WATER FOR PHARMACEUTICAL PURPOSESINTRODUCTIONWater is widely used as a raw material, ingredient, and solvent in the processing, formulation, and manufacture of pharmaceutical products, active pharmaceutical ingredients APIs and intermediates, compendial articles, and analytical reagents. This general information chapter provides additional information about water, its quality attributes that are not included within a water monograph, processing techniques that can be used to improve water quality, and a description of minimum water quality standards that should be considered when selecting a water source. This information chapter is not intended to replace existing regulations or guides that already exist to cover USA and International ICH or WHO GMP issues, engineering guides, or other regulatory FDA, EPA, or WHO guidances for water. Development As Freedom Ebook Pdf File. The contents will help users to better understand pharmaceutical water issues and some of the microbiological and chemical concerns unique to water. This chapter is not an all inclusive writing on pharmaceutical waters. It contains points that are basic information to be considered, when appropriate, for the processing, holding, and use of water. It is the users responsibility to assure that pharmaceutical water and its production meet applicable governmental regulations, guidances, and the compendial specifications for the types of water used in compendial articles. Compounding Sterile Preparations Third Edition' title='Compounding Sterile Preparations Third Edition' />Control of the chemical purity of these waters is important and is the main purpose of the monographs in this compendium. Unlike other official articles, the bulk water monographs Purified Water and Water for Injection also limit how the article can be produced because of the belief that the nature and robustness of the purification process is directly related to the resulting purity. The chemical attributes listed in these monographs should be considered as a set of minimum specifications. More stringent specifications may be needed for some applications to ensure suitability for particular uses. Basic guidance on the appropriate applications of these waters is found in the monographs and is further explained in this chapter. Control of the microbiological quality of water is important for many of its uses. All packaged forms of water that have monograph standards are required to be sterile because some of their intended uses require this attribute for health and safety reasons. This article is intended to provide a broad overview of sterile and nonsterile Compounding. This article will cover the following knowledge areas. Background Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and. Comment by Mark ZIERLR http Comment by Mark UR34ez http Comment by Jarvis. USP has determined that a microbial specification for the bulk monographed waters is inappropriate and has not been included within the monographs for these waters. These waters can be used in a variety of applications, some requiring extreme microbiological control and others requiring none. The needed microbial specification for a given bulk water depends upon its use. A single specification for this difficult to control attribute would unnecessarily burden some water users with irrelevant specifications and testing. Rg Veda Ita. However, some applications may require even more careful microbial control to avoid the proliferation of microorganisms ubiquitous to water during the purification, storage, and distribution of this substance. A microbial specification would also be inappropriate when related to the utility or continuous supply nature of this raw material. Microbial specifications are typically assessed by test methods that take at least 4. Because pharmaceutical waters are generally produced by continuous processes and used in products and manufacturing processes soon after generation, the water is likely to have been used well before definitive test results are available. Failure to meet a compendial specification would require investigating the impact and making a passfail decision on all product lots between the previous samplings acceptable test result and a subsequent samplings acceptable test result. The technical and logistical problems created by a delay in the result of such an analysis do not eliminate the users need for microbial specifications. Therefore, such water systems need to be operated and maintained in a controlled manner that requires that the system be validated to provide assurance of operational stability and that its microbial attributes be quantitatively monitored against established alert and action levels that would provide an early indication of system control. The issues of water system validation and alertaction levels and specifications are included in this chapter. The consistent increase in the use of potent pharmaceuticals, driven by both drug development and our aging population, is creating a corresponding increase in the. SOURCE OR FEED WATER CONSIDERATIONSTo ensure adherence to certain minimal chemical and microbiological quality standards, water used in the production of drug substances or as source or feed water for the preparation of the various types of purified waters must meet the requirements of the National Primary Drinking Water Regulations NPDWR 4. CFR 1. 41 issued by the U. S. Environmental Protection Agency EPA or the drinking water regulations of the European Union or Japan, or the WHO drinking water guidelines. In the second edition of Transdermal Magnesium Therapy now in production I wrote Sometimes very sick people or even animals with a lung ailment do better when. Limits on the types and quantities of certain organic and inorganic contaminants ensure that the water will contain only small, safe quantities of potentially objectionable chemical species. Therefore, water pretreatment systems will only be challenged to remove small quantities of these potentially difficult to remove chemicals. Also, control of objectionable chemical contaminants at the source water stage eliminates the need to specifically test for some of them e. Microbiological requirements of drinking water ensure the absence of coliforms, which, if determined to be of fecal origin, may indicate the potential presence of other potentially pathogenic microorganisms and viruses of fecal origin. Meeting these microbiological requirements does not rule out the presence of other microorganisms, which could be considered undesirable if found in a drug substance or formulated product. To accomplish microbial control, Municipal Water Authorities add disinfectants to drinking water. Chlorine containing and other oxidizing substances have been used for many decades for this purpose and have generally been considered to be relatively innocuous to humans. However, these oxidants can interact with naturally occurring organic matter to produce disinfection by products DBPs, such as trihalomethanes THMs, including chloroform, bromodichloromethane, and dibromochloromethane and haloacetic acids HAAs, including dichloroacetic acid and trichloroacetic acid. The levels of DBPs produced vary with the level and type of disinfectant used and the levels and types of organic materials found in the water, which can vary seasonally. Because high levels of DBPs are considered a health hazard in drinking water, Drinking Water Regulations mandate their control to generally accepted nonhazardous levels. Serif Photoplus X8 here. However, depending on the unit operations used for further water purification, a small fraction of the DBPs in the starting water may carry over to the finished water. Therefore, the importance of having minimal levels of DBPs in the starting water, while achieving effective disinfection, is important. DBP levels in drinking water can be minimized by using disinfectants such as ozone, chloramines, or chlorine dioxide. Like chlorine, their oxidative properties are sufficient to damage some pretreatment unit operations and must be removed early in the pretreatment process. The complete removal of some of these disinfectants can be problematic.