Anticoagulant Citrate Phosphate Dextrose (cpd) and As-5 Red Cell Preservative

1. INDICATIONS AND USAGE 1.1. Read these instructions carefully before use. 1.2. Rx ONLY. 1.3. Intended for the collection, processing and preservation of Whole Blood and blood components. Not intended for direct intravenous infusion. 1.4. For the collection of 500 mL ±10% Whole Blood. 1.5. Integral Diversion Blood Sampling Arm is intended to divert and obtain donor samples for laboratory testing prior to collection of the Whole Blood unit. 1.6. Integral filter unit intended for leukocyte reduction of Whole Blood up to 8 hours after blood collection when Whole Blood is stored at ambient temperature or cooled towards 1-10°C (transport temperature). 1.7. For further processing, use standard component processing techniques.

2. DOSAGE AND ADMINISTRATION 2.1. To open blister package, peel cover film back 4/5 of its length. 2.2. Prepare the blood bag following your institution's standard operating procedures. 2.2.1. Materials Needed: VENOJECT®@Tube Holder (code P-1316R) or equivalent VENOJECT@Multi-Sample Luer Adapter (code MN＊2000T) or equivalent Evacuated blood collection tubes (glass or plastic) 2.3. Make a loose knot in the donor tubing below the "Y" and CLIKTIP® (inline closure device) unless alternate methods are used to seal the tubing at the end of collection. 2.4. Temporarily clamp donor tubing between the phlebotomy needle and the "Y". 2.5. Close the White Clamp below the diversion pouch. 2.6. Assemble the luer adapter and the tube holder. 2.6.1. Connect the VENOJECT@Multi-Sample Luer Adapter to the VENOJECT@Tube Holder (or equivalent) (Fig. 1). 2.6.2. Twist and snap to remove the blue port cap at the end of the Diversion Blood Sampling Arm (Fig. 2a). 2.6.3. Insert the Holder/Luer assembly in the female luer port (Fig. 2b). 2.6.4. NOTE: Alternatively, steps 2.6.1., 2.6.2., and 2.6.3. (above) may be performed at any time during bag preparation or after the blood is collected into the diversion pouch. 2.7. Suspend the collection bag as far as possible below the donor's arm. 2.8. Apply blood pressure cuff or tourniquet to donor's arm. Disinfect site of phlebotomy. If blood pressure cuff is used, inflate to approximately 60 mmHg. 2.9. Remove the needle cover and perform phlebotomy. Remove the temporary clamp on the donor tubing to permit blood flow into the Diversion Blood Sampling Arm pouch. 2.9.1. CAUTION: Do not touch the needle after removing the needle cover. 2.9.2. CAUTION: Assure that the White Clamp below the pouch is closed prior to initiating phlebotomy. 2.10. Secure the needle safety device in place following the device instructions provided on the reverse side. 2.11. Secure donor tubing to donor's arm. 2.12. Position the diversion pouch with the notches up and the Tube Holder/Luer Adapter assembly (or port cap) down. When the level of blood in the pouch is approximately in line with the notches, the diversion pouch is full (Fig. 3a). 2.12.1. NOTE: The approximate fill volume of the pouch at the notches is 35 mL. 2.13. Permanently seal the tubing between the "Y" and the diversion pouch to maintain a closed system using an aluminum clip or a tube sealer approved for use with tubing connected to a donor (Fig. 3b). 2.13.1. CAUTION: Do not use a dielectric tube sealer to seal the tubing while the needle is connected to the donor's body unless it is approved for such a purpose. 2.14. To initiate blood flow into the collection bag, break the CLIKTIP between the "Y" and the collection bag. 2.15. To avoid clot formation, collect samples as soon as possible from the diversion pouch as follows (Fig. 3b). 2.15.1. CAUTION: Do not collect donor test samples until the tubing between the "Y" and the diversion pouch is permanently sealed. 2.15.2. Open the White Clamp on the tubing below the pouch to open the pathway for sampling. 2.15.3. Position the diversion pouch with the notches up and the Tube Holder/Luer Adapter assembly downward. Assure that any air in the pouch is at the top and will not enter the blood collection tubes. 2.15.4. Insert blood collection tube firmly into the tube holder; when full, remove sample tube from holder. Repeat to collect additional samples. 2.15.5. NOTE: The pouch may be removed after the donor test samples are collected. A second seal must be made between the diversion pouch and the permanent seal prior to removing the pouch. 2.16. Mix blood with anticoagulant in the collection bag and continue to mix at several intervals during collection and immediately after collection. If using an automated mixer, follow manufacturer's instructions. 2.17. Collect labeled volume of blood 500 mL ±10%. 2.18. When the desired amount of blood has been collected, seal the tubing or tighten the loose knot (white knot) prepared in Step 2.3. Make a second seal between the first seal or knot and the "Y". Various methods may be used to seal tubing. 2.19. Release pressure on the donor's arm and remove the needle into the needle safety device following the device instructions provided on the reverse side. Sever the donor tubing between the two seals previously made below the CLIKTIP and "Y". 2.19.1. CAUTION: Discard the Diversion Blood Sampling Arm and phlebotomy needle/donor tubing according to institutional standard operating procedures. 2.20. Seal and remove donor tubing from collection bag or strip donor tubing as follows: 2.20.1. To obtain a quality control prefiltration sample, strip blood from donor tubing into collection bag, mix well, and allow tubing to refill; repeat once. To prevent the blood from clotting in the tubing, work quickly as possible. Leave an adequate length of tubing containing the well-mixed anticoagulated whole blood attached to the collection bag. 2.20.2. Or, to maximize collection recovery, strip the tubing, mix well and seal tubing close to the collection bag without refilling. To prevent the blood from clotting in the tubing, work quickly as possible. Remove tubing from collection bag. 2.21. The blood filtration is executed according to the following operation. (see Fig.4 ) 2.21.1. NOTE: Red blood cells collected from certain donors may have extended filtration times and the potential for ineffective filtration and leukoreduction. 2.21.2. NOTE: Wait 30 minutes after collection before filtering. Filtration can be accomplished at room temperature for units maintained at room temperature and filtered within 8 hours of collection. Filtration can also be performed with units cooled towards 1-10°C within 8 hours of collection (e.g., during transport). If any unit has not completely filtered by 8 hours post collection, filtration must be completed at 1-6°C. Filtration can be unattended. 2.22. Mix the unfiltered whole blood unit by inverting the collection bag #1 (pre-filter bag) several times. 2.23. Hang the collection bag #1 and extend the filtration set to full length. Verify that the filter is vertical and ensure all tubing is freely suspended without kinks. 2.24. Break the CLIKTIP at the outlet of the collection bag #1. 2.24.1. The filter housing will begin to fill with blood and expand on the non-textured side. 2.24.2. Blood will flow across the filter pads and expand the textured side of the filter housing. 2.24.3. Air from the bag and filter will be forced into the primary bag #2 (post-filtration bag). 2.24.3.1. CAUTION: Do not squeeze or apply pressure on the filter while it is attached to the bag containing the filtered blood. 2.25. Filtration ends when the filter has emptied and the housing has collapsed onto the filter pads. 2.25.1. NOTE: Verify that collection bag #1 and pre-filtration tubing has emptied. 2.26. Gently squeeze the primary bag #2 to expel the air in the bag up the numbered segment tubing line and into the filter. To ensure ease of air removal ensure primary bag #2 is below the filter outlet. 2.27. Fill the numbered segment tubing with blood while expelling the air. 2.28. Clamp the blood filled tubing before blood enters the filter. 2.29. Seal the tubing as close as possible to the filter outlet and properly dispose of the filter and collection bag #1. 2.30. Strip the post filter tubing into the primary bag #2, mix well, and allow tubing to refill; repeat once. Make an appropriate number of segments of anticoagulated blood for testing by sealing on or near the X marks. Leave segments attached to the filtered whole blood unit. 2.31. The time between Whole Blood collection and component separation may vary depending on both the blood bag system and processing options selected. 2.31.1. NOTE: Production of Platelet concentrates is not intended with this product. 2.31.2. NOTE: Fresh Frozen Plasma should be separated from the Red Blood Cells and placed in a freezer at –18°C or colder within 8 hours of collection. 2.31

WARNINGS AND PRECAUTIONS Single-use product. Do not reuse. This product is intended to be single use only and is not intended to be reused or re-sterilized in any manner. Terumo Blood and Cell Technologies cannot ensure the functionality or sterility of the product if it is reused or re-sterilized. Reuse of a single-use disposable set may result in: Product performance issues due to loss of product integrity, including but not limited to the following: Fluid leaks Parts that are warped or deformed Plastics that are brittle and discolored Filters that have reduced filtration capabilities Viral infections such as hepatitis or human immunodeficiency virus (HIV) Bacterial infections Cross-contamination Any of these risks could result in serious injury or death. These risks are shared by product users, donors, patients, and recipients of the end product of the device. Inspect the packaging and the blood bag set prior to use. Do not use the set if any of the following conditions are present: There are tears or holes in the outer aluminum foil packaging or in the individual transparent packaging wrap. The tubing has severe kinks. The blood bag set is incorrectly assembled. The blood bag set is defective or damaged, or there are any leaks from the fluid-filled components of the set. Any clamps are closed. The needle cap is not in place. The solutions are cloudy or discolored or contain particulates. Using the blood bag set under these conditions may result in product contamination or poor performance during collection and/or processing. Note : It is normal to have some condensation in the outer aluminum foil pouch and individual transparent packaging wrap due to sterilization. The blood bag set is no longer sterile if any of the following conditions occur: You disconnect the sample/diversion bag before you seal the sample/diversion tubing. You remove blood samples before you seal the sample/diversion tubing. The integrity of the set is compromised for any reason. Manage the blood bag set according to your institution's SOP. Do not process whole blood less than 2 hours after collection. Processing blood too soon after collection may result in incomplete RBC leukoreduction and/or a reduced platelet yield. Residual leukocytes are a by-product of the processing procedure and contain mostly white blood cells (WBC), with some plasma, platelets, and red blood cells (RBC). Residual leukocytes are not intended for transfusion. Use aseptic technique during blood collection to ensure donor safety and product quality. Do not vent the blood bag set. Do not reuse. ( 5 ) Inspect the packaging and the blood bag set prior to use. ( 5 ) The blood bag set is no longer sterile under certain conditions. ( 5 ) Do not process whole blood less than 2 hours after collection. ( 5 ) Residual leukocytes are not intended for transfusion. ( 5 ) Use aseptic technique during blood collection to ensure donor safety and product quality. ( 5 ) Do not vent the blood bag set. ( 5 )

CONTRAINDICATIONS None. None. ( 4 )

6. ADVERSE REACTIONS To report SUSPECTED ADVERSE REACTIONS, contact Terumo BCT, Inc. at 1-877-339-4228 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. To report SUSPECTED ADVERSE REACTIONS, contact Terumo BCT, Inc. at 1-877-339-4228 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. ( 6 )

12.1. Mechanism of Action CPD Mechanism of Action CITRATE PHOSPHATE DEXTROSE acts as an extracorporeal anticoagulant by binding the free calcium in the blood. Calcium is a necessary co-factor to several steps in the clotting cascade. The following ingredients are key components of the solution: Citric Acid for pH regulation Sodium Citrate functions as an anticoagulant Dextrose for isotonicity Sodium Dihydrogen Phosphate for pH buffering This solution has no clinical effect in transfused patients. AS-5 Mechanism of Action ADDITIVE SOLUTION FORMULA 5 acts to preserve and extend the shelf life of packed RBC products for later transfusion to patients. The following ingredients are key components of the solution: Dextrose for RBC nutrition Sodium Chloride for isotonicity Mannitol to protect RBC membranes Adenine to support adenosine triphosphate (ATP) levels This solution has no clinical effect in transfused patients.