opening the kit (IDkit Hp One or IDkit Hp Two), verify that the entire package is intact [see How Supplied/Storage and Handling ( 16 )] . 2.2 Recommended Dosage for Adults and Pediatric Patients 3 Years of Age and Older IDkit Hp One Single-use Kit or IDkit Hp Two Single-use Kit A 75 mg 13 C-urea tablet for oral solution and 4 g Citrica (citric acid) for oral solution are dissolved in 150 to 200 mL of water for oral consumption, and the resulting solution is ingested by the patient. 2.3 Preparation of IDkit Hp One Single-use kit or IDkit Hp Two Single-use Kit Preparation Instructions with IDkit Hp One single-use kit or IDkit Hp Two single-use kit Dissolve the 13 C-urea tablet and Citrica (citric acid) for oral solution in 150 mL to 200 mL of tap water in a single drinking cup of at least eight ounces (236 mL) in capacity. In the IDkit Hp Two kit a drinking cup is provided. Stir thoroughly with the provided straw until the 13 C-urea tablet and Citrica (citric acid) for oral solution are completely dissolved. Tiny particles may remain visible after thorough mixing. However, if more substantial particulate matter is still present after five minutes of stirring, discard the solution and repeat the procedure with a new kit. Use the test drink within two hours of preparation, as this is the maximal time for maintaining solution stability. 2.4 IDkit Hp One Single-use Kit: Instruction for Performing the BreathID H. pylori Test Preparing the BreathID System Device Refer to the BreathID system device labeling for additional details. Ensure that the BreathID system device is activated, and the status is Ready . The status appears on the top right of the screen. Follow the screen instructions Connecting the IDcircuit ® : Take the IDcircuit ® out of its bag and slide the tubing sleeve down as far as it will go. Gently place the cannula tips into the patient’s nostrils, and place the cannula tubing over the ears, as shown in Figure 1. Figure 1 Slide the tubing sleeve up towards the neck to fit comfortably under the chin. Connect the IDcircuit to the BreathID system device by twisting the orange connector at the free end of the cannula clockwise until it is secured into the dedicated socket of the BreathID system device. Verify that the IDcircuit is not twisted or kinked and that the cannula tips are in the nostrils. Ensure that the IDcircuit cannula tips moldings are positioned inwards. Press the START button on the touch screen to proceed. The baseline values will be measured by the BreathID system device, and the results will be shown on the screen. Administering the Test Drink and Starting Measurement Do not administer the test drink until prompted by the screen instructions on the device (this makes certain that the baseline sample has been collected properly). Ensure that the patient drinks the solution through the straw. The patient, including pediatric patients 3 years of age and older, regardless of age and body weight, must drink the solution within two minutes and consume the entire amount. After the patient finishes drinking the solution, press the Continue button on the touch screen to proceed. Measurement with the BreathID System Device The BreathID system device continually analyzes the trend of measured results. When the device determines that the final value will be positive or negative, i.e., greater or less than 5 Delta Over Baseline, it will automatically end the test and print out the results. The breath sample is analyzed in real-time by the BreathID system device; therefore, the stability of the final breath sample will not affect the outcome of the results. Removing and Discarding the IDcircuit: When the measurement is complete, disconnect the IDcircuit from both the patient and the device. Dispose of the IDcircuit and all other used components of the kit according to standard operating procedures or local regulations for the disposal of used medical waste. If you do not disconnect the IDcircuit, instructions will appear on the device screen reminding you to do so. The device will not proceed to the next screen until the IDcircuit is disconnected. Printing Results: After the measurement is complete, the device will automatically print the test results. The printout contains the graph as seen on the screen, including the Patient ID (if entered), date, time, test number, and Delta Over Baseline value of the last point measured. Tear off the printed results and fill in additional patient data as required. Figure 1 2.5 IDkit Hp Two Single-use Kit: Instructions for Performing the BreathID H. pylori Test Identify the two Breath Sample Bags (the blue BASELINE bag and the gray POST INGESTION bag). Prior to sampling the patient’s breath, label each bag with the supplied barcode labels or write the necessary identification information in the appropriate fields on each bag. Collection of the BASELINE breath sample: Remove the cap from the mouthpiece of the blue BASELINE bag. Instruct the patient to take a deep breath, hold their breath for 4 to 5 seconds and then exhale directly into the mouthpiece of the blue BASELINE breath bag until completely full. If the bag is not full, repeat step b. If the patient has not held their breath for 4-5 seconds or does not fill the bag completely, there is a possibility that a test result will not be obtainable. Replace the cap on the bag mouthpiece and firmly press until it clicks and is securely locked into place. The bag is not fully closed if the cap does not click into place. Not fully closing the bag may cause the breath sample to slowly leak out. Administering the test drink: Give the prepared test drink to the patient. Ensure that the patient drinks the solution through the provided straw. The patient, including pediatric patients 3 years of age and older, regardless of age and body weight, must drink the solution within two minutes and consume the entire amount. Start the timer for 15 minutes. After the patient finishes drinking the solution, record the present time plus (+) another 15 minutes in the Time to Fill field on the gray POST INGESTION bag. Collection of the POST INGESTION breath sample: Fifteen minutes after the administration of the test drink (but not later than 20 minutes after administration) remove the cap from the mouthpiece of the gray POST INGESTION bag. Instruct the patient to take a deep breath, hold their breath for 4 to 5 seconds, and then exhale directly into the mouthpiece of the gray POST INGESTION bag until it is full. If the bag is not full, repeat step b. Note: If the patient has not held their breath for 4-5 seconds or does not fill the bag completely, there is a possibility that a test result will not be obtainable Replace the cap on the bag mouthpiece and firmly press until it clicks and is securely locked into place. Note: The bag is not fully closed if the cap does not click into place. Not fully closing the bag may cause the breath sample to slowly leak out. Storage of Breath Sample Bags for future measurement: Assure both filled Breath Sample Bags are correctly labeled, and all fields are complete for future identification. Place both filled Breath Sample Bags (the blue BASELINE bag and the gray POST INGESTION bag) into the provided sample transport bag. Until analyzed, Breath Sample Bags should be stored at room temperature (15°C to 30°C, 59°F to 86°F), protected from direct sunlight and sharp objects. Refrain from applying any external pressure on the Breath Sample Bags. 2.6 Interpretation of Results and Retesting Refer to the BreathID system device labeling for additional details. A negative result does not rule out the possibility of H. pylori infection. False negative results can occur with this procedure. If clinical signs suggest H. pylori infection, retest with a new sample or an alternate method. A false positive test may occur due to urease associated with other gastric spiral organisms observed in humans, such as Helicobacter heilmanni . A false positive test could occur in patients who have achlorhydria. False negative test results may be caused by: Ingestion of antimicrobials or bismuth preparations within two weeks prior to performing the breath test. Ingestion of proton pump inhibitors (PPIs) within two weeks prior to performing the breath test. If a negative result is obtained from a patient ingesting a PPI within two weeks prior to the breath test, the results cannot be considered indicative of the absence of urease associated with H. pylori, and the test should be repeated two weeks after discontinuing the PPI treatment. A positive result for a patient on a PPI could be considered as indicative of the presence of urease associated with H. pylori. Post-treatment monitoring of H. pylori should be performed after at least six weeks of treatment for H. pylori infection. An earlier assessment may give false results.

4 CONTRAINDICATIONS IDkit Hp One and IDkit Hp Two are contraindicated in patients with a known hypersensitivity to the 13 C-urea, Citrica (citric acid) or to any of the excipients [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.2 )] . Hypersensitivity to the 13 C-urea, Citrica (citric acid) or to any of the excipients in the drug. ( 4 )

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis, have been reported in patients using IDkit Hp. Institute appropriate supportive measures if an allergic reaction occurs. ( 5.1 ) Phenylketonuria: Citrica (citric acid) for oral solution, a component in the IDkit Hp, contains phenylalanine which can be harmful to patients with phenylketonuria. ( 5.2 ) 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who have used the IDkit Hp One and IDkit Hp Two for H. pylori diagnostic testing [see Adverse Reactions ( 6.2 )] . The IDkit Hp One and IDkit Hp Two are contraindicated in patients with known history of hypersensitivity to 13 C-urea, Citrica (citric acid) or the excipients [see Contraindications ( 4 )] . Before administering the IDkit Hp One or IDkit Hp Two, carefully inquire about previous hypersensitivity reactions. 5.2 Risks in Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU). In IDkit Hp One and IDkit Hp Two, the Citrica (citric acid) for oral solution contains phenylalanine, a component of aspartame. Each 4 g packet of Citrica (citric acid) for oral solution contains 84 mg of phenylalanine. Before prescribing IDkit Hp One or IDkit Hp Two to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including IDkit Hp One or IDkit Hp Two. 5.1 Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, have been reported in patients who have used the IDkit Hp One and IDkit Hp Two for H. pylori diagnostic testing [see Adverse Reactions ( 6.2 )] . The IDkit Hp One and IDkit Hp Two are contraindicated in patients with known history of hypersensitivity to 13 C-urea, Citrica (citric acid) or the excipients [see Contraindications ( 4 )] . Before administering the IDkit Hp One or IDkit Hp Two, carefully inquire about previous hypersensitivity reactions. 5.2 Risks in Patients with Phenylketonuria Phenylalanine can be harmful to patients with phenylketonuria (PKU). In IDkit Hp One and IDkit Hp Two, the Citrica (citric acid) for oral solution contains phenylalanine, a component of aspartame. Each 4 g packet of Citrica (citric acid) for oral solution contains 84 mg of phenylalanine. Before prescribing IDkit Hp One or IDkit Hp Two to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including IDkit Hp One or IDkit Hp Two.

7 DRUG INTERACTIONS No formal drug interaction studies were conducted. Information on drugs that may interfere with test results are listed in the Table 1. Table 1: Drugs That Interfere with Test Results Interfering Drug Clinical Effect Prevention or Management Antimicrobials, bismuth-containing preparations May suppress H. pylori or urease activity, leading to false negative results Avoid use within 2 weeks prior to testing. If used within 2 weeks, postpone testing until at least 2 weeks after discontinuation. Proton pump inhibitors (PPIs) May reduce urease activity or alter gastric conditions, potentially causing false negative results. A positive result during PPI use may still indicate H. pylori presence. Avoid use within 2 weeks prior to testing. If a negative result is obtained during PPI use, repeat the test 2 weeks after PPI discontinuation. Antimicrobials, Bismuth-containing preparations: Avoid use within 2 weeks prior to testing. ( 7 ) Proton pump inhibitors (PPIs): Avoid use within 2 weeks prior to testing. ( 7 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in the Warning and Precautions section of the labeling: Hypersensitivity Reactions [see Warning and Precautions ( 5.1 )] Adult Patients: The most common adverse reactions (incidence >0.3%) using the IDkit Hp included nausea, throat burning, and lightheadedness. ( 6.1 ) Pediatric Patients: The most common adverse reactions (incidence >1.5%) using the IDkit Hp included vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Meridian Bioscience Corporation at 1-800-543-1980 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience and Adverse Reactions in Adult Patients The safety of the IDkit Hp was evaluated in 465 adult patients who participated in two clinical trials (Trial 1 and Trial 2). All patients used the IDkit Hp Two kit for initial diagnosis and post-treatment monitoring of H. pylori infection. The most commonly observed adverse reactions associated with the use of the IDkit Hp were nausea (0.6%), throat burning (0.4%), and lightheadedness (0.4%). Clinical Trials Experience and Adverse Reactions in Pediatric Patients The safety of the IDkit Hp was evaluated in one multi-center, non-randomized, open-label study (Trial 3). A total of 53 pediatric patients, 3 to less than 18 years of age, were enrolled in the study and used the IDkit Hp Two. The only adverse reaction reported was vomiting (2%). 6.2 Post-marketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during post-marketing use of the IDkit Hp One and IDkit Hp Two based on patient and test administrator reports. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea General: Sweating, throat pain, malaise Immune: Anaphylactic reaction Neurologic: Dizziness, headache 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience and Adverse Reactions in Adult Patients The safety of the IDkit Hp was evaluated in 465 adult patients who participated in two clinical trials (Trial 1 and Trial 2). All patients used the IDkit Hp Two kit for initial diagnosis and post-treatment monitoring of H. pylori infection. The most commonly observed adverse reactions associated with the use of the IDkit Hp were nausea (0.6%), throat burning (0.4%), and lightheadedness (0.4%). Clinical Trials Experience and Adverse Reactions in Pediatric Patients The safety of the IDkit Hp was evaluated in one multi-center, non-randomized, open-label study (Trial 3). A total of 53 pediatric patients, 3 to less than 18 years of age, were enrolled in the study and used the IDkit Hp Two. The only adverse reaction reported was vomiting (2%). 6.2 Post-marketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during post-marketing use of the IDkit Hp One and IDkit Hp Two based on patient and test administrator reports. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal: Nausea, vomiting, abdominal pain, diarrhea General: Sweating, throat pain, malaise Immune: Anaphylactic reaction Neurologic: Dizziness, headache

8.1 Pregnancy Risk Summary Published data from other single oral dose 13 C-urea breath test kits containing urea and citric acid have not demonstrated a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are no available data on the use of IDkit Hp One or IDkit Hp Two use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. There are no animal data that meet current standards for nonclinical developmental toxicity studies. Based on available literature, no significant developmental or reproductive toxicities were observed in nonclinical studies with urea or citric acid. A single oral dose of 13 C-urea and citric acid at the maximum recommended human dose (MRHD) are unlikely to pose a significant developmental or reproductive risk, since humans typically have higher circulating levels of urea, and citric acid exposure from the test is within the range of normal dietary intake. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.