WO2022159132A1 - Systèmes et procédés de collecte de plasma - Google Patents

Systèmes et procédés de collecte de plasma Download PDF

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Publication number
WO2022159132A1
WO2022159132A1 PCT/US2021/033835 US2021033835W WO2022159132A1 WO 2022159132 A1 WO2022159132 A1 WO 2022159132A1 US 2021033835 W US2021033835 W US 2021033835W WO 2022159132 A1 WO2022159132 A1 WO 2022159132A1
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WIPO (PCT)
Prior art keywords
donor
plasma
anticoagulant
volume
whole blood
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PCT/US2021/033835
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English (en)
Inventor
Amit J. PATEL
Samantha M. PLANAS
Walter T. WATTS
Kyungyoon Min
Daniel R. Boggs
Katherine N. RADWANSKI
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Fenwal, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Priority claimed from US17/306,099 external-priority patent/US11412967B2/en
Application filed by Fenwal, Inc. filed Critical Fenwal, Inc.
Priority to CN202180091469.9A priority Critical patent/CN116801926A/zh
Priority to EP21921581.1A priority patent/EP4281137A4/fr
Priority to KR1020237028390A priority patent/KR20230133893A/ko
Priority to CA3206090A priority patent/CA3206090A1/fr
Priority to JP2023544359A priority patent/JP2023554695A/ja
Publication of WO2022159132A1 publication Critical patent/WO2022159132A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/3496—Plasmapheresis; Leucopheresis; Lymphopheresis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/26—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes and internal elements which are moving
    • A61M1/262—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes and internal elements which are moving rotating
    • A61M1/265—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes and internal elements which are moving rotating inducing Taylor vortices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3672—Means preventing coagulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/38—Removing constituents from donor blood and storing or returning remainder to body, e.g. for transfusion
    • A61M1/382—Optimisation of blood component yield
    • A61M1/385—Optimisation of blood component yield taking into account of the patient characteristics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2202/00—Special media to be introduced, removed or treated
    • A61M2202/04—Liquids
    • A61M2202/0413—Blood
    • A61M2202/0415—Plasma

Definitions

  • the present application relates to systems and methods for performing plasmapheresis and, more particularly, to plasmapheresis systems and methods in which the volume of pure plasma that may be collected from a particular donor is optimized.
  • Plasmapheresis is an apheresis procedure in which whole blood is withdrawn from a donor, plasma is separated from other cellular blood components (red blood cells, platelets, and leukocytes) and retained, and the cellular blood components are returned to the donor.
  • the separation of the plasma from the cellular components is typically accomplished in an automated procedure by centrifugation or membrane filtration.
  • plasma product In automated plasmapheresis, whole blood is drawn from the donor, mixed at a specified ratio with anticoagulant, and then separated into plasma, red blood cells, and other cellular components. Once a target volume of anticoagulated plasma (or “plasma product”) has been collected, as determined by a weigh scale associated with a plasma collection container, the withdrawal of whole blood from the donor ceases, and the red blood cells and other cellular components are returned to the donor. Often, the plasma product is collected in multiple collection and reinfusion cycles, until the total target volume of anticoagulated plasma has been collected. The anticoagulated plasma may be used for later transfusion or further manufacturing.
  • Plasma that is collected to serve as a source material (“source plasma”) for further manufacturing is collected from multiple donors and combined or pooled together for this purpose.
  • source plasma a source material
  • the FDA issued guidelines for registered blood collection centers as to the volume of plasma that may be collected as source plasma during plasmapheresis in order to improve the consistency of procedures for manufacturing source plasma, and to minimize the opportunity for staff error.
  • FDA Memo “Volume Li mits-Auto mated Collection of Source Plasma (11/4/92)”).
  • the FDA Memo set forth a simplified plasma volume nomogram, in which the volume (or weight) of pure (or raw) plasma that may be collected from a particular donor is limited to ensure donor safety and comfort. More specifically, the FDA nomogram limits the volume (or weight) of plasma based on the weight of the donor, and establishes the volume of anticoagulant that may be added to a 1 :16 ratio of anticoagulant to anticoagulated blood, or 0.06 parts anticoagulant to 1 part anticoagulated blood, to arrive at a maximum collection volume for the total of the plasma plus the anticoagulant for a particular donor.
  • the simplified nomogram set forth in the FDA Memo has been the predominant method for determining plasma product collection volumes used by blood collection centers. Therefore, the plasmapheresis devices used at such centers are commonly programmed to collect a specified volume /weight of anticoagulated plasma (assuming a known density) in accordance with the maximum collection volume permitted by the FDA nomogram, with the anticoagulant being added to the whole blood at a 1 : 16 or 0.06 ratio.
  • the amount of pure plasma that may be safely collected from a donor can depend on factors in addition to the donor’s weight and hematocrit that affect the donor’s total blood volume, such as the donor’s height.
  • the source plasma from multiple donors is combined, it is important to maximize the pure plasma volume that may be collected from each individual donor, as even small gains in volume collected from each individual donor, when added together, result in a meaningful increase in the total volume of the pooled plasma. If a plasmapheresis device were to be able to better target the pure plasma volume, more plasma proteins could be collected from each donor, improving the overall efficiency of the plasma collection center.
  • systems and methods for optimizing the volume of plasma collected are provided which are consistent with donor safety and comfort.
  • a touchscreen is provided for receiving input from an operator to a controller programmed to control operation of the system.
  • the controller is configured to determine a target volume of plasma product to be collected (TVPP), either based on the weight of the donor and the donor hematocrit, or based on the weight and height of the donor and the donor hematocrit, to control the system to operate a draw and return cycle to withdraw whole blood from the donor, to add anticoagulant to the whole blood at a pre-determined ratio (ACR), to separate the anticoagulated whole blood into the plasma product and the second component and to return the second component to the donor, and to stop withdrawing whole blood from the donor and initiate a final return of the second blood component when a measured volume of plasma product in a plasma collection container reaches the target volume for plasma product.
  • TVPP target volume of plasma product to be collected
  • methods are provided for performing plasmapheresis to collect a volume of plasma product (i.e. , anticoagulated plasma, VPP) so that that the targeted volume of pure plasma (TVP) in the plasma product is determined based on donor-specific characteristics, consistent with the donor’s safety and comfort.
  • VPP anticoagulated plasma
  • the targeted volume of pure plasma to be collected, TVP is based on the weight, or the weight and the height, of the donor.
  • the targeted volume of pure plasma to be collected may be a multiple of the donor’s weight.
  • TVP may be a multiple of the donor’s total blood volume, TBV, with the TBV of the donor being determined based on the donor’s weight and height, using well established methodology, such as the Lemmens equation or Nadler’s formula.
  • the plasmapheresis procedure is commenced, with whole blood being drawn from the donor, mixed at a specified ratio with anticoagulant, and then separated into plasma, red blood cells, and other cellular components.
  • the TVPP has been collected, as determined by, e.g., a weigh scale associated with a plasma collection container, the withdrawal of whole blood from the donor ceases, and the red blood cells and other cellular components are returned to the donor.
  • the hematocrit of the donor in determining the target amount for the plasma product to be collected, may be determined prior to the collection phase of each cycle, either by calculation or on the basis of a signal from a sensor or the like that is indicative of the donor’s hematocrit.
  • the amount of plasma product in the plasma collection container may be determined by, e.g., a weigh scale associated with the plasma collection container or an optical sensor that directly measures the volume.
  • a method for operating a plasmapheresis system to collect a plasma product volume that comprises the maximum allowable volume/weight of raw plasma in accordance with the limits set forth in the FDA nomogram based on the weight of the donor.
  • a modified nomogram that utilizes the donor’s hematocrit to calculate a target volume/weight for a plasma product having the maximum volume of raw plasma permitted by the FDA nomogram.
  • a calculated volume/weight of raw plasma is compared to the maximum volume/weight for the raw plasma permitted by the FDA nomogram. If the calculated volume/weight of raw plasma is less than the maximum permitted volume/weight, the volume/weight of the plasma product to be collected is adjusted upward from the maximum volume /weight permitted by the FDA nomogram for the plasma product by an amount equal to the difference plus the additional amount of anticoagulant that is added to process the additional volume/weight of plasma.
  • the volume of additional raw plasma that may be safely collected from the donor consistent with the limits set forth in the FDA nomogram is determined, and then the total volume/weight of plasma product to be collected based on the weight of the donor set forth in the FDA nomogram is adjusted accordingly.
  • plasmapheresis procedures involve sequential cycles of alternating phases, one in which whole blood is withdrawn from the donor and the plasma separated and collected, and the other in which the separated red blood cells and any other non-RBC cellular components are returned to the donor.
  • the donor’s hematocrit will change during the course of the plasmapheresis procedure, thus affecting the amount of anticoagulant in the plasma product collected from one cycle to the next.
  • the Vpp for the procedure is recalculated before each extraction/separation phase is commenced, based on a value for the hematocrit of the donor determined prior to the start of each draw phase, and the target volume for the plasma product adjusted accordingly.
  • VRP may be determined based on a calculated value for the donor’s total plasma volume, based on Vb and the donor’s hematocrit.
  • Vpp a volume of plasma product
  • VPP is equal to a volume of raw plasma (VRP) that may be collected plus a volume of anticoagulant (VAC) that is added to the VRP during the apheresis procedure.
  • VRP volume of raw plasma
  • VAC volume of anticoagulant
  • K (ACR*(1 -Hct/100) + 1)/(ACR*(1 -Hct/100)).
  • the red blood cells are returned to the donor. Then, the Het of the donor and Vpp are determined prior to each draw phase.
  • the draw and separation steps are repeated until the volume of plasma product in the collection container reaches Vpp.
  • the donor’s hematocrit subsequent to the first collection phase may be calculated by a volume balance, assuming that the donor’s quantity of red blood cells is the same at the start of each draw cycle, while the total volume of blood decreases from one cycle to the next in an amount equal to the amount of raw plasma collected.
  • the donor’s hematocrit at the start of each draw cycle can be measured by an optical or other sensor.
  • the volume of raw plasma that may be collected from a particular donor may be determined by any one of several different means.
  • Such means include, e.g., the FDA nomogram, taking into account only the donor’s weight; a modified FDA nomogram, further taking into account the donor’s hematocrit, and taking a fraction of a total blood volume or total plasma volume calculated for a particular donor.
  • the total blood volume or total plasma volume may be determined using, for example, Nadler’s equations, Gilcher’s Rule of Five, tables provided by the International Council for Standardization in Haematology (ICSH), or any other generally accepted method using the donor’s height, weight, sex, and age, consistent with the safety and comfort of the donor.
  • ICSH International Council for Standardization in Haematology
  • an automated system for separating plasma from whole blood comprises a reusable hardware component and a disposable kit.
  • the disposable kit further comprises i) a separator for separating whole blood into a plasma fraction and a concentrated cell fraction, the separator having an input having a blood line integrally connected thereto for transporting whole blood from a donor to the separator, a plasma output port integrally connected to a plasma collection container by a plasma line, and a concentrated cell outlet port integrally connected to a reservoir for receipt of concentrated cells prior to reinfusion to the donor; ii) a donor line terminating in a venipuncture needle for transporting whole blood from a donor to the blood line, iii) an anticoagulant line integrally connected to the blood line and configured to be connected to a source of anticoagulant for transporting anticoagulant to the donor line, and iv) a reinfusion line for transporting concentrated cells from the reservoir to the donor line.
  • the reusable hardware component further comprises i) a first peristaltic pump for delivering anticoagulant at a controlled rate into the blood line during a collection phase, ii) a second pump for delivering anticoagulated whole blood to the separator during the collection phase and for returning concentrated cellular components during a reinfusion phase, iii) a third pump for delivering concentrated cellular components from the separator to the reservoir during the collection phase, iv) a clamp associated with each of the blood line, plasma line, and reinfusion line, v) a weigh scale for weighing each of the plasma collection container, the reservoir and the source of anticoagulant, and vi) a programmable controller comprising a touch screen for receiving input from an operator, the programmable controller configured to receive a signal from each of the weigh scales and to automatically operate the first, second and third pumps and the clamps to separate whole blood into a plasma fraction and a concentrated cell fraction during the collection phase and to return concentrated cells to the donor during the reinfusion stage.
  • the programmable controller is further configured to determine a target amount for the plasma product to be collected in the plasma collection container in accordance with any of the methods described herein, and to terminate the collection phase upon receiving a signal that the amount of plasma product in the plasma collection container equal to the target amount of the plasma product determined by the controller.
  • the controller may be configured to calculate the hematocrit of the donor prior to the collection phase of each cycle. Alternatively, or additionally, the controller may receive a signal from a sensor or the like that is indicative of the donor’s hematocrit. Further, the amount of plasma product in the plasma collection container may be determined by, e.g., the weigh scale associated with the plasma collection container or an optical sensor that directly measures the volume.
  • Fig.1 is a perspective view of an exemplary plasmapheresis instrument suitable for use in the system and method of the present application.
  • Fig. 2 is a perspective view of a spinning membrane separator of the type incorporated in a disposable set, with portions broken away to show detail, usable with the plasmapheresis system of Fig. 1 .
  • FIG. 3 is a perspective view of the front panel of the plasmapheresis system of Fig. 1 showing the components of the disposable set that are mounted thereto.
  • Fig. 4 is a schematic view showing operation of the plasmapheresis system in the collection phase.
  • Fig. 5 is a schematic view showing operation of the plasmapheresis system in the reinfusion phase.
  • Figs. 6a and 6b are flow charts showing the steps of methods used in the present application for collecting a target volume of pure plasma.
  • Fig. 7 is a table that shows the volume of pure plasma, based on donor hematocrit, that is contained within a plasma product volume limit set by the FDA nomogram using a 1 :16 ratio of anticoagulant to whole blood.
  • Fig. 8 is a table that shows the volume of “unclaimed” pure plasma in the plasma product based on the difference between the values set forth in Fig. 7 and the maximum volume of pure plasma that may be collected based on the FDA nomogram.
  • Fig. 9 is a table that shows the volume of plasma product that may be collected from a donor, based on the donor’s weight and hematocrit, that results in the maximum permissible volume of pure plasma permitted by the FDA nomogram.
  • Fig. 10 is a table showing the inputs to a programmable controller for performing a hypothetical plasmapheresis procedure in accordance with the method of the present application.
  • Figs. 11 a, 11 b comprise a table, broken into two parts illustrating how the donor’s hematocrit increases over the course of a hypothetical plasmapheresis procedure based on the inputs from the table of Fig. 10, and resulting in an increase in the total collection volume of plasma product necessary to collect the target volume of pure plasma.
  • Fig. 12 is a graph illustrating IgG dilution during plasmapheresis.
  • plasmapheresis is performed on an automated system comprising a hardware component, generally designated 10, and a disposable set, generally designated 12, to collect plasma to be processed as source plasma.
  • a hardware component generally designated 10
  • a disposable set generally designated 12
  • the disposable set 12 consists of an integrally connected separator, containers, and tubing to transport blood and solutions within a sterile fluid pathway.
  • the separator 14 best seen in Fig. 2, has a spinning membrane filter 16 mounted to a rotor 18 for rotation within a case 20 to separate blood into components.
  • a detailed description of a spinning membrane separator may be found in US Pat. No. 5,194,145 to Schoendorfer, which is incorporated herein by reference.
  • separation of the whole blood may be accomplished by centrifugation. See, e.g., US 5,360,542 to Williamson et al.
  • anticoagulated whole blood enters the separator 14 through a whole blood input port 22.
  • the plasma is separated by the spinning membrane filter and then passes out of a plasma output port 24, through a plasma line 26, and into a plasma collection container 28. Concentrated cells are pumped out of a concentrated cell output port 30 into a reservoir 32, where the cells remain until reinfusion to the donor.
  • the disposable set 12 also includes tubing lines for introducing whole blood from the donor into the system during collection and returning concentrated cells to the donor during reinfusion (donor line 34, which terminates in the venipuncture needle 36), and for transporting anticoagulated whole blood to the separator (blood line 38), concentrated cells into the reservoir (cell line 40), concentrated cells from the reservoir to the donor line (reinfusion line 42), plasma into the plasma collection container (plasma line 44), saline (saline line 46), and anticoagulant (AC line 48).
  • donor line 34 which terminates in the venipuncture needle 36
  • Three peristaltic pumps are located on the front panel of the hardware component 10, including an AC pump 54, a blood pump 56, and a cell pump 58.
  • the AC pump 54 delivers anticoagulant solution (AC) at a controlled rate into the blood line 38 as whole blood enters the set from the donor.
  • the blood pump 56 delivers anticoagulated whole blood to the separator during the collection phase of the procedure and returns concentrated cellular components and, if desired, replacement fluid to the donor during the reinfusion phase of the procedure.
  • the cell pump 58 delivers concentrated cellular components from the separator 14 to a reservoir during the collection phase.
  • the front panel also includes four clamps into which tubings from the disposable set 12 are installed, including a reinfusion clamp 60, a blood clamp 62, a saline clamp 64, and a plasma clamp 66.
  • the reinfusion clamp 60 closes to block the reinfusion line (42) during the collection phase (Fig. 5) and is open during the reinfusion phase (Fig. 5) to allow the blood pump to reinfuse the concentrated cellular components from the reservoir 32 to the donor.
  • the blood clamp 62 opens during the collection phase to allow anticoagulated whole blood to be pumped to the separator 14 and closes during the reinfusion phase to block the blood line 38.
  • the saline clamp 64 closes to block the saline line 46 during the collection phase and during reinfusion of the separated cellular components. If saline is to be used as a replacement fluid, the saline clamp 64 opens during the reinfusion phase.
  • the plasma clamp 66 opens during the collection phase to allow plasma to flow into the plasma collection container 28 and closes during the reinfusion phase.
  • the hardware component 10 includes three weigh scales to monitor the current plasma collection volume (scale 68), the AC solution volume (scale 70), and the concentrated cellular content volume (scale 72).
  • the system also includes various sensors and detectors, including a venous pressure sensor 74, a separator pressure sensor 76, optical blood detectors 78, and an air detector
  • the disposable set 12 includes a single venipuncture needle 36, through which whole blood is drawn from the donor in a collection phase (Fig.
  • the plasmapheresis procedure may comprise a plurality of cycles each having a collection/separation phase followed by a return or reinfusion phase.
  • the disposable set includes a plasma collection container 28 for receipt of the separated plasma and a reservoir 32 for receipt of the concentrated cells.
  • the concentrated cells from the reservoir 32 are reinfused to the donor through the venipuncture needle 36.
  • Plasmapheresis performed with a single venipuncture needle 36 may involve multiple cycles of collection and reinfusion.
  • anticoagulant solution AC
  • AC anticoagulant solution
  • the cellular components are pumped from the separator 14 to the reservoir 32.
  • the collection phase stops when the reservoir 32 reaches an expected volume of concentrated cells or if the target plasma collection volume has been achieved.
  • the reinfusion phase begins.
  • the blood pump 56 reverses direction and pumps the concentrated cells from the reservoir 32 back to the donor through the apheresis needle 36. If a saline protocol was selected, by which saline is returned to the donor as a replacement fluid for the collected plasma, the final reinfusion phase is followed by saline infusion.
  • the automated plasma collection device is configured to collect a volume/weight of anticoagulated plasma (i.e. , the plasma product) having the maximum volume/weight of raw plasma permitted for the donor under the limits set forth in the FDA nomogram.
  • the device is programmed with a nomogram that accounts for the donor’s hematocrit.
  • the total volume/weight of plasma product to be collected can be determined such that the plasma product includes the maximum volume/weight of raw plasma fraction that may be collected from a donor, consistent with the limits for total volume/weight of raw plasma set forth in the FDA nomogram.
  • volume of Pure/Raw Plasma Volume of Whole Blood * (1 - Hct/100).
  • ACR AC Ratio
  • volume of Pure/Raw Plasma ACR * Volume of Anticoagulant * (1 - Hct/100).
  • Equations [5] and [6] can be combined to calculate the amount of anticoagulant in a given amount of collected plasma:
  • the volume of pure/raw plasma contained within the volume of plasma product permitted under the FDA nomogram can be determined based upon the hematocrit of the donor.
  • the results of such calculations are set forth in Fig. 7, which shows the volume of pure/raw plasma based on donor hematocrit that is contained within a plasma product volume limit set by the FDA nomogram.
  • the table set forth in Fig. 8 presents the volume of “unclaimed” raw plasma in the plasma product based the difference between the values set forth in Fig. 7 and the maximum volume of pure/raw plasma that may be collected based on the FDA nomogram.
  • the plasma product collected from any particular donor may be adjusted from that set forth in the FDA nomogram by an amount corresponding to the amount of “unclaimed” pure/raw plasma set forth in Fig 8 plus the amount of anticoagulant needed to process the additional volume.
  • the automated plasma collection device is configured to collect a volume/weight of plasma product (pure plasma + anticoagulant) having a volume/weight of pure plasma permitted for the donor as determined by either of the two methods set forth in greater detail below.
  • a first method (70) for collecting a target volume of plasma product, TVPP is illustrated.
  • a target volume of pure plasma may be collected directly from the weight of the donor.
  • the weight of the donor may be multiplied by an established constant “Ki” (such as 10 mL/kg).
  • the weight of the donor may be segregated into weight categories or ranges (e.g., at least three categories, at least six categories, etc.), with a fixed volume established for each category (as in the FDA nomogram discussed above, in which the ranges of donor weight are divided into three categories).
  • %ACTVPP 1/(1 + (ACR-1)(1- Hct)).
  • the ACR may be expressed as either a ratio or a percentage, and may vary from 7:1 to 20:1, or from about 5% to 14%.
  • An exemplary ACR is 16:1 , or 6.25%.
  • a second method (90) for collecting a target volume of plasma product, TVPP is illustrated.
  • the %ACrvpp may be determined as described above in connection with the first method. In this method no calculation of a total plasma volume of the donor is required to determine the target collection volume of plasma for the donor.
  • a donor’s plasma volume may be estimated based on the donor’s total blood volume, and a volume of plasma that may be harvested consistent with donor safety and comfort may be based on this estimation.
  • Methods utilizing donor parameters are commonly used estimate a donor’s total blood volume.
  • the donor’s total blood volume may be determined using one or more of Lemmens equation (that uses the donor’s body mass index to determine a total blood volume), Nadler’s equations (that take into account the height, sex and weight of the donor), Gilcher’s Rule of Five (that takes into account sex, weight and morphology (obese, thin, normal or muscular), or the standards of the International Counsel for Standardization in Haematology (“ICSH) as set forth in Br. J. Haem.
  • Lemmens equation that uses the donor’s body mass index to determine a total blood volume
  • Nadler’s equations that take into account the height, sex and weight of the donor
  • Gilcher’s Rule of Five that takes into account sex
  • any other methodology for determining donor’s total blood volume may also be used.
  • a plurality of such methodologies may be used and the average, mean, or a weighted average of the methodologies may be taken as the donor’s total blood volume.
  • the donor’s plasma volume may be estimated by multiplying the total blood volume by a constant “K2”, where or K2 equals (1 - Het of the donor).
  • the percentage by which TBV is multiplied to obtain TVP (and, ultimately TVPP) is selected to maximize the volume of pure plasma that is collected from the donor consistent with donor comfort and safety.
  • the percentage ranges in various embodiments may be variously between approximately 1 % and 15% of TBV, at least 15%, less than 18%, between about 15% and 17%, about 12%, about 16% or about 18%.
  • the TVPP may also be subject to a maximum volume of, e.g., 1000 mL or 1050 mL to be collected regardless of the donor’s TBV.
  • the collection volume (the volume of plasma product) is determined based on the volume of raw plasma volume that may be collected from a particular donor, the donor’s hematocrit, and the fixed anticoagulant ratio (ACR). Consequently, this methodology allows for more consistent control for the raw plasma volume of the donor, which is the variable most related to donor safety.
  • the operator enters into the system controller the collection volume for the plasma product for the particular donor, based on the target volume of raw plasma that may be harvested.
  • the target plasma collection volume may be as set forth in Fig. 9, based on the donor’s weight and hematocrit for the initial collection phase, or by any of the other methods as set forth above.
  • the controller is configured to calculate the target plasma product collection volume for the initial collection phase in accordance with a methodology such as those described above upon the operator entering, e.g., the donor’s weight and hematocrit, and/or any of the additional donor-specific information (such as the donor’s sex, height and age) required by the methodologies used for determining a donor’s total blood volume, total plasma volume, and the target volume of harvestable plasma that may be collected.
  • a methodology such as those described above upon the operator entering, e.g., the donor’s weight and hematocrit, and/or any of the additional donor-specific information (such as the donor’s sex, height and age) required by the methodologies used for determining a donor’s total blood volume, total plasma volume, and the target volume of harvestable plasma that may be collected.
  • the operator enters into the system controller the collection volume for the plasma product for the particular donor, based on the target volume of raw plasma that may be harvested.
  • the target plasma collection volume may be as set forth in Fig. 9, based on the donor’s weight and hematocrit for the initial collection phase, or by any of the other methods as set forth above.
  • the controller is configured to calculate the target plasma product collection volume for the initial collection phase in accordance with a methodology such as those described above upon the operator entering, e.g., the donor’s weight and hematocrit, and/or any of the additional donorspecific information (such as the donor’s sex, height and age) required by the methodologies used for determining a donor’s total blood volume, total plasma volume, and the target volume of harvestable plasma that may be collected.
  • the system administrator will initially set an indication of whether the targeted collection volume of plasma product, TVPP, will be determined by the system (e.g., in accordance with one of the methods described above) or entered directly by the operator into the system.
  • the system administrator will disable the controller’s capability to calculate a TVPP.
  • the system administrator will also set an AC ratio to be used for all procedures.
  • the controller is to determine the TVPP, the administrator will set the system to allow the appropriate donor specific characteristics for calculating the TVPP in accordance with any of the methods described above to be entered into the controller, either by the operator or a donor management system, by which donor parameters used for qualification screening (such as weight, height, and hematocrit) can be electronically sent to the instrument, avoiding operator error in entering the donor parameters.
  • the donor management system could also utilize the donor screening measurements, along with the relationship between pure plasma volume and collection volume, to automatically calculate a TVPP that it would transmit to the controller of the plasmapheresis device.
  • the controller will calculate the TVPP before collection of whole blood form the donor starts.
  • the administrator will set the system to enable the operator to enter a TVPP other than the calculated volume.
  • the system will permit the operator to change the TVPP from the calculated TVPP, either before or during the procedure, if, for example, the estimated time for running/completing the procedure needs to be shortened for reasons of donor comfort or convenience.
  • the actual volume of plasma product collected, VPP, and the target volume, TVPP will be displayed, as well as the actual volume of pure plasma collected and the target volume of plasma, TPV.
  • plasmapheresis procedures may be performed with multiple cycles of collection/draw phases and return/reinfusion phases. If the return/reinfusion phase does not include reinfusion of a replacement fluid, the donor’s hematocrit will increase from one cycle to the next. Consequently, if the target volume for plasma product is determined based only on the donor’s initial hematocrit, and does not consider the donor’s increasing hematocrit, the percentage of anticoagulant in the plasma product will be greater (and the volume of pure plasma less) than what was predicted by the initial calculation for determining the target volume of plasma product.
  • the target volume for plasma product is recalculated periodically throughout the plasmapheresis procedure, such as before the start of the collection phase of each cycle, to consider the change in the donor’s hematocrit.
  • the plasmapheresis procedure commences with a first draw phase until a specified volume of whole blood (e.g., approximately 500 mL) has been withdrawn from the donor.
  • a specified volume of whole blood e.g., approximately 500 mL
  • Anticoagulant is added to the whole blood and the anticoagulated whole blood is separated into a plasma product, red blood cells, and other non-RBC blood components.
  • the red blood cells and non-RBC blood components are returned to the donor.
  • the current volume of plasma product collected after the first draw phase is determined by, e.g., the weigh scale.
  • a current value for the hematocrit of the donor is established and a new target volume of plasma product to be collected is determined, and the second cycle of draw and return phases is performed.
  • the cycle of draw and return phases is repeated until the target volume of plasma product tor the plasmapheresis procedure is collected, as recalculated prior to the start of each draw phase.
  • the controller initiates the final red blood cell reinfusion stage, after which the donor is disconnected.
  • Fig. 10 displays the input data for a hypothetical plasmapheresis procedure for a donor weighing 190 lbs. (86.4 kg) and having an initial hematocrit of 44.
  • the simplified FDA nomogram would limit the volume of plasma to be collected from such a donor to 800 mL, and the total collection volume for the plasma product to 880 mL.
  • the FDA nomogram limit on the volume of raw plasma that may be collected is for illustrative purposes only.
  • other methodologies may be used to determine the amount of raw plasma that may be safely extracted from a donor that would differ from that indicated by the FDA nomogram.
  • the number of collection and reinfusion cycles in a plasmapheresis procedure may vary from three to twelve. In the hypothetical plasmapheresis procedure, there are five collection and reinfusion cycles, which are chosen for illustrative purposes.
  • the volume of raw plasma to be collected and the total target volume of plasma product to be collected are determined in accordance with the methodologies described above, based on the donor’s initial hematocrit.
  • the initial target volume for the plasma product to be collected is 889 mL, which is the same as indicated by the table of Fig.9 for a donor having a weight of 175 lbs. and up and a hematocrit of 44 in order to harvest the FDA limit of 800 mL of raw plasma from the donor.
  • each collection phase 500 mL of whole blood is drawn from the donor, to which anticoagulant is added at a predetermined ratio (i.e. , 1 :16), such that 31 mL is added for each collection cycle of 500mL.
  • the whole blood plus anticoagulant is separated into a plasma fraction and a red blood cell fraction.
  • the red blood cells and “non-RBC” blood components are returned to the donor, so that at the end of the first return cycle the donor’s hematocrit has increased to 45.6%, as calculated by the controller based on a blood volume being decreased by the amount of raw plasma collected, while the quantity of red blood cells in the total blood volume remains the same as at the start of the procedure.
  • the controller can also account for the volume of anticoagulant that is reinfused in each return phase along with the red blood cells, as well as the residual anticoagulant in the donor’s whole blood being drawn in cycles 2 and following, when determining the new hematocrit value for the next cycle.
  • the volume of raw plasma and the total target volume of plasma product to be collected for the procedure are then recalculated based on the donor’s new, increased hematocrit and raw plasma volume. This provides for a new total target collection volume of 891 mL.
  • the second collection phase is then performed, resulting in a total of 430 mL of plasma product comprising 386 mL of raw plasma being collected over the first two collection phases (Cycle 2 draw end).
  • the red blood cells and “non-RBC” blood components are again returned to the donor, after which the donor’s hematocrit is calculated to be 47.2%.
  • Two more collection phases of 500 mL are performed, each followed by a return phase, in which new values for the volume of raw plasma and total volume of plasma product to be collected are determined before the start of each collection phase.
  • the recalculated target collection volume for procedure increases to 893 mL (for the third collection phase) and then to 894 mL (for the fourth collection phase).
  • a fifth “mini” collection cycle is performed to bring the volume of raw plasma collected up to the 800 mL permitted by the FDA nomogram for the hypothetical donor.
  • the recalculated target collection volume of plasma product for the fifth collection phase remains at 894 mL.
  • a target collection volume for the plasma product is obtained, which is required in order to collect the target volume of raw plasma of 800 mL.
  • 889 mL of plasma product would have been collected if the target collection volume is determined based only on the donor’s initial hematocrit, or 880 mL if the target collection volume is based on the simplified FDA nomogram. In both cases, less than the target volume of 800 mL would have been collected.
  • the hematocrit of the donor during the procedure is based on the assumptions that 100% of the red blood cells that are withdrawn in each draw cycle are reinfused in each return cycle, along with 100% of the non-RBC cellular products and a volume of anticoagulant.
  • interstitial fluid can shift to the intravascular space, resulting in restoring half of the withdrawn volume.
  • the shift of interstitial fluid during plasmapheresis has been substantiated by tracking the level of Immunoglobulin G (IgG) of a donor over the course of a plasmapheresis procedure.
  • IgG Immunoglobulin G
  • Burkhardt et al. Immunoglobulin G levels during collection of large volume plasma for fractionation: Transfusion 2017; 56:417-420. If there were no shifting of interstitial fluid, the IgG level of the donor would be stable over the course of the plasmapheresis procedure. However, the IgG level has been shown to drop, and the amount that the IgG level drops is a function of the volume of interstitial fluid that has shifted to the blood system.
  • FIG. 12 a plot of volume of plasma collected (along the X-axis versus IgG concentration (along the Y-axis) that was developed empirically is shown. A 9% drop of the donor’s IgG is seen from the baseline of zero plasma collected (at the start of the procedure) to 200 mL of plasma collected, and a drop of an additional 4% from 200 mL to 800 mL collected.
  • the controller can be configured to automatically determine the volume of interstitial fluid that has shifted based on the volume of plasma collected, and to include the shifted volume when determining the donor’s hematocrit prior to each draw phase.
  • other methods that directly measure the donor’s hematocrit may be employed, such as an optical sensor or, if a centrifugal separator is being used, measuring the volume of red blood cells in the centrifuge.
  • anticoagulant may be introduced into the disposable kit prior to the commencement of the plasmapheresis procedure in pre-processing steps, such as for priming the disposable kit, performing one or more precycles, or for performing other pre-procedure steps.
  • pre-processing steps such as for priming the disposable kit, performing one or more precycles, or for performing other pre-procedure steps.
  • anticoagulant used for these purposes is ultimately directed to the plasma product collection container, it may be accounted for in determining the volume contained in the plasma collection container that results in the target volume of raw plasma being collected. This may be done, for example, by measuring the weight of the “full” container of anticoagulant and the weight of the container of anticoagulant prior to the commencement of the first draw cycle, and adding that volume of anticoagulant to the target volume of plasma product.
  • the controller can be configured to automatically perform the steps necessary to account for the anticoagulant introduced into the plasma collection container separately from the anticoagulated plasma.
  • a method for collecting plasma in which plasma product is collected in multiple collection phases between which separated red blood cells are reinfused to the donor comprises a) determining a volume of whole blood (Vb) and hematocrit (Het) for a donor; b) determining a volume of raw plasma (VRP) that may be collected from the donor; c) determining a volume of plasma product (Vpp) that may be collected, wherein the plasma product comprises the raw plasma volume plus a volume of anticoagulant; d) withdrawing whole blood from the donor; e) introducing anticoagulant into the withdrawn whole blood at a specified ratio (ACR); f) separating the withdrawn whole blood into a plasma product and a second component comprising red blood cells; g) collecting the plasma product in a plasma collection container; h) after a desired amount of whole blood has been withdrawn from the donor, returning the red blood cells to the donor; and
  • steps d)-i) are continued until a measured volume of plasma product in the collection container equals Vpp.
  • steps d)-j) are continued until a measured volume of plasma product in the collection container equals VPP.
  • Vb is determined based on one or more donor specific characteristics including a donor’s weight, height, sex, age, and morphology.
  • Vpp volume of plasma product
  • VRP volume of raw plasma
  • VAC volume of anticoagulant
  • steps c)-k) are repeated until a measured volume of plasma product in the collection container equals Vpp.
  • Vpp volume of plasma product
  • VRP volume of raw plasma
  • VAC volume of anticoagulant
  • the steps of the method comprise: a) determining a weight (Wkg) and sex (M or F) for the donor; b) determining a hematocrit (Het) for the donor; c) determining the volume of raw plasma (VRP) that may be collected based on the weight of the donor (Wkg) and the sex (M or F) of the donor; d) determining the VAC to be added to the VRP based on an anticoagulant ratio (ACR) and the Het of the donor, such that VAC
  • Vpp VRP + VAC
  • f withdrawing whole blood from the donor; g) introducing anticoagulant into the withdrawn whole blood at a specified ratio (ACR); h) separating the withdrawn whole blood into a plasma product and a second component comprising red blood cells; i) collecting the plasma product in a plasma collection container; j) after a desired amount of whole blood has been withdrawn from the donor, returning the red blood cells to the donor; and k) determining the Het of the donor and VPP prior to each collection phase.
  • steps d)-k) are continued until a measured volume of plasma product in the collection container equals Vpp.
  • VRP is determined by establishing the VRP for each of a plurality of ranges of donor weight, and selecting the VRP for the range of weight that is inclusive of the weight of the donor.
  • the ranges of donor weight may be in three categories from 110 to 149 lbs., 150 to 174 lbs., and 175 lbs. and up.
  • VRP KI * Wkg.
  • VRP is no greater than 28.6% of (1-Hct)*(Vb).
  • Vb is determined using one of Nadler’s equations, Gilcher’s Rule of Five, the standards of the ICSH, and any other generally accepted methodology.
  • VRP Wkg * 10 mL/kg.
  • VRP K2 * Vb.
  • an automated system for separating plasma from whole blood comprising a reusable hardware component and a disposable kit.
  • the disposable kit further comprises i) a separator for separating whole blood into a plasma fraction and a concentrated cell fraction, the separator having an input having a blood line integrally connected thereto for transporting whole blood from a donor to the separator, a plasma output port integrally connected to a plasma collection container by a plasma line, and a concentrated cell outlet port integrally connected to a reservoir for receipt of concentrated cells prior to reinfusion to the donor; ii) a donor line terminating in a venipuncture needle for transporting whole blood from a donor to the blood line, iii) an anticoagulant line integrally connected to the blood line and configured to be connected to a source of anticoagulant for transporting anticoagulant to the donor line, iv) a saline line configured to be attached to a source of saline for transporting saline to the blood line, and
  • the reusable hardware component further comprises i) a first peristaltic pump for delivering anticoagulant at a controlled rate into the blood line during a collection phase, ii) a second pump for delivering anticoagulated whole blood to the separator during the collection phase and for returning concentrated cellular components during a reinfusion phase, iii) a third pump for delivering concentrated cellular components from the separator to the reservoir during the collection phase, iv) a clamp associated with each of the blood line, plasma line, reinfusion line and saline line, v) a weigh scale for weighing each of the plasma collection container, the reservoir and the source of anticoagulant, and vi) a programmable controller comprising a touch screen for receiving input from an operator, the programmable controller configured to receive a signal from each of the weigh scales and to automatically operate the first, second and third pumps and the clamps to separate whole blood into a plasma fraction and a concentrated cell fraction during the collection phase and to return concentrated cells to the donor during the reinfusion stage.
  • the programmable controller is further configured to determine the weight of the plasma fraction to be collected in the plasma collection container in accordance with any of the aspects described herein, and to terminate the collection phase upon receiving a signal from the weigh scale for the plasma collection container equal to the weight of the plasma fraction determined by the controller.
  • the controller may be configured to calculate the hematocrit of the donor prior to the collection phase of each cycle.
  • the controller may receive a signal from a sensor or the like that is indicative of the donor’s hematocrit.
  • the amount of plasma product in the plasma collection container may be determined by, e.g., the weigh scale associated with the plasma collection.
  • the separator comprises a spinning membrane separator.

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  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Anesthesiology (AREA)
  • Biomedical Technology (AREA)
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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
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Abstract

L'invention concerne un système de plasmaphérèse et un procédé pour faire fonctionner un système de plasmaphérèse avec lesquels un volume de produit de plasma (c'est-à-dire un plasma anticoagulé) est collecté de sorte que le volume ciblé de plasma pur dans le produit de plasma est déterminé sur la base de caractéristiques spécifiques au donneur. En particulier, la quantité ciblée de plasma pur à collecter est basée sur le poids, ou sur le poids et sur la taille, du donneur. Le volume ciblé de plasma pur à collecter, TVP, peut être un multiple du poids du donneur. En variante, le TVP peut être un multiple du volume sanguin total du donneur, TBV, le TBV du donneur étant déterminé sur la base du poids et de la taille du donneur. Un volume cible pour le produit de plasma à collecter, TVPP, est établi, et la séparation du sang total en un composant de plasma et un second composant continue jusqu'à ce que le volume de produit de plasma dans un récipient de collecte soit égal à TVPP.
PCT/US2021/033835 2021-01-22 2021-05-24 Systèmes et procédés de collecte de plasma WO2022159132A1 (fr)

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CN202180091469.9A CN116801926A (zh) 2021-01-22 2021-05-24 用于血浆采集的系统和方法
EP21921581.1A EP4281137A4 (fr) 2021-01-22 2021-05-24 Systèmes et procédés de collecte de plasma
KR1020237028390A KR20230133893A (ko) 2021-01-22 2021-05-24 혈장 수집을 위한 시스템들 및 방법들
CA3206090A CA3206090A1 (fr) 2021-01-22 2021-05-24 Systemes et procedes de collecte de plasma
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KR20240017096A (ko) * 2017-10-25 2024-02-06 해모네틱스 코포레이션 혈장을 수집하기 위한 시스템 및 방법

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US20050131334A1 (en) * 1992-07-10 2005-06-16 Gambro, Inc. Apparatus for producing blood component products
US20030125881A1 (en) * 2001-11-26 2003-07-03 Ryan Vincent J. Apparatus and method for plasmapheresis
US20200345924A1 (en) * 2017-05-30 2020-11-05 Haemonetics Corporation System and method for collecting plasma
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JP2023554695A (ja) 2023-12-28

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