Pharmaceutical water and other ultra pure waters are generally produced by specific processes that include a multiplicity of unit operations such as filtration, reverse osmosis, multiple ion exchange, carbon adsorption and the like disposed in sequential fashion. The objective is to produce a type of product water capable of meeting the ultra-pure-water quality standards required by the commercial applications for which the product water is destined. Although ultra-pure-water quality standards are not always consistent worldwide, in the case of pharmaceutical water the quality standards usually require the conductivity of the product water to be less than 1.3 micro mhos (i.e., the resistivity must be more than 0.77 mega ohms), the content of endotoxins (fever-causing bacteria) in the product water to be less than 0.25 Eu/ml (endotoxin units per milliliter), and its TOC (total organic carbon content) to be less than 400 parts per billion. Water of this quality, sometimes referred to as “sterile water” or “water for injection”, is made by water purification processes that employ certain well-known unit operations, such as filtration, reverse osmosis, multiple ion exchange and carbon adsorption, arranged in specific process configurations in order to optimize efficiencies and obtain the desired purity. Under the normal operating conditions that usually exist in these water purification processes, pyrogens, bacteria, yeast, mold and other biological active constituents tend to form and accumulate in the mechanical equipment components of the unit operations. If allowed to grow unchecked, these materials will contaminate the components of the unit operation equipment and the water flowing through them, with the unwanted result that the product water made will also be contaminated. Control of the biological active constituents within this type of process, also referred to as “sanitization”, then becomes an important consideration in the commercial success of these processes, and is generally achieved by a number of conventional techniques that include, among others, the use of caustic biocides, hot water pasteurization and high-efficiency filtration.
An example of a process for manufacturing United States Pharmacopoeia-grade water is described in U.S. Pat. No. 4,610,790. In this process, water for injection is produced by passing tap or drinking-quality water through a purification system that includes carbon-based filtration, reverse osmosis, deionization and ultrafiltration. The system provides a sanitizing washing operation that uses hot water as an additional step to sterilize microorganisms and remove impurities accumulated in the deionization and ultrafiltration operations. Means are provided for pasteurizing the mechanical components in the system and for flushing it periodically to remove pyrogens and microorganisms retained therein during the purification of incoming water or that have grown in the system. The water purification system uses reverse osmosis to remove dissolved solids, pyrogens and microorganisms. A dedicated heater is needed to heat the wash water, which is kept at between about 65° and 95° C. The RO unit is flushed with unheated water and the carbon filters are replaced periodically. U.S. Pat. No. 5,032,265 describes the manufacture of water for injection from potable water by means of a sequence of purification operations similar to those disclosed in U.S. Pat. No. 4,610,790. The purification system of the U.S. Pat. No. 5,032,265 includes a preliminary filtration operation for removing particulates, followed by carbon-based filtration module for removing chlorine (dechlorination) and removing dissolved organics, a reverse osmosis unit to remove certain organics, dissolved solids, pyrogens and microorganisms, an ion exchange filtration step (deionization) to remove any remaining traces of ionic impurities, and a sterile microfilter that acts as a barrier to any remaining bacteria in the system. A sequential flushing technique is employed to sanitize the system periodically with heated water from an external source and with (non-heated) potable water. The RO membranes must be capable of withstanding the heat contained in the hot water used to effect the sanitization. A dedicated heater is needed in order to heat the wash water, which is kept at between about 80° and 100° C. U.S. Pat. No. 5,925,255 claims a process for treating water by means of an aggressive hardness and alkalinity removal step that is followed by treatment in a membrane separation unit operated at a pH higher than about 10 in order to produce ultra pure water. The high pH conditions are said to cause high degree of ionization in certain types of impurities that are then preferentially rejected by the membrane system. The high pH is also said to be responsible for the destruction of bacteria and endotoxins. U.S. Pat. No. 6,074,551 describes improvements to the configuration of a reverse osmosis water purification system that are designed to provide an automatic cleaning and sanitizing of the reverse osmosis unit. Cleaning and sanitizing are accomplished by an elaborate fluid conduit system that includes, among other things, chemical injection of certain alkali and acid sanitizing solutions like Tri-clean and Tri-stat. Hot water at a temperature of up to 90° C. may be employed for sanitizing the equipment. Another technique for manufacturing pharmaceutical water is described in U.S. Pat. No. 6,106,723, which discloses a method for producing large volumes of low cost water for injection directly from potable water in order to meet the needs of hemodialysis and other biological applications. The feedwater is processed through a membrane, an ion exchange unit, an endotoxin-specific adsorption process and sterile filtration in order to reduce contaminant levels below those specified by the United States Pharmacopoeia.
When chlorine treatment is employed as a means of biological active constituent control, i.e., as a means of sanitization, the presence of chlorine, or chlorine-containing compounds, cannot be tolerated past certain points in the process. This is particularly true when, as in the case of the instant invention, a distillation unit operation is used as the main purification step of the process. Such chlorinated waters usually exhibit chlorine contents higher than about 0.25 ppm, and often higher than about 2 ppm. Chlorine and chlorine-containing compounds tend to chemically attack the lining and other parts of certain components of the unit operation equipment used in these systems and render the systems inoperable or highly inefficient at best. For that reason, a dechlorination step is introduced in these processes in order to remove the chlorine and/or chlorine-containing compounds from the systems. However, when this is done, that is, when chlorine and/or chlorine-containing compounds are removed from the system, the process again becomes vulnerable to the proliferation of biological active constituents. Such circumstances tend to add contaminants to the incoming potable water and, in order to prevent biological contaminants from being added to the potable water, some means for sanitizing the dechlorination process must be employed by the industry. It is apparent that a need exists to provide a commercial process for the manufacture of pharmaceutical water that allows the use of distillation as a means of purification in conjunction with the use of chlorination as a means of sanitization. It is an object of this invention to provide such a process. It is also an object of this invention to provide an improved method and system for the manufacture of pharmaceutical water and for sanitizing the equipment used in the manufacture of pharmaceutical water. Another object of the instant invention is to provide a commercially efficient technique for the sanitization of equipment used in the distillation-based manufacture of pharmaceutical water when such distillation-based manufacture includes a dechlorination unit operation as part of the manufacturing process. A further object of the invention is to provide a commercially efficient technique for the steam sanitization of equipment used in the distillation-based manufacture of pharmaceutical water when such distillation-based manufacture includes a dechlorination unit operation as part of the manufacturing process. A specific object of this invention is to provide a commercially efficient technique for sanitizing pharmaceutical water manufacturing equipment components, which sanitizing technique is capable of utilizing a portion of the low-pressure steam generated within a purification still that is part of the manufacturing process as the means for sanitizing said equipment components and without the need to dedicate a steam generator or pipe pure steam from a central pure steam generator. Another object of the invention is to provide commercially efficient technique for manufacturing pharmaceutical water and sanitizing the equipment used in such manufacturing without the need of reverse osmosis. These and other objects of the present invention will become apparent from the description that follows.
USPTO Backgrounds
USPTO Backgrounds