Dryer for spray drying system

Abstract

The present invention includes a disposable spray drying device for use in a spray drying system. The disposable includes a spray drying head and a plasma drying chamber. The head includes a spray drying nozzle assembly in fluid communication with a plasma source and a pressurized aerosol gas source. The pressurized gas flows in a vortex pattern, atomizing the plasma droplets in the chamber. The head also includes a plenum with uniform air pressure of drying gas. A baffle plate forms the floor of the plenum with a drying gas jet that supplies drying gas to the chamber. The atomized plasma droplets evaporate in the presence of the drying gas emitted from the jet to obtain dried plasma particles and moist air. A capture filter captures the dried plasma particles and allows the moist air to pass through. The moist air passes through a gas outlet and an exhaust port.

Description

[Technical Field]

[0001] Related Applications This application is a continuation-in-part of U.S. Patent Application No. 17,945,124, entitled "Disposable For A Spray Drying System," by Robert R. Andrews et al., filed September 15, 2022.

[0002] The entire teachings of the above application are incorporated herein by reference.

[0003] government support This invention was made with government support under Contract Nos. HHSO100201200005C and 75A50121C00059 awarded by the Biomedical Advanced Research and Development Authority (BARDA). The government has certain rights in this invention. [Background technology]

[0004] The spray drying process is generally a well-known technique for drying a variety of liquid compositions for applications including cosmetics, animal feed, pharmaceuticals, and the like. Unfortunately, until the present invention, spray drying of plasma for transfusion has not been commercially viable; generally, spray drying has been an industrial or laboratory specialty involving complex, difficult-to-operate, and often large machinery for producing cosmetics, pharmaceuticals, animal feed, and the like. In many cases, the above-mentioned devices and methods have suffered from being impractical for use by a wide range of operators with little training, or for aseptically producing final products for human or veterinary medical use. These devices are intended for use by highly skilled, experienced operators and are not intended for use in the environment or personnel associated with the production of human plasma for transfusion in blood centers and other locations.

[0005] Regarding plasma, transfused human plasma is often important for hemorrhage control and wound treatment in trauma victims and in surgery. Unfortunately, plasma is not readily available in many settings worldwide, including battlefields, first responders, and rural settings away from large hospitals, as well as in the second and third world.

[0006] The primary reason human plasma is not as widely available as it should be is that it is generally frozen for long periods or can only be stored as a liquid for very short periods of time. Therefore, when large quantities of plasma are needed (e.g., in a mass casualty event), it may not be available in such quantities, or when plasma is needed in an emergency, it may not be available in time because it must be thawed, which can take 30-45 minutes or more.

[0007] The spray-drying plasma process involves drying liquid plasma, a biological component, into dry powder plasma. Maintaining the integrity of the disposable plasma drying chamber and plasma unit during spray drying helps prevent damage to the biological component and its exposure to pathogens. Summary of the Invention [Problem to be solved by the invention]

[0008] Therefore, there is a need to enhance the safety of plasma spray drying systems, disposables, and their dried plasma products. A need exists for disposables for spray dryers for use by a wide range of operators with little training, or for aseptically producing a final product for human or veterinary medical use. A further need exists for a spray drying system design in which the spray-dried plasma chamber and associated components provide dried plasma units aseptically. A further need exists for a spray drying system that provides dried plasma units from a disposable spray drying chamber used in the system to maintain system integrity. A further need exists for dried plasma to be readily available and capable of being rehydrated within minutes. [Means for solving the problem]

[0009] The present invention relates to a spray drying apparatus for use in a spray drying system having a disposable spray drying device and a spray drying apparatus, where the disposable acts as a barrier between the plasma and the dryer or external environment. This can be achieved in part because the nozzle is part of the disposable and all drying is performed on the disposable.

[0010] The spray drying disposable includes a spray drying head, a plasma drying chamber, and a gas outlet, the spray drying head having a spray drying nozzle assembly including a vortex generator and a plenum having a drying gas inlet communicating with a drying gas source, the plenum supporting the nozzle assembly, and a baffle plate forming the floor of the plenum having one or more drying gas jets, the plasma drying chamber being attached to the baffle plate. The spray drying disposable further includes a plasma drying chamber including, for example, a capture filter. In one aspect, a spray drying apparatus includes: a drying gas source that provides drying gas from a clean dry air (CDA) system, wherein, during use, the drying gas is present in a plenum at uniform air pressure, and during use, one or more drying gas jets provide the drying gas to a drying chamber; a plasma source that provides plasma from a donor; and a pressurized aerosol gas source that provides pressurized aerosol gas from the CDA system, wherein, during use, a spray drying nozzle assembly is in fluid communication with the plasma source and the pressurized aerosol gas source, and the pressurized aerosol gas atomizes the plasma entering the drying chamber, thereby obtaining atomized plasma droplets, and the atomized plasma droplets evaporate upon contact with the drying gas emitted from the one or more drying gas jets, thereby obtaining dried plasma particles and moist air, and a capture filter captures the dried plasma particles and allows the moist air to pass through; and an exhaust port in communication with an exhaust line, wherein the gas outlet is attached to the exhaust port of the spray drying system during operation, and moist air flows through the gas outlet. The drying gas source provides drying gas at a velocity ranging from 720 slpm to about 780 slpm as it enters the nozzle. The drying gas source provides drying gas at a temperature ranging from about 110°C to about 120°C and provides pressurized aerosol gas at a velocity ranging from about 20 slpm to about 60 slpm. In one embodiment, the pressurized aerosol gas is provided at a pressure ranging from about 180 kPa to about 260 kPa and the vortex generator provides a flow rate of about 2.54 x 10 1 Gas pressure ranges from psig to approximately -2.24 psig and approximately 2.00 x 10 1 m / s~approx.-3.75x10 2In one embodiment, the plasma source provides plasma as it enters the nozzle at a rate of about 6 mL / min to about 23 mL / min.

[0011] In yet another aspect, the exhaust temperature is in the range of about 62°C to about 68°C. In one embodiment, the exhaust temperature is in a closed loop in which the exhaust temperature controls the plasma feed rate. As the exhaust temperature increases, the plasma feed rate increases, and as the exhaust temperature decreases, the plasma feed rate decreases. In particular, the closed loop includes an exhaust temperature range of about 62°C to about 68°C and a plasma feed rate range of about 6 to about 23 mL / min.

[0012] The spray drying apparatus also includes one or more filters in communication with the drying gas, the pressurized aerosol gas, or both, and / or one or more filters in communication with the moist air.

[0013] In one embodiment, the spray drying apparatus uses a spray drying disposable having a spray drying head, a plasma drying chamber, and a gas outlet, the spray drying head including a spray drying nozzle assembly including a vortex generator, a plenum having a drying gas inlet communicating with a drying gas source, the plenum supporting the nozzle assembly, and a baffle plate forming the floor of the plenum having one or more drying gas jets and a baffle filter, the plasma drying chamber attached to the baffle plate, the plasma drying chamber including a capture filter. the spray drying apparatus includes a housing having an inner chamber and a housing exhaust line with a housing exhaust valve; a leak detection line with a leak detection valve and a flow sensor; a drying gas source providing drying gas through a drying gas inlet from a clean dry air (CDA) system, wherein, in use, the drying gas exists in a plenum at uniform air pressure, and in use, one or more drying gas jets provide the drying gas to the drying chamber; a plasma source providing plasma from a donor, the plasma source in communication with a scale; and a pressurized aerosol gas source providing pressurized aerosol gas from the CDA system, wherein, in use, a spray drying nozzle assembly is in fluid communication with the plasma source and the pressurized aerosol gas source, the pressurized aerosol gas atomizes the plasma entering the drying chamber, thereby obtaining atomized plasma droplets, the atomized plasma droplets evaporate when they come into contact with the drying gas emitted from the one or more drying gas jets, thereby obtaining dried plasma particles and moist air, and a capture filter captures the dried plasma particles and allows the moist air to pass through. The spray drying apparatus further includes an exhaust port in communication with a disposable exhaust line, wherein the gas outlet is attached to the exhaust port of the spray drying system during operation, and the humid air flows through the gas outlet, and the disposable exhaust line includes an exhaust valve, at least one pressure sensing device in the inner chamber, a drying gas inlet or exhaust port, and a computer system including at least one processor, at least one memory device, at least one data storage device, and at least one output device.The spray drying apparatus further includes at least one pressure sensing device, for example, on the inner chamber and on the outside of the spray drying disposable, which measures the pressure within the spray drying disposable. Because the spray drying disposable wall is flexible, the pressure sensing device on the outside of the wall can detect mechanical force and generate a proportional electrical output signal.

[0014] The present invention further relates to a leak detection method, called the pressure decay method, that uses the spray drying apparatus described herein to determine the integrity of spray dried disposables. The method includes starting the spray drying apparatus, providing drying gas at a temperature in the range of about 110°C to about 120°C, closing the exhaust valve in the disposable exhaust line, wherein either the housing exhaust valve in the housing exhaust line or the leak detection valve in the leak detection line is closed, providing pressurized aerosol gas or drying gas to the plasma drying chamber of the spray drying disposable up to a first pressure amount (e.g., about 1.5 psig to about 4 psig), and allowing a period of time (e.g., about 30 seconds to about 5 minutes) to pass, measuring the pressure with a pressure sensing device in the inner chamber, the drying gas inlet, or the exhaust port to obtain a measured pressure amount, and comparing the measured pressure amount with a threshold pressure amount (e.g., about 1 psig to about 3.5 psig) to obtain a pressure comparison, which pressure comparison indicates the integrity of the spray drying disposable, thereby obtaining a leak detection pressure value. If the leak detection pressure value is below the threshold pressure amount, the computer system determines that the leak detection pressure value is a failing pressure value and that the spray drying disposable should be discarded, and can communicate the failing pressure value to an output device. In one aspect, if the leak detection pressure value is above the threshold pressure amount, the computer system determines that the leak detection pressure value is a passing pressure value and that the spray drying disposable should be used by the spray drying system, and can communicate the passing pressure value to an output device. In one embodiment, the method further includes opening an exhaust valve in the disposable exhaust line.

[0015] The present invention further relates to another leak detection method, referred to as the flow sensor method, which allows for the determination of the integrity of spray dried disposables. The method includes the steps of starting a spray drying apparatus, providing drying gas at a temperature in the range of about 110° C. to about 120° C., closing an exhaust valve in the disposable exhaust line, closing a housing exhaust valve in the housing exhaust line, opening a leak detection valve in the leak detection line, measuring the flow rate of the drying gas from the leak detection line with a flow sensor to obtain a measured flow rate, and comparing the measured flow rate with a threshold flow rate (e.g., about 10 cm). 2 / min ~ approx. 30cm 2 / minutes) to obtain a flow rate comparison, wherein the flow rate comparison indicates the integrity of the spray dried disposable, thereby obtaining a leak detection flow rate value. If the leak detection flow rate value is above the threshold flow rate, the computer system determines that the leak detection flow rate value is a failing flow rate value and that the spray dried disposable should be discarded, and can communicate the failing flow rate value to an output device. If the leak detection flow rate value is below the threshold flow rate, the computer system determines that the leak detection flow rate value is a passing flow rate value and that the spray dried disposable should be used by the spray drying system, and can communicate the passing flow rate value to an output device. The method includes opening an exhaust valve in the disposable exhaust line, opening a housing exhaust valve in the housing exhaust line, and closing the leak detection valve in the leak detection line.

[0016] If either the pressure decay method or the flow sensor method fails, in one embodiment, the spray dryer disposable is discarded. Specifically, if either the leak detection flow rate value is a failing flow rate value or the leak detection pressure value is a failing pressure value, the spray dryer disposable should be discarded. In another aspect, if both the leak detection flow rate value is a passing flow rate value and the leak detection pressure value is a passing pressure value, the spray dryer disposable should be used with the spray dryer system.

[0017] The present invention further includes a method for determining the pressure inside a spray-dried disposable during use, referred to as the pressure sensing method. The pressure sensing method includes the steps of starting a spray-drying apparatus, measuring the pressure in the internal chamber with a pressure sensing device to thereby obtain a measured pressure amount, and comparing the measured pressure amount to a first threshold pressure amount and a second threshold pressure amount, the pressure comparison indicating the pressure inside the spray-dried disposable, thereby obtaining a disposable pressure value. The pressure sensing device, external to the spray-dried disposable, measures the pressure inside the spray-dried disposable. The pressure sensing device detects mechanical force and generates a proportional electrical output signal. In one embodiment, the method further includes providing a drying gas at a drying gas inlet temperature in the range of about 110°C to about 120°C, or an exhaust temperature in the range of about 55°C to about 75°C. The method is more effective when the disposable is heated, but also works when the disposable is not heated. If the disposable pressure value exceeds a second threshold pressure amount (e.g., between about 7.1 psi and about 8 psi), the computer system determines that the disposable pressure value is a failed disposable pressure value, and the spray drying system enters a fail-safe mode and can communicate the failed disposable value to an output device.

[0018] When the disposable pressure value exceeds a first threshold pressure amount (e.g., about 6.0 psi to about 7.0 psi) and is below a second threshold pressure amount (e.g., about 7.1 psi to about 8 psi), the computer system determines that the pressure value is a passing disposable pressure value and that the drying run for the disposable is complete, and then the spray drying system determines the amount of dried plasma. In this case, the spray drying system determines the amount of dried plasma. This method includes measuring the amount of mass in the plasma source at a first time point before spray drying begins to obtain a first plasma mass, measuring the amount of mass in the plasma source at a second time point after spray drying ends to obtain a second plasma mass, calculating the difference between the first and second plasma masses to thereby obtain a processed plasma mass, and comparing the measured processed plasma mass to a threshold plasma mass amount to thereby obtain a processed plasma pass / fail value. If the processed plasma mass value is below the threshold plasma mass amount, the computer system determines that the processed plasma mass value is an unsuccessful processed plasma mass value, and the spray-dried disposable is discarded. If the processed plasma mass value is above the threshold plasma mass amount, the computer system determines that the processed plasma mass value is an acceptable processed plasma mass value. The threshold plasma mass amount ranges from about the total amount of pre-processed donor plasma to be processed, from about 280 grams to about 390 grams. In one embodiment, the amount of processed dried plasma ranges from about 15 grams to about 20 grams, excluding the weight of the bag. The method further includes expanding and compressing the spray-dried disposable to remove dried plasma on the interior walls of the spray-dried disposable.

[0019] Yet another aspect of the present invention includes an integrity detection method, also referred to as a gradient detection method. The spray-drying head integrity detection method includes measuring the pressure during spray drying with a first pressure-sensing device at the drying gas inlet or a second pressure-sensing device at the inner chamber at two or more time points and determining the pressure gradient at the two or more time points over a period of time. If the gradient is above a gradient threshold, the integrity of the spray-drying head is maintained during spray drying. If the gradient is below the gradient threshold, the integrity of the spray-drying head is compromised during spray drying. This method can be used to directly detect failures of spray-drying disposables. This method evaluates the capture filter, baffle filter, and interface between the drying gas inlet and plenum to determine their integrity. The gradient threshold amount for the method ranges from about 0.02 psi / min to about 0.2 psig / min. In one embodiment, the pressure is measured at time points occurring in a range of about every 1 minute to about every 10 minutes.

[0020] The present invention also relates to a disposable spray dryer device having a spray dryer head and a drying chamber. The disposable spray dryer device is for use in a spray drying system having a drying gas source, a plasma source, and a pressurized aerosol gas source. In one embodiment, the disposable spray dryer device dries a single unit of donor plasma into a single unit of dried plasma. If desired, pooled plasma can also be prepared using the apparatus and process of the present invention.

[0021] The spray drying system of the present invention includes, for example, a disposable spray drying device and a spray drying apparatus, and includes a drying gas source that provides a drying gas, a plasma source that provides plasma, and a pressurized aerosol gas source that provides a pressurized aerosol gas.

[0022] The spray-drying head includes a spray-drying nozzle assembly in fluid communication with a plasma source and a pressurized aerosol gas source, the pressurized aerosol gas flowing in a vortex pattern, and in use, the pressurized aerosol gas atomizing the plasma entering the drying chamber to obtain atomized plasma droplets. The spray-drying head also includes a plenum having a drying gas inlet in communication with the drying gas source, and in use, the drying gas resides within the plenum at uniform air pressure, and the plenum supports the nozzle assembly. The spray-drying head further includes a baffle plate forming a floor of the plenum having one or more drying gas jets, the drying gas jets providing the drying gas to the drying chamber.

[0023] The drying chamber of the disposable spray drying device is attached to a baffle plate, where atomized plasma droplets evaporate in the presence of drying gas emitted from one or more drying gas jets, thereby producing dried plasma particles and moist air. The drying chamber further includes a trapping filter present within the drying chamber, which traps the dried plasma particles and allows the moist air to pass through. The drying chamber also includes a gas outlet, which is attached to an exhaust port of the spray drying system during operation, and through which the moist air flows.

[0024] In one embodiment, the spray drying nozzle assembly includes a cannula. In one aspect, the cannula has an inner diameter ranging from about 0.010 inches to about 0.040 inches and an outer diameter ranging from about 0.030 inches to about 0.060 inches.

[0025] In another embodiment, the disposable spray drying device further comprises a vortex generator in communication with the pressurized aerosol gas. In one aspect, the vortex generator has a plurality of channels and a plurality of pads for generating a vortex pattern in the pressurized aerosol gas. The plurality of channels and the plurality of pads can be curved, and / or the plurality of channels are curved and the plurality of pads have one or more curved edges.

[0026] In yet another embodiment, the nozzle assembly has an opening having a diameter. At the opening, the cannula emits plasma and pressurized aerosol gas. The nozzle opening has an inner surface. The cannula has inner and outer diameters and an outer surface. The opening emits the pressurized aerosol gas in a vortex pattern. In particular, the vortex pattern of the pressurized aerosol gas flows through the outer surface of the cannula and the inner surface of the opening. In one embodiment, the distance between the outer surface of the cannula and the inner surface of the opening is about 0.015 inches to about 0.091 inches. In one aspect, the nozzle assembly extends into the plasma drying chamber beyond a plane defined by the baffle plate.

[0027] In one embodiment, the dry gas inlet receives the dry gas source through a deflector that directs the dry gas to the inner sidewall of the plenum. The dry gas inlet receives the dry gas source through a deflector that includes a 90-degree elbow.

[0028] In yet another aspect, the plenum of the spray-drying head further includes a baffle filter (e.g., a 0.2 micron filter) through which the drying gas flows. In one embodiment, the baffle plate includes one or more ribs upon which the baffle filter is mounted. In one aspect, the baffle plate has one or more airflow channels in communication with one or more drying gas jets. The one or more channels define one or more pie-shaped air channels in communication with the one or more drying gas jets.

[0029] In one embodiment, the drying chamber of the spray-drying disposable device comprises a portion that, after sealing and separation, becomes the dried plasma unit product. Thus, this section further comprises at least one or more ports for injecting reconstitution fluid or transporting reconstituted plasma to a recipient, a slot for hanging the dried plasma unit, and a label. Along these lines, the drying chamber includes cut and seal locations that form the walls of the dried plasma unit.

[0030] In one embodiment, the drying chamber of the spray drying disposable device has a separator on the entrapment filter, which separates the entrapment filter from the inner wall of the spray drying chamber.

[0031] In yet another embodiment, the spray drying disposable device includes an arrangement for aligning the spray drying disposable device with a spray drying system.

[0032] The invention includes methods for making spray-dried plasma using the disposable spray-drying devices and spray-drying systems described herein and for storing spray-dried plasma units. The invention further includes kits and systems having the disposable spray-drying devices and spray-dried plasma units described herein.

[0033] Advantageously, the present invention includes a spray drying system having an easy-to-use spray dryer and a disposable device containing a drying chamber therein. The system determines whether a disposable is suitable for drying, measures the pressure inside the disposable during use, and determines whether the disposable is unacceptable during spray drying. An additional advantage of spray-dried disposables is that, once spray drying is complete, they are converted into a spray-dried plasma product that can be used on-site. The dried plasma of the present invention allows for simplified storage, transportation, and use options (e.g., refrigerated / ambient temperature storage) compared to frozen plasma, the current standard for plasma. The present invention overcomes the inadequacies of conventional spray drying systems and enables rapid, sterile production of small or single unit quantities of a wide range of materials by a wide range of minimally trained operators. The application of the present invention is broad, including dried human plasma. In particular, the present invention provides a process for transferring plasma to a desired compartment of a disposable and sealing the disposable at a specific location to create a packaged, ready-to-use container for the dried material. The present invention is advantageously applicable to the aseptic manufacturing of products for use in pharmaceuticals, such as pharmaceuticals or dried plasma. The plasma unit is rehydrated with sterile water and can be used within minutes, providing easy and rapid access to plasma.

[0034] The foregoing and other objects, features, and advantages of the present invention will become apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings, in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. [Brief explanation of the drawings]

[0035] [Figure 1] 1 is a black and white photograph showing phase contrast microscopy at 100x and 400x magnification of cholesterol crystals in freeze-dried plasma known as LYOPLAS™ plasma. [Figure 2] 1 is a black and white photograph showing phase contrast microscopy at 100x and 400x magnification of cholesterol crystals in freeze-dried plasma known as FLYP™ plasma. [Figure 3] 1 is a panel of black and white photographs showing phase contrast microscopy at 100x magnification of cholesterol crystals in freeze-dried plasma using LYOPLAS™ plasma (left) and FLYP™ plasma (right). [Figure 4] 1 is a panel of black and white photographs showing phase contrast microscopy of spray-dried plasma without visible cholesterol crystals observed as follows: donor plasma at 100x magnification before spray drying (top left panel), spray-dried plasma at 100x magnification (top right panel), donor plasma at 400x magnification before spray drying (bottom left panel), and spray-dried plasma at 400x magnification (bottom right panel). [Figure 5] 1 is a composite bar / line graph showing the microparticle concentration (microparticles / mL) and microparticle size (logarithmic scale (μm)) of single unit dried plasma at initial rehydration and after 7.5 months of room temperature storage 4 hours after rehydration compared to paired thawed frozen control plasmas as follows: Control plasma (CP) at time 0 (T=0), spray-dried plasma of the present invention (ODP) at time 0 (T=0), control plasma (CP) at time 4 hours (T=4), spray-dried plasma of the present invention (ODP) at time 4 (T=4). [Figure 6]1 is a composite bar / line graph showing particle concentration (particles / mL) and particle size (logarithmic scale (μm)) of single unit dried plasma at initial rehydration and after 12 months of refrigerated storage 4 hours after rehydration compared to its paired thawed frozen control plasma: Control plasma (CP) at time 0 (T=0), spray-dried plasma of the present invention (ODP) at time 0 (T=0), control plasma (CP) at time 4 hours (T=4), spray-dried plasma of the present invention (ODP) at time 4 (T=4). [Figure 7] 10A-10C are panels of black and white scanning electron microscope (SEM) photographs of spray-dried plasma particles from Run #3, with the top left panel at 2000x, the top right panel at 5000x, the bottom left panel at 5000x, the middle right panel at 1000x, and the bottom left panel at 5000x, with measurements overlaid and showing sizes ranging from 0.99 μm to 7.87 μm, and the bottom right panel at 2000x. These photographs demonstrate the small size and amorphous characteristics of the present invention. [Figure 8A] 10 shows panels of black and white scanning electron microscope (SEM) photographs of spray-dried plasma particles from run #7, with the top left panel at 2000x magnification, the top right panel at 1000x magnification, the bottom left panel at 5000x magnification, the middle right panel at 5000x magnification, the bottom left panel at 1000x magnification, and the bottom right panel at 2000x magnification. [Figure 8B] Panel of black and white scanning electron microscope (SEM) photographs of spray-dried plasma particles from run #7 at 5000x magnification with measurements overlaid on top, showing sizes ranging from 1.46 μm to 6.53 μm. [Figure 9A] 1 is a bar graph showing the results of clotting time (R) in minutes from a thromboelastography TEG study with reconstituted WB and mock resuscitation (abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 9B]1 is a bar graph showing the results of clotting rate (angle) from a thromboelastography TEG study with reconstituted WB and mock resuscitation (abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 9C] 1 is a bar graph showing results of clot strength (MA) in maximum amplitude (mm) from a thromboelastography TEG study with reconstituted WB and mock resuscitation (abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 9D] 1 is a bar graph showing the results of the lysis index (30 min) in LY30 as a percentage (%) from a thromboelastography TEG study with reconstituted WB and mock resuscitation (abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 9E] 1 is a bar graph showing the results of the lysis index (60 min) of LY60 in percentage (%) from a thromboelastography TEG study with reconstituted WB and mock resuscitation (abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 10A]1 is a bar graph showing the results of clotting time (R) in minutes from a thromboelastography TEG study using plasma only (abbreviations: FFP = fresh frozen plasma (FFP); ODP - spray-dried plasma (ODP) of the present invention; WB + 10% FFP = whole blood resuscitated with 2 units of FFP; WB + 10% ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 10B] 1 is a bar graph showing the results of clotting rate (angle) from a thromboelastography TEG study using plasma only (abbreviations: FFP = fresh frozen plasma (FFP); ODP - spray-dried plasma (ODP) of the present invention; WB + 10% FFP = whole blood resuscitated with 2 units of FFP; WB + 10% ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 10C] 1 is a bar graph showing the results of clot strength in maximum amplitude (MA) (mm) from a thromboelastography TEG study using plasma only (abbreviations: FFP = fresh frozen plasma (FFP); ODP - spray-dried plasma (ODP) of the present invention; WB + 10% FFP = whole blood resuscitated with 2 units of FFP; WB + 10% ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 11] 1 is a bar graph showing the results of vWF (von Willebrand Factor):Ristocetin (Rist) cofactor activity (percent (5)) from a ristocetin cofactor assay. (Abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP = whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 12] 1 is a bar graph showing the results of ADAMTS-13 (von Willebrand factor-cleaving protease) activity by the ADAMTS-13 assay. (Abbreviations: FFP = fresh frozen plasma (FFP); ODP - spray-dried plasma (ODP) of the present invention.) [Figure 13A]1A-1C are two bar graphs showing the results of a platelet adhesion Bioflux study, showing the percentage (%) of arterial shear at intensity NS(10min) 900 s-1 in fluorescence intensity units (FIU) and area NS(10min) coverage. (Abbreviations: NS = normal shear conditions; WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB + 10% FFP = whole blood resuscitated with 2 units of FFP; WB + 10% ODP = whole blood resuscitated with 2 units of ODP.) Reference ranges are indicated by dotted lines. [Figure 13B] Included are two bar graphs showing the results of a platelet adhesion Bioflux study, showing the percentage (%) of pathological shear at 4000 s of intensity HS(10 min) in fluorescence intensity units (FIU) and area HS(10 min) coverage. (Abbreviations: HS = high shear conditions; WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB + 10% FFP = whole blood resuscitated with 2 units of FFP; WB + 10% ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 14A] Included are two bar graphs showing the results of a CAT (calibrated automated thrombogram) thrombin generation assay, showing the lag time in minutes and the endogenous thrombin potential (ETP) (nM, min). (Abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB + 10% FFP = whole blood resuscitated with 2 units of FFP; WB + 10% ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. ETP reflects coagulation status and is a measure of whether someone is prone to bleeding (low ETP) or clotting (high ETP). [Figure 14B]1 includes two bar graphs showing the results of a CAT (calibrated automated thrombogram) thrombin generation assay, showing peak thrombin (nM) and time to peak (min). (Abbreviations: WB:FFP = whole blood (WB) reconstituted with fresh frozen plasma (FFP); WB:ODP - whole blood reconstituted with spray-dried plasma (ODP) of the present invention; WB+10%FFP = whole blood resuscitated with 2 units of FFP; WB+10%ODP = whole blood resuscitated with 2 units of ODP). Reference ranges are indicated by dotted lines. [Figure 15A] 1 includes three bar graphs showing the flow cytometry results of the remaining cellular material in total events, total labeled events, and CD41A (platelets) events. (Abbreviations: FFP = fresh frozen plasma (FFP); ODP - spray-dried plasma (ODP) of the present invention. [Figure 15B] Contains three bar graphs showing the results of flow cytometry of residual cellular material for CD45 (WBC) and CD235 (RBC). (Abbreviations: FFP = fresh frozen plasma (FFP); ODP - spray-dried plasma (ODP) of the present invention; WBC - white blood cells; RBC - red blood cells). [Figure 16] Panels A-C are schematic diagrams showing the unfolding / refolding model of the vWF A2 domain and proton cleavage by ADAMTS13. (A) Illustration of the vWF A2 domain in its native folded state. (B) The first step of unfolding occurs from the C-terminus of the vWF A2 domain and is influenced by the presence of a proximal disulfide bond (cysteine ​​indicated by C). Initial unfolding occurs up to and including the central b4 sheet, which contains the scissile bond (YM). This intermediate step of unfolding exposes the high-affinity ADAMTS13 spacer-binding site. (C) Once the stabilizing effect of the calcium-binding site (CBS) is overcome, this leads to the complete unfolding of the vWF A2 domain and positions the ADAMTS13 active site for nucleophilic attack of the Y1605-M1606 scissile bond. [Figure 17]This is a bar graph showing that formulations of citrated plasma stabilize during spray drying at approximately 50% von Willebrand factor:ristocetin cofactor (vWF:RCo) activity without any effect on other coagulation factors (prothrombin (PT), activated partial thromboplastin time (aPTT), fibrinogen (FGN), factor V (FV), factor VII (FVII), factor VIII (FVIII), factor IX (FIX), vWF antigen (vWF-Ag), % von Willebrand factor:ristocetin cofactor (vWF:RCo)). This is normalized to control plasma (fresh frozen plasma (FFP)) at time 0, the completion of spray drying. CP indicates control plasma; SpDP indicates spray-dried plasma; PreT indicates plasma formulation by SDSAS. [Figure 18] This is a bar graph showing that formulation of plasma with citrate confers stability to vWF and all other coagulation factors (prothrombin (PT), activated partial thromboplastin time (aPTT), fibrinogen (FGN), factor V (FV), factor VII (FVII), factor VIII (FVIII), factor IX (FIX), vWF antigen (vWF-Ag), and % von Willebrand factor:ristocetin cofactor (vWF:RCo)) during 6 weeks of storage at 4°C. SpDP indicates spray-dried plasma. PreT indicates plasma preparation by SDSAS. CP indicates control plasma, and FFP is fresh frozen plasma. [Figure 19] This bar graph shows that pre-treatment of plasma with citrate confers stability to vWF and all other coagulation factors (prothrombin (PT), activated partial thromboplastin time (aPTT), fibrinogen (FGN), factor V (FV), factor VII (FVII), factor VIII (FVIII), factor IX (FIX), vWF antigen (vWF-Ag), and % von Willebrand factor:ristocetin cofactor (vWF:RCo)) after 2 weeks of storage at 25°C. SpDP indicates spray-dried plasma. PreT indicates plasma preparation by SDSAS. CP indicates control plasma, and FFP is fresh frozen plasma. [Figure 20]1 is a bar graph showing that formulation of plasma with citrate confers stability to coagulation factors (prothrombin (PT), activated partial thromboplastin time (aPTT), fibrinogen (FGN), factor V (FV), factor VII (FVII), factor VIII (FVIII), factor IX (FIX), and vWF antigen (vWF-Ag)) during 2 weeks of storage at 37°C. SpDP indicates spray-dried plasma. PreT indicates plasma preparation by SDSAS. CP indicates control plasma, and FFP is fresh frozen plasma. [Figure 21] 1 is a photographic image showing that formulation of plasma with citrate stabilizes vWF during SpD (spray drying). CP indicates control plasma; SpDP indicates spray-dried plasma; PreT indicates plasma formulation with SDSAS; FFP indicates fresh frozen plasma. [Figure 22A] This is a line graph showing the CP / FFP and pH of delivered plasma under a constant plasma delivery rate of 10 mL / min but variable aerosol gas flow rates (0, 5, 10, 15, and 20 L / min). CP indicates control plasma; FFP indicates fresh frozen plasma; vWF indicates von Willebrand factor. [Figure 22B] 1 is a line graph showing the resulting activity (%, IU / dL) of vWF:RCo activity of CP / FFP and fed plasma under a constant plasma feed rate of 10 mL / min but variable aerosol gas flow rates (0, 5, 10, 15, 20 L / min). CP denotes control plasma; FFP denotes fresh frozen plasma. [Figure 23A] A line graph showing the pH of CP / FFP and supplied plasma at an aerosol gas flow rate of 10 L / min; fluid = 2 mL / min, 10 L / min; fluid = 4 mL / min, 10 L / min; fluid = 6 mL / min, 10 L / min; fluid = 8 mL / min, 10 L / min; and fluid = 10 mL / min. CP indicates control plasma; FFP indicates fresh frozen plasma; vWF indicates von Willebrand factor. vWF:RCo (vWF activity measured by vWF ristocetin assay). [Figure 23B]1 is a line graph showing the resulting vWF:RCo activity (%, IU / dl) of donated plasma at CP / FFP and aerosol gas flow rates of 10 L / min; fluid = 2 mL / min, 10 L / min; fluid = 4 mL / min, 10 L / min; fluid = 6 mL / min, 10 L / min; fluid = 8 mL / min, 10 L / min; fluid = 10 mL / min. CP indicates control plasma; FFP indicates fresh frozen plasma. [Figure 24] 1 is a bar graph showing the effect of different SDSAS formulations on vWF:RCo recovery and pH during nebulization. pH levels before and after nebulization are indicated above the bar graph. CP indicates control plasma; FFP indicates fresh frozen plasma; vWF indicates von Willebrand factor. [Figure 25A] Bar graphs showing the effect of different SDSAS formulations on vWF:RCo recovery and pH during spray drying. (A) Citric acid. pH levels before and after spraying are indicated at the top of the bar graph. vWF stands for von Willebrand factor. vWF:RCo (vWF activity measured by vWF ristocetin assay). [Figure 25B] (B) Bar graphs showing the effect of different SDSAS formulations on vWF:RCo recovery and pH during spray drying. (C) Lactic acid. pH levels before and after spraying are indicated at the top of the bar graph. vWF stands for von Willebrand factor. vWF:RCo (vWF activity measured by vWF ristocetin assay). [Figure 25C] (C) Bar graphs showing the effect of different SDSAS formulations on vWF:RCo recovery and pH during spray drying. (D) pH. pH levels before and after spraying are indicated at the top of the bar graph. vWF stands for von Willebrand factor. vWF:RCo (vWF activity measured by vWF ristocetin assay). [Figure 26] 1 is a color line graph showing the amount of C3 ang / mL and pH for batches 1543, 1542, 1541 and their respective control plasmas (CP) for the experiments performed in Example 16. [Figure 27] 1 is a line graph showing the amount of C5 ang / mL and pH for batches 1543, 1542, 1541 and their respective control plasmas (CP) for the experiments conducted in Example 16. [Figure 28] 1 is a bar graph showing C5a analysis of control plasma (CP) / tube with 400 mM glycine HCl, 400 mM glycine HCl + 1 M glycine, 148 mM citric acid, 148 mM citric acid + 1 M glycine (n=7) and non-frozen plasma (NFP) pretreated rapidly and slowly with control plasma / non-frozen plasma (CP / NFP). [Figure 29] 1 is a bar graph showing C3a measurements in ng / mL of CP / FFP (control plasma / fresh frozen plasma), CP / FFP / PreT (control plasma / fresh frozen plasma / pre-treated), and ODP / NFP / PreT (on-demand plasma (applicant's inventive spray-dried plasma), not frozen, pre-treated) mean of n=20±1 SD. [Figure 30] 1 is a bar graph showing mean C5a measurements in ng / mL for CP / FFP, CP / FFP / PreT, and ODP / NFP / PreT, n=20±1 SD. [Figure 31] 1 is a bar graph showing antigen measurements normalized to ODP / NFP / PreT activity and CP / FFP. [Figure 32] 1 is a bar graph showing aPTT (activated partial thromboplastin time), PT (prothrombin time), and TT (thrombin time) of ODP / NFP / PreT normalized by CP / FFP. [Figure 33] 1 is a bar graph showing vWF antigen (von Willebrand factor), vWF:RCo (vWF activity measured by vWF ristocetin assay), and vWF activity of ODP / NFP / PreT (on-demand plasma (applicant's inventive spray-dried plasma), not frozen, pre-processed) normalized to CP / FFP (control plasma / fresh frozen plasma). [Figure 34] 1 is a bar graph showing activation marks D-Dimer, TAT and F1+2 of ODP / NFP / PreT (on-demand plasma (applicant's inventive spray-dried plasma) not frozen, pre-processed) normalized with CP / FFP (control plasma / fresh frozen plasma). [Figure 35]1 is a bar graph showing chemistry analyzer results of ODP / NFP / PreT (on-demand plasma (applicant's inventive spray-dried plasma), not frozen and pre-processed) for IgG, IgM, IgA, total protein, albumin, triglycerides, cholesterol, LDL cholesterol, HDL cholesterol and calcium normalized to CP / FFP (control plasma / fresh frozen plasma). [Figure 36] 1 is a bar graph showing thromboelastography hemostasis system (TEG) results for R reaction time (min), K (min), α (angle), and MA (maximum amplitude (mm)) of ODP / NFP normalized to CP / FFP (control plasma / fresh frozen plasma). [Figure 37A] 1 is a bar graph showing clotting profile results and ELISA assay results for various clotting factors and complement activation for unfrozen plasma pretreated with 400 mM glycine HCl and spray-dried at exhaust gas temperatures of 49, 50, 51, and 52° C. [Figure 37B] 1 is a bar graph showing coagulation activation and complement activation marks (D-dimer, TAT, PF1.2, C3a, and C5a) of fresh frozen plasma normalized to control plasma pretreated with 400 mM glycine HCl and spray-dried at exhaust gas temperatures of 49, 50, 51, and 52° C. [Figure 38A] 1 is a bar graph showing C5a levels in ng / mL at 10 minutes, 1 hour, 2 hours, and 21 hours for rehydrated plasma pretreated with 400 mM, 280 mM, and 140 mM glycine HCl (GlyHCl) and 148 mM, 100 mM, and 50 mM citric acid (CA). [Figure 38B] 1 is a bar graph showing the pH of plasma pretreated with 400 mM, 280 mM, 140 mM glycine HCl (GlyHCl) and 148 mM, 100 mM, and 50 mM citric acid (CA). [Figure 39] 1 is a line graph plotting the pH level of the pretreatment solution and pretreatment plasma sample versus the glycine concentration (mM). [Figure 40]1 is a bar graph showing C5a levels (ng / mL) for 400 mM glycine HCl supplemented with increasing concentrations of glycine (0, 400, 600, 800, 1000, 1200, 1400, and 1600 mM) at 10 and 60 minutes using rapid mixing (e.g., when a larger volume of plasma is quickly added to a relatively small volume of pretreatment solution). [Figure 41A] 1 is a line graph showing the pH of plasma (batches 1949 and 1950) pretreated with pretreatment solution and 400 mM lactate and supplemented with increasing concentrations of glycine (0, 400, 600, 800, 1000, 1200, 1400, and 1600 mM). [Figure 41B] 1 is a bar graph showing C5a levels in ng / mL in plasma (batches 1949 and 1950) pretreated with 400 mM lactate and supplemented with increasing concentrations of glycine, where the pretreated plasma had concentrations of 0, 20, 30, 40, 50, 60, 70, and 80 mM glycine. [Figure 42A] Schematic diagram showing a perspective view of a spray drying disposable device including a liquid plasma bag, a spray drying head, and a spray drying chamber, the disposable having alignment elements that allow it to be aligned with the spray drying equipment and finishing equipment. [Figure 42B] 1 is a model representation of the three-dimensional flow geometry of the disposable flow model in operation, which is used to create the computer flow models described herein. [Figure 43A] FIG. 42B is a schematic diagram showing a perspective view of the spray drying head of the spray drying disposable device shown in FIG. 42A. [Figure 43B] 42B is a schematic diagram showing an exploded view of the spray drying nozzle assembly and spray drying head of the spray drying disposable device shown in FIG. 42A. [Figure 43C] FIG. 1 is a schematic diagram showing a perspective view of a spray drying nozzle assembly from the spray drying head of a spray drying disposable device. [Figure 43D] 43D is a schematic diagram showing a perspective view of the spray drying nozzle assembly of FIG. 43C, but with the aerosol reservoir housing transparent to show the internal structure of the assembly. [Figure 43E] FIG. 43D is a schematic diagram showing a perspective view of the spray drying nozzle assembly of FIG. 43C with the aerosol reservoir housing and the nozzle cap and nozzle cap insert removed to show the manifold and cannula. [Figure 43F] FIG. 1 is a schematic diagram showing a front view of one embodiment of a beveled edge cannula that is part of a spray drying nozzle assembly. [Figure 43G] FIG. 10 is a schematic diagram showing a perspective top view of the cannula and the nozzle cap insert that guides the aerosolized air. [Figure 43H] FIG. 10 is a schematic diagram showing a perspective bottom view of the nozzle cap insert with the cannula inserted. [Figure 43I] FIG. 2 is a schematic diagram showing a top view of the nozzle cap. [Figure 43Ia] FIG. 43I is a schematic diagram showing a bottom view of the nozzle cap of FIG. 43I, with the annular member residing within the cap opening. [Figure 43Ib] 43I is a schematic diagram showing three possible vortex generator flow patterns that can be used with the nozzle cap insert of FIG. 43I. [Figure 43Ic] FIG. 43I is a schematic diagram showing a cross-sectional view of the nozzle cap insert of FIG. 43H residing within the nozzle cap of FIG. 43I. [Figure 43J] FIG. 1 is a schematic diagram showing a perspective bottom view of the plenum of the spray drying head. [Figure 43K] FIG. 1 is a schematic diagram illustrating a partial front view of a spray dryer showing a portion of a drying gas deflector. [Figure 43Ka] FIG. 1 is a diagram showing modeled dry gas flow in a plenum chamber using a 15 m / s constant velocity amplitude surface. [Figure 43L] FIG. 2 is a schematic diagram showing a top perspective view of a baffle plate of a spray drying head. [Figure 43La] FIG. 43La is a schematic diagram showing a cut-out portion of the baffle plate rib design shown in FIG. 43L and a cut-out portion of another variation of the baffle plate rib design, and also shows a cross section of one of the ribs. [Figure 43M] FIG. 2 is a schematic diagram showing a perspective bottom view of a baffle plate of a spray drying head. [Figure 43Ma] Model representation showing uniform jet penetration and drying gas distribution at a constant velocity of 25 m / s, thus introducing uniform drying gas circumferentially around the spray plume. [Figure 43N] FIG. 1 is a schematic diagram illustrating droplet plume formation, aerosol gas flow, and drying gas flow to promote rapid mixing in a disposable device of the present invention. [Figure 43Na] FIG. 10 is a model diagram showing gas velocity magnitude contours within the disposable center plane, illustrating the drying jet penetration into the drying chamber and the effect of the baffle plate flow paths and their interaction with the high velocity spray plume, which acts to draw the drying gas jet radially inward to aid in the desired rapid mixing of the droplets with the gas flow. [Figure 43O] FIG. 1 is a model diagram showing the gas pressure flow (psig) (top) and tangential velocity flow (m / s) (bottom) of the vortex generated within the nozzle insert and cap assembly. [Figure 43P] 1 is a model diagram showing gas velocity amplitude flow (m / s) in the components of a vortex generator. [Figure 43Q] FIG. 1 is a schematic diagram showing the transformation of droplets into dry particles using a disposable of the present invention. [Figure 43R] 1 is a line graph showing droplet wet bulb temperature (° C.) and drying gas temperature (° C.) for droplets dried to particles with 0% relative humidity (RH), 10% RH, and 20% RH. This particular graph illustrates the concept but is not specific to plasma. [Figure 43S] 1 is a line graph showing the evaporative mass transfer of droplet temperature over time for all mean droplet trajectories averaged over three simulated drying gas inlet temperatures in the model: 80° C., 100° C., and 114° C. Note that the evaporation process cools the droplets to keep the delicate liquid protein below 30° C. [Figure 43Sa]Line graph of temperature in °C vs. time (seconds) of plasma droplets as they become particles in the model. Once evaporation is complete, the proteins encased in solid particles are more resistant to high temperatures because they equilibrate with the dryer outlet temperature. In this case, evaporation occurs in less than a fraction of a second (e.g., 0.01-0.05 seconds). [Figure 43T] FIG. 1 is a model diagram showing the paths of droplets having sizes of 5 microns, 15 microns, and 25 microns during evaporation. The diagram shows that smaller droplet size allows for more rapid evaporation mass transfer over a shorter path, allowing for a physically smaller drying chamber. [Figure 44A] FIG. 42B is a schematic diagram showing an exploded view of the drying chamber of the spray drying disposable device shown in FIG. 42A. [Figure 44B] FIG. 1 is a schematic diagram showing a front view of a separator or spacer that can be used in the drying chamber of a spray drying disposable. [Figure 45A] FIG. 2 is a schematic diagram showing a front view of the spray drying apparatus with the door closed. [Figure 45B] FIG. 1 is a partial front view of the spray drying apparatus without the door to reveal the drying chamber housing with alignment elements that allow alignment with the spray drying disposable device. [Figure 45C] FIG. 1 is a schematic diagram showing a front view of the spray drying apparatus with the door handle engaged and the door open. [Figure 46A] 1 shows an alignment element for aligning the spray drying disposable device with the spray drying apparatus. [Figure 46B] FIG. 1 is a schematic diagram showing a partial front view of a spray drying apparatus without the door, with the spray drying disposable device installed, and with the deflector engaged. [Figure 46C]2 is a schematic diagram showing the structure of dryer 200. Abbreviations included are: AM - air manifold, B - transfer bag, CN - connector, DPT - differential pressure transducer, F - filter, FS - flow sensor, H - heater, MFC - mass flow controller, OS - sensor, P - peristaltic pump, PP - pneumatic piston, PR - pressure regulator, PRV - pressure relief valve / rupture disc, PT - pressure transducer, PV - valve (downward arrow is fail closed, upward arrow is fail open), S - scale, SS - solenoid, TC - thermocouple, TS - thermocouple sensor, and TT - temperature transducer. [Figure 46D] 1 is a flow chart showing the steps of a leak detection method using a spray dryer and spray dried disposables. [Figure 46E] 1 is a flowchart showing the steps of a pressure detection method using a spray dryer and spray drying disposables. [Figure 46F] 1 is a flow chart showing the steps of a method for detecting the integrity of a filter and disposable interface using a spray dryer and spray dried disposables. [Figure 46G] 1 is a line graph showing the slope using a method to detect filter integrity and demonstrating that the filter is intact by measuring pressure (psig), elapsed time (min), and rate of pressure change (psi / min). [Figure 46H] 1 is a line graph showing the slope using a method to detect filter integrity and demonstrate that the capture filter failed intact by measuring pressure (psig), elapsed time (minutes), and rate of pressure change (psi / minute). [Figure 46I] 1 is a line graph showing the slope using a method to detect filter integrity and showing that a baffled filter failed intact by measuring pressure (psig), elapsed time (minutes), and rate of pressure change (psi / minute). [Figure 47A] FIG. 1 is a schematic diagram showing a front view of the finishing device in the loading position with no spray drying disposables attached. [Figure 47B]47B is a schematic diagram showing a front view of the finishing device of FIG. 47A without the front cover with the shuttle in the lowered position. FIG. [Figure 47C] FIG. 47C is a schematic diagram showing a front view of the finishing device of FIG. 47B with the shuttle in the raised position and no disposables attached. [Figure 47D] FIG. 10 is a schematic diagram showing a front view of another embodiment of the finishing device in a raised position and without spray drying disposables attached. [Figure 47E] FIG. 47D is a schematic diagram showing a front view of the finishing device of FIG. 47D without the front cover with the shuttle in the raised position. [Figure 47F] FIG. 47D is a schematic diagram showing a front view of the finishing device of FIG. 47D without the front cover with the shuttle in the lowered position. [Figure 47G] FIG. 47D is a schematic diagram showing a front view of the finishing device of FIG. 47D but without the front cover with the shuttle in the raised and inverted position. [Figure 47H] FIG. 47D is a schematic diagram showing a front view of the finishing device of FIG. 47D without the front cover with the shuttle in a lowered and inverted position. [Figure 47I] FIG. 47D is a schematic diagram showing an enlarged perspective view of a portion of the rail system of the finishing device of FIG. 47D. [Figure 48A] FIG. 1 is a schematic diagram showing a front view of the finishing device with the disposable spray drying head in the aligned and mounted position. [Figure 48B] FIG. 1 is a schematic diagram showing a front view of the finishing device with the disposables in an aligned, raised position. [Figure 48C] A schematic diagram showing a front view of the finishing device in a raised position with a portion of the disposable attached after the first sealing and separation step has been completed and the frame has been rotated into place. [Figure 48D] FIG. 10 is a schematic diagram showing a front view of another embodiment of the finishing device in a raised position with spray drying disposables attached. [Figure 48E] FIG. 48E is a schematic diagram showing a front view of the finishing device shown in FIG. 48D in the lowered position with spray dryer disposables attached. [Figure 48F] FIG. 48D is a schematic diagram showing a front view of the finishing device shown in FIG. 48D in the raised and inverted positions with spray dryer disposables attached. [Figure 48G] FIG. 48E is a schematic diagram showing an enlarged top view of the receiver of the finishing device shown in FIG. 48D. [Figure 48H] FIG. 48E is a schematic diagram showing an enlarged perspective view of the receiver of the finishing device shown in FIG. 48D. [Figure 48I] FIG. 48E is a schematic diagram showing an enlarged perspective view of the tensioner of the finishing device shown in FIG. 48D. [Figure 48J] FIG. 48E is a schematic diagram showing an enlarged perspective view of a separator having a roller that engages with a tensioner of the finishing device shown in FIG. 48D. [Figure 48K] FIG. 48E is a schematic diagram showing an enlarged perspective view of the impactor, separator, and sealer of the finishing device shown in FIG. 48D. [Figure 48L] FIG. 48E is a schematic diagram showing a side view of the impactor, separator, and sealer of the finishing device shown in FIG. 48D. [Figure 49A] FIG. 1 is a schematic diagram showing a front view of a spray-dried plasma unit obtained from a spray-drying disposable device after processing by a finishing apparatus. [Figure 49B] 4 is a schematic diagram showing the structure of a finisher 400'. Abbreviations included are: AM - air manifold, CN - connector, CV - check valve, EM - electric motor, FS - flow sensor, FR - flow restrictor, PP - pneumatic piston, PR - pressure regulator, PT - pressure transducer, PV - valve arrow (downward arrow is fail closed, upward arrow is fail open), SC - speed controller, SR - sensor, and VG - vacuum generator. [Figure 50] 1 is a bar graph comparing the vWF% ratio of reconstituted plasma (vs. undried control aliquots) dried using disposable devices with composite nozzle assemblies without a bevel, with a bevel and a reference stainless steel nozzle. [Figure 51A] 1 is a flowchart illustrating steps of a pre-processing methodology. [Figure 51B] 1 is a flow chart showing steps of a spray drying method using a spray dryer and spray drying disposables. [Figure 51C] 1 is a flow chart showing the steps of a finishing method using a finisher and spray-dried disposables to create dried plasma units. [Figure 51D] 1 is a flow chart showing steps of a storage method after the spray drying unit has been prepared. [Figure 52] Schematic diagram showing cannula geometry to demonstrate shear on vWF protein as it exits the cannula. The curved arrow indicates the aerosol gas vortex direction within the annulus. To demonstrate the amount of shear impact on the liquid plasma at the cannula exit region, the diagram shows cannula edges at 15, 90, 45 degrees (with chamfers and sharp edges), and 60 degrees, showing how the angled edges reduce the shear contact of the cannula. DETAILED DESCRIPTION OF THE INVENTION

[0036] A description of a preferred embodiment of the present invention follows.

[0037] The present invention relates to components and systems for using disposable spray-drying devices. The spray-drying system includes a spray-drying apparatus (hereinafter referred to as a "drying apparatus," "machine," "spray dryer," or "dryer"), a spray-drying finishing apparatus (hereinafter referred to as a "finisher," "seal and separator," or "finisher"), and a disposable spray-drying device (hereinafter referred to as a "disposable device" or "disposable"). The present invention includes a system that enables a disposable spray-drying device with a liquid spray nozzle and drying chamber to efficiently dry liquids, including human or animal plasma, while protecting active components such as plasma proteins. The disposable spray-drying device is installed in a spray dryer, which controls the plasma flow, pressurized aerosol gas flow, drying gas flow, temperature, pressure, etc., within the disposable. Upon completion of the spray-drying process, the disposable containing the dried plasma powder is aligned and processed by the spray-drying finishing apparatus, where portions of the disposable are sealed and separated to form a dried plasma unit. Furthermore, the present invention advantageously provides an apparatus for performing the functions of spray-drying and finishing products containing dried human plasma.

[0038] The disposable spray dryer of the present invention has a compact drying chamber that produces dry powder (<2% residual moisture) at a high powder production rate. The disposable is small, easy to handle, and provides a high-performance, easy-to-use drying chamber. The drying system of the present invention is a significant improvement, providing a removable, disposable drying chamber for spray drying that is suitable for processing small batch sizes such as individual blood units.

[0039] Certain of Applicant's older disposable drying chambers were very long, measuring 58 inches to 66 inches or more in length, allowing sufficient time (flight path) to dry plasma to acceptable residual moisture levels. See Applicant's Patent Nos. 8,533,971, 8,595,950, 8,434,242, 8,601,712, 8,533,972, and 10,843,100. However, their lengths made these prior art disposables unacceptable for practical use because they were difficult and inefficient to handle during installation in spray dryer equipment. As further described herein, the shorter disposables of the present invention are easier to handle than these prior art disposables, which required user reach and bending distances of more than 6' and less than 5', respectively. The shorter disposables make spray drying of human plasma practical for real-world applications by real-world people. Additionally, the disposable drying chamber of the present invention is a removable, disposable drying chamber that maintains the quality and integrity of the plasma while improving processing time and product quality at a low cost.

[0040] Several challenges have been overcome by shortening the drying chamber of the present invention. For example, drying any product to a predetermined degree of dryness involves exposing the material being dried to sufficient heat energy to achieve the desired level of dryness while maintaining the functionality of the substance being dried. However, shortening the drying chamber also shortens the drying path.

[0041] The disposable drying chamber of the present invention is improved by: more efficiently produced plasma; Fairly short; Easy to use for people of a wide range of status; Drying materials in less time; Decrease in inlet air temperature; A nozzle assembly and dry environment are achieved to obtain rapid mixing of the atomized droplets with the drying gas and rapid evaporation; Achieve a lower level of residual dryness, e.g., less than 2.5% residual moisture; and As further described herein, a specially designed, cost-effective composite spray drying nozzle is utilized.

[0042] Overview of spray dryers The spray dryer 200 of the present invention provides a donor plasma liquid flow (e.g., pretreated), a drying air flow, a pressurized aerosol gas flow, a disposable compressed air line, a disposable exhaust line, a housing exhaust line, and a leak detection line.

[0043] Along with these flow lines, the spray dryer 200 of the present invention further includes a leak detection method 1000 that utilizes a series of pressure transducers, flow sensors and valves to assess whether the disposable 100 has a leak during spray drying.

[0044] The spray dryer 200 further includes a pressure detection method 1200 that enables a pressure transducer present on the outside of the wall of the disposable 100 to measure the pressure inside the disposable 100. This process involves heating the wall of the disposable, allowing it to soften. During use, the wall of the disposable exerts a force on force sensors PT08 224A and PT09 224B, which measure such force. The amount of force is used to calculate the amount of pressure within the disposable. If the pressure within the disposable 100 exceeds a set amount (e.g., greater than 7.02 psi), the computer system causes the dryer 200 to enter fail-safe mode. If the pressure is within a set acceptable amount (e.g., between about 6.7 psi and less than about 7.02 psi), the computer system determines whether enough plasma has been dried by determining the amount of donor plasma remaining in the donor plasma bag. If a sufficient amount of plasma has been dried, the computer system communicates that the drying run was successful and the finishing process can begin. If an insufficient amount is dried, the drying run fails and the disposable 100 is discarded.

[0045] Additionally, the dryer 200 includes a method 1400 for determining the integrity of the bottom filter 36, the baffle filter 94, and / or the plenum interface. This methodology utilizes pressure transducers in the inlet and housing to determine the pressure gradient during spray drying. The gradient is compared to a model, and if the gradient deviates from the model, the computer system determines that the disposable 100 has failed.

[0046] Overview of spray-dried disposables In particular, the disposable 100 has two general regions: a spray drying head 2 and a plasma drying chamber 28 .

[0047] Overview of the spray drying head The disposable 100 spray-drying head 2 includes a guide 4 offset so as to be positioned above a plenum 6 and a baffle plate 8 having ridges 9 (FIGS. 42A and 43A). The plenum 6 includes the guide 4 at the top of the spray-drying head 2. Within the guide 4 is a spray-drying nozzle assembly 20 having a plasma flow inlet 18 connected to liquid plasma via a plasma tube 16 and a pressurized aerosol gas inlet 14 connected to pressurized gas via an aerosol tube 10 and an aerosol filter 12. Also shown is a drying gas inlet port 22, which communicates with a drying gas source (not shown), which may be air, nitrogen, or another source of drying gas. Optionally, the drying gas inlet port 22 may be covered by a removable cover, such as a self-adhesive paper label. This cover should be removed immediately prior to installation of the disposable 100 in the spray dryer 200. The drying case source may optionally be in communication with a moisture-reducing drying system. In one embodiment, the drying gas source is an Atlas-Copco SF22+ compressor (Atlas Copco, Nacka Municipality, Sweden) with an Atlas-Copco CD45 desiccant drying system, which supplies clean dry air (CDA) to the spray dryer and heats the air to the appropriate temperature for spray drying. In one embodiment, the drying gas flows through a filter from the CDA, such as a Millipore Series 3000 0.2 micron filter CTGB71TP3 manufactured by Millipore Sigma, Danvers, MA, USA. The CDA source, in one embodiment, is used to supply the drying gas and pressurized gas. In certain embodiments, the spray drying nozzle assembly 20 includes a "manifold" that regulates the plasma and aerosol lines. When the plasma source, pressurized gas source, and drying gas source are combined, liquid plasma droplets are formed and dried into dried plasma (e.g., fine amorphous plasma powder). The plenum 6 has a notch, which is a locator, referred to herein as a locator 26 or a second locator, as further described herein.

[0048] Briefly, guide 4 fits into receiver 204 of spray dryer 200, which also properly aligns disposable 100 with dryer 200 (FIGS. 45B and 45C). Guide 4 also aligns spray dryer head 2 in a specific orientation relative to spray dryer 200 so that drying gas inlet 22 receives a drying gas source (not shown). Ridge 9 fits into and supports ridge receiver 207 of spray dryer 200. Guide 4, together with ridge 9, allows disposable 100 to be aligned with spray dryer 200 in a lateral orientation (e.g., in the plane defined by the top and bottom surfaces of the spray dryer) that keeps the disposable stationary so that it does not move up and down within the spray dryer's spray drying chamber housing. Additionally, the ridges 9 of the disposable 100 mate with the receivers 404 of the finisher 400 to secure the disposable 100 to the finisher 400 while the finisher 400 transfers the plasma and seals and separates the disposable into dried plasma units 60. See Figures 46A-C. This alignment configuration also provides for easy and versatile attachment of the disposable to both the dryer and the finisher.

[0049] A first locator, locator 206 (FIGS. 45B, 45C, and 46A), is positioned on the spray dryer apparatus 200, and a second locator, locator 26 (FIGS. 42A and 43A), is positioned on the spray dryer disposable 100 such that the first and second locators engage during installation of the disposable 100 on the spray dryer apparatus 200, allowing alignment of the disposable with the spray dryer apparatus. The same locator 26 (second locator) on the disposable apparatus is also used to align the disposable apparatus with a third locator 452 (see FIGS. 47A-C) on the spray dryer finishing apparatus 400, which directs the dried plasma to specific compartments of the disposable apparatus, seals the dried plasma, and separates it into plasma units with dried plasma. This arrangement aligns the disposables axially to the spray dryer, for example, about an axis defined by the center of the receiver (see axis A in FIG. 43A) of guide 4. This arrangement allows for easy overall attachment of the disposables to both the dryer and the finisher.

[0050] The spray-drying head 2 includes a nozzle assembly 20 as part of the disposable. This nozzle assembly allows for spray drying of plasma within the disposable. The overall system design is modified to include a spray dryer and a nozzle as part of the disposable, replacing the spray dryer, so that spray drying occurs entirely within the disposable. This design helps keep the plasma disposable throughout the drying and finishing process and away from dryer or finisher parts that require decontamination between uses. This design also minimizes contamination of external pathogens by keeping the plasma disposable throughout the process. The nozzle assembly regulates the plasma flow and the pressurized / aerosolized gas flow, both of which are released at the appropriate velocity and airflow to atomize the liquid plasma at the tip of the nozzle, ready for rapid mixing with the drying gas. The disposable 100 spray-drying head 2 further includes a plenum 6 and a baffle plate 8, which directs the drying air for rapid mixing with the aerosolized plasma and forms an air curtain to minimize the accumulation of dried plasma on the drying chamber walls.

[0051] Overview of the plasma drying chamber The drying chamber 28 is a disposable area where the plasma dries. The drying chamber is designed to capture the dried plasma while allowing humid air to evacuate. The design of the drying chamber also allows it to be sealed and separated to form a commercially available dried plasma unit.

[0052] Drying chamber 28 has three general regions: an upper portion defined by dimension X (see FIGS. 44 and 46A ); a middle portion defined by dimension U, which is the region between positions 44A and 44B; and a lower portion defined by dimension V, with the portion below position 44B including filter 36 and separator 38. The upper portion is the space where the atomized liquid plasma encounters the drying gas, evaporating the liquid within the droplets and drying them. In particular, the atomized plasma rapidly mixes with the drying gas and dries, as further described herein. As the plasma rapidly mixes and dries, it circulates and moves downward toward the filter. While the majority of evaporation occurs in the upper portion (dimension X) of drying chamber 28, the plasma continues to dry as it falls into the middle (dimension U) and lower portion (dimension V) of drying chamber 28.

[0053] Drying chamber 28 also includes a central section 46 defined by dimension U, which has "seal and separate" locations 44A and 44B, label 40, spike ports 42A and 42B, and hanging slot 34. Central section 46 also includes locator pin opening 32C. The central section is then processed by a spray dryer finishing device, which moves the dried plasma to specific locations in the plasma drying chamber and seals and separates it at or near cut locations 44A and 44B. The portion between locations 44A and 44B becomes dried plasma unit 60, which is ultimately rehydrated and transfused to the patient.

[0054] The disposable 100 further includes a positioning device for reversibly attaching the outer wall of the disposable 100 to the finisher 400. The outer edges of the walls of the spray drying disposable device 100 are provided with positioning openings 32A, 32B, and 32C (FIGS. 42A and 48A). The positioning pins 432A, 432B, and 432C are positioned on the finisher 400 such that when the positioning openings 32A, 32B, and 32C are positioned around the positioning pins 432A, 432B, and 432C of the finisher 400, the drying chamber 28 of the disposable 100 is aligned on the finisher. See FIGS. 47C, 48B, and 48C.

[0055] The lower part of the drying chamber 28 is provided with a lower filter 36 (also referred to herein as a "trap filter"), a lower filter separator 38, a drying gas outlet 30, and locator pin openings 32A and 32B. Optionally, the gas outlet 30 may be covered by a removable cover, such as a self-adhesive paper label. In one embodiment, this cover should be removed immediately before installing the drying chamber in the spray dryer 200. Simply put, the lower filter separates the dried plasma from the moist air, and the separator acts as a spacer between the drying chamber wall and the filter, allowing air to pass more easily and preventing pressure buildup. Moist air refers to the air moving through the drying chamber and includes a combination of the drying gas, aerosolized gas, and moisture removed from the plasma droplets. During plasma drying, the moist air passes through the lower filter 36 and lower filter separator 38, passes through the air flow path, and exits through the gas outlet 30, leaving the dried plasma behind in the lower filter 36.

[0056] The disposable 100 further includes an alternative alignment configuration for the gas outlet 30 of the disposable 100 and the gas exhaust port 208 of the dryer 200. The spray dryer has a gas exhaust port 208 for exhausting the drying gas, and the bottom of the disposable 100 has a gas outlet 30 that mates with the exhaust port 208 of the dryer 200 (FIGS. 45B and 46A). Additionally, the spray dryer finisher 400 has a receiver 414 for the drying gas outlet 30 to secure the bottom of the disposable 100 to the finisher 400 (FIGS. 48B, 48C). Again, this drying gas device allows for universal attachment of the disposable to both dryers and finishers.

[0057] Additionally, the overall length of the disposable (measured from the top of the spray-drying head to the bottom of the drying chamber) is limited to about 40 inches or less (e.g., about 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, or 24 inches or less), preferably about 34.8 inches. Disposables having a length of about 40 inches or less have been difficult to achieve because drying of the plasma occurs in a smaller space and volume, but is done gently without degrading plasma proteins. The disposable length, measured from the bottom of the spray-drying head 2 or the bottom of the baffle plate 8 to the bottom of the filter 36, shown as dimension Y in FIG. 46A, is about 31 inches or less (e.g., about 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, or 19 inches or less), and in one embodiment, is preferably about 25.9 inches. In another aspect, the area of ​​the disposable region 100 encompassed by dimension Z, which is the length from the bottom of the spray-drying head 2 and the top of the filter 36, is about 22 inches or less (e.g., about 22, 21, 20, 19, 18, 17, 16, 15, or 14 inches), preferably about 19.11 inches. In yet another example, the length of dimension X, which is the length between the bottom and top 46 of the spray-drying head 2, is less than about 16 inches (e.g., about 16, 15, 14, 13, 12, 11, 10, 9, or 8 inches), preferably about 12.14 inches. In one embodiment, the length of a disposable can be varied or shortened. For example, the length of a disposable of the present invention can be further shortened by about 1 inch to about 8 inches (e.g., 1, 2, 3, 4, 5, 6, 7, or 8 inches) along dimension X, thereby shortening the overall length by the same amount. In other embodiments, the disposable can also be shortened by the same amount everywhere along dimensions Y and Z.

[0058] Computational model In some figures, computational models were used to show flow paths, particle evaporation, etc. Figure 42B shows the three-dimensional flow geometry of the disposable in operation that was used in the model.

[0059] The 3D model shown in Figure 42B was based on the disposable shown in Figure 42A and the dryer shown in Figure 42B. Figures 45A-45C. These computer simulations show that the flow and mixing process was created by first constructing a 3D flow field geometry. See Figure 42B. This geometry was extracted from a computer-aided design (CAD) model of the system hardware to create a high-fidelity representation of the flow field within the ODP system. 0.0195m 3 The volumetric flow domain was discretized into 3.3M spatial cells, and a computational mesh was generated using the commercially available Ansys-Gambit meshing software. The flow model was calculated using a commercially available computer code; Ansys-Fluent version 2019-R1, running on an HPZ840 multiprocessor workstation.

[0060] The simulations utilized ideal gas properties, a KE turbulence model, and a steady-state segregation solver that assumed the following: Drying gas inlet temperature = 114C Drying chamber exhaust temperature = 65C System heat loss = 0.18kW Drying gas flow = 750 slpm Atomizer aerosol gas flow = 40 slpm Supply rate = 13.5 mL / min, varies depending on exhaust temperature Liquid droplets with a non-volatile mass of 8.5% and a diameter of 5 microns (monodisperse size) Exhaust port pressure = 2.76 kPa (0.4 psig)

[0061] The inlet and product capture filters are modeled using a "porous zone" function with flow resistance values ​​set to match the measured operating pressures in the drying gas manifold of 71.7 kPa (10.4 psig) and 27.6 kPa (4 psig) in the drying chamber at the start of the batch.

[0062] To calculate the average droplet diameter and temperature during a constant-rate evaporation period for a given set of process conditions, two customized C programs, "prsc_udf_multi_2017.c" and "processdata_multi_2017.c," were developed in PARSEC to obtain the average droplet drying path from the converged Fluent-coupled DPM solution. The program "prsc_udf_multi_2017.c" is used to incrementally export the droplet tracking data for information of interest. The program "prsc_udf_multi_2017.c" reads the exported data file generated from the first program and then obtains the averaged path from all tracked particles. The output file can be loaded into an Excel file.

[0063] The data shown in Figure 42B, 43Ka, 43Ma, 43Na, 43O, 43P, 43S, 43Sa, and 43T were generated using this model.

[0064] Finishing machine overview Once spray drying is completed on dryer 200, a finisher 400 or 400' of the present invention moves the plasma to the desired compartment, then seals the disposable walls and cuts the disposable walls to form the dried plasma units. The finisher 400 or 400' provides an impactor, sealer, separator, and air extraction.

[0065] Workflow Overview A summary of the process using the disposables, spray dryer, and finisher described herein is as follows: The spray-drying plasma methodology of the present invention includes pre-treating a provided liquid plasma unit or a thawed previously frozen liquid plasma unit, drying the liquid plasma using a spray-drying apparatus equipped with a spray-drying disposable device to obtain a disposable with dried plasma, and finishing the disposable using a finishing apparatus designed to seal and separate the disposable, converting it into a dried plasma unit. The unit can be used or stored. Once ready for use, the plasma unit is rehydrated and ready for transfusion to a recipient.

[0066] Regarding pretreatment, the pretreatment process involves adding a biocompatible component (e.g., a spray-drying stable acidic substance) to liquid plasma (or thawed fresh frozen plasma) that protects plasma proteins during the spray-drying process, which involves high temperature and pressure.

[0067] In one embodiment, creating the pretreatment solution involves adding to a solvent such as SWFI about 3.0 to about 7.0 (e.g., 3.0, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, and 7.0) mmol of HCl and about 15 to about 30 mmol of glycine (e.g., about 15, 17, 20, 22, 25, 27, and 30 mmol of glycine) in 50 mL of solvent to obtain 260 mL of formulated plasma, i.e., about 440 mM glycine and about 106 mM HCl are present in the pretreatment solution. In one embodiment, about 290 mM to about 570 mM (e.g., about 290, 300, 350, 400, 450, 500, 550, and 570) glycine and about 70 mM to about 140 mM (e.g., 70, 80, 90, 100, 110, 120, 130, 140 mM) HCl are present in the pretreatment solution. Pretreatment vessels are commercially available and can be formulated, filled, and finished, for example, by Berkshire Sterile Manufacturing (Lee, Massachusetts, USA). In one embodiment, the pretreatment solution has about 440 mM / 50 ml glycine and 106 mM / 50 ml hydrochloric acid. (United States Pharmacopeial Convention ("USP") Monographs (12601 Twinbrook Parkway, Rockville, MD 20852-1790, USA). The pretreatment solution, when combined with liquid plasma to form formulated plasma, protects plasma proteins during the drying process. The formulated plasma has a pH in the range of about 5.5 to about 7.2, which offsets the effects of spray drying on pH, and is generally closer to normal physiological pH, about 6.5 to 7.8 (e.g., about 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4). The resulting rehydration product is in the pH range of 7.5, 7.6, 7.7, and 7.8 (7.5, 7.6, 7.7, and 7.8), although in some cases, a pH lower than 6.5 or higher than 7.8 may be harmful to the recipient. The dried plasma product obtained from this invention retains its von Willebrand factor and other blood proteins, and is plasma with low cholesterol crystals, low particulates, low pathogens, and well-controlled pH due to the pretreatment steps described above. Furthermore, the resulting dried plasma has certain properties that are distinct from and superior to freeze-dried plasma.

[0068] As known in the art, a sterile connection device (SCD) is used to connect the plasma unit to the pretreatment container and the liquid plasma; in one embodiment, a volume of plasma is transferred using, for example, a blood collection monitor / mixer. After the liquid plasma is transferred to the pretreatment container, in one embodiment, it is gently mixed in the pretreatment container by inversion. Other mixing methods, such as rocking, shaking, and stirring, can be used. Additionally, mixing can be performed by an operator or by devices known in the art. The bag containing the liquid plasma is tubing sealed, separated, and discarded. The pretreatment container 64 with the pretreatment solution and liquid plasma (i.e., formulated plasma 66) is then connected to the disposable device with the plasma tubing 16 using the SCD, resulting in the improved spray-drying disposable device shown in FIG. 42A.

[0069] The spray dryer disposable device 100 is a sterile, non-pyrogenic, single-user container (e.g., approximately 35 inches long) that utilizes a pathogen-retaining filter to filter the air before it enters the drying chamber and as it exits the drying chamber. See FIG. 42A. The spray dryer disposable apparatus is sterilely connected to liquid plasma with plasma tubing, tubing 16.

[0070] Briefly, the drying process is as follows. See Figures 45A-4C, 46A-5B. In one embodiment, pre-treated plasma is aseptically spray-dried in a disposable spray dryer device 100. See Figures 45A-4C. During the process, in one embodiment, a positive air flow is maintained. The pre-treated plasma is atomized using a nozzle contained within the single-use disposable spray dryer device to generate fine plasma droplets. These droplets are then exposed to heated air. The resulting dried plasma particles are captured in filter 36 of drying chamber 28. The disposable spray dryer device is then undocked from the spray dryer and transported to a finishing device.

[0071] The finishing process is outlined below. See Figures 47A-47C, 48A-48C, and 34. Once undocked from the spray-drying apparatus 200, the disposable device 100 with dried plasma is transferred to the finishing apparatus 400. The finishing apparatus 400 mechanically, acoustically, or otherwise impacts or agitates the spray-drying disposable device containing dried plasma to consolidate the dried plasma powder into what will eventually become the spray-dried plasma unit of the spray-drying disposable device. The finishing apparatus utilizes an impactor to assist the dried plasma in moving first to the bottom of the disposable and then to the compartment that will become the spray-dried plasma unit 60 in the second example. The spray-dried plasma unit 60 is sealed and separated from the rest of the disposable device using an impulse seal. This is the final closure step to produce the plasma unit 60. In one embodiment, the seal is visually inspected, the excess portion of the disposable device is discarded, and the dried plasma unit 60 is produced (see Figure 49).

[0072] For an overview of the dried plasma storage process, dried plasma units 60 are removed from the finishing equipment and stored in resealable, moisture-barrier foil pouches containing desiccant. See Patent No. 9,561,184. In one embodiment, the dried plasma units are quarantined and stored refrigerated until all required blood screening tests are completed. Once final release criteria are met, the pouches are opened and the dried plasma units are relabeled for release. The dried plasma units are then placed in resealable or other pouches, sealed, and stored according to the storage protocol.

[0073] In one embodiment, the dried plasma unit is compatible with commercially available fluids or other transfer sets for rehydration with sterile water for injection (SWFI). Once rehydrated, the dried plasma unit 60 is also compatible with blood administration sets for transfusion. In certain embodiments, the spray-dried plasma unit 60 is rehydrated in its existing container using an appropriate amount of sterile water for injection (e.g., 200 mL, 208 mL) prior to transfusion.

[0074] Detailed description of spray dryer The spray dryer 200 provides pressurized aerosol gas, plasma, and drying gas to the disposable 100 and an exhaust for moist air. The disposable device 100 is placed within the dryer, which provides pressurized gas, plasma, and drying gas so that drying can occur within the disposable.

[0075] Figure 45A is a front view of the spray drying apparatus 200 with the door closed, and Figure 45B shows the spray drying apparatus 200 without the door to allow a view into the dryer. Disposables are placed into the dryer for spray drying. Figure 45B shows the projected locator 206, which is a first locator that receives the notch locator 26 of the disposable device 100. Additionally, a receiver 204 (see Figures 45B and 46A) above the projected locator 206 allows the disposable to be easily received so that it is aligned. Figures 45B and 45C also show the spray drying head receiver 210 for receiving the spray drying head 2, including the baffle 6.

[0076] At the top, spray dryer 200 includes an aerosol line 216 that provides a pressurized atomizing gas source (not shown). The gas source provides clean, dry air with a dew point of minus 40° C., such as an Atlas-Copco SF22 oil-free scroll compressor combined with an Atlas-Copco CD45 desiccant dryer (Atlas Copco Manufacturing company, Nacka, Sweden). The pressurized gas source need not be located near spray dryer 200, but can optionally be located at a distance and in a different space. Such a device is intended to be easily connected to or in communication with a device that receives pressurized air. The spray dryer apparatus 200 heats the air from the source to an appropriate temperature (e.g., about 100 to about 120°C (e.g., about 100, 105, 110, 115, 120°C), in one embodiment at about 114°C. See Figures 45A-45C. In one embodiment, there are redundant in-line filters (e.g., commercially available filters of 0.2 μm or less) in the drying gas line and aerosolization gas line in addition to the filters in the spray dryer disposable device, as further described herein.

[0077] A display 212 provides instructions and information to the operator. An aerosol line 216 is adjacent to the spray dryer head 2 installed in the dryer 200. The aerosol line 216 has a luer lock that attaches to the aerosol filter 12 (which may be a luer lock). In one embodiment, they thread together. The aerosol line 216 is adjacent to the aerosol filter 12 and the aerosol tube 10 when the spray dryer head 100 is installed in the dryer 200. In one embodiment, the aerosol line 216 exits the dryer head 2 between about 4 inches and 10 inches, with about 6 inches being the preferred distance, measured from the top of the spray dryer head 2 to the attachment point of the aerosol filter 12. Furthermore, the aerosol line 216 is directed downward with the luer lock filter at the bottom so that an operator can easily reach and attach the aerosol filter 12 to the aerosol line 216 about 4'6" and 5'6" above the floor, with about 5' being the preferred distance.

[0078] Indicator lights 234 (see FIG. 45A) are located above the display 212 and provide color / visual information (e.g., green = proceed, red = problem, yellow = assistance needed) to the operator. Below the display 212 is a peristaltic pump 214 that pumps liquid plasma through guides 226 into the nozzles of the spray-drying head 2. The peristaltic pump 214 has a plunger latch 214A that is used to secure the plasma tubing 16. The peristaltic pump 214 disposably dispenses plasma at the rates described herein. The dryer 200 also includes a hook 222 for hanging the plasma bag, an emergency shut-off switch 218, and a circuit breaker 220. See FIGS. 45A, 45B, and 45C. The tube guides 226 allow the user to easily position and align the plasma tubing 16 that leads to the pretreated liquid plasma bag 64 and the aerosol tubing 10 that attaches to the aerosol line 216. The aerosol tube 10 is attached to an aerosol line 216 via an aerosol filter 12 with a thread lock (eg, luer lock or luer taper) and provides a source of pressurized gas (not shown).

[0079] FIG. 46B shows the disposable spray dryer 100 installed in the dryer 200. This figure illustrates the position of the aerosol filter 12 in the aerosol line 216 of the disposable 100. A plasma / aerosol guide, guide 226, is provided to protect the path of the plasma tubing 16 and aerosol tube 10. The plasma tubing provides the flow of liquid (to be dried) plasma 66, which travels from the liquid plasma bag 64 through the pump 214 to the disposable 100 during spray drying. The aerosol tube 10 provides a continuous flow of pressurized air from the aerosol line 216 to the disposable 100. A continuous flow of plasma and pressurized air is necessary to ensure continuous spray drying, making this guide an important aspect of the present invention. The plasma / aerosol guide 226 allows the tubing to be properly positioned to ensure it does not kink or buckle during operation. The plasma / aerosol guide 226 is positioned sufficiently between the plasma bag hook 222 and the plasma flow inlet 18 on the installed disposable, and between the aerosol tube 10, the aerosol line 216, and the aerosol inlet 14 on the installed disposable. The placement of the plasma / aerosol guide 226 allows for easy threading of both the plasma tube 16 and the aerosol tube 10. Once the disposable 100 is aligned, the operator threads the tubes 10 and 16 through the plasma / aerosol guide 226. In one embodiment, the plasma / aerosol guide 226 has a retention notch for retaining the plasma tube and / or the aerosol tube within the plasma / aerosol guide during operation of the spray dryer. In one embodiment, the plasma / aerosol guide 226 is readily visible to an operator with a height between the 5th and 95th percentiles when standing in front of the dryer (e.g., approximately 2 feet from the dryer) under load.

[0080] 46B also shows the placement of the aerosol line 216, which provides the source of pressurized gas. Once the operator threads the aerosol tube 10 through the plasma / aerosol guide 266, the operator attaches the aerosol filter 12 to the aerosol line 216 by connecting a luer lock or thread lock. In this embodiment, the connection is easy to make and involves only aligning and rotating the luer lock / thread lock. The proximity of the spray drying head 2, plasma / aerosol guide 226, and aerosol line 216 allows the operator to quickly and easily screw in and attach the aerosol line.

[0081] Similarly, once threaded through the plasma / aerosol guide 226, the plasma tube 16 is threaded through the peristaltic pump 214 and a latch 214A is closed onto the plasma tube to hold the plasma tube 16 in place during spray drying. Again, the proximity of the spray drying head 2, plasma / aerosol guide 226 and peristaltic pump 214 allows for quick and easy screwing and fastening.

[0082] The operator controls (e.g., display 212, pump latch 214A, tube guide 226, aerosol line 216, door handle 230) are positioned to be easily visible and operable by a wide range of stator operators. Operators of shorter stature could not easily see the display 212 in previous versions. This problem has been addressed with the present invention, and the display 212 is now easily visible and accessible to 99% of all people with a variety of conditions. These controls are within approximately 12, 13, 14, 15, 16, 17, 18, 19, or 20 inches of each other, and in one embodiment, they are within approximately 15 inches of each other. In one embodiment, the controls are readily visible to operators with heights between the 5th and 99th percentiles when standing in front of the dryer (e.g., about 2 feet from the dryer) and under load. The controls are positioned not only in close proximity to each other, but also in close proximity to the components on which they are attached or used. Furthermore, the controls are oriented in the direction of attachment of their respective components. Additionally, the layout of the plasma / aerosol guide 226, pump latch 214A, and aerosol line 216 are logically arranged according to the air / plasma flow.

[0083] Dryer 200 has a gasket 203. Gasket 203 resides around the perimeter of housing 202 and / or along the inside of door 228. Gasket 203 has a partial hourglass shape when dryer 200 is viewed from the front. Gasket 203 helps form a seal between door 228 and housing 202 to help retain gas between housing 202 and disposable 100 during spray drying operations. Gasket 203 acts as an insulator to prevent gas from escaping dryer 200. Gasket 203 can be made from rubber or a similar material that can be molded into the slot or recess where it resides.

[0084] Similarly, emergency shutoff 218 is located so that it can be easily located by the operator, specifically, it is located lower and further away from the operator controls mentioned above. The idea is that by locating emergency shutoff 218 away from the main controls, it encourages the operator to make a deliberate decision to use it. Next to emergency shutoff 218 is circuit breaker 220. Emergency shutoff 218 and circuit breaker 220 provide two ways to turn off dryer 200 in the event of an emergency.

[0085] 45A-45C also show the spray drying apparatus 200 including an exhaust port 208 that accepts the gas outlet port 30 of the disposable device 100. The alignment apparatus of the present invention, in one embodiment, includes attaching the gas outlet 30 of the disposable 100 to the gas exhaust port 208 of the spray dryer 200 or to the gas outlet receiver 414 of the finisher 400. (See FIGS. 46A-46C and 47A-47C.) By attaching the gas outlet 30 of the disposable 100 to the gas exhaust port 208 of the spray dryer 200 during spray drying, the bottom of the disposable 200 can be secured to the dryer, thereby holding the disposable in place during the plasma drying process. Similarly, the finisher 400 is designed to accept the gas outlet 30 of the disposable 100 via the gas outlet receiver 414 to keep the disposable in place during the plasma drying process by shaking / impinging the plasma in place, removing air, sealing, and separating the plasma. The gas outlet 30 of the disposable device 100 is a cylindrical outlet with a lip made from a strong, rigid plastic material. The exhaust port 208 of the spray dryer 200 has an O-ring and a gasket that secure the lipped cylindrical gas outlet 30 to form a strong attachment. The gas outlet receiver 414 of the finisher 400 has a receiver with a "U"-shaped slot so that the gas outlet can be securely attached to the finisher and remain attached during the finishing process. The disposable gas outlet, the spray dryer gas exhaust port, and / or the gas outlet receiver can include any configuration for attaching the disposable gas outlet so that it remains intact during use of the device or finisher to which it is attached. The gas exhaust port or gas outlet receiver can be made from stainless steel, plastic, rubber, etc.

[0086] Stated differently, in the embodiment shown in FIG. 46A, to align the spray-drying disposable device 100 within the spray-drying apparatus 200, the operator must insert the offset guide 4 of the disposable 100 into the receiver 204 of the dryer 200, align the positioning features of the disposable and the dryer, thereby engaging the retaining clip, and insert the gas outlet of the disposable into the exhaust gas port of the dryer. Once these alignment elements are engaged, the disposable is aligned and ready to be locked into place. After attaching the plasma source and pressurized gas source, the operator can lock the door of the spray-drying chamber housing and begin the spray-drying process. The operator locks the door 228 by swinging the handle 230 side to side to engage and lock it into place. See FIG. 45C. The operator can lock the door by inserting the key 236 into the keyhole 238. In another embodiment, one or any combination of these alignment arrangements can be engaged to align the disposable with the spray drying equipment.

[0087] If the operator improperly aligns the disposable 100 with the dryer 200 (e.g., inserts the spray-drying head 2 with the locator notch 26 facing outward), the ridge 9 will not fully seat in the groove 207 and the spring clip 232 will not engage the spray-drying head 2. In this case, even if the operator attempts to close the door 228, the door 228 will not close. If the door 228 is not fully closed and the handle 230 cannot lock into place, the dryer will not be able to proceed with drying. Preventing drying when the disposable 100 is not properly aligned and installed ensures safe operation.

[0088] In another embodiment, the operator inserts a disposable 100 having a locator notch 26 within 30 degrees (e.g., within 30, 25, 20, 15, 10, or 5 degrees) of the locator protrusion 206. In other words, the operator can approach, but not fully align, the locator notch device. In this case, when the operator closes the door 228, the spray drying head 2 self-aligns so that the locator protrusion 206 is inserted into the locator notch 26. As the door 228 closes, it applies a force to the spray drying head 2, causing it to slide circularly along the receiver 210 until the locators 26 and 206 are aligned, the ridge 9 is fully seated within the groove 207, and the spring clip 232 engages. Aligning the spray drying head is an easy task that does not require a lot of force and / or training, but if the operator mistakenly inserts the spray drying head 2 within about 30 degrees of the correctly positioned notch alignment, the system will automatically correct the spray drying head installation.

[0089] In one embodiment, dryer 200 automatically monitors and controls at least four processes (e.g., pretreated plasma flow, aerosol air flow, drying air flow, and exhaust air flow) to ensure that the drying process is completed within operating ranges. In one embodiment, dryer 200 includes an array of sensors and actuators that allow for automatic control of the spray drying process.

[0090] In one embodiment, the dryer may be run according to the following parameters:

[0091] [Table 1]

[0092] Dryer Architecture The architecture of dryer 200 is shown in Figure 46C. Dryer 200 regulates and / or drives at least the following flow paths: pretreated or donor plasma flow line (lines C, I), dry air line (lines B, E, G), pressurized aerosol gas air line (lines A, D, H), disposable compression line (line F), disposable exhaust line (line J), ​​enclosure / housing exhaust line (line K), and leak detection line (line L). Such flow lines are examples providing plasma, drying gas, pressurized aerosol gas, and / or exhaust flow. Any number of flow configurations can be arranged as long as the dryer provides donor plasma, drying gas, and pressurized aerosol gas to the exhaust lines for disposable and humid air. Additional or fewer flow lines than shown in the figure can provide these flow lines. For example, in one embodiment, clean dry air is the source of both the drying gas and the pressurized aerosol gas. In this embodiment, lines are shared until the pressurized aerosol line branches off into another line. Similarly, the disposable exhaust line and the housing exhaust line can be combined into a single line before passing through a filter and mixing with outside air.

[0093] Plasma Flow Line The plasma flow line provides donor plasma in liquid form to nozzle 20 of disposable 100 at a rate ranging from about 5 to about 20 mL / min for atomization and drying. In one embodiment, the donor plasma is pretreated as described herein.

[0094] The plasma flow line is labeled Line C in FIG. 46C. Plasma flow begins with plasma bag B01, also referred to herein as plasma bag 66. As mentioned above, plasma bag 66 is attached to hook 222. In this embodiment, hook 222 is a hook scale S01, which provides the weight of plasma bag 66. After and during the spray-drying process, the plasma bag 66 and any amount of donor plasma are weighed, and the weight is transmitted to a computer system having, among other things, memory, storage, and a processor. The weight of the plasma bag with the pretreated plasma can determine the amount of pretreated donor plasma to be dried. In one embodiment, the pretreated plasma weighs 330 to about 385 g, which means the volume of the pretreated plasma is about 335 ml to about 395 ml. This is determined using calculations for the density of the pretreated plasma, which is about 1.02 to 1.025 g / mL. The plasma tubing 16 is 1 / 8 inch, and in one embodiment, the flow rate is set at 13 g / min.

[0095] The pretreated plasma travels through the plasma tubing 16 and the peristaltic pump 214, P01, which regulates the plasma flow rate. A tubing clamp 244 is located between the plasma bag 66 and the peristaltic pump 214 and can be used to manually open and close the plasma tubing 16. The peristaltic pump 214 has a door or latch 214A. A sensor 246, shown as sensor OS10 in FIG. 46C, is located on the peristaltic pump latch 214A and evaluates the latch state, either open or closed. When the sensor detects a closed latch 214A, a signal is communicated to a computer system that communicates with the peristaltic pump 214 to proceed with the pumping of the pretreated plasma. If the peristaltic pump latch 214A is not closed, the computer system displays a message to the user to close the latch 214A. The sensor is generally a device that provides input data to the system, which converts analog data from the sensor (e.g., when the latch is closed) into digital data. The plasma flows through the peristaltic pump 214 at a rate specified by the pump 214 to the nozzle assembly 20, shown as position I in FIG. 46C. The pump 214 is instructed by the computer system as to speed and to proceed or stop once drying is complete or the desired weight of the pre-treated plasma bag is achieved (e.g., between about 66 grams and about 85 grams). At the nozzle assembly, the plasma contacts the pressurized aerosol gas and atomizes, as described herein. Note that FIG. 46C shows the position of the nozzle assembly 20 when the disposable 100 is inserted into the dryer 200. The plasma flow rate at the nozzle is about 5 to about 20 mL / min.

[0096] Dry Gas Flow Lines As further described herein, the dry gas flow line provides clean, heated, dry air to the atomized liquid plasma droplets to dry them during rapid mixing within the disposable 100.

[0097] In the embodiment shown in Figure 46C, the dry air line is the source of the drying gas and the pressurized aerosol gas. In other embodiments, they may be separate systems.

[0098] The dry air line, as shown in FIG. 46C, begins with a compressed dry air (CDA) supply, continues through lines B, E, and ends at G when the dryer is operating. As mentioned above, CDA is commercially available. The CDA system connects to the dryer 200 via connector 248, designated CN01 in FIG. 46C. Upon entering the dryer 200, the clean air travels through pressure transducer PT01 250, ball valve PV01 254, and pressure regulator PR01 256. A pressure transducer is an electromechanical device designed to measure pressure. The pressure transducer senses the applied pressure and provides an output consisting of an electrical signal indicative of the amount of pressure. In one embodiment, the pressure transducer has an electrical output that is directly proportional to the applied air pressure. Pressure transducer PT01 250 measures the pressure of the dry gas in the line and communicates the pressure to the computer system via a digital signal. The pressure of the clean air at pressure transducer PT01 250 ranges from about 80 psig to about 120 psig. The wire, in one embodiment, is a 1-inch wire moving at a speed of 790 sLpm. The drying gas velocity ranges from about 10 to about 1000 sLpm. The solenoid valve is an electrically controlled valve. The solenoid valve in dryer 200 has an electric coil with a movable ferromagnetic core and a plunger at its center. The solenoid valve drives valve PV01 254, which is a pneumatically actuated three-way ball valve whose actuating air pressure is controlled by the solenoid valve. When commanded open, the solenoid valve is energized, thereby allowing actuating air to flow to the pneumatic actuator. This air pressure then rotates the ball valve 90 degrees, allowing the drying gas to flow. Specifically, this valve uses air pressure to rotate a ball 90°, allowing the downstream line to connect to ambient air (when in "closed" or "off") or pressurized CDA air (when in "open" or "on"). The control air pressure itself is enabled / disabled via a solenoid valve, which controls only the air that actuates valve PV01 254.Downstream of the pneumatically actuated ball valve PV01 254 is a tie port, which allows for in-line supply of drying gas but also allows a small amount to be diverted to an air manifold, as described further herein. Similarly, a pressure regulator, such as PR01 256, adjusts the system flow pressure in response to upstream or downstream pressure changes. When the drying gas exits pressure regulator PR01 256, the purified air has a pressure of approximately 70 to 80 psig and flows at a rate of approximately 10 to 790 slpm. The purified air then passes through filter F01 258, a 0.2-micron hydrophobic polytetrafluoroethylene filter suitable for removing pathogens. This filter ensures that pathogens from the CDA supply do not contaminate the drying process. After passing through filter F01 258, excess pressure, if any, is relieved via pressure relief valve PRV04260 by allowing the pressurized air to exit the system through a secondary passageway and vent to the room. Pressure transducer PT02 262 measures the pressure clean air in the line to ensure the pressure is within the desired range before heating. The pressure of the clean air at pressure transducer PT02 262 ranges from about 70 psig to about 80 psig.

[0099] Following line B in FIG. 46C, clean, dry air flows through mass flow controller MFC02264. A mass flow controller is a device used to measure and control the flow of clean, dry air. The mass flow controller used with the dryer of the present invention has an inlet port, an outlet port, a mass flow sensor, and a proportional control valve. Mass flow controller MFC02264 regulates the flow of clean, dry air in a range of about 0 to about 1,000 slpm. The clean, dry air flows through temperature transducer TT03 266, which measures the temperature of the air and converts the temperature into a digital signal that is sent to a computer system. During use, the temperature of temperature transducer TT03 266 measures a range of about 10°C to 35°C. Based on the clean, dry air temperature measured by temperature transducer TT03 266, the computer system calculates the amount of heat required to raise the temperature of the clean, dry air to a range of about 110°C to about 120°C. This amount needed to heat the clean air is communicated by the computer system to heater H01 275, which applies the calculated amount of heat to the clean dry air, thereby obtaining heated dry gas that is used to dry the atomized liquid plasma. Thermocouple sensors TT04 278 and TT05 280 measure the temperature to ensure the proper temperature range is achieved.

[0100] After passing through mass flow controller MVC02 264 and temperature transducer TT03 266, the heated drying air flows through pneumatically controlled ball valve PV03 268 and filter F04 270. The pneumatically controlled ball valve opens and closes the valve using air pressure. Station 1A of air manifold AM01 330 is used to control valve PV03 268. The pneumatically controlled ball valve PV03 268 is activated when MFC02 is commanded to begin flowing. This serves as a safety control in case MFC02 fails to control the air flow and the valve closes. During the spray drying process, pneumatic valve PV03 is opened and solenoid valve PV06 322 is closed to direct air to line B. When the disposable compression line is used after spray drying is complete, air pressure valve PV03 268 is closed and solenoid valve PV06 322 diverts the air flow from clean drying air from line B to line F. Filter F04 270 is a redundant filter to prevent pathogens from being introduced into the plasma during drying. Filter F04 270 is a 0.2 micron hydrophobic polytetrafluoroethylene filter.

[0101] Continuing along line E, the heated drying gas passes through pressure transducer PT05 276, which measures the pressure of the heated drying gas immediately before entering disposable 2 when disposable 2 is installed. The clean air pressure at pressure transducer PT05 276 ranges from about 10 to about 20 psig. In addition to measuring the pressure, temperature transducers TT04 278 and TT05 280 redundantly measure the temperature of the heated drying gas, which ranges from about 110°C to about 120°C. At position G in Figure 46C, the heated drying gas enters inlet deflector 242 (elbow) and enters plenum 6 of spray-drying head 2, which provides uniform air pressure as described herein. The heated drying gas flow rate upon entering the nozzle is about 720 to about 780 slpm, and the temperature is about 110°C to about 120°C.

[0102] Pneumatic piston PP01 324 lowers deflector 242 into spray-drying head 2 during spray drying and raises deflector 242 when spray drying is complete. Piston PP01 can be locked or unlocked and is in an up position (when not in use) and a down position (during spray drying). Piston PP01 324 has sensors OS06 326, which detect when piston PP01 324 is in the up position, and OS05 328, which detect when piston PP01 324 is in the down position. When not moving, the piston is locked to prevent unwanted movement. Before spray drying begins, a computer system signals piston PP01 324 to lower into plenum 6 of spray-drying head 2 to provide uniform air pressure for spray drying. Deflector 242 includes a ball-in-socket style gimble. During manufacturing, the gimble allows deflector 242 to be aligned with disposable 2 to form a leak-tight seal during use.

[0103] The drying gas line has an internal path used for the compression line of the disposable. Once spray drying is complete, removal of moist air is assisted by the bag compression line, line F. The bag compression line actually injects air between the outer wall of the disposable 100 and the inner wall of the plasma drying chamber housing 202, effectively compressing the air within the disposable 100 through line J and out the exhaust port 208.

[0104] The air used for the disposable's compression line branches off from the clean air drying gas line, line B, after passing through mass flow controller MFC02264 and travels through solenoid valve PV06 322 using line F. To divert the air to line F, pneumatic valve PV03 is closed and solenoid valve PV06 322 is opened. Meanwhile, during the spray drying process, pneumatic valve PV03 is opened and solenoid valve PV06 322 is closed to direct the air to line B. As the air travels through line F, the disposable's compression line, the flow enters housing 202 through connector CN05 296. After drying is complete, the disposable's compression line is used, and pneumatic valve PV03 268 is closed and solenoid valve PV06 322 is opened, allowing air to travel into housing 202 and help push the moist air out of disposable 100.

[0105] Pressurized Aerosol Gas Flow Lines The pressurized aerosol gas flow line provides pressurized gas flow at a rate sufficient to atomize donor plasma droplets at the nozzle 20 of the disposable 100. The pressurized aerosol gas flow rate as it enters the nozzle is about 30 to about 50 slpm.

[0106] The aerosol pressurized line also originates from a compressed clean air source. After passing through filter F01 258, the clean air line supply branches off to line A in Figure 46C. A portion of the clean, dry air branches off and follows line D through mass flow controller MFC01 282. A mass flow controller is a device used to measure and control the flow of clean, dry air. In this case, the mass flow controller increases the flow of clean, dry air sufficiently so that when it reaches nozzle 20 in the drying chamber 28 of disposable 2, the donor plasma is atomized. Mass flow controller MFC01 282 pressurizes the clean, dry air flow to a flow rate in the range of approximately 30 to approximately 50 slpm. This results in aerosol pressurized air that atomizes the liquid plasma droplets. The aerosol pressurized air passes through solenoid valve PV02 284 and pressure transducer PT10 286. Solenoid valve PV02 284 has a plunger that, in its rest position, closes the opening in the line. When current is applied, the coil generates a magnetic field that applies a force to the plunger, opening the line. Pressure transducer PT10 286 measures the pressure and provides an output consisting of an electrical signal indicative of the amount of pressure. In one embodiment, pressure transducer PT10 288 measures the pressure of the pressurized aerosol gas in the line and communicates the pressure to a computer system via an electrical signal. The pressure of the purified air measured by pressure transducer PT10 286 ranges from approximately 20 to approximately 40 psig. The pressurized aerosol gas passes through filter F08, a 0.2-micron hydrophobic polytetrafluoroethylene filter to remove pathogens, and continues on line D. Filter F08 is another redundant filter to prevent pathogens in the purified dry air from entering the drying chamber.

[0107] The aerosol pressurized air passes through the aerosol line 216 of the dryer 200, passes through the aerosol filter 12 of the disposable 2, and terminates at location H at the nozzle 20, as shown in FIG. 46C, as further described herein.

[0108] Plasma drying chamber housing 202 of dryer 200 The drying chamber housing 202 of the dryer 200 houses the disposable 100 during use and is described in detail herein.

[0109] With reference to FIG. 46C, baffle filter 94 is designated as filter F05, and lower / trap filter 36 is designated as filter F06, both of which are described in detail herein. A disposable is attached to receiver and drying gas inlet 204, also referred to as connector CN03, which is described further herein. Dryer 200 includes pressure transducer PT08 224A and pressure transducer PT09 224B, which are described further herein. Dryer 200 further includes sensor OS04 292 for determining whether door 228 is closed and sensor OS07 294 for ensuring door 228 is locked with door handle 230 (SS01). Gas exhaust port 208 is designated as connector CN06 and leads to line J for the disposable exhaust line for the exit of wet air. Connector CN05 296 is a connector to a disposable compression line, designated line F, as further described herein, and connector CN07 298 is a connector to an enclosure exhaust line, designated line K, as further described herein.

[0110] Disposable Exhaust Line A disposable exhaust line designated as line J exhausts humid air during spray drying. As described herein, humid air is a mixture of drying gas, pressurized aerosol gas, and evaporated water from the plasma droplets. The humid air within the disposable 100 during spray drying exits through this disposable exhaust line, line J.

[0111] Referring to FIG. 46C, in one embodiment, the disposable exhaust line is a 1-inch internal diameter flowing at 790 slpm. The moist air first exits the gas exhaust port 208 and passes through temperature transducers TT06 300 and TT07 302, which measure the temperature of the moist air as it exits the disposable 100, followed by pressure transducer PT06 304, which measures pressure and flow. During spray drying, the temperature range of temperature transducers TT06 300 and TT07 302 is between about 15°C and about 75°C. During spray drying, pressure transducer PT06 304 measures pressures ranging from about 0 to about 5 psig and flow rates ranging from about 10 to about 790 slpm. The exhaust air passes through normally open pneumatic valve PV04 306, which uses air pressure to open and close the valve. Station 1B of air manifold AM01 330 is used to control valve PV04 306. Air pressure valve PV04 306 is normally open and will remain open in the event of a system shutdown or overpressurization. This acts as a safety control as it allows airflow to exit the system. The moist air passes through filter F07 308 to mix with the ambient air before exiting connector CN02 310. Filter F07 308 is a 0.1 micron hydrophobic polytetrafluoroethylene filter.

[0112] Housing / Enclosure Exhaust Line The enclosure exhaust line is for removing air that is within the plasma drying chamber housing but outside of the disposable 100. Moist air within the disposable 100 is exhausted through line J, while after drying is complete or if there is a failure, residual air within the housing between the outer wall of the disposable 100 and the inner wall of the housing 202 is removed through this path, line K.

[0113] Residual air from the housing 202 exits through connector CN07 298 and flows through pressure transducer PT07 312, which measures pressure and flow. Residual air passes through normally open pneumatic valve PV05 314, which uses air pressure to open and close the valve. Station 2A of air manifold AM01 330 is used to control valve PV05 314. This valve remains open in the event of a system shutdown or overpressurization. This serves as a safety control, allowing air to freely flow out of the system even when power is removed. Before exiting through connector CN02 310, the residual air passes through filter F09 316 before the moist air exits. Filter F09 316 is a 0.1 micron hydrophobic polytetrafluoroethylene filter.

[0114] Line K further includes an internal path for leak detection, methods of which are described further herein. This line measures the flow of residual air between the disposable and the housing. The inner loop includes solenoid valve PV07 318 and flow sensor FS01 320. The solenoid valve has an electric coil with a movable ferromagnetic core and a plunger at its center. During spray drying, solenoid valve PV07 318 remains closed. In the rest position, the plunger remains closed. When current is applied, the coil generates a magnetic field that applies a force to the plunger, opening the line. The FS01 320 flow sensor measures the air flow. Flow sensor FS01 320 includes a pressure transducer that measures the pressure across an internal flow restriction, from which the flow rate can be calculated. In this case, the flow sensor measures the actual mass flow rate of residual air. This inner loop is used for leak detection, as described further herein.

[0115] Dryer Air Manifold The air manifold AM01 330a branch chamber extracts a small amount of clean, dry air to create mechanical motion. The extracted air is used to actuate the pneumatic valves (PV) and pneumatic pistons (PP) within the spray dryer 200. The manifold shows three stations: Station 1, Station 2, and Station 3. Multiple actuators are part of each station. Station 1 actuates pneumatic valves PV03 268 and PV04 306; Station 2 actuates pneumatic valve PV05 314 and piston PP01 324 (unlock); and Station 3 actuates piston PP01 324 (down) and piston PP01 324 (up). Air manifolds are commercially available, including multi-port solenoid valves such as the SMCSY3000 (Airline Hydraulics, North Kingstown, RI). In the unpowered state, pneumatic valve PV03 268 is normally closed, and pneumatic valves PV04 306 and PV05 are normally open. In the unpowered state, pneumatic piston PP01 is locked, and during drying, pneumatic piston PP01 324 is in the down position. The arrangement of stations and actuators can be modified as needed. A pneumatic manifold is used to operate the spray dryer valves and pistons, although any commercially available device such as a motor could be used.

[0116] Leak Detection Method and System 1000 The present invention, in one embodiment, includes a leak detection method 1000 that the dryer 200 undergoes. (FIG. 46D) The dryer 200 is designed to determine if a leak exists in the disposable 100, or, in other words, to determine the integrity of the disposable 100. In one embodiment, the leak detection function of the dryer 200 is performed after installation of the disposable 100 and after spray drying. This test helps determine if the disposable 100 can withstand or has withstood the pressure and flow of the dryer 200. The dryer 200 and method 1000 utilize two methods to determine if a disposable leak exists. The first method is a pressure decay method, i.e., method 1030, and the second method is a flow sensor method, i.e., method 1032. The two leak detection methods can be used individually or together.

[0117] Both methods involve starting the dryer 200 and loading the disposable 100 as described herein. The dryer 200 heats until the exhaust temperature, as measured by temperature transducers TT06 300 and TT07 302, is measured at a set temperature, e.g., 65°C. The temperature transducers signal that the set temperature has been met, and the computer system commands the mass flow controller MFC02 to shut down. In this step 1002, the drying gas is stopped by commanding the mass flow controller MFC02 to stop flow and close the pneumatic valve PV03.

[0118] In addition to stopping the flow of drying gas, the exhaust line is also closed in step 1004. In step 1004, the computer system communicates with pneumatic valve PV04 306 to temporarily close the pneumatic valve during the leak detection test.

[0119] In the pressure decay method, methodology 1030, in step 1006, dry gas slowly pressurizes the disposable container at a flow rate of about 50 SLPM to a pressure of about 2 psig at the dry gas outlet 208 as measured by pressure transducer PT06 304. In this step, the disposable can be pressurized to a range of about 1.5 psig to about 4 psig, and the flow rate can range from about 1 SLPM to about 50 SLPM. This pressurization is accomplished using mass flow controller MFC02 264.

[0120] Next, the pressure decay method includes waiting 1008 for a period of time (e.g., about 30 seconds, 1 minute, 1.5 minutes, 2 minutes, 2.5 minutes, 3 minutes, 3.5 minutes, 4 minutes, 4.5 minutes, 5 minutes). In one embodiment, the method includes waiting about 1 minute.

[0121] After a period of time has elapsed, pressure transducer PT06 304 measures the pressure in step 1010 and sends a digital signal representing the value to the computer system's memory. If the pressure value is such that there is a decrease below a set amount (e.g., a threshold amount), the disposable is discarded in step 1012. If the pressure value in step 1014 is above an acceptable set amount, the disposable is determined to be acceptable for spray drying by this test. The threshold amount of pressure ranges from about 1 psig to about 3.5 psig, and in one embodiment, is about 1.3 psig. In other embodiments, instead of using a set amount, the computer system using a processor can calculate the rate of change of pressure decrease, or can calculate pressure decay by determining the change in volume instead of pressure.

[0122] In a second leak detection method, methodology 1032, the flow sensor method includes closing pneumatic valve PV05 314 in the enclosure's relief line, line K in FIG. 46C, in step 1016. Closing pneumatic valve PV05 314 allows dry gas to flow through the leak detection line, line L. The computer system sends a signal to pneumatic valve PV05 314 to close in step 1016, and then sends a signal to solenoid valve PV07 318 to open in step 1018. Steps 1016 and 1018 can occur simultaneously or sequentially. Once both steps are completed, airflow is measured using sensor FS01 320 in step 1020. Instead of measuring pressure and inferring airflow, airflow is measured directly in this step. The computer system uses a processor to compare the measured airflow to a set airflow. If the average air flow is less than the set amount, then in step 1022 the software determines that the disposable 100 is suitable for use in the spray drying process. However, if the air flow is greater than the set amount, then in step 1024 the computer system determines that the disposable 100 should be discarded. The set air flow rate (e.g., threshold flow rate) for comparing the measured air flow rate is 10 cm 2 / min~30cm 2 / min (e.g., 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30 cm 2 / min). In one embodiment, the set air flow rate is 20 cm 2 / min.

[0123] Once one or both tests are complete, in step 1026 the computer system communicates that the tests are complete and actuates the valves as follows: pneumatic valve PV04 306 is opened on the exhaust line, line J, pneumatic valve PV05 314 is opened on the enclosure / housing exhaust line, line K, and solenoid valve PV07 318 on the leak detection line, line L is closed.

[0124] In one embodiment, the pressure decay method 1030 or the flow sensor method 1032 can be used independently or together. If one of the methods is used in a spray drying system, the results of that test determine whether the disposable 100 is suitable for use in the spray drying process. If both methods are used, as in step 1028, the results of both tests (e.g., leak detection pressure values ​​or leak detection flow rate values) are compared, and if both results indicate the disposable 100 is suitable for use, the computer system communicates that the disposable 100 can be used for spray drying or that spray drying can proceed. If both methodologies are used and one test indicates the spray drying disposable 100 should be used and the other test indicates it should not be used, the disposable 100 should be discarded and not used in the spray drying process. This comparison is embodied in step 1028 and is performed by a processor in the computer system according to a programmed routine. The results of the determination are communicated to the user. In one embodiment, the result is communicated that the disposable 200 is suitable or unsuitable to an output device such as the display 212 on the dryer 200. In other embodiments, the communication may be printed, provided audibly (e.g., by a digital voice instructing the user to remove the disposable 200), or provided visually by an indicator light 224 (e.g., red to stop and remove the disposable 100, or green to go).

[0125] Disposable Pressure Sensing Method and System 1200 The present invention further includes a disposable pressure detection method and system 1200. See FIG. 46E. This methodology allows the dryer 200 to measure the pressure inside the disposable 100 using a pressure sensor located outside the disposable 100. Although the sensor resides within the housing 202, the wall material of the disposable 100 partially conforms to the shape of the inner wall of the housing 202, especially when heated drying gas floods the disposable 100. This is due to the flexibility of the disposable wall. In doing so, the pressure sensor attached to the inner wall of the housing 202 measures the pressure exerted by the outer wall of the disposable 100, which represents the air pressure inside the disposable 100. This test can be performed before, during, and after the spray drying process.

[0126] Disposable pressure sensing methodology 1200 begins at step 1202, where dryer 200 is started and the drying gas is run and heated to an inlet temperature of at least about 65°C or higher (e.g., up to about 130°C), as measured by either temperature transducer TT04 278 or temperature transducer TT05 280, or both. In one embodiment, this method can be performed with or without heated disposables. In another embodiment, the spray dryer is heated to an exhaust temperature of about 55°C to about 75°C, or an inlet temperature in the range of about 110°C to about 120°C. In one embodiment, one, two, or three temperature sensors or transducers can be used.

[0127] As heated dry air from line E enters the dry gas inlet 204, the heated air causes the outer wall of the disposable to exert a force on one or both of pressure transducers PT008224A or PT009224B. The pressure transducers detect the pressure and generate an electrical signal proportional to the detected pressure. The detected pressure is proportional to the amount of mechanical force exerted on the pressure transducer. A proportional digital signal value is generated and transmitted to the computer system's memory. The computer system's processor calculates the amount of pressure within the disposable 100 according to the following equation in step 1206: Drying chamber pressure (PT08 / PT09) = (digital signal mV) x (gain) - offset Where, gain: approximately 2, offset: approximately -0.1

[0128] During manufacturing, the gain and offset of patents 008224A and 009224B are determined by referencing the digital signal to a known, calibrated pressure gauge. The disposable 2 is pressurized to various pressures (e.g., 1.0, 3.0, 5.0, approximately 6.0 psig) as described herein. The output digital signal is then plotted on a chart against the calibrated gauge pressure. A line of the form y=(m)x(x)+b can then be drawn, where (m) is the gain and b is the offset. This is repeated for both PT008224A and PT009224B.

[0129] If the pressure becomes too high, the dryer enters its failsafe mode in step 1210. Specifically, the dryer enters failsafe mode if the set failsafe pressure (e.g., a second threshold pressure amount) is equal to or greater than 7.1 psi to about 8 psi (e.g., about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, about 8.0 psi). In this case, the computer system communicates that a pressure in this range will enter failsafe mode. This is communicated to the operator via an output device (e.g., display 212), as described herein. In other embodiments, the communication can be printed, provided audibly, or provided visually via indicator light 224. Failsafe mode generally means, in one embodiment, that dryer 200 is shut down, drying gas and plasma are stopped from flowing in, and humid air is allowed to flow out. Step 1212. Thus, the computer system communicates and activates the following valves on the inlet side by closing pneumatic valve PV02 284, pneumatic valve PV03 268, solenoid valve PV06 322, mass flow controller MFC01 264, and mass flow controller MFC02 282, and deactivating heater H01 275 and peristaltic pump PO1 214. On the outlet side, the computer system communicates and activates by opening output valves (PV04, PV05) and disabling PV07 to allow the humid air to be filtered and outflow / mixed with ambient air. If the system detects excessive heater temperature at TS01 272 or TS02 274, excessive aerosol pressure at PT10 286, or excessive dry air pressure at PT05 276, a fail-safe mode can also be entered.

[0130] When the pressure reaches within a set pressure amount (e.g., a first threshold pressure amount), the drying run ends. In one embodiment, the set pressure amount when the drying run ends is in the range of about 5.0 to about 7.0 psi (e.g., about 5.0, 5.5, 6.0, 6.5, and 7.0 psi). In one embodiment, the set pressure amount is about 6.7 psi to about 7.02 psi. Step 1208. In this case, the computer system communicates to the operator via an output device (e.g., display 212) that the drying run of the disposable 100 has ended, as described herein.

[0131] Once the pressure reaches the set pressure amount in step 1208, the computer system determines whether enough pre-processed plasma has been processed for a finished dried plasma unit (e.g., a plasma unit with a sufficient amount of plasma that can be used for transfusion after reconstitution). During the drying operation, the pressure through the disposable 100 gradually increases by approximately 2 psi. The end of the drying run can be determined by the pressure exceeding the limit set forth in step 1208 or by detecting a sudden increase in the exhaust temperature as measured by TT06 300 or TT07 302. When the exhaust temperature increases by approximately 1.5°C above the set point (e.g., 66.5°C), the computer system communicates to the operator via an output device (e.g., display 212) that the drying run of the disposable 100 has ended, as described herein.

[0132] The amount of dried or processed plasma can be measured directly or indirectly. In one embodiment, the amount of dried plasma is measured indirectly by determining the amount of donor plasma remaining in the formulated pre-processed plasma bag 66. The less volume remaining in the plasma bag 66, the more volume will be dried, and vice versa. A minimum amount of plasma remains in the tubing. Thus, in one embodiment, to obtain a processing volume of about 15 grams to about 20 grams (e.g., 15, 16, 17, 18, 19, or 20 grams) of dried plasma without bag weight, the total amount of pre-processed donor plasma to be processed (e.g., a threshold processing plasma mass) ranges from about 280 grams to about 390 grams (e.g., about 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, or 390 grams). In one embodiment, the amount of starting pretreated donor plasma is about 320 grams to about 390 grams (e.g., 320, 330, 340, 350, 360, 370, 380, or 390 grams). Note that the pretreated donor plasma has about 50 to about 60 grams of pretreatment solution and about 220 to about 340 grams of donor plasma.

[0133] In other embodiments, other indirect measurements can determine the amount of plasma processed, including determining the volume moved through plasma tubing 16 or pump 216. Because the density of pre-processed donor plasma is 1.02 grams / milliliter to 1.03 grams / milliliter, the mass of processed plasma can be determined if the volume is known.

[0134] Other embodiments include direct measurement of the processed dried plasma. In such embodiments, the weight of the disposable before and after spray drying can be obtained, and the difference is the weight of the spray-dried plasma.

[0135] The indirect mass measurement of the donor pre-treated plasma bag or the direct measurement of the dried plasma in the disposable 100 is communicated to a computer system whose processor determines whether a sufficient amount of pre-treated plasma has been processed. If a sufficient amount of pre-treated plasma has been processed, as described herein, the drying run is considered complete and successful, step 1214. This result is communicated to an operator as described herein, and optionally, in step 1216, the disposable 100 is expanded and compressed to help remove the dried plasma from the interior walls of the disposable 100. Expansion of the disposable 100 occurs by flowing a drying gas through it, and compression of the disposable 100 occurs via line F, as described herein.

[0136] If an insufficient amount of dried plasma powder has been processed, the drying run fails and the disposable 100 with the partial amount of dried plasma is discarded in step 1212. This result is communicated to the operator as described herein.

[0137] Method and system for detecting spray drying head interface integrity 1400 The present invention includes a method for detecting the integrity of a spray drying disposable 100, including its filter and its interface with the dryer 200. In particular, the present invention includes a method 1400 for determining whether the interface between the bottom filter / trap filter 36, the baffle filter 94, or the deflector 242 and the plenum 6 is compromised. Additionally, the method 1400 also detects seal or integrity defects in the disposable 100.

[0138] This methodology allows for direct detection of spray dried disposable failure and allows for maintaining plasma separation to protect the operator.

[0139] Method 1400 begins by monitoring the pressure above the spray-drying head 2 of the disposable 100 and the pressure within the housing 202 of the dryer 200. Generally, monitoring these pressures and comparing their values ​​at various times allows for a determination of the integrity of the disposable 100 or the integrity of the interface between the disposable 100 and the dryer 200. The pressure generally increases over time in a controlled manner at a constant slope during a spray run. Simply put, if the pressure measurements deviate from this slope, such deviation indicates a failure of the disposable 100 or its interface with the dryer 200.

[0140] Referring to FIG. 46F, step 1402 begins method 1400 by monitoring the pressure with pressure transducer PT05 276 present in dry gas line E just before or as the dry gas enters the disposable 100 at dry gas inlet 242. The method also includes monitoring pressure transducers PT08 224A and PT09 224B, which are located within housing 202 and used to measure the pressure within the disposable 100. Monitoring these pressures refers to measuring pressure at two or more points in time and comparing them to determine a slope step 1404, in step 1402. As described herein, the pressure measurements are converted to a digital value proportional to the amount of pressure sensed. The digital value of pressure from any one of these transducers is communicated to a computer system that performs the comparison of these pressure values ​​and uses its processor to determine the slope.

[0141] In one embodiment, there are two pressure transducers in the housing 202, so the average of the two sensors is used in the calculations below.

[0142] In particular, the formula used to compare pressure values, which is performed periodically, is as follows: Current pressure (psig) - Past pressure (psig) from time X minutes = Y psig / X minutes

[0143] In step 1406, the slope is determined by comparing Y psi / X min at multiple time points from step 1404.

[0144] In other words, the equation that determines the slope is:

number

[0145] Using the slope equation above, the slope is equal to the change in psi over time. The slope of a drying run can be determined, in one embodiment, by performing a drying run, measuring the pressure, and determining the slope, as described herein. After each drying run, the disposable dryer can be visually inspected to determine whether the integrity of the filters and / or interfaces has been compromised. In the inventive spray drying system described herein, if the slope exceeds about 0.02 psig / min or is in the range of about 0.02 psi / min to about 0.2 psig / min (e.g., the slope threshold), the capture / lower filter 36, the baffle filter 94, and the interface between the deflector 242 and the plenum 6 are considered intact, and the drying run is determined to be successful. See step 1408. If the baffle filter 94 and / or the lower filter 36 are defective, the slope will be outside this range. See step 1410. In practice, in certain cases, a momentary drop in pressure (e.g., the slope is still less than 0.02 psig / min) can reflect a defect.

[0146] In one aspect, the slope calculation is determined after at least about 4 minutes of passage and measured periodically over a period of about 35 minutes, which is a typical duration of a spray drying run. In one embodiment, the slope is calculated periodically at time points ranging from every 1 minute to every 10 minutes (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 minutes). In the embodiment shown in Figure 46F, the slope is calculated every 3 minutes (180 seconds).

[0147] An example of a calculated slope for a spray drying run can be seen in Figure 46G, which shows the pressure values ​​(on the left Y-axis) of pressure transducer PT05 176 at the drying gas inlet and pressure transducers PT08 224A and PT09 224B located within housing 202 over time (on the X-axis) from approximately 6 minutes to approximately 32 minutes. The right Y-axis shows the slope or rate of pressure change in psi / min. As can be seen, the slope (e.g., rate of pressure change) is approximately 0.02 psi / min. Figure 46H shows a failure of lower / trap filter 36, and Figure 461 shows a failure of baffle filter 94. In both cases, there is a rapid drop below the 0.02 psi / min slope.

[0148] If the slope is determined to be below a set amount (e.g., 0.02 psi / min), the computer software sends instructions to terminate the drying run and notify the operator via an output device, as described herein. The disposable is discarded.

[0149] Computer Systems In addition to the sensors and actuators described herein (e.g., connectors, differential pressure transducers, flow sensors, heaters, mass flow controllers, sensors, pumps, pneumatic pistons, pressure regulators, pressure relief valves, pressure transducers, valves, scales, solenoids, thermocouples, thermocouple sensors, temperature transducers, etc.), the spray dryer 200 shown in FIGS. 45A-45C and 46A-46B and the finisher 400 or 400′ shown in FIGS. 47-48 further include a computer system. The computer system includes, among other devices, a controller including one or more processors, a bus or other communication mechanism coupled to the one or more processors for communicating information, and a main memory (e.g., RAM) and / or other dynamic storage device coupled to the bus for storing information and instructions executed by the processor. The computer system is integrated with the sensors / actuators and control system to enable computer control of the sensor / actuator operation and data collection and communication. The main memory can also be used to store temporary variables (e.g., pressure, flow rate, time, etc.) or other intermediate information during execution of instructions executed by the controller. Such a computer system also includes a ROM or other static storage device coupled to the bus for storing static information and instructions for the processor. Physical computer-readable storage devices, such as solid-state memory devices, are provided and coupled to the bus for storing information. Output devices of the computer system can be provided, for example, to allow various information to be viewed or perceived in connection with the execution of the instructions. Input devices can be provided, for example, to allow a user to make selections, input data or various other information, or interact in any of a variety of ways with the processor during execution of the instructions. The computer system is also coupled via the bus to one or more display or output devices (e.g., screen displays, touch screens, light beacons, sound indicators, etc.), one or more input devices (e.g., touch screens, etc.).

[0150] In accordance with the disclosed methods, in at least some aspects, the methods are implemented using a computer system in response to a controller executing one or more sequences of one or more instructions contained in a physical memory device attached to a bus, such as a main memory, Execution of the sequences of instructions causes the controller to perform at least some of the process steps described herein.

[0151] The memory device has instructions configured to cause the controller, in combination with inputs from the sensors / actuators, to determine to perform the steps of the dryer 200 or finisher 400 or 400' described herein.

[0152] As used herein, the term "computer-readable medium" refers to any physical medium that participates in providing instructions to a processor for execution (e.g., nonvolatile media, volatile media, magnetic media, optical media, solid-state media, etc.). A computer system utilized in conjunction with dryer 200 or finisher 400 or 400' also advantageously, but optionally, includes a communications module coupled to a bus; such communications interface provides a two-way data communication coupling to a network link (e.g., an Integrated Services Digital Network (ISDN) card, a modem, a Local Area Network (LAN) card, a wireless link, etc.). The network link provides data communication through one or more networks to other data devices (e.g., a network link may provide a connection through a local network to a host computer or to data equipment operated by an Internet Service Provider (ISP)), and the computer system is configured to send and receive data through the networks, network links, and communications interfaces. The communication module can be configured to implement a communication protocol based on Bluetooth® technology, Wi-Fi, Wi-Max, IEEE 802.11 technology, radio frequency (RF) communications, an Infrared Data Association (IrDA) compatible protocol, or a Shared Wireless Access Protocol (SWAP).

[0153] Detailed explanation of spray dried disposables Detailed description of the spray drying head 42A, there is shown a perspective view of a spray drying disposable device 100. As mentioned above, the disposable generally has two parts: a spray drying head 2 and a drying chamber 28. The spray drying head includes a plenum 6, a guide 4, a baffle plate 8, a baffle filter 94, a nozzle 20, and a locator notch 26 (also referred to herein as a "second locator").

[0154] In one embodiment, the purpose of the spray drying head 2 is, in part, to A) help secure the disposable 100 to the dryer 200, B) regulate the flow of drying air, aerosolized pressurized gas, and plasma flow, C) house the nozzle assembly, and D) house the baffle filter.

[0155] With regard to securing the disposable 100 to the dryer 200, the system of the present invention includes an integrated universal alignment system. In one embodiment, the locator notch 26 of the plenum 6 is shown in FIG. 43A. FIG. 43A also better illustrates the plenum 6, guide 4, baffle plate 8, and ridge 9. The locator notch 26, also referred to as the second locator, aligns with the locator protrusion 206, also referred to as the first locator, on the spray dryer 200 (shown in FIGS. 43K, 45B, 45C, and 46A). This arrangement allows for axial alignment of the spray drying head 2 of the disposable 100 with the spray dryer 200. The arrangement can include any configuration that attaches, matches, complements, or otherwise communicates with a locator on the dryer. Examples of positioning arrangements include recess / protrusion arrangements, complementary shape arrangements, hook / receiver arrangements, channel and groove arrangements, latch and catch arrangements, magnetic arrangements, etc. In FIG. 46A, a male locator is on the spray dryer and a complementary female locator is on the disposable, but the arrangements can be reversed. The complementary nature of the devices allows for easy adjustment and alignment by the operator and can prevent the door from closing unless the disposable is aligned within the spray dryer. In one embodiment, the arrangement configuration can include any configuration that allows alignment between the locator on the disposable and the locator on the dryer, and also allows alignment between the disposable and the finisher. In another embodiment, the dryer and finisher have the same locators that mate with the disposable to create universal alignment. Having a universal arrangement reduces the training required and increases muscle memory, as operators insert disposables into the spray dryer and finisher in a similar manner.

[0156] Once the first locator of the spray dryer and the second locator of the disposable are aligned, in one embodiment, the system of the present invention provides positive feedback to the operator. In one embodiment, the spray dryer 200 has a spring clip 232 attached to the top of the drying chamber housing that engages with guide 4 when the disposable is aligned and secured within the spray dryer. See FIG. 46A. The spring clip 232 is optional. In this case, the positive feedback to the operator is an audible "click." Such feedback can include an audible indicator (e.g., an audible click) or a visual indicator (e.g., a sensor that provides communication to a display indicating alignment). The retaining clip 232 is also an alignment element because it aligns with ridge 9, described further below.

[0157] FIG. 43A also shows the guide 4 offset from the center of the baffle plate 8. The offset design of the guide on the plenum 6 allows the disposable 100 to be attached to the receiver 204 (shown in FIGS. 45B and 46A ) of the spray dryer 200 in a specific orientation. Before inserting the disposable device into the dryer, the operator removes and discards the adhesive cover, if present, from the top, exposing the drying gas inlet port 22 and the gas outlet 30. The use of such a cover is optional. In a preferred embodiment, the operator removes and discards the adhesive cover from only the drying gas inlet 22 and inserts the spray dryer head 2 into the spray dryer head receiver 404. The cover for the drying gas outlet 30 at the bottom of the disposable can be removed later just before it is ready to be attached to the gas exhaust port 208. The operator typically aligns the ridge 9 formed by the baffle plate 8 over the spray dryer head 2 of the disposable 100 and inserts it into the groove 207 of the spray dryer 200. See FIG. 46A. Once engaged, the operator can manually push the spray drying head 2 further inward, and it will self-align with the groove receiver 207 as long as the notch locator 26 on the spray drying head 2 is within approximately 30 degrees (e.g., within approximately 30, 25, 20, 15, 10, or 5 degrees) of alignment with the projected locator 206 on the dryer 200. Insertion and alignment of the spray drying head can be accomplished quickly, for example, within 10 seconds (2-5 seconds). The receiver 204 on the guide 4 also serves as the drying gas inlet for the spray dryer and provides a drying gas source (not shown). The ridge 9 on the spray drying head 2 also provides support and complementarily fits into the groove 207 on the receiver 210. This also allows the spray drying head 2 of the disposable 100 to be laterally aligned with the dryer 200.

[0158] In one embodiment, the receiver 210 has grooves 207, as shown in Figure 45B. The arrangement of ridges and grooves between the spray drying head and the dryer can be any arrangement that allows the spray drying head to fit within the drying chamber housing 202, and such an arrangement provides support and lateral alignment. In addition to grooves 207, the receiver may be a shelf, ledge, arm, stop, base, or other structure that engages with a baffle plate and allows the spray drying head to remain stable throughout the spray drying process.

[0159] The operator then inserts the disposable device by placing the guide 4 into the receiver 204 of the spray drying apparatus 200. Once inserted and aligned, the spray drying disposable can no longer move up or down. When using this guide and arrangement described above, they align the disposable so that it cannot move up or down, and cannot move axially about the axis defined by the center of the guide 4. As shown in the figures, the guide fits into the receiver 204 such that the fit is snug or tight, as shown in FIGS. 45B and 46A. In this embodiment, once the spray drying end is aligned and in the engaged position, the operator can remove the bottom adhesive cover at the drying chamber gas outlet 30 and attach it to the gas exhaust port 208, as described further herein.

[0160] Once the arrangement (locators 26 and 206) are aligned, guide 4 is inserted into receiver 204, ridge 9 is inserted into groove receiver 207, and retaining clip 232 is engaged, in one embodiment, the spray drying head is inserted, secured, and aligned. Specifically, in one embodiment, retaining clip 232 engages with ridge 9 to hold spray drying head 2 in place. Retaining clip 232 provides an audible indicator that the spray drying head is properly aligned and inserted. In the embodiment shown in FIGS. 45B, 45C, and 31A, the retaining clip is a spring clip. The retaining clip engages with ridge 9 and can be any type of retainer, including, for example, a fastener, pin, catch, slide, etc. The retainer can be made of metal, plastic, rubber, etc. The retainer that engages with the spray drying head is optional.

[0161] While the embodiments shown in Figures 45B, 45C, and 46A use a spring clip as the audible indicator, any type of indicator can be provided that allows the operator to know when the spray drying head 2 of the disposable 100 is properly inserted and aligned with the dryer 200. The indicator can be audible, visual, or tactile. In one embodiment, an audio indicator provides audible feedback that the loading of the spray drying head 2 of the disposable 100 has been completed correctly, mechanically or otherwise. The audible indicator can be mechanical, such as the sound of a spring clip locking into place, or it can be generated by a sensor (mechanical or pressure / contact sensor) in communication with an actuator or processor that receives a signal of correct positioning of the spray drying head 2 within the dryer 200 and provides a visual indicator to the operator, for example, on the display 212 or indicator light 234. In an alternative embodiment, the sensor can send feedback to the processor, which can activate an audio indicator on a speaker to notify the operator of proper placement. In yet another embodiment, the feedback may be in the form of a tactile response, for example, a vibration to alert the operator to incorrect or correct placement. The feedback may include an audible indicator (e.g., an audible click) or a visual indicator (e.g., a sensor may provide a communication to a display indicating alignment).

[0162] 43B is an exploded view of the spray drying head 2, showing a portion of the spray drying nozzle assembly 20, along with the plenum 6, outer filter seal ring 90, inner filter seal ring 92, plenum filter 94, and baffle plate 8 having ridges 9. From top to bottom in FIG. 43B, the nozzle assembly 20 includes a strain relief valve 75, a plasma and pressurized aerosol gas manifold 72, an aerosol reservoir 74, a cannula 78 having an opening 79, a liquid nozzle cap insert 80, and a nozzle cap 76. The nozzle cap 76 has an inner wall with a diameter D o(See FIG. 43Ia) also shows an opening 110 having a diameter D c 1 shows a cannula 78 having an outer wall (outer diameter) defined by a diameter D o is the diameter D c The difference is defined as the distance Dd. The resulting difference in diameter is the distance D d forms an annulus 81 that allows pressurized air received from aerosol reservoir housing 74 to form a vortex, facilitating the formation of small droplets of fluid that flow into drying chamber 28 and are dried. See Example 27.

[0163] Thus, the length of the cannula ranges from about 2 to about 5 inches, and in one embodiment is 3.500 inches + / - 0.005 inches.

[0164] More specifically, with reference to Figures 43A and 43B, the spray-drying nozzle assembly 20 has a plasma flow inlet 18 connected to pre-treated liquid plasma 66 (shown in Figure 42A) via plasma tubing 16, and a pressurized aerosol gas inlet 14 connected to a pressurized gas source (not shown) via aerosol tubing 10 and aerosol filter 12. Also shown in Figures 42A and 43A is a drying gas inlet 22 that communicates with a drying gas source (not shown). When the plasma source, pressurized gas source, and drying gas source are combined, liquid plasma particles are formed under the pressurized (aerosolized) gas and dried into finely divided dry plasma (e.g., plasma powder).

[0165] Figures 43C and 43D show detailed perspective views of the spray drying nozzle assembly 20. In particular, Figures 43B and 43J show where and how the spray drying nozzle assembly fits within the assembly opening 96 of the plenum 6 of the spray drying head 2. A plasma and pressurized aerosol gas manifold 72 accommodates the plasma source via inlet 18 and directs the pressurized aerosol gas source via inlet 14. A strain relief 75 mates with and communicates with the manifold 72 to support the tubing 10 and 16 and prevent the tubing from collapsing under pressure during packaging, shipping, and spray drying. The strain relief 75 also prevents the tubing from collapsing in packaging and during shipping. The spray drying nozzle assembly 20 includes an aerosol gas reservoir housing 74 in which pressurized aerosol gas is held and builds before being released through the liquid nozzle cap insert 80 and nozzle cap opening 110 (Figures 43G, 43H, 43I, 43Ia, 43Ic). The nozzle assembly 20 is housed by the aerosol gas reservoir housing 74 and secured by the nozzle cap 76. The liquid nozzle cap insert 80 guides the cannula 78 and holds it in place during use. The annulus 81 is positioned between the outer surface of the cannula 78 and the inner surface of the opening 110. As described further herein, the design of the liquid nozzle cap insert 80 and the nozzle cap 76 allows the pressurized aerosol gas to flow through the annulus 81 in a vortex pattern, maximizing aerosolization and promoting rapid mixing of the aerosolized plasma droplets with the drying gas. The entire nozzle assembly 20 is secured to an opening 96 in a plenum 6, which includes a baffle plate 8 having ridges 9, between which is a filter 94, sealed by an inner filter seal ring 92 and an outer filter seal ring 90. See FIG. 43B.

[0166] Figure 43D shows the aerosol gas reservoir housing 74 as transparent so that the cannula 78 and its attachment to the liquid nozzle cap insert 80 and nozzle cap 76 can be seen, while Figure 43E shows the manifold 72 and cannula 78 with the aerosol gas reservoir housing 74, liquid nozzle cap insert 80, and nozzle cap 76 removed. Figure 43F shows the bottom tip, the end opposite the manifold, of the cannula 78, which has an outer wall surface 84, an inner wall surface 86, a flat edge 88, and a sloped or beveled edge 82 (e.g., a chamfer) on the bottom surface of the cannula.

[0167] It has been discovered that when used in spray drying to produce atomized plasma particles, a cannula having a beveled edge (e.g., a chamfer) on its inner diameter assists or allows more of the proteins in the plasma to remain intact, functional, or both. Thus, the angled edge cannula of the present invention reduces the amount of protein degradation during spray drying because it reduces shear on the liquid plasma film passing through it.

[0168] In a specific embodiment, the blood protein vWF was measured. vWF is considered a more fragile and easily degradable protein, as further described herein. In one embodiment, using a spray-drying nozzle with an angled cannula of the present invention maintains vFW recovery compared to a nozzle with a non-angled cannula. Indeed, based on the data described in Example 28, using a composite nozzle with a beveled cannula increased vFW recovery compared to both a composite nozzle with a non-angled cannula and a benchmark stainless steel nozzle (Buchi Model no. 4244 Buchi Corporation of New Castle, Delaware, United States). In one embodiment, using a nozzle with an angled cannula resulted in an increase in functional vFW recovery in an amount ranging from at least about 1% to 25% (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, and 25%) compared to a nozzle with a non-angled cannula. In particular, as described in Example 28, the data show that spray drying using a beveled cannula having a 45 degree angle and a length of 0.005 inches increased vWFRCO assay results by approximately 9%-22% compared to the same system operated with a composite nozzle having a cannula without a beveled edge, and surprisingly, an improvement of 3.7% compared to the benchmark control Buchi nozzle.

[0169] Plasma proteins preserved through the spray-drying process using a beveled edge cannula include von Willebrand factor (vWF). vWF is involved in coagulation, repair of vascular injury, and platelet adhesion. In particular, vWF is a large adhesive glycoprotein with established functions in hemostasis. It acts as a vascular injury sensor by acting as a carrier of factor VIII and attracting platelets to sites of vascular injury. Regulation of vWF multimer size and platelet tethering function is mediated by ADAMTS13, a constitutively active plasma metalloprotease. It is secreted into the blood and degrades large vWF multimers, reducing their activity. Unusually, the protease activity of ADAMTS13 is controlled not by a natural inhibitor but by a conformational change in its substrate induced when vWF is subjected to elevated rheological shear stress. This results in the conversion of vWF from a globular to an elongated protein. This conformational transformation unfolds the vWFA2 domain and reveals cryptic exosites and cleavage bonds. To enable vWF proteolysis, ADAMTS13 makes multiple interactions that position the protease as a substrate and engage the cleavage site when exposed by shear forces. ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13), also known as von Willebrand factor-cleaving protease (vWFCP), is a zinc-containing metalloprotease enzyme.

[0170] Without being limited to a theory of operation, it is believed that during spray drying, plasma proteins are subjected to significant shear forces due to the spraying mechanism as the solution is fluidized from the end of a fine nozzle and comes into contact with drying air to form droplets. The process of unfolding multimeric vWF is expected to be caused by the hydrodynamic forces of high shear stress during spray drying, combined with air-liquid interfacial stress. Shear-induced structural changes in vWF, when combined with other physical factors associated with spray drying, such as high temperature and / or unfavorable pH, as well as air-liquid interfacial stress, can lead to protein denaturation (when unfolded vWF cannot properly refold after spray drying) and proteolysis (when unfolded vWF exposes proteolytic sites of ADMATS13), potentially compromising vWF activity and other proteins in spray-dried plasma.

[0171] The spray drying system of the present invention can be optimized to reduce protein damage caused by shear forces and temperature, and the specially designed cannula of the present invention helps minimize shear and damage to proteins, including vWF.

[0172] In one embodiment, the cannula of the present invention has a bottom edge, at least a portion of which is beveled and is referred to herein as a beveled edge cannula. In one example, the entire bottom edge can be beveled, or a portion of the bottom edge can be a flat edge (e.g., at an angle of about 90° from the outer or inner wall surface). In another embodiment, as shown in FIG. 43F, a portion of the cannula's lower edge is a flat edge, such as flat edge 88 (e.g., at an angle of about 90° from the outer or inner wall surface), and a portion of the cannula's lower edge is beveled, such as beveled edge 82 (e.g., at a 45° angle from the outer wall surface or a 135° angle from the inner wall surface). This embodiment, shown in FIG. 43F, refers to an edge having a flat edge (90° from the outer wall) that forms a 45° angle, referred to as a "chamfer" or "beveled edge."

[0173] When the cannula has a bottom edge, and the entire bottom edge is beveled from the outer wall to the inner wall, the angle measured from the outer wall surface is in the range of about 30° to about 60° (e.g., about 30°, 35°, 40°, 45°, 50°, 55°, 60°), and the angle measured from the inner wall surface is in the range of about 120° to about 150° (e.g., about 120°, 125°, 130°, 135°, 140°, 145°, 150°). The length of the beveled bottom edge is in the range of 0.001 inch to about 0.010 inch (e.g., about 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.007, 0.008, 0.009, 0.010 inch).

[0174] When the cannula has a bottom edge with a flat edge and an angled edge, the flat edge is angled at about a 90° angle (e.g., about 85% to about 95%) from the outer wall surface. The angled edge has an angle ranging from about a 30° angle to about a 60° angle measured from the outer wall surface (e.g., about a 30°, 35°, 40°, 45°, 50°, 55°, or 60° angle), and in one embodiment, 45° + / - 5°, and an angle ranging from about a 120° angle to about a 150° angle measured from the inner wall surface (e.g., about a 120°, 125°, 130°, 135°, 140°, 145°, or 150° angle), and in one embodiment, 135° + / - 5°. See FIG. 52 for examples of 45° and 30° angled edges. The length of the flat edge portion ranges from 0.001 inch to about 0.009 inch (e.g., about 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.007, 0.008, 0.009 inch), and the length of the angled edge portion ranges from about 0.001 inch to about 0.009 inch (e.g., about 0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.007, 0.008, 0.009 inch), and in one embodiment, is 0.005 + / - 0.003. The ratio of the length of the flat edge to the length of the angled edge ranges from about 5 to about 500%. In one embodiment, the flat edge is adjacent to the outer wall surface and the beveled edge is adjacent to the inner wall surface.

[0175] Angled edge cannulas, with or without flat edges, exert less stress / shear on plasma droplets exiting the cannula compared to non-angled cannulas with a 90° angle. Without being bound by any particular theory, it is believed that when a plasma droplet exits a non-90° angled cannula edge, the plasma droplet or a portion of the plasma film is subjected to a shearing effect, degrading a high percentage of the plasma proteins therein. In this case, a non-90° angled cannula exerts shear forces on the droplet, thereby degrading the proteins in the plasma. When plasma droplets exit a cannula with a beveled edge, as in the present invention, less shear force is exerted on the plasma droplet. As the plasma is drawn by the airflow of the beveled edge cannula, it accelerates based on the plasma feed rate, pulling the plasma around the cannula edge. Unlike a cannula with a non-90° angled edge, the plasma is not rotated 90 degrees. Angling the edges of the cannula softens the turn the plasma makes as it exits the cannula, thereby subjecting the liquid film to less shear as it is withdrawn. The liquid plasma film exiting a beveled cannula is thicker and accelerates more slowly, thereby reducing the shear exerted on the liquid.

[0176] The inner diameter of the cannula ranges from about 0.010 inches to about 0.040 inches, and in one embodiment, is 0.030 inches + / - 0.002 inches. The outer diameter ranges from about 0.030 inches to about 0.060 inches, and in one embodiment, is 0.050 inches + / - 0.0005 inches. The beveled edge of the cannula affects the size of the atomized droplets. Upon exiting the angled cannula, droplet sizes range from about 5 microns to about 35 microns, and in one embodiment, the droplet size is about 10 microns. The small droplet size, defined in part by the beveled edge of the cannula, promotes rapid mixing, faster evaporation, and reduced drying time. See Figure 43T, which shows that larger droplet sizes increase the time it takes for the droplets to evaporate at higher drying gas temperatures. The droplet shape is dictated by its surface tension, creating a sphere after exiting the cannula. Droplet size is also primarily affected by the liquid feed rate (ALR) and the relative pressurized gas velocity to the nozzle design.

[0177] The cannula of the present invention can be made from stainless steel materials suitable for medical devices. Examples of usable stainless steel grades include grades 304 and 316. Stainless steel for use in the cannula of the present invention is commercially available, for example, from Bergsen Metals (Santa Fe Springs, California, USA) or Fort Wayne Metals (Fort Wayne, Indiana, USA). The nozzle assembly (excluding the cannula), nozzle insert, nozzle cap, plenum and baffle plate, outer filtering, inner filtering, etc., can be made from plastics used in medical devices, such as polycarbonate, polypropylene, polysulfone, or combinations thereof. Each of the aforementioned components can be made from the same material, different materials, or combinations thereof. Such plastics are commercially available and can be purchased from, for example, Covestro AG (Kaiser-Wilhelm-Allee 6051373 Leverkusen, Germany), Teknor Apex (Pawtucket, Rhode Island, USA), Colorite Plastics of NJ Inc. (101 Railroad Ave., Ridgefield, New Jersey, USA), American RENOLIT Corporation (301 Berkeley Drive, Suite B, Swedesboro, New Jersey, USA), and Exxon Mobile (Technology Centers, Baytown, TX, USA 77520, United States), or can be molded, for example, from Egli Machine Co. (Sidney, NY, USA) and Southwest Mold, Inc. (Tempe, AZ, USA). Other now-known or later-developed materials can be used for the cannula and / or nozzle, as long as, when combined, they result in maintaining or increasing vWF recovery in plasma after spray drying.

[0178] Stainless steel nozzles, such as Buchi Model No. 4244 (Buchi Corporation of New Castle, Delaware, United States), are often used in spray drying but are expensive to manufacture or purchase, especially for disposable devices that are discarded after each spray drying run. For example, a typical Buchi stainless steel nozzle body, Part No. 4244, costs between $1,000 and $2,000. The nozzle assembly of the present invention is a composite nozzle for use in spray drying, and particularly for spray drying, of delicate materials such as human plasma, at a cost of less than $30.00, orders of magnitude less than a stainless steel nozzle such as Buchi Model No. 4244. The described Buchi nozzle serves as a useful benchmark for composite nozzles, as it has been used by the present applicant to produce dried human plasma that regularly preserves proteins in the plasma to acceptable levels.

[0179] As shown, except for the cannula, which is made of stainless steel, most of the nozzle assembly is made of cheaper plastic material, as mentioned above. Therefore, the nozzle assembly is also called a "composite nozzle" or "composite nozzle assembly," which refers to two or more different types of materials used to make the nozzle assembly (e.g., stainless steel cannula and polycarbonate nozzle insert and nozzle cap). Example 28 shows that the beveled cannula of the composite nozzle assembly provides improved vWF recovery compared to those with non-beveled cannula and vWF recovery as good as that of the expensive stainless steel nozzle.

[0180] As the plasma exits the tip of the cannula, it is exposed to pressurized aerosol gas at the nozzle cap 76. More specifically, the pressurized aerosol gas exits in a vortex pattern through the annulus 81 and impinges on the liquid plasma droplets flowing from the beveled / beveled edge 82 of the cannula 78, atomizing the plasma and forming a plume. As the atomized plasma exits the spray-drying nozzle assembly, it is exposed to drying gas and dries into plasma powder in the drying chamber. In one embodiment, the tip of the cannula 78 is flush with the distal end of the opening 110.

[0181] The liquid nozzle cap insert 80 secures the bottom of the cannula 78 and guides the pressurized aerosolized gas flow. FIG. 43G shows a perspective top view of the liquid nozzle cap insert 80. As can be seen, the cap insert 80 has an insert wall 116 and a cannula anchor 120 with an opening (not shown) through which the cannula 78 extends. The top of the insert wall 116 forms a ridge, and the sides of the insert wall 116 define a series of recesses 118 and protrusions 119. The cannula anchor 120 supports the tip of the cannula 78 during plasma flow. The beveled edge 82 of the cannula 78, where the plasma exits, and the annular portion 81, through which the pressurized aerosol gas is released, form the actual nozzle. The cannula anchor 120 is a hollow, cylindrical base, but can be any shape as long as it supports the cannula and maintains its position during spray drying. A recess in the wall, recess 118, allows pressurized air to pass from the reservoir (defined by reservoir housing 74) to the region between nozzle cap insert 80 and nozzle cap 76 before exiting central opening 110 in nozzle cap 76. As the pressurized air exits central cap opening 110, it exits through annular portion 81 defined by the outer wall of cannula 78 and the inner wall of opening 110. More specifically, when cap insert 80 is secured to cap 76 and cannula 78 is within opening 110, the pressurized air exits through annular portion 81. See FIG. 43Ia. Thus, the diameter of opening 110 is larger than the outer diameter of cannula 78. Notably, opening 110 in nozzle cap 76 has a diameter D o(See FIG. 43Ia) also shows a diameter D c 1 shows a cannula 78 having an outer wall defined by a diameter D o is the diameter D c The difference is the distance D d The resulting difference in diameter is the distance D d The cannula 78 has an outer diameter, diameter D c The distance D is between about 0.30 and about 0.70 inches (e.g., 0.30, 0.40, 0.50, 0.60, 0.70), and the diameter of the opening 110 is between 0.075 and 0.100. Also, for ease of use, the "distance D d " is also referred to as "the radial distance of the valve ring 81." In one embodiment, the diameter D c is 0.50+ / -0.005 inches, and the diameter D o The radial distance D between the outer surface of the cannula 78 and the inner surface of the opening 110 is 0.082 + / - .001 inches. d is the space through which the rotating vortex of the pressurized aerosol gas flows, aiding in the generation of plasma droplets for mixing with the hot drying gas during spray drying. d has a range of 0.005 inches to 0.030 inches (e.g., 0.015 to 0.021 inches).

[0182] Along these lines, the data from Example 27 shows that the radial distance D d It has been shown that the drying process affects both the yield of the dried product and the preservation of vWF. The yield is the ratio of the starting solids in the liquid material being dried by weight to the dry material recovered by the drying process by weight.

[0183] Prior to the present invention, one source of yield loss occurred when dried spray material that was not completely dried and retained more than about 2.5% residual moisture could not be recovered and contacted and adhered to the internal structure of the disposable dryer during drying.

[0184] Example 27 illustrates the reduction in the amount of material visibly adhering to the underside of baffle plate 8 after the completion of the drying cycle. The data presented in Example 27 is for annulus 81D. d 1 shows that the overall weight yield increased by changing the radial distance of the annulus from 0.021 inches to 0.015 inches. The yield was acceptable at the 0.021 inch annulus size. However, by decreasing the annulus width / diameter to 0.015 inches, the yield improved by over 2.2%. Other features of the disposable 100 increase yield and include, in part, the drying jets 142 that form an air wall within the plasma drying chamber 28, as further described herein.

[0185] Example 27 also describes an increase in vWF recovery as measured by Ristocetan (RCO) assay by changing the radial distance of the annulus 81 from 0.021 inches to 0.015 inches. vWF recovery was acceptable at a valve annulus dimension of 0.091 inches. However, vWF recovery increased by more than 2.0% by decreasing the annulus width to 0.082 inches. Other features of the disposable 100 also increase vWF recovery, including, in part, the beveled edge cannula 78, as described herein.

[0186] The space between the nozzle cap insert 80 and the nozzle cap 76 prior to exiting the central opening 110 of the nozzle cap 76 is generally referred to herein as a "vortex generator" and includes a series of channels and curved pads, as further described below. Pressurized air passes through recesses 118, which function as openings in the nozzle assembly 20, allowing the air to enter the channels and travel down the channels and between the curved pads. See Figures 43G, 43H, 43I, and 43Ic.

[0187] Referring to FIG. 43H, the bottom surface of the cap insert 80, unoccupied by the pads 122 beneath the protrusions 119 / recesses 118, serves as the walls of the vortex generator channels. The pads 122 form a kidney-like shape that aids in locating the recesses 118 for the vortex airflow pattern. The nozzle cap shown in FIG. 43I, cap 76, has a complementary receiver 112 for receiving the pads from the cap insert 80. The complementary fit between the nozzle insert 80 and nozzle cap 76 is shown (in cross section) in FIG. 43Ic. The nozzle cap 76 also has a nozzle cap channel 106 extending from the bulbous head 108 and terminating in an opening 110. The bottom surface of the cap insert 80 not occupied by the pads 122 and further complemented by the channel 106 of the cap 76 is the space through which pressurized air flows. The vortex generator includes the recess 118 and the surface of the bottom of the cap insert 80 not occupied by the pad 122, the bulbous head 108, and the channel 106 of the cap 76, the shapes and positions of which cause the pressurized air to form a vortex airflow pattern. The bulbous head 108 receives the pressurized airflow through the recess 118, and the curved, sloped surface of the channel 106 provides a curved boundary for the air to flow through. In other words, the recess 118 is the inlet port, providing the airflow, and the channel 106 provides the vortex. The channel 106 is arched, further enhancing the curved airflow and directing the tangential airflow toward the opening 110 where the cannula 78 resides. These channels, the channel 106, guide the air in a circular motion from the bulbous head 108 to the nozzle cap opening 110, all working together to exhaust the pressurized air as a vortex through the opening 110. The design provides tangential momentum to provide efficient vortex generation. The channels 106 are in the form of an arc or curve, with a radius of curvature ranging from about 0.10 inches to about 0.25 inches, and in one embodiment, a radius of about 140 + / - 0.10 inches. The vortex generated includes four channels, but can have between about 2 and 12 channels (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 channels).Other types of molded channels can be used. Figure 43I shows designs molded into a nozzle cap 76. Designs A and B both show more linear channels, but Design A does not correspond to a bulbous head, while Design B shows a bell-shaped head. Design C is similar to the design shown in Figure 43I but has leaves rather than bulbous ends. The present invention includes nozzle caps with designs A and B, but it has been found that Design C appears to be a more efficient vortex generator. The various designs demonstrate that any combination of channels, heads, and shapes can be used to generate vortexes at the valve annulus. Other types of channels include conical-shaped channels, including diverging or diverging conical shapes, etc.

[0188] Once a vortex is generated, the pressure and velocity flow patterns are shown in Figures 43O and 43P. Figure 43O shows the contours of static gas pressure in PSig at the top and tangential velocity of the pressurized aerosol gas flow in m / s at the bottom. As can be seen, there is an inverse relationship between pressure and velocity. In regions where pressure increases, velocity decreases, and vice versa. In particular, at the bulbous head 108 where the pressurized gas enters the vortex generator, there is a higher relative static gas pressure (e.g., about 2.54x10 1 psig) and a relatively low velocity flow rate (e.g., about 2.00x10 1 Conversely, in annulus 81, there is a relatively low or negative gas pressure (e.g., about -2.24 psig) and a higher velocity (e.g., about -1.58x10 2 ~Approx.-3.75x10 2 m / s). When the pressurized aerosol gas moves along the curved nozzle cap channel 106, the pressure and velocity are the velocity between them. Therefore, the vortex generator of the present invention has a velocity of about 2.54x10 1 psig to approximately -2.24 psig gas pressure and approximately 2.00 x 10 1 m / s~approx.-3.75x10 2m / s. In one embodiment, any vortex generator can be used with the present invention as long as it generates gas pressures and velocities in these ranges. Similarly, Figure 43P shows in more detail the velocity pattern that occurs at the valve annulus 81. The pressurized gas travels between the outlets of the channel 106 as it becomes incorporated into vortices. As the pressurized gas enters the annulus 81, it accelerates and becomes a vortex.

[0189] The vortex generator in this embodiment includes a curved pad / ramp, a bulbous head that receives the pressurized airflow, and a curved channel that extends to the exit opening. The present invention can include other vortex generator elements, such as wings, edges, wedges, vanes, etc. Other shaped channels can also be used to create vortex generators. Those skilled in the art can utilize other vortex generators present in the inserts and caps of the nozzle assemblies of the present invention, so long as the pressurized air exits between the inner surface of the opening 110 and the outer surface of the cannula 78 in a vortex.

[0190] Pressurized air circulates between the exterior surface of cannula 78 and the interior surface of opening 110. Specifically, the pressurized gas exits through annulus 81. Plasma is pumped through cannula 78 by peristaltic pump 214 at approximately room temperature. The plasma travels down the interior of stainless steel cannula 78 and is drawn out of cannula 78 by the pressurized aerosol air stream exiting annulus 81. The high-velocity aerosolizing air stream atomizes the droplets. In one embodiment, the steady-state plasma delivery rate is about 6 to about 23 mL / min (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23). In a preferred embodiment, 13.5 mL / min is the steady-state delivery rate after the system has warmed to thermal equilibrium.

[0191] In one embodiment, the plasma feed rate is related to or dependent on the outlet temperature. This is done in a closed loop. As the outlet temperature decreases, the system adjusts to decrease the plasma feed rate. Conversely, as the outlet temperature increases, the system increases the plasma feed rate. The outlet temperature may be lower, for example, when the spray dryer is warming up or as time passes during a spray drying run. Specifically, in one embodiment, the plasma feed rate can be adjusted as follows:

[0192] [Table 2]

[0193] Chart values ​​calculated based on thermodynamic principles, assuming constant system heat loss, complete droplet evaporation, and dryer outlet relative humidity less than 11.8%.

[0194] Thus, at lower outlet temperatures, the plasma feed rate is reduced to maintain the target drying chamber outlet temperature required to dry the plasma to less than 2% residual moisture. At higher outlet temperatures within this range, the plasma feed rate can also be increased, and a plasma residual moisture content of less than 2% can still be maintained only if the total gas flow rate can be increased and / or the drying chamber outlet temperature can be increased to maintain the target system relative humidity.

[0195] In one embodiment, the closed loop comprises an exhaust temperature in the range of about 62° C. to about 68° C. and a plasma feed rate in the range of about 6 to about 23 mL / min.

[0196] There is negative pressure directly below the cannula, and the pressurized gas flow is high velocity. Generally, velocity increases along the path of decreasing static pressure. The pressurized aerosol gas travels through a series of channels 106, atomizing the plasma droplets and generating a vortex flow that guides the initial droplet trajectory. The aerosol flow rate is about 20 slpm to about 60 slpm (e.g., about 20, 25, 30, 35, 40, 45, 50, 55, 60 slpm), and in one embodiment, about 40 slpm. This occurs at a pressure of about 180 kPa to about 260 kPa (e.g., about 180, 190, 200, 210, 220, 230, 240, 250, 260 kPa), and in one embodiment, about 227.5 kPa (33 psig). The aerosol flow acts to draw the liquid supply from the cannula, where it forms a film across the end. The expansion of the aerosol gas as it exits the orifice locally cools the gas field near the nozzle, which also acts to cool the droplets and slightly retard evaporation. Also, in one embodiment, the pressure just below the end of the cannula is lower than the pressure inside the cannula, and the pressurized gas velocity accelerates as it travels along the outer surface of the cannula. Upon exiting, the spherical plasma droplets collide with the pressurized gas and aerosolize, forming a spray plume surrounded by a ring of drying gas jets, as described further below. See Figure 43N. Mixing of the aerosol and drying gas sets the initial conditions for the evaporation process.

[0197] Figure 43Q is a schematic diagram showing liquid plasma droplets undergoing a drying process. The plasma droplets are atomized and approximately spherical as they exit the nozzle assembly cannula into the drying chamber. Dried plasma particles are formed by heat and mass transfer. Drying occurs in two stages: evaporative drying (constant rate) drying, which occurs during initial drying (e.g., less than 1 second), and drop velocity drying (diffusion limited), which occurs after the evaporative drying stage and continues as long as the dried particles are exposed to an ambient relative humidity lower than their internal relative humidity.

[0198] Factors involved in the evaporative drying phase of plasma droplets include the temperature of the plasma and drying gas, the surface area of ​​the droplets, the humidity in the drying gas, and the air circulation within the plasma drying chamber. As shown in Figure 43Sa, when the drying gas initially exits the nozzle assembly, its temperature is approximately 90°C to approximately 130°C (e.g., approximately 100°C to approximately 114°C), and the temperature of the plasma droplets within the plume is approximately 20°C to approximately 65°C. Heat flows from points of higher temperature to points of lower temperature, in this case, drying gas heat, which flows to the plasma droplets. Regarding surface area, the droplets are spherical, thereby maximizing their surface area, and the droplet size is very small, so mass and heat transfer can occur rapidly. Because the relative humidity in the drying gas is very dry (e.g., approximately 0.1% RH), the low humidity of the surrounding drying gas facilitates evaporation of plasma particles. Finally, as described in more detail below, drying gas is emitted into the plasma drying chamber at an angle downward into the plume of sprayed droplets using several drying gas jets, initiating rapid mixing of the drying air with the sprayed droplets and increasing the evaporation rate of the droplets. The drying rate is constant; as the droplets evaporate and lose moisture, moisture is transferred from the liquid plasma droplets to the drying gas, and heat from the drying gas is transferred to the plasma droplets, resulting in dry particles. The plasma droplets enter the drying chamber at essentially room temperature, and the temperature remains constant for most of the evaporation period. See Figure 43S. As most of the moisture leaves the particles, their temperature increases and equilibrates with the dryer chamber exit temperature of 65°C. During evaporation, the droplets are maintained at a lower temperature, thereby protecting heat-sensitive proteins such as vWF. See Figure 43S. During the evaporation process, the droplets and the proteins therein experience a lower temperature, i.e., the thermodynamic wet-bulb temperature, compared to the inlet drying gas temperature, thereby protecting the proteins. See Figure 43R. Evaporation reduces the protein temperature to near the thermodynamic wet bulb value, and evaporation slows the increase in particle temperature. See Figure 43Sa.

[0199] The starting droplet size generated by the nozzle assembly influences the residence time in the drying chamber required to complete evaporation. Larger droplets have a smaller ratio of evaporation surface area to droplet mass, resulting in a slower mass transfer rate from the droplet. This slower rate requires a greater distance between the nozzle assembly 20 and the lower filter 36 to prevent excessively wet particles from depositing on the filter membrane of the lower filter 36. Excessively wet particles can cause "clogging or plugging" of the porous filter membrane, preventing the process from completing due to excessive chamber pressure buildup, preventing powder production. See Figure 43T.

[0200] Furthermore, Figure 43T shows that in all cases, the majority of evaporation occurs at the top of the disposable 148. This is particularly evident when using small droplet sizes, e.g., less than 15 microns. As can be seen from Figure 43T, the drying chamber can be shortened to a chamber where the majority of evaporation occurs, yet the dried particles can achieve less than 2.5% residual moisture before being deposited on the lower filter 36. In other words, in one embodiment, when the droplet size is less than about 15 microns and less than about 2.5% residual moisture is achieved, the drying chamber 28 can be shortened by an amount of about 8 inches to 1 inch.

[0201] Turning to the plenum, its functions include 1) allowing the introduction and flow of drying gas into the disposable device, 2) housing the nozzle assembly, and 3) supporting the drying chamber during the spray drying process. The underside of plenum 6 is shown in Figure 43J. Plenum 6 has two openings: opening 96 for receiving nozzle assembly 20 and drying gas inlet port 22 for receiving drying gas.

[0202] The nozzle assembly receiver opening 96 is complementary in shape to the top of the nozzle reservoir housing 74 and manifold 72. The top of the nozzle assembly 20 is secured within the opening 96. The length of the nozzle assembly matches the height of the plenum 6 so that the bottom of the nozzle assembly 20 extends beyond the baffle plate 8. See Figures 46A and 46B. In certain embodiments, the cannula is flush with the nozzle assembly and baffle plate. The nozzle assembly 20 can be secured with adhesive, fasteners, or an interlocking assembly (e.g., spring latch, threaded fit, etc.).

[0203] The other opening in plenum 6 is drying gas inlet port 22, which accepts drying gas. A drying gas source (not shown) enters the plenum through drying gas inlet deflector 242, shown in Figure 43K. The disposables are secured and aligned, the door to the spray dryer is closed, and spray drying begins. Drying gas inlet deflector 242 descends through drying gas inlet port 22 and provides drying gas to plenum 6. Drying gas inlet deflector 242 has an elbow shape, as shown in Figure 43Ka, so that the drying gas flows toward the far inner sidewall of the plenum, creating a tangential mixture. The right angle of deflector 242 distributes the drying gas throughout plenum 6, creating a low-velocity, highly uniform pressure reservoir. Uniformity is desirable to create a low-velocity, uniform pressure of the drying gas as it exits each of the drying jets 142. If the drying gas is not deflected away from the side of the plenum 6 but instead deflected downward, the air pressure may be asymmetric, with drying jets closer to the drying gas inlet experiencing higher pressures compared to those further from the inlet. Therefore, the present invention includes drying gas inlets that are deflected toward the side of the plenum with a 90-degree elbow, as in the case of deflector 242. Other shapes for deflector 242 can be used to create uniform air pressure within the plenum 6. For example, the deflector can be angled at an angle less than 90 degrees, measured from the top of the plenum. For example, the deflector can have an angle ranging from about 60 to about 110 degrees relative to the top of the plenum 6, such that the drying gas pressure across the width of the plenum 6 is substantially uniform. Alternatively, two or more drying gas inlets from opposite sides can be used to create substantially uniform drying gas pressure across the width of the plenum 6.

[0204] As shown in FIG. 43J, the plenum 6 has concentric ribs 98 and radial ribs 102. These ridges provide structural support to the plenum 6. The additional support provided by the concentric radial ribs allows the plenum to withstand the pressure and heat of the spray drying process. Because the drying gas is a low-velocity, uniform-pressure air container, the concentric ribs 98 and radial ribs 102 do not contribute to or affect the airflow of the drying gas. Similarly, the protrusions 104 on the inner sidewall of the plenum are used in the injection molding process when manufacturing the plenum and do not participate in the drying gas flow.

[0205] See Figures 43L, 43La, and 43M. The baffle plate has several functions: A) it acts as a support for securing the disposable device 100 when the disposable device is aligned and inserted into the spray dryer 200, B) it provides a drying gas air flow path, releasing drying air into the plasma drying chamber 28 of the disposable device 100, and C) it supports the baffle filter 94.

[0206] FIG. 43L shows a top inside view of the baffle plate 8. The inner surface of the baffle plate 8 has a baffle plate nozzle opening 140 through which a portion of the nozzle assembly 20 resides. The baffle plate 8 also includes a raised outer ring 124 having a base 126 and a raised inner ring 128 having a base 130. The outer seal ring 90 is disposed around the outer ring 124, and the inner seal ring 92 is disposed around the inner ring 128. The seal rings prevent dry gas from escaping the edge of the filter 94; instead, dry gas flows through it. The inside of the baffle plate 8 further includes a locator 132 for inserting the locator notch 26 of the plenum 6. The plenum and the baffle plate have locators for aligning them with each other. The baffle plate 8 has a baffle locator 132 that receives a plenum locator 152 on the plenum 6.

[0207] The baffle plate ribs 134, 136, and 138 support the baffle plate filter 94 (shown in FIG. 43L) during use, while keeping the majority of the filter's surface elevated from the baffle plate. The baffle plate ribs also act as guides for the dry gas flow. It has been determined that if the baffle plate filter 94 were to lie flat on the inside of the baffle plate 8 without the ribs, the dry gas flow would be slowed and would not flow freely through the multiple dry jets 142. Specifically, to avoid this phenomenon, the baffle plate 8 has radial ribs 134 connecting the inner ring base 130 to the outer ring base 126. Each radial rib 134 has a consistent contour throughout its length, allowing the filter to be positioned in an elevated position compared to when it rests directly on the inner surface of the baffle plate. The radial ribs 134 also form pie-shaped air channels 139 that lead to the dry jets 142. The radial ribs 134 are the sidewalls of the pie-shaped air channels 139. The baffle plate 8 has two types of ribs that extend from the outer ring base 126 but do not connect to or reach the inner ring base 130. These ribs include shorter radial ribs 136 and intermediate radial ribs 138. Both the shorter radial ribs 136 and the intermediate radial ribs 138 have a consistent height profile as they extend inward from the outer ring base 126 and then rapidly taper to a tapered end 137. The tapered end 137 helps support the filter without creating corners through which the filter can penetrate. Specifically, the baffle filter 94 rests on the ribs 134, 136, and 138 and is pressed against them by air pressure, e.g., about 11.5 psig, during spray dryer operation. The tapered ends of the ribs 136 and 138 reduce stress on the baffle filter, preventing damage to the filter and reducing loss of filtration efficiency. See Figure 43La. The ribs prevent the baffle filter 94 from adhering to the inner baffle plate surface. The connecting and non-connecting ribs are interspersed on the inner surface of the baffle plate and, in the embodiment shown in FIG. 43L, form a pattern within the pie-shaped air channels 139 (e.g., a connecting rib, a short non-connecting rib, two middle non-connecting ribs, a short non-connecting rib, a connecting rib, etc.).Each pie-shaped air passage 139 is defined by two connecting ribs on either side. The connecting and non-connecting ribs can be in any pattern as long as they support the baffle filter 94 while allowing drying gas to flow through and under the filter 94, through the air channels 139, and to the drying jets 142. For example, Figure 43La shows another arrangement of ribs 136 and 138.

[0208] In one embodiment, the pressure is reduced as the drying gas passes through the baffle filter 94. The input drying air pressure in the plenum 6 before passing through the filter and into the pie-shaped air flow passage 139 is approximately 8 to 15 psig during operation, and in one embodiment, approximately 10.4 psig. As the drying gas passes through the baffle filter 94, the pressure is reduced by approximately 40 to 60%, or in one embodiment, approximately 6 psig. The pressure drop across the baffle filter 94 is utilized to aid in the even distribution of the drying gas injected into the drying chamber, as shown in FIG. 43Ma. This feature helps minimize asymmetric drying within the chamber and shorten the overall length. The resulting pressure within the drying chamber 28 in the area defined by dimension Z ranges from approximately 4 psig to approximately 7 psig, and in one embodiment, is approximately 5.5 psig. As discussed further herein, the lower filter 36 of the disposable 100 causes a pressure drop of about 40-80%, or in one embodiment, about 3.0-5.5 psig, which increases as dried plasma accumulates on the filter, resulting in an outlet air pressure of about 1-2.5 psig. In one embodiment, the gas exhaust port 208 of the spray diaphragm 200 is slightly constricted so that the exhaust gas venting to the outside is about 1.5 to about 3 psig. Any valves, sensors, or tubing lengths beyond the exhaust outlet will add a small pressure increase.

[0209] In one embodiment, the flow of dry gas through the baffle plate 8 is not restricted. In one aspect, the height and arrangement of the ribs 134, 136, 138 of the baffle plate 8 are such that the baffle plate filter 96 distorts somewhat under the pressure of the dry air, but does not materially affect the pressure drop. Note that, as noted above, the baffle plate filter 96 creates a pressure drop as the dry gas passes through it, but the baffle plate 8 itself does not. The cross-sectional area of ​​the pie-shaped channel 139 is equal to or greater than the cross-sectional area of ​​the opening of the dry gas inlet deflector 242. Alternatively, the cross-sectional area of ​​the pie-shaped channel 139 is equal to or greater than the sum of the cross-sectional areas of all the openings of the dry gas jets 142.

[0210] The data presented in Example 8 demonstrates that the air passages 139 of the baffle plate 8 shown in Figure 43L do not interfere with the bacterial filtration efficiency (BFE) of the baffle filter 94, allow for greater than a log 6 reduction in pathogens when challenged by Staphylococcus aureus in the BFE under American Society for Testing and Materials (ASTM) F2101-14, and do not damage the baffle filter 94 during operation of the spray dryer 200. See Examples 8 and 9.

[0211] In one embodiment, the baffle filter 94 is a 0.2 micron filter (e.g., a 0.22 micron filter) that prevents pathogens that may be introduced into the drying gas from entering the drying chamber. The filter can be at least a 0.2 micron filter, e.g., a 0.1 micron filter or smaller, as long as it allows the drying gas to flow as described herein. The filter is strong enough to withstand the heat and pressure of the spray drying process, but flexible enough not to tear when pressed against the ribs as air flows through it. The baffle filter can be a 4 micron deep or membrane filter. Filters are commercially available from Gore (231 East Oak Street, Bozeman, Montana, USA), Lydal (Rochester, New Hampshire, USA), Tenjin (Chiyoda-ku, Tokyo, Japan), or Sabeu (Northeim, Germany). Any type of commercially available filter can be used as long as it prevents pathogens from being introduced into the drying chamber, but is porous enough to allow the drying gas to pass through at the specified flow rate. The baffle filter and bottom filter may be made, for example, from a polyethylene filter matrix. In one embodiment, the baffle filter 94 is commercially available from Sabeu of Northem Germany under art. no. 063090.

[0212] Referring to Figure 43M, the underside of the baffle plate can be seen. After passing through the baffle filter 94, the drying gas exits through a plurality of drying gas jets 142. In one embodiment, the drying gas jets 142 are parallel to one another and have centerlines along their lengths that are perpendicular to the baffle plate 8. Despite the mechanical structure described for the jets 142, the drying gas air exiting the jets is angled inward toward the centerline of the drying chamber 28. Figures 43N and 43Na show the flow pattern of the drying gas jets 142.

[0213] The drying gas jet 142 effectively creates a "wall of dry gas" within the plasma drying chamber 28, as shown in FIG. 43Ma, while promoting rapid mixing with the atomized plasma particles. The dry jet airflow is partially directed at the plume of atomized liquid plasma droplets for rapid mixing. The wall of dry gas minimizes the accumulation of dried plasma on the interior walls of the plasma drying chamber 28.

[0214] Within the multiple drying gas jets 142 are multiple recesses 144. The recesses 144 are used to provide additional support to the structure so that the plenum 6 and baffle plate 8 do not buckle and contribute to the airflow during spray drying. The drying gas jets 142 are arranged concentrically with the recesses 144. In the embodiment shown in FIG. 43M, there are 16 drying jets 142. The present invention can have more or fewer drying jets ranging from 2 to 32 jets.

[0215] Additionally, the drying gas jet 142, like the nozzle assembly, is not flush with the baffle plate but extends beyond the plane of the baffle plate. Extending the nozzle assembly 20 and drying gas jet 142 beyond the plane of the baffle plate allows the plasma to dry away from the baffle plate surface, reducing the accumulation of dried plasma on the outer surface of the baffle plate and / or the bottom of the nozzle assembly during the drying process.

[0216] In light of the above structure, the heated drying gas dries the atomized plasma droplets as follows: The heated drying gas is supplied to the top of the plenum through deflector 242 at a flow rate of about 500 slpm to about 1000 slpm (e.g., about 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, or 1000 slpm), and in one embodiment, about 750 slpm. The heated drying gas enters the plenum at a temperature of about 100°C to about 130°C (e.g., about 100, 105, 110, 115, 120, 125, or 130°C), and in one embodiment, about 114°C. Deflector 242 redirects the gas 90 degrees to aid in uniformity of airflow within the plenum. The drying gas is forced through baffle filter 94 (e.g., a 0.2 micron sterilization-rated filter) located on the top surface of the baffle plate. As mentioned above, the baffle plate 8 is designed with channels to form pie-shaped air channels 139, with the filter providing the upper surface of the channels. The pie-shaped ducts 139 direct the drying gas into 16 individual drying gas jets 142. This flow configuration creates jets directed inward toward the atomizer to aid in plume containment. The mixture of heated drying gas, aerosol gas, droplets, and water vapor drives evaporation, converting the plasma into dry powder. The process is completed in less than one second under the spray-drying process conditions of the present invention, with individual particles formed at the top, defined by the dimension X of the drying chamber 28.

[0217] An inner concentric ridge 146 on the exterior of the baffle plate 8 is a base for attaching the walls of the plasma drying chamber 28. The plasma drying chamber 28 can be attached to the baffle plate 8 using a collar or ring, adhesive, fasteners, etc. The plasma drying chamber 28 can also be attached to the baffle plate 8 at the ridge 146 by heat welding the chamber to the baffle plate 8. The attachment points can also be molded as part of the baffle plate. The drying chamber can be attached to the baffle plate by any number of commercially available methods.

[0218] Detailed description of the drying chamber As described herein, the purpose of drying chamber 28 is to: A) allow drying of nebulized plasma while preserving proteins and their function, B) capture dried plasma while allowing gases to be vented, and C) for subsequent conversion to commercially available dried plasma units without filters. The drying chamber in one embodiment is a sterile, non-pyrogenic, disposable, dual-purpose chamber in which plasma is dried, collected, and stored in a portion of the chamber for use.

[0219] 44 and 46A, the drying chamber 28 is shown, which includes an upper section defined by a length X, a middle section defined by a length U, and a lower section defined by a length V.

[0220] The upper portion 148 is attached to the baffle plate 8 via the baffle plate ring 156 at the outer concentric ring 146. The baffle plate 8 protrudes the nozzle assembly 20. As mentioned above, the nozzle assembly 20 and the drying gas jet 142 extend beyond the plane defined by the baffle plate 8. Therefore, the convergence of the atomized plasma occurs at the upper portion 148 of the plasma drying chamber 28. While the majority of the drying of the atomized plasma particles occurs at the upper portion 148, the plasma continues to dry as it travels along the length of the drying chamber 28. When the pressurized air is within the nozzle assembly, it forms a vortex configuration. As the plasma film exits the cannula and the pressurized air exits the valve annulus as a vortex, the droplets aerosolize or atomize, forming a plume, as shown in Figure 43N. The vortex configuration weakens and expands as it travels downward. Meanwhile, the drying gas jet 142 directs the gas so that the flow slopes inward toward the plume, containing the plume and rapidly mixing with the aerosolized plasma droplets. The combination of the weakened vortex and the flow from the inclined drying gas flow dilutes the spray plume of plasma droplets, resulting in more drying gas surrounding the plasma droplets and promoting rapid mixing of the drying gas with the droplets. This action promotes efficient evaporation of the plasma droplets, which occurs throughout most of the upper part of the drying chamber. As rapid mixing occurs, the droplets evaporate relatively quickly at a lower temperature than the drying gas, similar to the present invention, preserving plasma proteins. See Figure 43S. In contrast to freeze-dried plasma, the rapid drying of plasma in the present invention largely avoids the formation of crystals in the dried plasma, especially undesirable cholesterol crystals.

[0221] The gas flow from the drying air jets 142 forms an air curtain that prevents dried plasma particles from depositing on the inner sidewalls of the drying chamber. Additionally, the sloping air wall formed from the drying jets 142 also helps direct the dried plasma particles downward toward the lower filter 36.

[0222] While the majority of the plasma evaporates and dries in the upper section 148, drying of the plasma continues in the central section 46, defined by the dimension U that includes the “seal and separate” positions 44A and 44B, the label 40, the spike ports 42A and 42B, and the hanging slot 34. The “seal and separate” positions 44A and 44B are where the drying chamber 28 is severed to form the dried plasma unit 60 (shown in FIG. 49 ). As described herein, the finishing device 400 moves the plasma within the disposable, seals and separates the central section 46 at positions 44A and 44B, and removes the upper and lower portions 148 and 150 of the disposable to create the dried plasma unit. The spike ports 42A and 42B are intended for use with the dried plasma unit. The spike ports can be used to reconstitute the dried plasma with a reconstitution solution or sterile water for injection (SWFI). The spike port is a plugging and / or connection device and can be in the form of a "twist-off" to expose a connection port for use in a sterile environment. Other commercially available spike port connectors and adapters can be used as long as they are suitable for a sterile environment. The hanging slot 34 is an opening used to attach the plasma bag 64 to an IV (intravenous) pole. The spike ports 42A and 42B and the hanging slot 34 are fabricated and used in the same manner as those for IV medical bags. The center section 46 also includes a locator pin opening 32C. As described further herein, the locator pin opening 32C is used to secure the disposable 100 to the finishing apparatus 400 so that the disposable 100 remains in place during sealing and separation.

[0223] While most of the plasma evaporates and dries in the upper section 148, drying continues in the lower section 150 defined by dimension V. Referring to the exploded view of the disposable in FIG. 44, the lower section of the drying chamber 28 includes the lower filter 36, the lower filter separator 38, the drying gas outlet port 30, and the locator pin openings 32A and 32B. Moist air (e.g., the drying gas, the aerosolized gas, and moisture removed from the aerosolized plasma droplets) flows into the lower section 150 through the lower filter 36, the lower filter separator 38, and the gas outlet 30 secured to the gas exhaust port 208. After passing through a channel or space between the filter 36 and the outer wall of the drying chamber 28, the moist air exits through the gas exhaust port 208, where it is filtered and released to the outside air. When the air is released to the outside air, a filter is used to prevent contamination of the plasma within the spray dryer in the event of a breakage. Such a filter can be a HEPA filter, a UPLA filter, or the like. HEPA filters for filtering the exhausted air are commercially available.

[0224] The lower / trapping filter 36 separates the dried plasma from the moist air. Specifically, the lower filter 36 traps dried plasma particles / powder while allowing moist air to pass through. The dried plasma accumulates on the filter throughout the drying process. The goal of the drying process is to complete the majority of the evaporation of the plasma droplets (i.e., complete the mass transfer process) before the dried particles hit the filter surface. Effective evaporation occurs upon rapid mixing of the dry air with the atomized plasma droplet size distribution, which ranges from about 1 micron to about 35 microns. The rapid mixing described herein is enhanced by the vortex flow of the pressurized air, the droplet size of the atomized plasma droplets, and the drying gas flow. The length of the drying chamber depends on the atomized plasma droplet size. A shorter drying chamber allows for less time for the droplets to complete evaporation / mass transfer, while a longer drying chamber allows for larger droplets to be used. Completion of the evaporation process for a particular droplet size depends in part on the length of the drying chamber. As the initial plasma particles collect on the filter, the subsequent dried plasma particles create a depth of powder through which the airflow penetrates and pressure builds in the system, yet still allows moist air to pass through effectively. If the residual moisture of the dried plasma particles is less than 2%, moist air can pass through the dried plasma on the lower filter 36, pass through the lower filter 36, and exit through the gas outlet 30 / gas exhaust port 208.

[0225] The dried plasma produced by the present invention is a fine, highly amorphous, and very dry (eg, less than 2% residual moisture) powder such that little or no clogging of the lower filter 36 occurs.

[0226] While the initial powder entering the lower filter is exposed to the chamber outlet temperature for the duration of the batch, subsequent powders have a shorter residence time in the filter. The residual moisture content of plasma dried with the disposable dryer of the present invention is very low, e.g., less than about 2.5%, 2%, 1%, and preferably less than about 1.46% residual moisture, as measured, for example, by a Karl Fischer moisture sensor, Model No. C30S Compact KF Coulometer (Mettler, Toledo Billerica, Massachusetts, USA). This very low moisture level results from effective and efficient evaporation of plasma droplets occurring at the top of the drying chamber 28 and at the process conditions. In this embodiment, the powder moisture level is in equilibrium with the relative humidity of the chamber outlet airflow. Plasma particles with higher moisture levels accumulate on the lower filter 36, forcing moist air to pass through the filter at a slower rate, thereby increasing the pressure within the chamber. Essentially, plasma particles that are too moist to evaporate efficiently clog the filter, preventing or significantly reducing the flow of moist air. However, the present invention has efficient evaporation, thereby allowing moist air to pass through the trapped dried plasma particles. Dried plasma with less water content improves protein stability during storage.

[0227] In one embodiment, the lower filter 36 is a 0.2 micron filter so as to be small enough to prevent plasma particles from passing through while allowing moist air to pass through with minimal pressure rise. The filter can be at least a 0.2 micron filter, for example, a 0.1 micron filter or smaller, so long as it allows moist air to flow through as described herein. The lower filter 36 is commercially available from Lydall Inc. of Rochester, New Hampshire, USA, under model number 70L02A.

[0228] The lower filter 36 may be supported by a filter frame built into or attached to the filter 36 and attached to the inner wall of the plasma drying chamber 28. The filter 36 is attached around the entire periphery of the inner wall. In other words, the filter frame or the filter itself is attached around the entire periphery of the inner wall so that there are no openings between the inner wall of the drying chamber 28 and the attachment point of the filter 36. Attaching the filter to the inner wall in this manner forms a barrier against dried plasma particles and moist air, which causes the plasma and moist air to move downward toward the gas outlet 30, with the filter 36 capturing the dried plasma while allowing the moist air to pass through. A filter frame 37 is attached to the inner surface of the drying chamber 28 by heat welding. In another embodiment, the filter frame may be attached to the inner surface of the drying chamber 28 by a combination of adhesive (e.g., UV adhesive) and RF welding, for example, by a dielectrics unit at UFP, Inc., Chicopee, Massachusetts, USA.

[0229] As shown in Figures 44A and 44B, the lower filter separator 38 is positioned between the filter 36 and the inner wall of the drying chamber 28. The separator 38 acts similarly to the ribs on a baffle plate, lifting the filter away from the inner wall of the drying chamber 28. This prevents the filter from adhering to the inner wall of the drying chamber 28, allowing moist air to pass through more easily and preventing pressure buildup. The lower filter separator 38 can be textured or ribbed to maintain space between the filter 36 and the inner wall of the drying chamber 28. In one embodiment, the filter separator 38 is ribbed with multiple spacers. See Figures 42A and 44A. In another embodiment, the filter separator 38' comprises a porous, coarse circular woven fabric of filaments. See Figure 44B. In the embodiment shown in Figure 44B, there are two separators. The separator can be made from a single piece or multiple pieces (e.g., 1, 2, 3, 4, 5, or 6 pieces). Any type of spacer or standoff can be used to maintain separation between the filter 36 and the inner wall of the drying chamber 28. Another example of a separator includes a flexible three-dimensional matrix of polymer filaments. In the embodiment shown in FIG. 44, the separator 38 surrounds most of the filter 36. In other embodiments, the separator 38 only needs to surround the filter 36 sufficiently to maintain space between the filter 36 and the inner wall of the drying chamber 28. The spacer / separator 38 is made from a material that can withstand the heat and pressure of the spray drying process and is non-invasive to the plasma. In one embodiment, the separator is injection molded and can be made from a thermoplastic elastomer such as olefin or polyester or polypropylene. In another embodiment, the separator can be made from nylon with a thermoplastic polyurethane frame. In the embodiment shown in FIGS. 42A and 44A, the separator 38 is Baltex NPD88 grade, has a width of 8.750 mm (±0.65 in), a height of 13.000 mm (±0.65 in), and a thickness of approximately 0.197 inches. The material used in this embodiment is a 100% polyester spacer mesh fabric.44B, separator 38' is two pieces, model 02257 (Freudenberg Filtration Technologies Weinheim, Baden-Wuerttemberg, Germany), and is approximately 8.80 inches + / - 0.06 inches wide, approximately 6.40 inches + / - 0.06 inches high, and approximately 0.197 inches + / - 0.030 / -0.010 inches thick. During drying of the plasma, moist air passes through lower filter 36 and lower filter separator 38 or 38' and exits through gas outlet 30, leaving the dried plasma behind in lower filter 36.

[0230] Another important aspect relates to the length of the disposable 100. In previous versions, the disposable length was approximately 66 inches. Longer disposable lengths allowed for more time, space, and heat to dry the plasma particles. However, longer disposables were difficult, cumbersome, and hard to handle for operators to install and use. See Examples 30 and 31. In fact, according to CDCMHANES 2015-2016 data, a 66-inch long disposable is longer than the height of many operators, such as the 79th percentile of U.S. women who are 5'6" tall. Men under 5'6" comprise the 14th percentile of U.S. men, according to the same data, who still represent a significant number of potential operators of the present invention.

[0231] Shortening the disposable to that shown in Figure 42A presented several challenges. A shorter disposable meant a shorter drying chamber. A shorter drying chamber meant that the plasma particles had to be evaporated and dried over a shorter distance, in a smaller volume, and in a shorter time, all without damaging the proteins in the plasma. In other words, the plasma had to be dried gently, but more quickly, and in less space.

[0232] Despite these obstacles, the present invention includes disposables 100 having a length of about 40 inches or less (e.g., about 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, or 24 inches or less), preferably about 34.8 inches. The 34.8 inch long disposables 100 are easily handled, installed, and removed from dryers and other parts of processing equipment by minimally trained personnel ranging in height from the 5th percentile (4'11") to the 99th percentile (6'6") for men and women, according to U.S. data. See Examples 30-33.

[0233] The disposable length, shown as dimension Y in Figure 44, measured from the bottom of the spray dry head 2 or the bottom of the baffle plate 8 to the top of the bottom filter 36, is about 31 inches or less (e.g., about 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19 inches or less), and in one embodiment, is preferably about 25.90 inches. In another aspect, the area of ​​the disposable region 100 encompassed by dimension Z, which is the length from the bottom of the spray dry head 2 and the top of the filter 36, is about 22 inches or less (e.g., about 22, 21, 20, 19, 18, 17, 16, 15, 14 inches), and preferably about 19.11 inches. In yet another example, the length of dimension X, which is the length between the bottom and top 46 of the spray drying head 2, is less than about 16 inches (e.g., about 16, 15, 14, 13, 12, 11, 10, 9, 8 inches), preferably about 12.14 inches.

[0234] Indeed, when comparing a disposable of the present invention to an earlier development version in which the disposable is approximately 66 inches long and has dimension Z of approximately 48 inches, the difference in overall length is approximately 30 inches, or a 46% reduction, and the difference in dimension Z is approximately 29 inches, or a 60% reduction. A significant difference can be achieved by shortening the overall length of the disposable or along dimensions X, Y, and / or Z. In another embodiment, the length of the present invention can be further shortened by about 1 inch to about 8 inches (e.g., 1, 2, 3, 4, 5, 6, 7, or 8 inches) along dimension X, thereby reducing the overall length by the same amount. In one embodiment, length X ranges from about 30 to about 37 inches. In other embodiments, the disposable can also be shortened by the same amount everywhere along dimensions Y and Z.

[0235] This shorter disposable 100 dries liquid plasma that preserves protein function of even the most fragile proteins, such as von Willebrand factor and other proteins. The spray drying system of the present invention and the spray drying system shown in the figures meets FDA vWF requirements.

[0236] Reducing the length of the disposable 100, including the spray drying head 2 and plasma drying chamber 28 of the present invention, results in a system that is significantly more usable by operators in a variety of situations than those of the prior art. For example, the top loading slot height of a prior art dryer using the described 66-inch disposable was 72.5 inches (over 6'), compared to only 54 inches for the dryer 200 shown in Figures 45 and 46. The lower (exhaust) flexed or flexed stack height of the prior art dryer using the 66-inch dryer described herein was only 16 inches above the floor, while the stack height of the disposable 100 for the dryer 200 described herein is a much more comfortable 27.5 inches. Multiple episodes of human factors testing (see Examples 30-33) demonstrated that the shorter disposable allows for unhindered installation of the disposable 100 into the spray dryer 200 by operators in the 5th percentile (4'11") to 95th percentile (6'6") height range in the United States. A shorter disposable allows for easier reach and bending or flexing movements required by the operator to install the disposable in the spray dryer and to safely and effectively attach and detach the disposable before and after operation of the spray dryer.

[0237] The plasma drying chamber tubing, baffle plate ring 156, exhaust port, etc. are made from blown or flat polyvinyl chloride (PVC) and heat-sealed to form the drying chamber. The baffle plate ring 156 is heat-sealed for disposable use, and once heat-sealed, it can be attached to the baffle plate with adhesive or the like. In one embodiment, the drying chamber expands during use to take the shape of the enclosure that is the spray-drying chamber housing of the dryer. Other commercially available materials and other vinyl materials can be used to fabricate the plasma drying chamber of the present invention. A sheet of PVC material is formed by injection molding and / or heat welding to form the spray-drying chamber and then sterilized.

[0238] In one embodiment, the plasma drying chamber of the present invention functions as a single-use chamber in which spray drying occurs. Sterilization by gamma or X-ray irradiation provides sterility for the plasma drying chamber. Development and manufacturing of the drying chamber are performed under ISO 13485 design control. Certification of materials in contact with the drying air or donor plasma within the drying chamber assembly provides lot traceability. Certification provides for toxicity testing and certification for human use.

[0239] The overall size of the spray dryer is generally much smaller than other production spray dryers, which are often too large and unsuitable for use in blood centers, military medical units, or similar locations. The spray drying system of the present invention is designed to accommodate and be used in blood component laboratories, whereas other production spray dryers are typically used in large, industrial-scale facilities.

[0240] As discussed above and in co-pending application No. (Attorney Docket No. 0118.0168-000, entitled "Usability Of A Disposable For A Spray Drying Plasma System," filed on the same day, the entire teachings of which are incorporated herein by reference), the spray dryer of the present invention is largely automated and can be used by persons with limited training. This is in contrast to the advanced training and skill requirements associated with industrial or laboratory spray drying, such as with spray dryers sold by Buchi Corporation, 19 Lukens Drive, Suite 400, New Castle, DE 19720 United States, Model No. 4244.

[0241] As further described in a co-pending related patent application (Application No. 17945126), the liquid plasma was pretreated before undergoing the spray-drying process. The pretreatment solution protects plasma coagulation factors during the spray-drying process. A volume of frozen or unfrozen plasma (e.g., approximately 260 ml) is transferred to a plasma pretreatment vessel containing a spray-drying stable acidic substance (SDSAS), such as 50 mL of a glycine and hydrochloric acid solution. In one embodiment, single-donor plasma expressed from collected whole blood or by apheresis that has never been frozen and is less than 24 hours old is desirably utilized in this process. Plasma is harvested from the blood by standard techniques known to those skilled in the art, as described herein. Plasma is collected by a process-call plasma analysis. Plasmapheresis refers to the procedure of separating plasma from blood by either centrifugation or membrane filtration. The system process can also use pooled plasma, if desired, and the starting plasma material is produced with any currently available anticoagulation system, such as those known as CPD, CP2D, ACD-A, and ACD-B. A sterile, non-pyrogenic, single-use container with SDSAS, e.g., a 50 ml solution of glycine and hydrochloric acid packaged in a 500 ml container in an overwrap pouch. In one embodiment, the process of the invention involves converting a single donor unit of plasma collected by standard procedures into a single unit of spray-dried plasma.

[0242] In vitro characterization data demonstrate that the effects of the system's spray-drying process are comparable between units spray-dried using different starting materials. Units manufactured from apheresized plasma (ACD-A anticoagulated) showed similar percentage changes due to manufacturing effects on the starting material compared to units spray-dried from whole blood-derived plasma (CPD anticoagulated). Statistical analysis (ANOVA) was performed on the percentage changes between the two starting materials before and after manufacturing across 20 assays, including clotting time, coagulation function, and activation markers. Of the 20 assays, total protein concentration, PT, TT, and factor VIII and factor XIII activity were determined to be statistically significantly different, but the mean percentage changes were similar, and the mean values ​​were all within the clinical reference range. In summary, the in vitro test results support the conclusion that manufacturing effects on both apheresized and whole plasma are comparable, with coagulation profiles within ±20% of their paired controls or within the normal reference range.

[0243] Detailed description of the finishing machine Once spray drying is complete, the disposables with the spray-dried plasma are transferred to a finishing device.

[0244] 47A-47F, finishing devices 400 and 400' are shown. Specifically, the function of the finishing device is to transfer plasma from a designated portion of a disposable, remove excess air, if any, from the disposable, and seal and separate the plasma to provide a plasma unit (dried plasma unit 60) with dried plasma. Plasma unit 60 can be rehydrated and transfused to a patient within, for example, five minutes.

[0245] Specifically, the finishing device 400 or 400' includes a base 440 or 440' and a shuttle 418 or 418'. The base 440 or 440' includes a power source, an impactor 442 or 442', a heat sealer and separator 448 (heat sealer 448' and separator 450'), and an air extractor 456 or 456'. In the illustrated embodiment, the impactor 442 includes a magnet and spring and impactor 442' in Figures 47B and 47C. Figures 47E-H and 47D-F use a pneumatic cylinder. In one embodiment, the impactor 442 or 442' can include any combination of elements that allow it to disposably apply sufficient impact force to move the dried plasma into the desired compartment, as further described herein. The sealer 448 or 448' can be an impulse sealer, a heat sealer, an electric heater, a radio frequency sealer, or the like. Separator 448 or 450', in one embodiment, is a cutting wire or heat cutter, but can be any device capable of separating and cutting the disposable once sealed. The sealer and separator can be the same device, as shown in Figures 47B-47C as sealer / separator 448, or they can be two separate devices, as shown in Figures 47E, 47F, 48E, and 48F as sealer 448' and separator 450'.

[0246] The finishing device 400 has a sliding frame 402 and shuttle 418 that move together, while the finishing device 400' has a fixed frame 402' that guides the movable shuttle 418'. Figures 47A, 47B, and 48A show the finishing device 400 with the shuttle and frame in a lowered position. Figures 47C, 48B, and 48C show the shuttle and frame in specific upper positions. Figures 47F and 48E show the finishing device 400' with the shuttle in a lowered position, while Figures 47D, 47E, 48D, and 48F show the shuttle in specific upper positions. Figure 47G shows the shuttle in an inverted upper position, and Figure 47H shows the shuttle in an inverted lower position. The fixed frame 402' of the finishing device 400' has a rail system that allows the shuttle 418' to move up and down. In particular, rails 472A' and 472B' are attached to backplate 403' and utilize guides 474A' and 474B'. See FIG. 47I. The guides 474A' and 474B' and rails 472A' and 472B' shown in FIG. 47I are tongue and groove fits. The rails 472A' and 472B' are fixed, and the guides 474A' and 474B' move up and down the rails, which in turn move the shuttle 418'. The mechanism that drives the shuttle 418' shown in FIG. 47I is a lead screw 476'. The end of the lead screw is fixed by rotating a nut while moving back and forth along the length of the threaded shaft. The rotation of the nut is driven by a motor. In addition to using a lead screw, the finishing machine can use any method for moving the shuttle, including chains, straps, and any other mechanism that allows the shuttle to move up and down the rails. In embodiments using a rail system and lead screw, the lead screw moves precisely up and down.

[0247] More specifically, the spray drying disposable device 100 is aligned within the finishing apparatus 400 or 400′ as follows. In one aspect, this is accomplished by inserting the plenum 6 of the spray drying head 2 into the spray drying head receiver 404 or 404′ (by aligning the locator notch 26 with the ridge 9), attaching the gas outlet 30 of the disposable to the gas outlet receiver 414 or 414′, and securing the locating pin openings 32A-C around the locating pins 432A-C or 432A′-C′. See FIGS. 48A-48D. In one embodiment, the disposable device is aligned and secured in the finishing apparatus when all three alignment elements—the locator device, the gas port device, and the locating devices on the outer wall of the disposable—are engaged. In other embodiments, any combination of these alignment elements can be utilized, as long as the disposable device is aligned and secured in the finishing apparatus.

[0248] In a further embodiment, the gas outlet receiver is positioned to accommodate any changes in the length or configuration of the disposable gas outlet 30 caused by the thermal and pressure stresses of the spray drying process achieved by the spray dryer apparatus. Similarly, the location of the locating pins 432A-C or 432A'-C' is positioned to accommodate and accommodate any changes in the length of the disposable or configuration of the locating pin openings 32A-C caused by the thermal and pressure stresses of the spray drying process achieved by the spray dryer apparatus.

[0249] As described above, the second locator 26 on the disposable 100 is aligned with the third locator 452 or 452' in the spray dryer head receiver 404 or 404' during the finishing process. In one embodiment, the spray dryer head 2 is inserted into the spray dryer head receiver 404 with the locator aligned when the finisher 400 is in the loading position, as shown in Figures 47A, 47B, and 48A (shown in the loading position with the spray dryer attached). In the finisher 400', the spray dryer head 2 is dropped into the spray dryer head receiver 404' with the locators aligned when the finisher 400' is in the loading position. In the embodiment shown in Figures 47E and 46D, the loading position is approximately two-thirds of the way up the rail. In one aspect, the third locator on the finisher and the first locator on the spray dryer are the same shape and size and align with the locator on the spray dryer disposable. Similar to the spray dry head arrangement, this arrangement axially aligns the finisher and spray dryer disposable. The positioning device can include any device that attaches to, mates with, complements, or communicates with a locator on the disposable and a locator on the finisher. Examples of positioning arrangements include a recess / protrusion arrangement, a complementary shape arrangement, a hook / receiver arrangement, a channel and groove arrangement, a latch and catch arrangement, a magnet arrangement, etc. In the embodiment of Figure 48A, a male locator is on the spray dryer finisher and a complementary female locator is on the disposable, although the arrangement can be reversed.

[0250] The spray drying head receiver 404 or 404' also aligns the spray drying head 2 laterally. The spray drying head receiver 404 allows the spray drying head 2 of the disposable 100 to be aligned laterally relative to the finisher 400 or 400'. In one embodiment, a spray dryer head retaining clip 454 secures the spray dryer head 2 during the finishing process. See FIG. 47A. The retaining clip 454 is optional. The baffle plate ridge 9 of the spray drying head 2 also provides additional support when inserted into the receiver 404 or 404'. Once inserted and aligned, the spray drying disposable 100 can no longer move up and down. When the receiver and arrangement are used, they align the disposable so that it cannot move up and down, and once inserted into the finisher, it cannot move axially as defined by the axis through the center of the spray drying head. As shown in Figure 48A, the spray drying head fits into the receiver 404 such that the fit is snug or tight.

[0251] In one embodiment, the receiver 404' can be further configured to facilitate insertion, alignment, and retention of the spray drying head 2. The finisher 400' has a receiver 404' shown in a top view in FIG. 48G and a perspective view in FIG. 48H. The baffle plate ridge 9 of the spray drying head 2 slides into the receiver 404 or 404'. In the case of the receiver 404', the top and front surfaces have ramps 458A and 458B, which are partially tapered edges, allowing an operator to slide the spray drying head 2 from above into the receiver 404' in an angled downward motion, generally along axis C. The partially tapered surfaces taper from the top surface to the inner surface along the front surface forming the ramp. In one embodiment, the ramps in FIG. 48H are partially tapered, leaving only a portion of the front and inner surfaces, with the untapered inner front surface forming lip 462A' or lip 462B'. Lips 462A' and 462B' form part of bumpers 460A' and 460B', which prevent the spray drying head 2 from being removed along axis D, for example, after baffle plate 8 of the spray drying head 2 is fully inserted and flat.

[0252] Bumpers 460A' and 460B' are curved and configured to receive baffle plate ridge 9. The bumpers are formed when the receiver continues more than 180 degrees around a circular circumference. The receiver has a circular parameter ranging from about 210 degrees to about 260 degrees, including bumpers 460A' and 460B', with bumpers 460A' and 460B' each forming about 15 degrees to about 40 degrees (e.g., about 15, 20, 25, 30, 35, or 40 degrees) of the circumference. Receiver 404' also includes spring-loaded ball detents 464A' and 464B' instead of retaining clips. These detents function as fasteners to secure baffle plate ridge 9 to receiver 404'. The detents are optional and can be other types of fasteners (e.g., used to further secure the baffle plate ridge 9 to the receiver 404'. In one embodiment, the detents 464A' and 464B' provide an audible "click" to notify the operator that the baffle plate ridge is properly secured.

[0253] Positioning devices (e.g., pin and opening arrangements 32A-C and 432A-C or 432A-C') are preferably located at each corner of the plasma unit's outer wall, as well as above and below seal and separation locations 44A and 44B. The positioning devices shown are pin and opening arrangements, but can be any arrangement that allows the side walls of the disposable to be properly secured to the finisher while the finisher is in use. Compare Figures 47C and 48B. In addition to pin and opening arrangements, other examples of positioning devices include hook / receiver arrangements, channel and groove arrangements, latch and catch arrangements, etc. In embodiments, pins are located on the finisher and openings are located on the disposable, although these can be reversed.

[0254] The finisher 400 or 400' can include a tensioning system that stretches the walls of the disposable 100 during sealing and / or separation. In one aspect, stretching the disposable walls helps ensure a better, more complete seal and reduces wrinkles in the seal. In certain embodiments, if the disposable walls do not have enough tension, wrinkles can become embedded in the seal, potentially causing it to break. Increasing the tension in the disposable walls results in fewer wrinkles and / or broken seals compared to untensioned disposable walls. The finisher 400' has two locating pins 432C' attached to each tensioner 466A', 466B', 466C', and 466D'. See FIG. 47D. Any arrangement of locators and tensioners can be used as long as the disposable 100 remains secured to the shuttle frame and the disposable walls are in tension during sealing and / or separation. During sealing and / or separation, the tensioners move apart along axis E, creating tension in the disposable wall.

[0255] In the embodiment of FIG. 48I, the structure of tensioners 466A', 466B', 466C', and 466C' each have a sideways "U" shape with two locating pins 432C'. Tensioner 446C' structure includes ramps that engage with rollers 470A' or 470B' of the sealer and / or separator, and when engaged, the tensioners move away from each other along axis E (FIGS. 47D, 48J). This movement creates tension in the disposable wall during sealing by heat sealer 448' or separator 450', reducing wrinkled seals and / or broken seals. In one embodiment, the tension is measured to be approximately 2 lbf and approximately 3 lbf.

[0256] Tension can also be generated vertically along axis F. Tensioning can be achieved by repositioning the pins farther apart to stretch the disposable in any direction. Finisher 400' also includes pins 432A and 432B positioned a short distance from 42C, which create tension along axis F. In one embodiment, the tension is measured to be about 1 lbf and about 2 lbf.

[0257] The tensioning system can be accomplished in other ways, so long as the disposable walls are held in tension during sealing and / or separation. In some embodiments, after sealing the disposable with a heat sealer, the process can stretch the disposable somewhat during the heating process, so applying tension during the separation step aids in a cleaner separation. Such tensioning can include springs, reversible locks, slides, belts, etc. Any type of tensioner can be used with this system, so long as the disposable walls are under tension during sealing, separation, or both.

[0258] Once the disposable device is aligned and secured in the finisher, as shown in FIGS. 48B and 48D, the shuttle 418 or 418' lowers into the finisher, where the impactor 442 or 442' repeatedly impacts the sidewall of the disposable 100. This "impacting," or alternatively, shaking, action applied to the disposable 100 allows the dried plasma, which may be adhered to the interior wall of the disposable 100 or embedded in a filter, to be released and move to the bottom of the disposable 100. In one embodiment, the impacting action can be accomplished in several ways, as long as the dried plasma moves to the desired portion of the disposable 100. In the embodiment shown in FIG. 48B, the finisher 400 utilizes a spring magnet attached to a plate as the impactor. In the embodiment shown in FIG. 48D, the impactor 442' of the finisher 400' is a pneumatic cylinder attached to a plate or paddle. In addition to a magnet system or a pneumatic system, several other types or combinations of systems can be used for impacting. For example, a combination of compressed air and a plate can be used to create an impact action on the disposable wall. In this embodiment, the compressed air can be obtained from a dry gas source and any suitable line regulator or controller. In yet another embodiment, the vibrational motion can be applied using a vibration source (e.g., magnetic coil, piezo crystal, etc.) or a sonic source that is converted to mechanical motion (e.g., shaking or impact action). The impact action can be achieved by other methods, including conventional shaking action, vacuum action, etc.

[0259] 48K and 48L show the impactor 442', separator 450', and sealer 448'. The separator 450' and sealer 448' are attached to the jaws. In this embodiment, the separator 450' is a cutting wire and the sealer 448' is a flat heat-sealed strip. Tensioning rollers 470A' and 470B' that engage the tensioner ramps are more easily seen in FIG. 48L, and are attached to the jaws of the separator 450' and sealer 448'.

[0260] After impact and migration of the dried plasma to the lower compartment, e.g., defined by dimension V, the finishing device applies tension to the disposable 100 and heat seals (e.g., using an impulse sealer 448 or 448') to separate the top of the bag, i.e., the disposable top 48, at location 44A. See Figures 44, 48A, 48D, and 48E. This first sealing and separation action effectively forms one of the side walls of the dried plasma unit 60. The remainder of the disposable device, the bottom disposable portion 50 (i.e., defined by the combined dimensions U and V), includes the bottom of the bag up to location 44A where it is cut and sealed. This disposable device with a single cut may also be referred to as an improved spray-drying disposable device. The shuttle 418 or 418' automatically or manually raises upward once the initial sealing and separation is complete. The operator then inspects the seal for any open areas, voids, or wrinkles extending across the entire width of the seal. The top disposable portion 48, the disposable portion from locator line 44A to spray dry head 2, can now be discarded.

[0261] Next, as shown in FIGS. 48C and 48F, the operator rotates or flips the lower shuttle disposable shuttle frame 408 or 408' around pivot point 420 using knobs 412A and 412B or knobs 412A' and 412B' to secure the lower disposable shuttle frame 406 over the upper disposable shuttle frame 408. In one embodiment, the operator grasps knobs 412A and 412B or knobs 412A' and 412B' and rotates the shuttle 180 degrees clockwise until it is in place. This can also be done automatically or mechanically by engaging a switch or computer display. A lock can be used to hold the lower disposable shuttle frame 408 in place before or after rotation. FIG. 48D shows lock 478', a spring user-activated lock to hold the lower shuttle frame in place. The lock can lock onto the frame during use. Because the bottom disposable portion 50 is still attached to the lower frame of the finishing apparatus by the positioning and gas outlet features, the bottom disposable portion (e.g., the portion from location 44A to the gas outlet 30) also rotates and locks into place (FIGS. 48C and 48F). In one embodiment, a sensor can be used to ensure the frame is in the locked position. As shown in FIGS. 48C and 48F, the disposable is upside down with the gas outlet 30 and gas outlet receiver 414 or 414' on top.

[0262] Once the operator indicates to the finisher that the bottom frame is locked and stacked onto the top frame, the finisher repeats the impacting process to further shake or loosen any dried plasma that may be in the filter or surrounding area, causing the dried plasma to fall into the portion of the disposable that will become the dried plasma unit 60, i.e., the plasma unit portion 46. An air extractor engages the disposable 100 and removes any remaining air through the gas outlet 30 and an exhaust port (not shown) of the finisher. In one embodiment, some air remains within the dried plasma unit 60 (e.g., less than about 15 mL per plasma unit). In one embodiment, the finisher measures a vacuum level of about -4 psi to about -0.5 psi. The vacuum level is an indication of the amount of air remaining within the plasma unit. In one aspect, at a vacuum level of -3 psi, less than about 15 mL remains within the plasma unit 60. The alignment elements of the present invention, including the gas outlet / gas outlet receiver and positioning configuration, allow the modified spray drying disposable device to remain aligned even after its top portion, which includes the spray drying head, is separated. The finisher then performs a second seal and separates the disposable at line location 44B above port 42A. See FIG. 48C and step 820, FIG. 51C. Upon completion, the finisher raises shuttle 418 or 418', and the operator can discard the disposable device filter portion 52, including the gas outlet, lower filter, and filter separator. Upon completion, the finisher manually or automatically raises shuttle 418 or 418', and the operator inspects the seal. The second sealing and separation action effectively seals the entire disposable from the atmosphere, forming plasma unit 60. As shown in FIG. 49A, the disposable portion 46, now sealed and separated on both sides, yields dried plasma unit 60 with dried plasma 62.

[0263] Sensors can be used to ensure that the shuttle 418 or 418' is in the proper position for impact, sealing, and / or separation. The sensors can be located on the base of the finisher 400 or 400', and in one embodiment, a reflector can be attached to the shuttle. When a reflector attached to the shuttle reflects a sensor signal or laser back to the sensor as it passes, the finisher's computer system can determine where the shuttle is relative to the impactor, sealer, and / or separator. In one embodiment, the computer system stops the shuttle approximately 1 inch after the reflector has passed.

[0264] While the finishing process described herein as performed by finisher 400 or 400' is a preferred embodiment, the process (moving the plasma to the desired compartment and sealing the plasma drying chamber to form the dried plasma unit) can be performed manually using readily available tools such as appropriately sized scissors and a heat sealer to create the two seals described.

[0265] The sealing and separation of the units in the preferred embodiment of the present invention described herein is a multi-step, semi-automated process that takes place within the finisher 400 or 400'. The finisher 400 or 400' is responsible for monitoring and controlling at least five processes to create the units: solidification of the dried plasma powder on the outlet filter, sealing and removal of the top of the disposable 100, inversion and solidification of the dried plasma powder, removal of excess air, and sealing and separation of the bottom of the disposable 100. The finisher 400 or 400' ensures that the sealing process is completed within specific operating ranges. The finisher 400 or 400' includes an array of sensors and actuators that enable automated control of the sealing process and provide a backlit operator visual inspection of each heat seal of the film.

[0266] Finisher Architecture The architecture of the finisher 400 or 400' is shown in Figure 49B. The finisher 400 or 400' regulates and / or drives at least the following flow paths: an air line (line A), an extraction vacuum line (line B), an extraction piston line (lines C, D), impactor lines (lines E, F, G, H, N, O, T, U), cut lines (lines I, J, P, Q, V, W), and seal lines (lines K, L, M, R, S, X, Y). Any number of flow configurations can be arranged as long as the finisher provides pressure, sealing, and separation for disposables with dried plasma. Additional or fewer flow lines than shown in the figure can provide these flow lines.

[0267] Finishing Machine - Airline The air line begins with a compressed dry air (CDA) source, as described herein, and continues to line A. The air line does not need to be clean, dry air and can be any air source. In one embodiment, the same CDA source for the dryer 200 can be used for the finisher 400', or a separate one can be used. The CDA system connects to the finisher 400' via connector CN101 502, FIG. 49B. Upon entering the finisher 400', the compressed air travels through solenoid valve PV101 504. As described herein, a solenoid valve is an electrically controlled valve. The solenoid valve of the finisher 400 or 400' has an electric coil with a movable ferromagnetic core and a plunger at its center. In the rest position of solenoid valve PV101 504, the plunger closes the opening in the line. When an electric current is applied, the coil generates a magnetic field that exerts a force on the plunger, opening the line. The solenoid valve PV101 504 is an L-port that allows for an in-line supply of compressed air, but also allows a small amount to be diverted to an air manifold, as described further herein. The compressed air passes through PR101 506. A pressure regulator, such as PR101 506, adjusts the system flow pressure in response to upstream or downstream pressure changes. When the dry gas leaves the pressure regulator PR101 506, the compressed air pressure is about 70 psi to about 80 psi. Typically, the finish includes a static pressure system. The compressed air passes through pressure transducer PT101 508. Pressure transducer PT101 508 measures the pressure of the dry gas in the line and communicates the pressure to the computer system via a digital signal. The compressed air pressure at pressure transducer PT101 508 ranges from about 70 psi to about 80 psi. After passing through pressure transducer PT101 508, excess pressure, if any, is released through pressure relief valve PRV101 510 by allowing the pressurized air to flow out of the system through an auxiliary passage and vent to the room.

[0268] The compressed dry air lines supply flow to the air manifold ARM101 572 to pneumatically actuate pistons used for impingement, sealing, air extraction, and separation.

[0269] Finishing Machine - Extraction Vacuum Line The extraction vacuum line exits the air manifold ARM101 572 and travels to the vacuum generator VG101 512, following line B. The generated vacuum is used to remove excess air from the disposables to facilitate long-term storage. Excess air from the disposables 100 is removed by creating a vacuum and drawing the air through filter F101 514. Filter F101 514 is a 0.1 micron filter suitable for removing pathogens before the air exits the atmosphere. This filter ensures that pathogens from the finishing process do not contaminate the outside air. After passing through filter F101 514, the excess air passes through pressure transducer PT102 516. The pressure of the excess air at pressure transducer PT101 516 ranges from approximately -2 psi to approximately -13 psi. The air then passes through check valve CV101, a one-way valve that prevents backflow of air. The air then passes through a speed controller SC101 518, which is used to slow the air extraction rate so that the system can react at the ideal moment corresponding to the ideal amount of air remaining in the disposable. The excess air leaves the vacuum generator VG101 512 through a muffler to combine with the outside air. The muffler is intended to reduce the noise level of the air leaving the vacuum generator and entering the ambient air.

[0270] Finishing Machine - Air Extraction Piston Line The air extraction piston line, as described herein and continuing through lines C and D, is used to engage and disengage the air extraction nozzle that removes excess air from the disposable. The air passes through speed controller SC102 520, which is used to slow down the air extraction slide piston to reduce wear. The air travels to air extraction slide PP101 522, which is a pneumatic piston that actuates the air extraction slide to remove residual air from the disposable 100 containing dried plasma. Air extraction home sensor SR101 524 is used to determine when the air extraction piston is at its home position.

[0271] Finishing Machine - Impactor Line The impactor line, used to transfer dried plasma particles to the desired compartment of the disposable as described herein, continues through lines E, F, G, H, N, O, T, and U. This line has two lines, one to the front impactor plate and the other to the rear impactor plate. Lines come from the air manifold and power the plasma release slide front face 528 of pneumatic piston PP102 through speed controller SC104 526 and the plasma release slide front face 532 of pneumatic piston PP103 through speed controller SC106 530. The pneumatic pistons actuate the impactor plates or paddles. The front home sensor SR106 534 and the front extended plasma release sensor SR116 536, as well as the plasma release home sensor SR107 538 and the extended plasma release sensor SR117 540, are used to verify the piston position during the impaction process to ensure operator safety. These sensors use a laser and reflector mounted on the shuttle such that when the reflector mounted on the shuttle reflects the laser, the sensor receives a signal indicative of the position of the shuttle's piston within the base. The signal is sent to the finisher's computer system to determine the position of the piston, and when in the properly determined position, provides a command to the impactor to proceed with impact application.

[0272] Finishing machine - separator line The separator lines, used to cut one portion of the disposable 100 away from another portion of the disposable 100 to form a dried plasma unit, as described herein, continue through lines I, J, P, Q, V, and W. These lines have two lines, one to the front cutting slide and the other to the rear cutting slide. The lines come from the air manifold and travel through speed controller SC109 542 to power pneumatic piston PP104, which cuts the front slide 544, and speed controller SC113 546 to power pneumatic piston PP105, which cuts the rear slide 548. This pneumatic piston activates the wire cutter, or separator. The front home sensor SR108 550 and the front cutting system extension sensor SR118 552, as well as the cutting system home sensor SR109 554 and the rear cutting system extension sensor SR119 556, are used to verify the position of the pistons to ensure functionality and operator safety. These sensors, such as the SR121 557, use a laser and reflector mounted on the shuttle such that when the shuttle-mounted reflector reflects the laser, the sensor receives a signal indicating the shuttle's position within the base to locate the separation location. The signal is sent to the finisher's computer system to determine the shuttle's position, and when it is in the properly determined location, it instructs the separator to proceed with cutting the heat seal.

[0273] Finishing machine - sealing line The sealing lines, as described herein and continuing as lines K, L, M, R, S, X, and Y, are used to seal the disposable wall to itself and form dried plasma. This line has two sets of two lines. The first set is a low-pressure line coming from Station 6 of the manifold, connecting to the extension sides of both the front and rear seal pistons PP106, 568 and PP105, 569. The pressure is regulated to 10 to 20 psi using a regulator SY30M-N6-A1 mounted on the manifold. A speed controller SC112 566 is located on the rear piston extension line. This speed controller slows the movement of the rear piston slide, thereby providing the appropriate tension on the disposable before the front piston slide engages the tensioner and seal begins. A pressure transducer PT103 560 measures the air pressure in the line and transmits the pressure to the computer system via a digital signal. The clean air pressure at pressure transducer PT103 560 ranges from approximately 10 to approximately 20 psi when low pressure is applied. The second set of lines is at high pressure, between 70 and 80 psi. The high-pressure and low-pressure lines are connected through shuttle check valve CV102 558, a three-way shuttle valve that prevents reverse air flow. Check valve CV102 558 allows the seal piston to first engage low-pressure air from station 6 and then high-pressure air supplied through station 7 of the manifold. When high pressure is engaged, pressure transducer PT103 560 reads between 70 and 80 psi. Home sensors, SR110 562, SR111 563, SR112 567, and SR113 564, determine the position of both the front and rear seal pistons to ensure proper functionality and safety.

[0274] These sensors use a laser and a reflector attached to the shuttle, and when the reflector attached to the shuttle reflects the laser, the sensor SR120 565 receives a signal indicating the position of the shuttle within the base to determine alignment with the sealing jaws. The signal is sent to the finisher's computer system to determine the position of the shuttle and, when in the properly determined position, instructs the sealer to proceed with heat sealing at a set location on the disposable, as described herein.

[0275] Finished Air Manifold The air manifold AMC101 572, a branch chamber, extracts a small amount of clean, dry air to generate mechanical motion. The extracted air is used to actuate the pneumatic valves (PV) and pneumatic pistons (PP) within the finisher 400'. The manifold shows seven stations, with multiple actuators part of each station. Station 1 actuates the extraction line, Station 2 actuates the extraction piston line, Stations 3 and 4 actuate the impactor lines, Station 5 actuates the separator line, Station 6 actuates the low-pressure sealing line, and Station 7 actuates the high-pressure sealing line.

[0276] The arrangement of stations and actuators can be varied as required. An air manifold is used to actuate the valves and pistons of the spray dryer, however any commercially available device can be used.

[0277] Detailed workflow description Before spray-drying liquid plasma, the operator must prepare the spray-drying apparatus (FIGS. 45A-45C) and finishing apparatus (FIGS. 47A-47C and 48A-48C). The operator ensures that the spray-drying apparatus 200 and finishing apparatus 400 are on and ready. In one aspect, the operator should also tap "WAKE" on the display 212 and open the door of the spray dryer (e.g., by pulling the large hinged handle 230 to the right to unlatch the door 228, then pulling the handle 230 to the left). See FIG. 45C. Optionally, paper labels or other removable closures may be attached over the inlet port 22 and the gas outlet port 30. In another embodiment, the operator can alternately attach the appropriate portion of the disposable to the dryer. For example, the operator can attach the guide 4 of the spray-drying head 2 to the dry receiver 204 of the spray dryer 200, and then attach the gas outlet 30 to the gas exhaust port 208.

[0278] To pretreat liquid plasma, referring to FIG. 51A, an operator follows the steps of pretreatment methodology 600. Beginning at step 602, the operator prepares the equipment (e.g., sterile connection device (SCD), collection monitor / scale, tubing sealer, and barcode scanner) and collects supplies (e.g., plasma unit, pretreatment bag, spray-dried disposables, site-specific supplies (labels, tracking documentation)) in step 604. Next, the operator makes a sterile connection between the liquid plasma bag tubing and the pretreatment container tubing (step 606). See FIGS. 42A and 51A. Here, the liquid plasma bag and pretreatment container have a sterile connection. In doing so, in one embodiment, the total tubing length after the sterile connection is preferably approximately 15 inches to 20 inches long to allow the plasma unit to hang for transfer to the pretreatment container without tension, so that the blood collection monitor can precisely control the transfer of plasma to the pretreatment bag. The pretreatment container with the pretreatment solution is appropriately labeled. In particular, the pretreatment solution is a glycine and hydrochloric acid solution having about 15 mmol to about 30 mmol (e.g., about 15, 20, 25, and 30 mmol) of glycine and 3 mmol to about 7 mmol (e.g., about 3, 4, 5, 6, and 7 mmol) of hydrochloric acid. The combined plasma has a pH in the range of about 5.5 to about 7.2, which offsets the effects of spray drying on pH, resulting in a final rehydrated product at normal physiological pH, in the pH range of about 6.8 to 7.6. In another embodiment, pretreatment of the plasma is optional.

[0279] In one embodiment, mixing of the liquid plasma with the pretreatment solution is accomplished by transferring the plasma to a pretreatment container. This can be accomplished by first suspending the liquid plasma bag from the upper bag hook of the collection monitor / scale and the pretreatment container from the lower hook. See step 608 in Figure 51A. The tubing is guided through a mechanical tubing clamp on the collection monitor / scale (step 610) and secured in place. The weld on the tubing is clamped, and the Hemostat / manual clamp is released to ensure plasma flow. See step 612.

[0280] Mixing of the liquid plasma with the pretreatment container containing the pretreatment solution (e.g., 50 mL) can be done manually or can be automated via a commercially available collection monitor, tray-shaped scale, or other similar device. In one embodiment, the process is automated and the transfer volume is set to 260 mL (e.g., between 240 and 280 mL). The start button is pressed and the plasma is transferred. Step 614. In one embodiment, once 260 mL of plasma has been transferred, a mechanical clamp on the collection monitor automatically closes, stopping the flow of plasma. The tubing is disconnected from the collection monitor, and the pretreated liquid plasma can be manually stirred, shaken, rocked, or otherwise mixed as described in step 616. This process can also be automated using commercially available laboratory rockers, agitators, etc.

[0281] A tube sealer is used to separate the pretreatment container with the pretreated liquid plasma from the remainder of the tubing and the original liquid plasma bag. In one embodiment, the operator uses the tube sealer to triple heat seal the tubing above the manual clamp in step 618. The middle seal separates the tubing.

[0282] In another embodiment, the pretreatment solution can be added to the liquid plasma bag, or the two can be mixed in a third bag.

[0283] In one embodiment, once the plasma is transferred, it is placed in a dryer and dried for 4 hours or less (e.g., about 4 hours, 3 hours, 2 hours, 1 hour, 30 minutes, 15 minutes, 10 minutes, 5 minutes or less).

[0284] The plasma pretreatment bag containing the pretreated plasma is also referred to herein as a "plasma bag," "liquid plasma bag," or "pretreated plasma bag." The pretreated plasma bag is connected to the spray dryer disposable device with the plasma inlet tube, tubing 16, as described in step 620, thereby obtaining a modified disposable. The tubing from the pretreated plasma bag is connected to the plasma inlet tube via an SCD connection. In one embodiment, the operator must make a connection long enough to fit the modified spray dryer disposable into the dryer. In one aspect, the operator can position the SCD union about 1 to about 2 inches (e.g., about 101.6 cm) from the distal end of the spray dryer disposable device tubing to ensure that the total tubing length after sterile connection is about 43 inches (e.g., about 2.54 cm to about 5.08 cm). This facilitates installation into the spray dryer. After the connection is made, the operator can label the disposable, for example, to apply a matching blood center number or other identifier. The operator can then hang the modified disposable on the dryer bag hook 222 and clamp the tube to ensure the SCD weld is open.

[0285] Prepare the Spray Dryer. FIG. 51B shows a flowchart illustrating method 700, detailing the steps an operator takes to dry plasma using a spray dryer. To prepare the spray dryer, the operator ensures that the spray dryer 200 displays the READY screen by pressing WAKE, as needed, as shown in step 702. The screen then prompts the user to load the drying chamber 202. As described in step 704 (FIG. 51B), the operator opens the door 228 of the spray dryer 200, as shown in FIG. 45C. The operator can unlatch the door by pulling the large hinged handle 230 to the right, and then pull the handle to the left to open the entire door panel. See FIG. 45C. The operator hangs a pre-processed plasma bag from the plasma bag hook 222, and the disposable device 100 is aligned and inserted into the spray dryer 200 as described herein. See step 706 of FIG. 51B and FIG. 46A.

[0286] Once the guide 4 is attached to the receiver 204, the operator pulls the edge and port of the disposable device into the spray dryer. The port is pushed in for the port receiver (not shown). The operator ensures that the drying chamber is fully installed and all edges are pushed into the drying chamber cavity. As shown in FIG. 46A, the operator connects the gas outlet 30 at the bottom of the disposable device 100 to the exhaust port 208 of the dryer 200. The operator removes the aerosol filter cap from the aerosol filter, if present, and attaches the aerosol tube 10 to the aerosol filter 12. This step connects the aerosol tube 10 to the aerosol line that runs through the filter 12 to the pressurized gas source 216.

[0287] Once the disposable device is aligned and connected to the drying gas source, pressurized gas source, plasma source, and exhaust port 208, the operator prepares the peristaltic pump 214 to pump liquid plasma into the disposable device. This is done by opening the peristaltic pump latch 214A and forcing the pretreated plasma bag tubing 16 through the peristaltic pump 214 and plasma / aerosol guide 226 in the direction of flow (i.e., plasma flows from the pretreated plasma bag into the disposable device). Step 708, FIG. 51B. Once the plasma is pumped in the direction of flow, the operator closes the pump latch.

[0288] The operator closes the door and inserts the key 236 into the manual safety lock 238. Step 710, FIG. 51B. In one embodiment, the key 236 is attached to the door handle 230, with the keyhole 238 located on the left side of the spray dryer 200. This is a safety feature; the spray dryer will not allow the operator to proceed to the next step until this step is performed. This is indicated on the display 212. Once closed and locked, the screen prompts the user to unclamp the plasma line. The operator releases the plasma by unclamping any hemostat or manual clamp. At this point, the cover is removed and the door is closed, and the disposables are no longer exposed to the outside air / environment. In this case, the time from when the operator removes the first adhesive cover and closes the door is approximately 30 to 90 seconds.

[0289] Once the door is closed and the key is inserted, the operator confirms this step is complete by using the interactive display and pressing "CONFIRM," and the spray dryer automatically performs an integrity check. See steps 710-712 in Figure 51B.

[0290] If there are no issues, the drying device will automatically begin the drying process. The screen will display the estimated time remaining until completion. In one embodiment, the drying beacon indicator on the machine will remain green as normal operation of the equipment continues. The rapid drying process time is approximately 35 minutes, but can range from approximately 20 to 60 minutes (e.g., approximately 20, 25, 30, 25, 40, 45, 50, 55, 60 minutes).

[0291] 45A-45C and 46A, to align the spray drying disposable device 2 within the spray drying apparatus 200, the operator must insert the offset guide 4 of the disposable 100 into the receiver 204 of the dryer 200, align the disposable with the dryer's positioning device, and insert the disposable's gas outlet into the dryer's exhaust gas port. Once these three alignment elements are engaged, the disposable is aligned and ready to be locked into place. After attaching the plasma source and pressurized gas source, the operator can lock the spray drying chamber housing door and begin the spray drying process. In alternative embodiments, any combination of these alignment arrangements can be engaged to align the disposable with the spray drying apparatus.

[0292] The parameters for drying are described herein.

[0293] Once drying is complete, a screen prompts the operator to clamp and remove the plasma pretreatment container, which should be hanging from a hook 222 on the outside of the closed door. The indicator light 234 indicates that the drying process is complete by changing its flashing color or pattern; in one embodiment, the indicator light flashes green. Step 712, FIG. 51B.

[0294] To remove the disposable device, the operator re-engages the clamp on the plasma tubing, sealing and disconnecting the plasma tubing after flow or lift from the pump. Step 712, FIG. 51B. This step prevents any residual liquid plasma in the pretreated plasma bag from entering the disposable device. Once the plasma tubing 16 is sealed and disconnected, the operator can open the door and open the spray-drying apparatus 200. The operator can then open the latch 214A on the peristaltic pump 214, remove the plasma tubing from the peristaltic pump 214, and discard the tubing with combined plasma 66 and the pretreated plasma bag 64.

[0295] Once the operator communicates to the spray dryer that this step is complete, for example by pressing CONFIRM on the interactive display, the operator can remove the disposable device, which involves using a key to release the manual safety lock and engaging the door handle to unlock and open the door.

[0296] Once the spray dryer door is opened, the operator disconnects the disposable's gas outlet 30 from the gas exhaust port 208 of the spray dryer. Step 714, FIG. 51B. The operator then disconnects the aerosol line 10 from the pressurized gas source 216. The disposable device with dried plasma can be removed from the spray dryer. In one embodiment, the operator closes the spray dryer door to warm the machine and prepare for the next drying run. Step 716, FIG. 51B. The operator is now ready to move the spray dried disposable with dried plasma to the finishing equipment. Step 718, FIG. 51B.

[0297] The next part of the process, the finishing process, involves sealing and separating the portion of the disposable device with the dried plasma to make it into a spray-dried plasma unit. Finishing method 800 in Figure 51C refers to the steps required to convert a spray-dried disposable 100 with spray-dried plasma into a spray-dried plasma unit 60.

[0298] 47 and 48, the finishing apparatus 400 or 400' is shown. As described herein, FIGS. 47A-47H show the finishing apparatus 400 or 400' and views without a disposable device 100 attached. FIGS. 48A-48F show the finishing apparatus 400 or 400' with a disposable device 100 attached. Specifically, FIG. 47A shows the finishing apparatus 400 in a lowered position ready for loading, and FIG. 47D shows the finishing apparatus 400' in an upper position ready for loading. FIG. 47B shows the interior of the base 440 when the apparatus 400 is in the lowered position, and FIG. 47F shows the interior of the base 440' when the apparatus 400' is in the lowered position. FIG. 47C shows the finishing apparatus 400 in a raised position without a disposable 100 attached, and FIG. 47E shows the finishing apparatus 400' in a raised position without a disposable 100 attached.

[0299] The screen 401 or 401′ of the finisher 400 or 400′ displays the word “STANDINGBY.” When the operator communicates with the finisher, for example, by tapping “WAKE,” the screen 401 or 401′ prompts the operator to load the plenum 6 of the disposable device 100 onto the spray dryer head receiver 404 in the lower position of the finisher 400 or into the spray dryer head receiver 404′ in the load position of the finisher 400′. See step 802, FIG. 51C. The finisher may have additional positions for loading, rotating the frame, inspecting the seal, and / or removing the finished product. In one embodiment, the finisher may have two or three additional positions. In an embodiment, if there are two positions, the lower position is the loading and processing position, and the upper position is for inspection, rotating the frame, and removing the dried plasma unit. In an embodiment, where there are three positions, one position is a middle position for loading, one position is a lower position for processing the disposable, and an upper position is for inspection, frame rotation, and removal of the dried plasma unit. In yet another embodiment, there are the following positions: Start - Load disposable spray drying head, Home up position load pin of disposable, Seal - Bottom position - Sealed position, End - End of travel for plasma discharge operation, Cut - Separation position, and Inspect - Position for inspection.

[0300] The operator loads the disposable device with dried plasma into the shuttle 418 or 418' as shown in Figure 48A or 48D by inserting the plenum 6 of the disposable device into the spray-drying head receiver 404 at the top of the shuttle. See step 804 in Figure 51C. The operator can then coil the remaining tubing and insert it into the guide 4 of the spray-drying head 2.

[0301] As described herein, the second locator 26 on the disposable device is aligned with the third locator 452 or 452' in the spray-drying head receiver 404 or 404' during the finishing process.

[0302] Once the disposable spray drying head is attached to the finisher as shown in Figure 48A or 48D, the operator communicates this to the finisher by, for example, pressing CONFIRM. See step 806 in Figure 51C. When the shuttle is in the raised position, the operator secures the remaining portion of the disposable device with the dried plasma as shown in Figures 48B and 48D. See step 806 in Figure 51C. This is the raised position (Figures 48B and 48D). When in the raised position, the gas outlet 30 is attached to the bottom of the shuttle by inserting the exhaust outlet downward into the "U" shaped exhaust outlet receiver 414 or 414.

[0303] In particular, the finisher is designed to accept the gas outlet 30 of the disposable to hold the disposable in place during the process of moving the plasma into place, removing air, sealing, and separating. The gas outlet receiver 414 or 414' of the finisher has a receiver with a "U" shaped slot so that the gas outlet can be securely attached to the finisher and remain attached during the finishing process.

[0304] The operator then uses a positioning device to attach the disposable device with the dried plasma. Positioning devices (e.g., pin and opening devices or pin and grommet devices) are preferably located at each corner of the plasma unit's outer wall (see positioning opening 32C) and above and below the positioning lines 44A and 44B for sealing and separation. Positioning openings 32A and 32B are located on either side of the outlet port and are attached to positioning pins 432A and 432B or pins 432A' or 432B'. The positioning device shown is a pin and opening device, but it can be any device that allows the side walls of the disposable to be secured to the finisher while the finisher is in use. In addition to pin and opening devices, other examples of positioning devices include hook / receiver devices, channel and groove devices, latch and catch devices, etc. In the embodiment, the pins are located on the finisher and the openings are located on the disposable, but these can be reversed.

[0305] Once the disposable device is aligned and securely loaded, the operator communicates this to the finishing machine, for example, by pressing CONFIRM. The operator then instructs the finishing machine to proceed with the finishing process, for example, by pressing RUN. See step 808, FIG. 51C. The shuttle 418, now aligned and secured to the disposable, automatically begins to lower. In the embodiment shown in FIGS. 47A-47C and 48A-48C, the finishing machine 400 raises and lowers the shuttle 418 and slide frame 402, the upper disposable shuttle frame 406, and the lower disposable shuttle frame 408 into position, as described herein. In another embodiment, the frame 402′ is a fixed upper disposable shuttle frame 406, and the lower disposable shuttle frame 408 moves along rails. In the embodiment shown in Figures 47D-47I and 48D-48L, the finishing device 400' has a shuttle 418' that moves along a stationary frame 402' using a rail system, as described herein.

[0306] The finisher 400 or 400' automatically begins the plasma solidification and performs the first sealing and separating process, step 810, FIG. 51C. In one embodiment, a screen displays an estimated time remaining until completion. The shuttle 418 or 418' lowers into the finisher 400, and the dried plasma powder is displaced, for example, by impact action, as described herein. A first sealing and separating action seals the upper disposable portion 48 (see FIG. 48A).

[0307] Once the shuttle reaches the top and stops moving, the screen prompts the user to inspect seal #1, and the inspection light illuminates. Figure 51C, step 812. The operator inspects the seal to ensure it is fully formed and uniform. The operator can optionally tilt the shuttle outward by a hinge (not shown) if necessary to obtain a better view of the seal for inspection purposes. Upon inspection, in one aspect, the seal should not contain channels (gaps or unsealed areas) through the full width of the weld or seal. Ideally, a flat-welded plasma unit with a channel-free seal, but with wrinkles on the interior of the unit bag, is acceptable. Discoloration and small gaps or wrinkles that do not span the full width of the weld are acceptable.

[0308] If the seal is acceptable, the operator can indicate this to the finisher by, for example, pressing "ACCEPT" and continue the process. If the seal is not acceptable, the operator can also indicate this by, for example, pressing REJECT, discarding the entire plasma drying chamber, and pressing CONFIRM.

[0309] Once the operator determines that the seal has been properly made by the finisher, the disposable top portion 48 from location 44A to spray-drying head 2 can be discarded. See FIG. 48 and step 814, FIG. 51C. This first sealing and separation action effectively forms one of the side walls of the dried plasma unit, with the seal located above port 42A. The top disposable portion 48, the disposable portion from location 44A to spray-drying head 2, can now be discarded.

[0310] Next, as shown in Figure 48C, the operator uses knobs 412A / 412A' and 421B / 412B' to rotate or flip the lower shuttle disposable shuttle frame 408 / 408' about pivot point 420 / 420' to secure the lower disposable shuttle frame 406 / 406' over the upper disposable shuttle frame 408 / 408'. Step 816, see Figure 51C.

[0311] Once the operator indicates that the bottom frame is locked and nested onto the top frame, for example, by pressing "CONFIRM" and then "RUN," the finishing device lowers. See step 818, FIG. 51C. In one embodiment, the screen flashes a warning notice and the shuttle automatically begins lowering. As described further herein, the finishing device 400 or 400' automatically activates the impactor to allow for plasma solidification, air evacuation, and performs a second seal at location 44B above port 42B (in the inverted position shown in FIG. 48C). In one embodiment, the screen displays an estimated time remaining until completion.

[0312] Once the shuttle reaches the top and stops moving, a screen, in one embodiment, prompts the operator to inspect the second seal, and an inspection light is illuminated. See step 822, FIG. 51C. Again, the operator can optionally tilt the shuttle outward, as may be necessary to properly inspect the second seal. The seal is located above the rehydration port. If the seal is acceptable, the operator can notify the finishing device, for example, by pressing "ACCEPT," to continue the process. Again, if the seal is not acceptable, the operator can notify the finishing device, for example, by pressing "REJECT," and the entire plasma drying chamber can be discarded.

[0313] Once the seal is accepted, in one embodiment, the screen displays "RUN COMPLETE" or a similar indicator on the finisher screen. The operator can discard the disposable device filter portion 52, including the gas outlet, bottom filter, and filter separator. See step 824, FIG. 51C. As shown in FIG. 49A, the remaining disposable portion 46, now sealed and separated on both sides, provides the dried plasma unit 60, including the dried plasma 62. See step 824, FIG. 51C. In one embodiment, the operator rotates the shuttle 418 or 418' back to its home position, or original position as shown in the figures. See FIGS. 47C and 48B. See step 824, FIG. 51C.

[0314] The dried plasma unit 60 is then stored. In one embodiment, storage involves two stages of storage method 900 of Figure 51D. The first stage is storage until the plasma tests are competed and cleared for use (e.g., called "quarantine storage"), and the second stage involves storage of the unit after clearance but before transfusion to a recipient.

[0315] For initial or quarantine storage, the operator places the dried plasma unit 60 into a storage pouch so that the label on the plasma unit is visible through the transparent side. Step 902, FIG. 51D. In one embodiment, the storage pouch has a transparent side and a foil side. A desiccant is placed in the storage pouch between the plasma unit and the foil side of the pouch. Step 904, FIG. 51D. The operator then creates an initial seal at the top of the pouch. Step 906, FIG. 51D. A commercially available pouch sealer can be used to create a more permanent seal sufficient for longer storage. An example of a commercially available pouch sealer is the Midwest Pacific Impulse Heater Sealer model number MP-12 from PackCo Inc. of Lake Ozark, Missouri, USA. The operator ensures that the storage pouch sealer is turned on and places the pouch across the welding surface. The operator closes the welding arm and holds it in place for a sufficient time to perform the weld, e.g., about 1 to 60 seconds, and in one embodiment, less than 10 seconds. An acceptable weld, for example, is one that does not contain channels (gaps or unsealed areas extending through the entire width of the weld) and is free of discoloration. A weld that contains wrinkles on the interior of the storage bag but is flat-welded with a channel-free seal is also acceptable. However, if the weld contains channels (gaps or unsealed areas extending through the entire width of the weld), has discoloration, or contains wrinkles on the interior of the storage pouch that extend through the entire width of the weld that form the channel, the weld is unacceptable.

[0316] Once an acceptable weld is achieved, the operator then places the sealed dried plasma unit in isolation, step 908, FIG. 51D. In one embodiment, the sealed dried plasma unit is stored in isolation during the first stage at a temperature in the refrigerated range of about 1° C. to about 6° C. In another aspect, the dried plasma unit can be stored at room temperature (e.g., between about 18 and 25° C.).

[0317] After release testing is complete and the product is determined to be safe for use, the dried plasma units can be stored until they are ready to be used for transfusion. This is the second storage stage.

[0318] The operator can open the sealed outer pouch using, for example, scissors and mark with a notch the point where the seal will be cut, step 910, FIG. 51D.

[0319] The operator can then label the dried plasma unit with a final product label and place the unit with the final label in the same storage pouch. Steps 912 and 914, FIG. 51D. The storage pouch sealer is again used to form a final seal on the pouch containing the dried plasma unit approved for use. Step 916, FIG. 51D. The criteria for an acceptable seal are described above. The process described for the initial seal is repeated to complete the seal. The dried plasma unit is ready for use or placed in inventory. Step 918, FIG. 51D.

[0320] The tested, approved, and pouched spray-dried plasma units are then stored at temperatures ranging from about 1°C to about 45°C for periods ranging from about 1 minute to about 30 months. In one embodiment, the spray-dried plasma of the present invention can be stored at room temperature for about 1 hour to about 12 months. In one embodiment, the spray-dried plasma of the present invention can be stored at refrigerated temperatures for about 1 hour to about 24 months. In one aspect, the refrigerated temperature is about 1°C to about 6°C, and the room temperature is about 20°C to about 25°C.

[0321] In one embodiment, plasma unit 60 is packaged in a pouch that is a high moisture barrier bag made of an opaque polyethylene terephthalate (PET) aluminum foil laminate on one side and a transparent PET bilayer laminate on the other. In this embodiment, a 10 gram molecular sieve desiccant packet is placed inside the pouch before sealing. Plasma unit 60 can be packaged in an overwrap pouch with the desiccant so that the label is visible through the transparent laminate. Such pouches are commercially available, for example, from Technipaq Inc. (Crystal Lake, IL USA).

[0322] The method of the present invention further includes reconstituting the dried plasma using a reconstitution solution. The reconstitution solution can be mixed with the dried plasma using one of the spike ports 42A or 42B of the dried plasma unit 60. In a preferred embodiment, sterile water for injection is used for the reconstitution solution. In other embodiments, the reconstitution solution includes distilled water, or if no pretreatment step is performed, the reconstitution solution can be, for example, an amino acid (e.g., glycine) and / or a buffer solution (e.g., an acid such as hydrochloric acid or citric acid). The amount of reconstitution solution used to rehydrate the dried plasma ranges from about 218 ml to about 200 ml. Once the reconstitution solution is added, a further step of the method includes shaking the reconstituted plasma unit to ensure mixing and homogeneity of the reconstitution solution and the dried plasma. The reconstituted plasma is ready for transfusion into a recipient. The recipient can be a human, a primate, an animal, or the like.

[0323] The method further includes transfecting a recipient in need thereof. The reconstituted plasma unit is administered in the same manner as any plasma. In one embodiment, the method includes intravenously transfecting the reconstituted plasma into the recipient.

[0324] Detailed description of methods and parameters Generally, in the embodiment shown in Figures 47A-47C and 48A-48C, to align the spray drying disposable device 2 with the finisher 400, an operator uses the apparatus described above to align the positioning features and ridges on the disposable with the finisher, insert the gas outlet of the disposable into the gas port receiver on the finisher, and position the opening of the bag over the locating pin on the finisher. Once these alignment elements are engaged, the disposable is aligned in place and ready to be processed. In alternative embodiments, one or any combination of these alignment or positioning features can be engaged to align the disposable with the finisher.

[0325] The alignment and positioning arrangements described herein can be used independently or in any combination with each other.

[0326] In addition to securing, aligning, and / or positioning a spray-drying disposable device within a spray-drying apparatus using one or more of the alignment elements described herein, a method for spray-drying plasma further includes providing the plasma to the spray-drying apparatus. Engaging the spray-drying apparatus to spray-dry the plasma to form a dried plasma powder, and engaging a finisher to produce a dried plasma unit. The method further includes storing the dried plasma unit until ready for rehydration and transfusion.

[0327] In addition to aligning / securing the spray-dried disposable device within the spray-dryer finisher using one or more of the alignment elements described herein, a method for completing the process (e.g., converting a disposable plasma unit with dried plasma into a plasma unit with dried plasma) further includes engaging the finisher and lowering the shuttle, whereby the finisher impacts, seals, and separates the spray-dried disposable at a first point. As the shuttle rises, the operator discards the top of the disposable as described herein and rotates the lower frame so that it overlaps the upper frame. The shuttle with the overlapped frames is then lowered, and the finisher impacts, seals, and separates the modified disposable at a second point, thereby producing a plasma unit with dried plasma. The method further includes storing the dried plasma unit until ready for rehydration and transfusion.

[0328] In some embodiments, spray drying the plasma includes directing the plasma to a spray nozzle at a plasma flow rate; directing a heated drying gas to a drying chamber at an inlet temperature and a drying gas flow rate; directing the spray gas to the nozzle at a pressurized aerosol gas flow rate; combining the plasma and the pressurized aerosol gas at the nozzle to atomize the plasma and dry the plasma; and combining the atomized plasma with the drying gas to dry the atomized plasma.

[0329] Some embodiments include maintaining the plasma at a temperature of about 55°C to about 85°C during spray drying. The average temperature to which the plasma particles are exposed is about 65°C.

[0330] In some embodiments, the spray dryer inlet temperature is in the range of 100-130°C (e.g., 114°C). In one embodiment, the spray dryer exhaust temperature is 55-85°C (e.g., about 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, ...

Claims

1. 1. A spray drying apparatus for use in a spray drying system comprising a spray drying disposable device and a spray drying apparatus, wherein the spray drying disposable has a spray drying head, a plasma drying chamber, and a gas outlet, the spray drying head comprising a spray drying nozzle assembly including a vortex generator, a plenum having a drying gas inlet in communication with the drying gas source, the plenum supporting the nozzle assembly, and a baffle plate forming a floor of the plenum having one or more drying gas jets, the plasma drying chamber attached to the baffle plate, the plasma drying chamber including a capture filter, the spray drying apparatus comprising: A) a dry gas source providing dry gas from a clean dry air (CDA) system, wherein, in use, the dry gas resides in the plenum at uniform air pressure, and wherein, in use, the one or more dry gas jets provide the dry gas to the drying chamber; B) a plasma source providing plasma from a donor; C) a pressurized aerosol gas source that provides pressurized aerosol gas from the CDA system, wherein in use, a spray-drying nozzle assembly is in fluid communication with the plasma source and the pressurized aerosol gas source, the pressurized aerosol gas atomizes the plasma entering the drying chamber, thereby obtaining atomized plasma droplets, the atomized plasma droplets evaporate upon contact with the drying gas emitted from the one or more drying gas jets, thereby obtaining dried plasma particles and moist air, and the capture filter captures the dried plasma particles and allows the moist air to pass through; D) an exhaust port in communication with an exhaust line, wherein the gas outlet is attached to the exhaust port of the spray drying system during operation and the moist air flows through the gas outlet; Including, The disposable acts as a barrier between the plasma and the dryer or external environment. Spray drying equipment.

2. 10. The spray drying apparatus of claim 1, wherein the drying gas source provides drying gas at a velocity in the range of 720 slpm to about 780 slmp as it enters the nozzle.

3. 10. The spray drying apparatus of claim 1, wherein the drying gas source provides the drying gas at a temperature in the range of about 110°C to about 120°C.

4. 10. The spray drying apparatus of claim 1, wherein the pressurized aerosol gas has a velocity ranging from about 20 splm to about 60 slpm.

5. 10. The spray drying apparatus of claim 1, wherein the pressurized aerosol gas is at a pressure of about 180 kPa to about 260 kPa.

6. The vortex generator has a velocity of about 2.54×10 １ 10. The spray drying apparatus of claim 1 having a gas pressure in the range of from about 100 psig to about -2.24 psig.

7. The vortex generator has a flow rate of about 2.00×10 １ m / s ~ approx. -3.75×10 ２ 2. The spray drying apparatus of claim 1, having a velocity range of 1000 rpm to 1000 rpm.

8. 10. The spray drying apparatus of claim 1, wherein the plasma source provides plasma as it enters the nozzle at a rate of about 6 mL / min to about 23 mL / min.

9. 10. The spray drying apparatus of claim 1, wherein the exhaust air temperature ranges from about 62°C to about 68°C.

10. 10. The spray drying apparatus of claim 1, further comprising a closed loop, wherein the exhaust temperature controls the plasma feed rate.

11. 11. The spray drying apparatus of claim 10, wherein an increase in the exhaust gas temperature increases the plasma feed rate, and a decrease in the exhaust gas temperature decreases the plasma feed rate.

12. 11. The spray drying apparatus of claim 10, wherein the closed loop comprises an exhaust temperature range of about 62°C to about 68°C and a plasma feed rate range of about 6 to about 23 mL / min.

13. 10. The spray drying apparatus of claim 1, further comprising one or more filters in communication with the drying gas, the pressurized aerosol gas, or both.

14. 10. The spray drying apparatus of claim 1, further comprising one or more filters in communication with the moist air.

15. 1. A spray drying apparatus for use in a spray drying system comprising a spray drying disposable device and a spray drying apparatus, wherein the spray drying disposable has a spray drying head, a plasma drying chamber, and a gas outlet, the spray drying head comprising a spray drying nozzle assembly including a vortex generator, a plenum having a drying gas inlet in communication with the drying gas source, the plenum supporting the nozzle assembly, and a baffle plate forming a floor of the plenum having one or more drying gas jets and a baffle filter, the plasma drying chamber attached to the baffle plate, the plasma drying chamber including a trap filter, the spray drying apparatus comprising: A) a housing having an inner chamber and a housing exhaust line having a housing exhaust valve; B) a leak detection line containing a leak detection valve and a flow sensor; C) a dry gas source providing dry gas from a clean dry air (CDA) system through a dry gas inlet, wherein, in use, the dry gas resides in the plenum at uniform air pressure, and wherein, in use, the one or more dry gas jets provide the dry gas to the drying chamber; D) a plasma source providing plasma from a donor, the plasma source in communication with the scale; E) a pressurized aerosol gas source that provides pressurized aerosol gas from the CDA system, wherein in use, a spray-drying nozzle assembly is in fluid communication with the plasma source and the pressurized aerosol gas source, the pressurized aerosol gas atomizes the plasma entering the drying chamber, thereby obtaining atomized plasma droplets, the atomized plasma droplets evaporate upon contact with the drying gas emitted from the one or more drying gas jets, thereby obtaining dried plasma particles and moist air, and the capture filter captures the dried plasma particles and allows the moist air to pass through; F) an exhaust port in communication with a disposable exhaust line, the gas outlet being attached to the exhaust port of the spray drying system during operation, the moist air flowing through the gas outlet, and the disposable exhaust line including an exhaust valve; and G) at least one pressure sensing device in the inner chamber, the drying gas inlet, or the exhaust port; H) A computer system including at least one processor, at least one memory device, at least one data storage device, and at least one output device. A spray drying apparatus comprising:

16. 16. The spray drying apparatus of claim 15, wherein the at least one pressure sensing device is present in an interior chamber and outside the spray drying disposable, the pressure sensing device measuring pressure within the spray drying disposable.

17. 17. The spray drying apparatus of claim 16, wherein the pressure sensing device detects mechanical force and generates a proportional electrical output signal.

18. The leak detection method determines the integrity of the spray dried disposable, the method comprising: A) starting a spray dryer; B) providing a drying gas at a temperature in the range of about 110°C to about 120°C; C) closing the exhaust valve of the disposable exhaust line, wherein one of the housing exhaust valve of the housing exhaust line or the leak detection valve of the leak detection line is closed; D) providing the pressurized aerosol gas or drying gas to the plasma drying chamber of the spray dryer disposable to a first pressure amount; E) allowing a period of time to pass; F) measuring pressure with a pressure sensing device in the inner chamber, the drying gas inlet, or the exhaust port, thereby obtaining a measured pressure quantity; G) comparing the measured pressure amount to a threshold pressure amount to obtain a pressure comparison, the pressure comparison indicating the integrity of the spray dried disposable, thereby obtaining a leak detection pressure value; 16. A method of leak detection using the spray drying apparatus of claim 15, comprising:

19. 20. The leak detection method of claim 18, wherein if the leak detection pressure value is below the threshold pressure amount, the computer system determines that the leak detection pressure value is a failing pressure value and that the spray drying disposable should be discarded.

20. 20. The leak detection method of claim 18, further comprising communicating the failing pressure value to the output device.

21. 19. The leak detection method of claim 18, wherein if the leak detection pressure value exceeds the threshold pressure amount, the computer system determines that the leak detection pressure value is a passing pressure value and that the spray drying disposable should be used by the spray drying system.

22. 22. The leak detection method of claim 21, further comprising communicating the passing pressure value to the output device.

23. 20. The leak detection method of claim 18, wherein the first amount of pressure ranges from about 1.5 psig to about 4 psig.

24. 20. The leak detection method of claim 18, wherein the period of time ranges from about 30 seconds to about 5 minutes.

25. The leak detection method of claim 18, wherein the threshold pressure amount ranges from about 1 psig to about 3.5 psig.

26. A) opening the exhaust valve in the disposable exhaust line 20. The leak detection method of claim 18, further comprising:

27. The leak detection method determines the integrity of the spray dried disposable, the method comprising: A) starting the spray dryer; B) providing said drying gas at a temperature in the range of about 110°C to about 120°C; C) closing the exhaust valve in the disposable exhaust line; D) closing the housing exhaust valve in the housing exhaust line; E) opening the leak detection valve in the leak detection line; F) measuring the flow rate of the drying gas from the leak detection line with the flow sensor, thereby obtaining a measured flow rate; G) comparing the measured flow rate to a threshold flow rate, thereby obtaining a flow rate comparison, wherein the flow rate comparison indicates the integrity of the spray dried disposable, thereby obtaining a leak detection flow rate value; 16. A method of leak detection using the spray drying apparatus of claim 15, comprising:

28. 28. The leak detection method of claim 27, wherein if the leak detection flow rate value exceeds the threshold flow rate, the computer system determines that the leak detection flow rate value is an unacceptable flow rate value and that the spray dryer disposable should be discarded.

29. 30. The leak detection method of claim 28, further comprising communicating the failing flow rate value to the output device.

30. 28. The leak detection method of claim 27, wherein if the leak detection flow rate value is below the threshold flow rate, the computer system determines that the leak detection flow rate value is an acceptable flow rate value and that the spray drying disposable should be used by the spray drying system.

31. 31. The leak detection method of claim 30, further comprising communicating the passing flow value to the output device.

32. The method comprises: A) opening the exhaust valve in the disposable exhaust line; B) opening the housing exhaust valve in the housing exhaust line; C) closing the leak detection valve in the leak detection line; 28. The leak detection method of claim 27, further comprising:

33. The threshold flow rate is about 10 cm ２ / minute ~ approx. 30cm ２ 28. The leak detection method of claim 27, wherein the number of pulses per minute is in the range of 1 / min.

34. 34. The leak detection method of claim 33, wherein if the leak detection flow rate value is a failing flow rate value or the leak detection pressure value is a failing pressure value, the spray dryer disposable should be discarded.

35. 34. The leak detection method of claim 33, wherein if the leak detection flow rate value is an acceptable flow rate value and the leak detection pressure value is an acceptable pressure value, the spray drying disposable should be used with the spray drying system. Pressure detection

36. The pressure within the spray-dried disposable is measured, and the method further comprises: A) starting the spray dryer; B) measuring pressure in the inner chamber using the pressure sensing device, thereby obtaining a measured pressure quantity; C) comparing the measured pressure amount to a first threshold pressure amount and a second threshold pressure amount, the pressure comparison indicating the pressure inside the spray-dried disposable, thereby obtaining a disposable pressure value; Including, The pressure sensing device, external to the spray-dried disposable, measures the pressure within the spray-dried disposable. A method of detecting pressure using the spray drying apparatus of claim 15.

37. 38. The method of claim 37, wherein the pressure sensing device detects a mechanical force and generates a proportional electrical output signal.

38. 38. The pressure sensing method of claim 37, further comprising providing the dry gas at a dry gas inlet temperature in the range of about 110°C to about 120°C or providing an exhaust temperature in the range of about 55°C to about 75°C.

39. 38. The pressure detection method of claim 37, wherein if the disposable pressure value exceeds the second threshold pressure amount, the computer system determines that the disposable pressure value is a failing disposable pressure value and the spray drying system enters a fail-safe mode.

40. 41. The method of claim 40, further comprising communicating the fail disposable value to the output device.

41. 38. The pressure detection method of claim 37, wherein when the disposable pressure value exceeds the first threshold pressure amount and is below the second threshold pressure amount, the computer system determines that the pressure value is a passing disposable pressure value and that the drying operation execution for the disposable is complete, and then the spray drying system determines the amount of plasma dried.

42. 38. The method of claim 37, wherein the first threshold amount of pressure ranges from about 6.0 psi to about 7.0 psi.

43. 38. The method of claim 37, wherein the second threshold amount of pressure ranges from about 7.1 psi to about 8 psi.

44. the spray drying system comprising: A) measuring the amount of mass within the plasma source at a first time before spray drying is initiated to obtain a first plasma mass; B) measuring the amount of mass in the plasma source at a second time after spray drying is completed to obtain a second plasma mass; C) calculating the difference between the first plasma mass and the second plasma mass, thereby obtaining a processed plasma mass; D) comparing the processed measured plasma mass to a threshold plasma mass, thereby obtaining a processed plasma pass / fail value; 43. The method of claim 42, wherein the amount of dried plasma is determined by a step comprising:

45. 46. ​​The pressure detection method of claim 45, wherein if the processed plasma mass value is below the threshold plasma mass amount, the computer system determines that the processed plasma mass value is an unacceptable processed plasma mass value and the spray-dried disposable is discarded.

46. 46. ​​The pressure detection method of claim 45, wherein if the processed plasma mass value exceeds the threshold plasma mass amount, the computer system determines that the processed plasma mass value is a passing processed plasma mass value.

47. 46. ​​The pressure sensing method of claim 45, wherein the threshold plasma mass amount ranges from about the total amount of pre-processed donor plasma to be processed to about 280 grams to about 390 grams.

48. 49. The pressure sensing method of claim 48, wherein the amount of processed dried plasma, excluding the weight of the bag, ranges from about 15 grams to about 20 grams.

49. 38. The method of claim 37, further comprising expanding and compressing the spray-dried disposable to remove dried plasma on an inner wall of the spray-dried disposable.

50. 16. A spray dryer head integrity detection method using the spray dryer apparatus of claim 15, wherein the spray dryer head integrity detection method determines the integrity of the trap filter, baffle filter, or interface between the drying gas inlet and the plenum, the spray dryer apparatus having at least one first pressure sensing device at the drying gas inlet and at least one second pressure sensing device in the inner chamber, the method comprising: A) measuring the pressure during spray drying at the first pressure sensing device of the drying gas inlet or the second pressure sensing device of the inner chamber at two or more points in time; B) determining the pressure gradient at said two or more points in time over a period of time; Including, When the gradient is above a gradient threshold, the integrity of the spray drying head is maintained during spray drying, and when the gradient is below the gradient threshold, the integrity of the spray drying head is compromised during spray drying. Spray drying head integrity detection method.

51. 52. The method of claim 51, wherein direct detection of failure of the spray dryer disposable is detected.

52. 52. The method of claim 51, wherein the capture filter, the baffle filter, and the interface between the drying gas inlet and the plenum are intact.

53. 52. The spray dryer head integrity detection method of claim 51, wherein the slope threshold amount ranges from about 0.02 psi / min to about 0.2 psig / min.

54. 52. The spray dryer head integrity detection method of claim 51, wherein the slope threshold is greater than about 0.02 psig / min.

55. 47. The method of claim 46, wherein the pressure is measured at times occurring in the range of about every 1 minute to about every 10 minutes.

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