STORAGE AND HANDLING SECTION.


STORAGE. It is recommended that the product be stored at 15 25 (59 77 F). Protect from freezing. Exposure to temperatures near or below freezing may produce white precipitate in the solution; this precipitate will dissolve upon brief incubation at room temperature. Alternatively, the product may be warmed at 37 for up to one hour in dry air incubator to dissolve the precipitate.

CLINICAL PHARMACOLOGY SECTION.


CLINICAL PHARMACOLOGY. gradual depletion of red blood cell adenosine triphosphate (ATP) and 2,3 diphosphoglycerate (2,3-DPG) occurs with storage of RBC at 1-6 C. The level of 2,3-DPG in RBC stored for greater than 14 days is less than 10% of normal 1,2,12,17,18. Rejuvenation of RBC with rejuvesol (R) Solution increases the levels of ATP and 2,3-DPG. 1-5,8,13,17-22,24, 25 An in vitro loss of red blood cells occurs with the preservation and processing of RBC. Thus, the effectiveness of transfusion is influenced by both the total number of red blood cells transfused and the number of those cells which remain in circulation. Therefore, the dose of transfusion is defined as the percentage of pre-transfusion recovered red blood cells multiplied by the 24 hour post-transfusion survival value.Rejuvenation is accomplished by incubating the contents of one 50 mL vial of rejuvesol (R) Solution with one unit of RBC (prepared from up to 550 mL of whole blood) for sixty (60) minutes at 37 C. Citra recommends that the entire 50 mL of rejuvesol (R) Solution be added to smaller than normal RBC as long as the prerejuvenation net packed cell weight is greater than 110 grams. 1,9.

DESCRIPTION SECTION.


DESCRIPTION. Rejuvesol (R) Red Blood Cell Processing Solution rejuvesol (R) Solution) is sterile, non-pyrogenic solution of sodium pyruvate, inosine, adenine, dibasic sodium phosphate, and monobasic sodium phosphate in water for injection intended only for use in the extracorporeal rejuvenation of unit of red blood cell concentrate (RBC). Each 50 mL of rejuvesol (R) Solution contains sodium pyruvate 0.550 g, inosine 1.34 g, adenine 0.034 g, dibasic sodium phosphate (heptahydrate) 0.730 g, and monobasic sodium phosphate (monohydrate) 0.311 g, in water for injection, pH 6.7-7.4.

HOW SUPPLIED SECTION.


HOW SUPPLIED. PN 7012: 50 mL vial; 12 vials per case.

INDICATIONS & USAGE SECTION.


INDICATION AND USAGE. Rejuvesol (R) Solution is intended only to be used as an in vitro processing solution for the rejuvenation of unit of RBC. RBC may be rejuvenated after storage in CPD (non-leukocyte reduced), CPDA-1, (non-leukocyte reduced), CPD/ADSOL (R) (CPD/AS-1 leukocyte reduced), or CP2D/Nutricel (R) (CP2D/AS-3, leukocyte reduced). The final concentration of ATP and 2,3-DPG achieved after rejuvenation will vary depending on the number of days of liquid storage at 1-6 prior to rejuvenation. NOTE: For simplicity, RBC stored in CPD (non-leukocyte reduced), CPDA-1 (non-leukocyte reduced), CPD/ADSOL (R) (CPD/AS-1 leukocyte reduced), CP2D/Nutricel (R) (CP2D/AS-3, leukocyte reduced) are referred to hereafter as CPD, CPDA-1, CPD/AS-1, and CP2D/AS-3, respectively. Citra Labs, LLC, recommends that rejuvenation of RBC be performed after 14 days or longer of liquid storage. RBC (CPD, CPDA-1, CPD/AS-1, and CP2D/AS-3) rejuvenated before days of storage may achieve 2,3-DPG levels in excess of times normal and ATP levels in excess of 1.5 times normal 5,6 (See Warning and Contraindications). Rejuvenation of CPD or CPDA-1 RBC for Immediate use or for Cryopreservation. RBC which have been collected and stored in CPD or CPDA-1 anticoagulant may be rejuvenated up to three days after the expiration date of the RBC, as long as storage at 1-6 is not interrupted. 3,4 After rejuvenation, RBC (CPD and CPDA-1) must be either washed and stored at 1-6 for up to 24 hours prior to transfusion or glycerolized and frozen at -80 (below -65 C). Red Blood Cells Frozen Rejuvenated which were collected and stored in CPD or CPDA-1 may be stored frozen up to 10 years. 10 When RBC are rejuvenated after maximum liquid storage, i.e., CPD RBC at 24 days or CPDA-1 RBC at 38 days, the concentrations of 2,3-DPG and ATP increase typically to above normal. 1,3-5,6 CAUTION: RBC collected in CPD or CPDA-1 cannot be leukocyte reduced prior to rejuvenation. Rejuvenation of CPD/AS-1 RBC or CP2D/AS-3. Rejuvesol (R) Solution has not been approved for the rejuvenation of RBC stored in any additive systems other than AS-1 or AS-3. RBC stored in CPD/AS-1 or CP2D/AS-3 at 1-6 may be rejuvenated up to, but not exceeding, 42 days of storage as long as storage at 1-6 is not interrupted. Rejuvenated CPD/AS-1 RBC must be either washed and stored at 1-6 for up to 24 hours prior to transfusion or glycerolized and frozen at -80 (below -65 C). Red Blood Cells Frozen Rejuvenated which were collected and stored in CPD/AS-1 may be stored for up to years. Rejuvenated CP2D/AS-3 RBC must be washed and stored at 1-6 for up to 24 hours prior to transfusion. Unlike rejuvenated CPD, CPDA-1, CPD/AS-1 RBC, and CP2D/AS-3, rejuvenated RBC collected and stored in any other anticoagulant/additive solution combination have not been approved to be immediately washed and transfused or for cryopreservation. Rejuvenation of CPD/AS-1 RBC for Cryopreservation. When CPD/AS-1 RBC are rejuvenated at 42 days of liquid storage, frozen, deglycerolized, and stored for 24 hours, the concentration of 2,3-DPG and ATP increases to above normal. In limited study, the average 24 hour post-transfusion survival value of these cells was statistically higher than the reported 12 survival value of CPD/AS-1 red blood cell concentrates which are stored for 42 days prior to transfusion. The dose may be equivalent for CPD/AS-1 RBC whether the unit is stored for 42 days prior to transfusion or stored for 42 days, rejuvenated, frozen, deglycerolized, and stored for 24 hours prior to transfusion. Unlike rejuvenated CPD/AS-1 RBC, rejuvenated RBC (CP2D/AS-3) has not been approved for cryopreservation. Rejuvenation of CPD/AS-1 RBC or CP2D/AS-3 for Immediate Use. When CPD/AS-1 RBC are rejuvenated at 42 days of liquid storage, washed, and stored for 24 hours, the concentration of ATP increases to day values. For 2,3-DPG rejuvenation of RBCs stored in CPD/AS-1 for 42 days, the range of 2,3 DPG relative to day value was 46%-172% with mean of 98% +- 29%. For 66% of the RBC units (44/67, 33/33 in Site and 11/34 in Site B) the concentration of 2,3-DPG reached at least 80% of the day value.When CP2D/AS-3 RBC are rejuvenated at 42 days of liquid storage, washed, and stored for 24 hours, the concentration of ATP increases to day values. For 2,3-DPG rejuvenation of RBCs stored in CPD/AS-1 for 42 days, the range of 2,3 DPG relative to day value was 48%-150% with mean of 96% +- 23%. For 76% of the RBC units (52/68, 30/35 in Site and 22/33 in Site B) the concentration of 2,3-DPG reached at least 80% of the day value.

INSTRUCTIONS FOR USE SECTION.


DIRECTIONS FOR REJUVENULLTION OF CPD, CPDA-1, CPD/AS-1, OR CP2D/AS-3 RBC PRIOR TO IMMEDIATE USE 3,11,25 NOTE: REJUVENULLTED RBC STORED IN ANY OTHER ANTICOAGULANT/ADDITIVE SOLUTION COMBINULLTION HAVE NOT BEEN APPROVED TO BE IMMEDIATELY WASHED AND TRANSFUSED. MATERIALS AND EQUIPMENT. (As Suggested or Equivalent)An FDA cleared cell washer/washing system.Temperature-controlled (circulating) water bath (Blue-M MW-1140A, Helmer DH-4).Integral tubing sealer (Sebra 1100).Alcohol swabs (70%) (B-D 6894).One vial (50 mL) of rejuvesol (R) Red Blood Cell Processing Solution, rejuvesol (R) Solution (Citra PN 7012) Y-type Rejuvenation Set for the addition of rejuvesol (R) Solution (Citra PN 7212) or equivalent. Two watertight plastic overwrap bags (Kapak, Scotchpack, 404).Waterproof tape (3M R202).Overwrap bag impulse sealer (Stericon 210X).. An FDA cleared cell washer/washing system.. Temperature-controlled (circulating) water bath (Blue-M MW-1140A, Helmer DH-4).. Integral tubing sealer (Sebra 1100).. Alcohol swabs (70%) (B-D 6894).. One vial (50 mL) of rejuvesol (R) Red Blood Cell Processing Solution, rejuvesol (R) Solution (Citra PN 7012) Y-type Rejuvenation Set for the addition of rejuvesol (R) Solution (Citra PN 7212) or equivalent. Two watertight plastic overwrap bags (Kapak, Scotchpack, 404).. Waterproof tape (3M R202).. Overwrap bag impulse sealer (Stericon 210X).. PROCEDURE. I. TO COMBINE rejuvesol (R) Solution WITH THE RBC Remove the flip-off protective cap from the rejuvesol (R) Solution vial and swab the exposed rubber stopper surface with an alcohol swab. Close all slide clamps of the Y-type Rejuvenation Set (Citra PN 7212). Heat seal the integral tubing between the 300 mL transfer bag and the connector, detach and discard the empty transfer bag.Aseptically, insert the vented spike of the Y-type Rejuvenation Set into the stopper of the vial of rejuvesol (R) Solution. Join the tubing of the Y-type Rejuvenation Set to the integral tubing of the primary collection bag using sterile docking device. Alternately, aseptically insert the bag spike of the Y-type Rejuvenation Set into one of the administration ports of the primary collection bag.Elevate the rejuvesol (R) Solution vial approximately 28 inches above the primary collection bag. Squeeze the drip chamber to prime the system and open the slide clamp of the Y-type Rejuvenation Set.Allow the entire contents of the rejuvesol (R) Solution vial to flow into the primary collection bag while gently agitating the mixture. This typically takes between 15 and 30 seconds. After all the rejuvesol (R) Solution has been transferred, close the slide clamp and heat seal the tubing three times between the portion of the Y-type Rejuvenation Set that connects the rejuvesol (R) Solution vial to the primary collection bag. Cut the middle heat seal and discard the used tubing and empty rejuvesol (R) Solution vial. Proceed immediately to Section II.. Remove the flip-off protective cap from the rejuvesol (R) Solution vial and swab the exposed rubber stopper surface with an alcohol swab. Close all slide clamps of the Y-type Rejuvenation Set (Citra PN 7212). Heat seal the integral tubing between the 300 mL transfer bag and the connector, detach and discard the empty transfer bag.. Aseptically, insert the vented spike of the Y-type Rejuvenation Set into the stopper of the vial of rejuvesol (R) Solution. Join the tubing of the Y-type Rejuvenation Set to the integral tubing of the primary collection bag using sterile docking device. Alternately, aseptically insert the bag spike of the Y-type Rejuvenation Set into one of the administration ports of the primary collection bag.. Elevate the rejuvesol (R) Solution vial approximately 28 inches above the primary collection bag. Squeeze the drip chamber to prime the system and open the slide clamp of the Y-type Rejuvenation Set.. Allow the entire contents of the rejuvesol (R) Solution vial to flow into the primary collection bag while gently agitating the mixture. This typically takes between 15 and 30 seconds. After all the rejuvesol (R) Solution has been transferred, close the slide clamp and heat seal the tubing three times between the portion of the Y-type Rejuvenation Set that connects the rejuvesol (R) Solution vial to the primary collection bag. Cut the middle heat seal and discard the used tubing and empty rejuvesol (R) Solution vial. Proceed immediately to Section II.. II. TO INCUBATE THE RED BLOOD CELL/ rejuvesol (R) Solution MIXTURE FOR 60 MINUTES AT 37 3,11,25 NOTE: The timing of incubation is measured from the time the red blood cell/ rejuvesol (R) Solution mixture is introduced into the water bath. The actual temperature of the red blood cell/ rejuvesol (R) Solution mixture does not reach 37 (the final temperature is usually 29-31 C). Place the primary collection bag containing the red blood cell/ rejuvesol (R) Solution mixture into plastic overwrap bag and flatten the overwrap bag to remove all air prior to sealing Seal the plastic overwrap bag with tape or heat seal.Place the sealed overwrapped unit inside second overwrap bag containing lead weights (to keep the unit submerged during incubation); flatten and seal.Place the overwrapped unit in the water bath and secure the overwrapped unit to the inside wall of the water bath with waterproof tape.Incubate the overwrapped unit in 37 water bath for 60 minutes with agitation.Remove the overwrapped bag from the water bath, dry the outer overwrap bag with clean, disposable toweling and carefully remove the plastic overwraps from the red blood cell/ rejuvesol (R) Solution mixture assuring that the primary collection bag and mixture are not contaminated with any water from the water bath. Place the primary collection bag containing the red blood cell/ rejuvesol (R) Solution mixture into plastic overwrap bag and flatten the overwrap bag to remove all air prior to sealing Seal the plastic overwrap bag with tape or heat seal.. Place the sealed overwrapped unit inside second overwrap bag containing lead weights (to keep the unit submerged during incubation); flatten and seal.. Place the overwrapped unit in the water bath and secure the overwrapped unit to the inside wall of the water bath with waterproof tape.. Incubate the overwrapped unit in 37 water bath for 60 minutes with agitation.. Remove the overwrapped bag from the water bath, dry the outer overwrap bag with clean, disposable toweling and carefully remove the plastic overwraps from the red blood cell/ rejuvesol (R) Solution mixture assuring that the primary collection bag and mixture are not contaminated with any water from the water bath. III. TO PROCESS THE RED BLOOD CELL/rejuvesol (R) Solution MIXTURE AFTER INCUBATION 3,11 Remove the excess rejuvesol (R) Solution after rejuvenation by use of an approved cell washing system and standard operating procedures for that system. The rejuvenated, washed RBC may be stored at 1-6 for up to 24 hours prior to transfusion. 3,10,11 NOTES:No more than four (4) hours should elapse between the time the unit is removed from the refrigerator and the time the cells are placed in the refrigerator. 11 Rejuvenated-washed RBC not intended for immediate use should be resuspended in 0.9% Sodium Chloride, 0.2% Dextrose for storage at 1-6 C. Then, just prior to use, to ensure <1% hemolysis in the final product, concentrate the RBC according to local SOP proven to achieve hematocrit of approximately 80%. 9,24 No more than four (4) hours should elapse between the time the unit is removed from the refrigerator and the time the cells are placed in the refrigerator. 11 Rejuvenated-washed RBC not intended for immediate use should be resuspended in 0.9% Sodium Chloride, 0.2% Dextrose for storage at 1-6 C. Then, just prior to use, to ensure <1% hemolysis in the final product, concentrate the RBC according to local SOP proven to achieve hematocrit of approximately 80%. 9,24.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PRINCIPAL DISPLAY PANEL 50 mL Vial Label. rejuvesolred blood cell processing solution STERILE 15C 25C Not for direct administration to patients. To be used only for extracorporeal processing of red blood cells. PN 7012 50 mLCitraLabs LA7012 02/15 Manufactured for: Citra Labs, LLC. 55 Messina Drive Braintree, MA 02184 USA 1-800-299-3411 Fax 781-848-6781 Manufactured by: Grand River Aseptic Manufacturing, Inc. 140 Front Ave. SW, Suite o Grand Rapids, MI 49504 USA PRINCIPAL DISPLAY PANEL 50 mL Vial Label.

PRECAUTIONS SECTION.


PRECAUTIONS. Aseptic technique must be maintained at all times. Do not use unless solution is clear/colorless and seal is intact. Product that exhibits slight yellow color should not be used. Product instability has been observed after continuous exposure at high temperature (after months at 40 and after months at >30 C). This product contains no bacteriostatic or antimicrobial agents and is intended for single use only. Rx Only Federal (USA) law prohibits dispensing without prescription. Aseptic technique must be maintained at all times. Do not use unless solution is clear/colorless and seal is intact. Product that exhibits slight yellow color should not be used. Product instability has been observed after continuous exposure at high temperature (after months at 40 and after months at >30 C). This product contains no bacteriostatic or antimicrobial agents and is intended for single use only. Rx Only Federal (USA) law prohibits dispensing without prescription.

REFERENCES SECTION.


REFERENCES. Valeri CR, CG Zaroulis, Rejuvenation and Freezing of Outdated Stored Human Red Blood Cells; NEJMED 1972;287:1307-1313. Valeri CR. Unpublished Data.Valeri CR, AD Gray, GP Cassidy, et al.; The 24-hour posttransfusion survival, oxygen transport function, and residual hemolysis of human outdated-rejuvenated red cell concentrates after washing and storage at C for 24 to 72 hours. Transfusion 1984; 24:323-6. Valeri CR, CG Zaroulis, JJ Vecchione, et al.; Therapeutic effectiveness and safety of outdated human red blood cells rejuvenated to restore oxygen transport function to normal, frozen for to years at -80 C, washed, and stored at C for 24 hours prior to rapid infusion. Transfusion 1980; 20:159-70. Valeri, CR, DA Valeri, JJ Vecchione, and CP Emerson; Biochemical modification and freeze preservation of red blood cells, Critical Care Med. (9):439-477, 1979. Valeri CR; Status report on rejuvenation and freezing of red blood cells. Plasma Therapy (3): 155-170, 1981. Boston University School of Medicine/Naval Blood Research Laboratory, Boston, MA Standard Operating Procedure--Red Blood Cells Collected in the CPDA-1 800 mL Primary PVC Plastic Collection Bag System and Stored for to 35 Days (Indated-Rejuvenated) or for 36 to 38 Days (Outdated-Rejuvenated), Biochemically Modified with PIPA Solution Prior to Glycerolization in the Primary 800 mL Bag with the Special Adaptor Port Using 40% W/V Glycerol and Storage at -80 C, Washed in the Haemonetics Blood Processor 115, and Stored at C for 24 Hours Prior to Transfusion (Revised 5/91).Whitely, PH, et al; Improved recovery of ATP and 2,3-DPG with agitation during incubation at 37 in rejuvesol (R) Solution treated CPD/AS-1 RBC. Transfusion 53 (supp), SP81, 2013. Valeri CR; Simplification of the Methods for Adding and Removing Glycerol During Freeze-Preservation of Human Red Blood Cells with the High or Low Glycerol Methods: Biochemical Modification Prior to Freezing Transfusion 15(3): 195-218, 1975. AABB Standards for Blood Banks and Transfusion Services, 27th Edition.American Association of Blood Banks Technical Manual, pages 946-953, 17th Edition, 2011.Valeri CR, LE Pivacek, Palter, RC Dennis, Yeston, CP Emerson, and MD Altschule; clinical experience with ADSOL (R) preserved erythrocytes. Surgery, Gynecology, and Obstetrics 166:33-46, 1988. Szymanski IO, Teno RA, Lockwood WB, Hudgens, R, and Johnson, GS; Effect of rejuvenation and frozen storage on 42-day-old AS-1 RBCs. Transfusion 41: 550-555, 2001. Gelderman MP and Vostal JG; Rejuvenation Improves Roller Pump-Induces Stress resistance of Fresh and Stored Red Blood Cells. Transfusion 51:1096-1104, 2011. Meyer EK, et al; Rejuvenation Capacity of Red Blood Cells in Additive Solutions Over Long-Term Storage. Transfusion, 51(7):1574-1579, 2011.Koshkaryev A, et al; Rejuvenation Treatment of Stored Red Blood Cells Reverses Storage-Induced Adhesion to Vascular Endothelial Cells. Transfusion, 49:2136-2143, 2009. Dennis RC, et al; Transfusion of 2,3-DPG-Enriched Red Blood Cells to Improve Cardiac Function. Ann. Thor. Surg., 26:16-17, 1978. Valeri CR, et al; Improved Oxygen Delivery to the Myocardium During Hypothermia by Perfusion with 2,3-DPG Enriched Red Blood Cells. Ann. Thorac. Surg., 30(6): 527-535, 1980. Valeri CR, et al; Human Red Blood Cells with Normal or Improved Oxygen Transport Function Prepared and Frozen in the Primary Polyvinyl Chloride Plastic Blood Collection Container. Transfusion and Immunohaematology, 22:467-486, 1979. Ragno and Valeri, CR, Salvaging of Liquid-Preserved O-Positive and O-Negative Red Blood Cells by Rejuvenation and Freezing. Transfus. Apher. Sci., 35(2): 137-143, 2006. Valeri CR, et al; Automation of the Glycerolization of Red Blood Cells with the High-Separation Bowl in the Haemonetics ACP 215 Instrument. Transfusion 45: 1621-1627, 2005 Lockwood WB, et al; Effects of Rejuvenation and Frozen Storage on 42-Day-Old AS-3 RBCs. Transfusion 43(11): 1527-153, 2003. Loeb, WF, V.M.D, Ph.D; Literature Review to Investigate the Feasibility of Modifying the Current Protocol for Use and Developing New Applications. unpublished communication, 19 Oct 2000.Valeri CR, et al; The Survival, Function, and Hemolysis of Human RBCs Stored at C in Additive Solution (AS-1, AS-3, and AS-5) for 42 Days and then Biochemically Modified, Frozen, Thawed, Washed, and Stored at C in Sodium Chloride and Glucose for 24 Hours. Transfusion 40: 1341-1345, 2000. Whitely, PH, et al; Improved ATP and 2,3-DPG recovery using the Sahara III dry-air blood warmer in CPD/AS-1 RBC treated with rejuvesol (R) Solution. Transfusion 54 (supp), SP69, 2014. Whitely PH, et al; Restoration of morphology following rejuvenation of stored red blood cells (RBC), Transfusion 55 (supp 3), 74A-75A, 2015.Gray AD, et al; Extended Storage (>24 Hours) of Rejuvenated and Washed RBC, Transfusion 55 (supp 3), 68A-69A, 2015.. Valeri CR, CG Zaroulis, Rejuvenation and Freezing of Outdated Stored Human Red Blood Cells; NEJMED 1972;287:1307-1313. Valeri CR. Unpublished Data.. Valeri CR, AD Gray, GP Cassidy, et al.; The 24-hour posttransfusion survival, oxygen transport function, and residual hemolysis of human outdated-rejuvenated red cell concentrates after washing and storage at C for 24 to 72 hours. Transfusion 1984; 24:323-6. Valeri CR, CG Zaroulis, JJ Vecchione, et al.; Therapeutic effectiveness and safety of outdated human red blood cells rejuvenated to restore oxygen transport function to normal, frozen for to years at -80 C, washed, and stored at C for 24 hours prior to rapid infusion. Transfusion 1980; 20:159-70. Valeri, CR, DA Valeri, JJ Vecchione, and CP Emerson; Biochemical modification and freeze preservation of red blood cells, Critical Care Med. (9):439-477, 1979. Valeri CR; Status report on rejuvenation and freezing of red blood cells. Plasma Therapy (3): 155-170, 1981. Boston University School of Medicine/Naval Blood Research Laboratory, Boston, MA Standard Operating Procedure--Red Blood Cells Collected in the CPDA-1 800 mL Primary PVC Plastic Collection Bag System and Stored for to 35 Days (Indated-Rejuvenated) or for 36 to 38 Days (Outdated-Rejuvenated), Biochemically Modified with PIPA Solution Prior to Glycerolization in the Primary 800 mL Bag with the Special Adaptor Port Using 40% W/V Glycerol and Storage at -80 C, Washed in the Haemonetics Blood Processor 115, and Stored at C for 24 Hours Prior to Transfusion (Revised 5/91).. Whitely, PH, et al; Improved recovery of ATP and 2,3-DPG with agitation during incubation at 37 in rejuvesol (R) Solution treated CPD/AS-1 RBC. Transfusion 53 (supp), SP81, 2013. Valeri CR; Simplification of the Methods for Adding and Removing Glycerol During Freeze-Preservation of Human Red Blood Cells with the High or Low Glycerol Methods: Biochemical Modification Prior to Freezing Transfusion 15(3): 195-218, 1975. AABB Standards for Blood Banks and Transfusion Services, 27th Edition.. American Association of Blood Banks Technical Manual, pages 946-953, 17th Edition, 2011.. Valeri CR, LE Pivacek, Palter, RC Dennis, Yeston, CP Emerson, and MD Altschule; clinical experience with ADSOL (R) preserved erythrocytes. Surgery, Gynecology, and Obstetrics 166:33-46, 1988. Szymanski IO, Teno RA, Lockwood WB, Hudgens, R, and Johnson, GS; Effect of rejuvenation and frozen storage on 42-day-old AS-1 RBCs. Transfusion 41: 550-555, 2001. Gelderman MP and Vostal JG; Rejuvenation Improves Roller Pump-Induces Stress resistance of Fresh and Stored Red Blood Cells. Transfusion 51:1096-1104, 2011. Meyer EK, et al; Rejuvenation Capacity of Red Blood Cells in Additive Solutions Over Long-Term Storage. Transfusion, 51(7):1574-1579, 2011.. Koshkaryev A, et al; Rejuvenation Treatment of Stored Red Blood Cells Reverses Storage-Induced Adhesion to Vascular Endothelial Cells. Transfusion, 49:2136-2143, 2009. Dennis RC, et al; Transfusion of 2,3-DPG-Enriched Red Blood Cells to Improve Cardiac Function. Ann. Thor. Surg., 26:16-17, 1978. Valeri CR, et al; Improved Oxygen Delivery to the Myocardium During Hypothermia by Perfusion with 2,3-DPG Enriched Red Blood Cells. Ann. Thorac. Surg., 30(6): 527-535, 1980. Valeri CR, et al; Human Red Blood Cells with Normal or Improved Oxygen Transport Function Prepared and Frozen in the Primary Polyvinyl Chloride Plastic Blood Collection Container. Transfusion and Immunohaematology, 22:467-486, 1979. Ragno and Valeri, CR, Salvaging of Liquid-Preserved O-Positive and O-Negative Red Blood Cells by Rejuvenation and Freezing. Transfus. Apher. Sci., 35(2): 137-143, 2006. Valeri CR, et al; Automation of the Glycerolization of Red Blood Cells with the High-Separation Bowl in the Haemonetics ACP 215 Instrument. Transfusion 45: 1621-1627, 2005 Lockwood WB, et al; Effects of Rejuvenation and Frozen Storage on 42-Day-Old AS-3 RBCs. Transfusion 43(11): 1527-153, 2003. Loeb, WF, V.M.D, Ph.D; Literature Review to Investigate the Feasibility of Modifying the Current Protocol for Use and Developing New Applications. unpublished communication, 19 Oct 2000.. Valeri CR, et al; The Survival, Function, and Hemolysis of Human RBCs Stored at C in Additive Solution (AS-1, AS-3, and AS-5) for 42 Days and then Biochemically Modified, Frozen, Thawed, Washed, and Stored at C in Sodium Chloride and Glucose for 24 Hours. Transfusion 40: 1341-1345, 2000. Whitely, PH, et al; Improved ATP and 2,3-DPG recovery using the Sahara III dry-air blood warmer in CPD/AS-1 RBC treated with rejuvesol (R) Solution. Transfusion 54 (supp), SP69, 2014. Whitely PH, et al; Restoration of morphology following rejuvenation of stored red blood cells (RBC), Transfusion 55 (supp 3), 74A-75A, 2015.. Gray AD, et al; Extended Storage (>24 Hours) of Rejuvenated and Washed RBC, Transfusion 55 (supp 3), 68A-69A, 2015.

SPL UNCLASSIFIED SECTION.


For Use in the Extracorporeal Rejuvenation of Red Blood Cells50 mL Glass Vial NDC 23731-7000-5 PN 7012 12 Vials/Case.

WARNINGS SECTION.


WARNING AND CONTRAINDICATIONS. Rejuvesol (R) Solution is intended only for the extracorporeal rejuvenation of RBC. It should never be directly administered to Humans. Rejuvesol (R) Solution must not be added to whole blood because the additional plasma may reduce the effectiveness of the rejuvenation process. Immediately after rejuvenation, RBC must either be washed via an approved protocol prior to transfusion or glycerolized and frozen. RBC which have been rejuvenated, glycerolized, and frozen must be deglycerolized via an approved protocol prior to transfusion. RBC rejuvenated before days of storage may achieve 2,3-DPG levels in excess of times normal and ATP levels in excess of 1.5 times normal. 5,6 In patients with reduced arterial blood p0 of less than 40 torr, the use of RBC rejuvenated before days of storage are contraindicated because their high 2,3-DPG levels and low oxygen affinity may impair proper oxygenation of the red blood cells in the lung. Rejuvenated RBC are further processed prior to transfusion to remove the un-used portion of rejuvesol (R) Solution, by-products of the rejuvenation process, and any other potential storage-related impurities in rejuvesol (R) Solution. Based on the concentration of the residual inosine in rejuvenated RBC that are either washed or deglycerolized, the average washout of inosine was calculated to be 97.4%. literature search for potential toxicity associated with the ingredients that comprise rejuvesol (R) Solution, including potential metabolites, was conducted. 23 This report concludes that no theoretical contraindications would be associated with the transfusion of single unit of unwashed, rejuvenated RBC that would contain amounts of pyruvate, inosine, adenine, phosphate, hypoxanthine, uric acid, and lactate that exceed reference values (excluding lactate) as these substances are naturally metabolized and/or are excreted. 23 The maximum number of properly processed rejuvenated RBC that can be transfused to single recipient over their entire lifetime has not been determined.