Process for producing sterile water for injection from...

Details Process for producing sterile water for injection from... Process for producing sterile water for injection from...

2001-01-30

2003-07-01

Hoey, Betsey Morrison (Department: 1724)

Liquid purification or separation

With heater or heat exchanger

C210S180000, C210S181000, C210S188000, C210S198100, C210S259000, C210S900000

Reexamination Certificate

active

06585890

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a process and apparatus for producing sterile water for injection from potable water.
BACKGROUND OF THE INVENTION
Sterile and pyrogen-free water for injection (WFI) is an essential material for field medical operations requiring parenteral procedures. Producing, transporting, and storing sufficiently large amounts of WFI is a key logistical problem. This challenge necessitates the development of a compact, reliable, and automatic system that can continuously produce sterile and pyrogen-free WFI from potable water sources. Furthermore, sterile and pyrogen-free WFI can be used to produce intravenous (IV) fluids and reconstitute freeze-dried blood products. Such devices are particularly useful for ocean vessels to reduce shipboard WFI storage burdens.
The elimination of all living microorganisms (sterilization) and fever-causing agents i.e. pyrogens (depyrogenation) from water can be accomplished by physical methods (heat), chemical agents (ethylene oxide, formaldehyde, alcohol, ozone), radiation, or mechanical methods (filtration). Steam and dry heat are widely used means of sterilization, which can be achieved at temperatures of 121° C. (15 min.) and 180° C. (20 min.), respectively.
Pyrogens, or bacterial endotoxins, are either metabolic products of living microorganisms or the constituents of dead microorganisms. Chemically, pyrogens are lipopolysaccharides (LPS) with molecular weights ranging from 15,000 to several million. Both dry pyrogen extracts and pyrogenic aqueous solutions lose little of their activity over years. Therefore, depyrogenation requires satisfactorily high temperatures and long holding times. Some of the reported data indicate that 180° C. for 3 to 4 hours, 250° C. for 30 to 45 minutes, or 650° C. for 1 minute under any heat will destroy pyrogens.
In addition to sterilization and depyrogenation, injectable water must also be virtually free from particulate matter, oxidizable substances, dissolved gases, and metals. Currently, the only acceptable ways of manufacturing WFI are distillation and reverse osmosis (RO). However, both methods have limitations when intended for field deployment.
Although distillation is the oldest and most effective method to remove LPS, the distillation still operated under low pressures is bulky and heat recovery is limited. Distillation and reverse osmosis physically separate pyrogen from water but neither destroys the pyrogens. The pyrogens concentrated in the distillation still residues or reverse osmosis retentate must be purged continuously or intermittently from the system. To ensure consistent production of pyrogen-free water, the equipment must be periodically sterilized to destroy the residual pyrogens that would accumulate on the walls of the equipment.
As for RO, typically 99.5% to 99.9% of endotoxin load can be removed in a single pass, and RO filters are not absolute. To produce WFI, both of these methods require additional treatment steps, typically involving active carbon filters, deionizers, and ultrafiltration filters. There is currently a lack of a final heat sterilization method, which is currently required for FDA approval.
SUMMARY OF THE INVENTION
The present invention includes a fully continuous process to convert treated potable water to sterile and pyrogen-free water for injection (WFI) by integrating:
Hydrothermal processing (HTP) for sterilization and depyrogenation
Multi-stage flash evaporation for salt removal and heat recovery
In-situ filtration for particulate removal
The key feature of this approach is to expose both feed water and process equipment to high temperatures. During the HTP stage of the process, the system is maintained at sufficient pressures to prevent water from evaporating. This high-temperature water environment results in extremely short treatment times required for sterilization and depyrogenation, hence enabling the development of a compact and efficient system. To remove electrolytes, the pressure of the system is reduced stepwise to achieve unit operations similar to that of a multi-stage flash evaporation process. By incorporating the microchannel technology into the evaporator design, effective heat recovery can be achieved. The entire system including filters is under high heat sterilization conditions so that the possible buildup of bacteria and/or pyrogens during normal operations can be eliminated.
Since the destruction of pyrogens by HTP is the most critical step among the three basic processing steps, initial efforts were made to prove the proposed HTP concept. To this end, a laboratory-scale HTP system was designed, constructed, and operated with a design capacity of treating 35 gram/min water at temperatures up to 600° C. (1,112° F.) and pressures up to 31 Mpa (4,500 psig). Variations of the reactor residence time were achieved by adjusting either the feed flow rate (i.e., pump stroke length and/or frequency) or reactor volume, or both. The feed flow rate typically ranged from 2 ml/min to 30 ml/min. Three reactor assemblies were used to cover a wide range of reactor volumes. Dimensions of these reactor assemblies, reflecting two orders of magnitude reactor volume variation from 29.3 ml (1/4-in reactor assembly) to 0.4 ml (1/16-in reactor assembly).
Using this HTP system, the destruction of an endotoxin (
E.coli
0113:H10) reached six-orders of magnitude within less than one second of exposure time. Results derived from these proof-of-concept experiments are given in Tables 1 to 2.
Furthermore, a simplified process of the present is invention includes stacked microchannel chambers consisting of at least two repeat modules. Each of the microchannel modules consists of independently integrated heat exchanger and evaporator components. These modules are connected in series.
As the water leaves the HTP reactor and passes through the pressure letdown device, the pressure of the water is reduced. As a result, a portion of the water flashes off in the evaporator section. The vapor portion goes through heat exchange with the incoming feed stream and after pressure reduction is collected as WFI product. The liquid portion of the water from the evaporator section goes through the pressure letdown device and enters the next microchannel module. The liquid fraction of the last module, which contains the accumulated electrolytes, is discarded as waste stream (reject).
Sterile, pyrogen-free water is an essential material for medical operations requiring parenteral procedures, for producing intravenous (IV) fluids and reconstituted freeze-dried blood products for injection. The process of the invention allows the continuous production of pyrogen-free water for injection (WFI) from potable water under field conditions. The very short treatment time required to produce WFI using the process of the invention allows the use of compact, reliable, automated equipment easily deployable in remote locations where simplicity of operation, reliability, and small space requirement are critical. This process will be particularly useful aboard ships, in combat support medical units, during humanitarian relief operations following natural disasters and in rural hospitals.
The process of the invention, by treating potable water at a temperature of at least 230° C. (446° C.) and at a pressure sufficient to keep water in liquid state, i.e. at least the pressure of saturated steam at said temperature, can produce pyrogen-free water using treatment times of 0.05 to 5 seconds or less. The addition of an oxidant, in the form of a gas, a liquid, or a solid and preferably hydrogen proxide, further decreases the required treatment time to less than 0.05 second. The reduction in equipment size achieved with this rapid treatment time allows the utilization of treatment units small enough to be easily transported to remote locations or installed in the restricted space environment existing in ships and submarines.
Furthermore, the total destruction of pyrogens achieved, eliminates the need for periodic heat sterilization of the equipment. This ensures the

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