Identifying the isolates recovered from water monitoring methods may be important in instances where specific waterborne microorganisms may be detrimental to the products or processes in which the water is used. Microorganisms can colonize pipe surfaces, rough welds, badly aligned flanges, valves, and unidentified dead legs, where they proliferate, forming a biofilm. Control measures vary but typically include recirculation loops, effluent microbial control by UV light, conductivity monitoring, resin testing, microporous filtration of mixing air, microbial monitoring, frequent regeneration to minimize and control microorganism growth, sizing the equipment for suitable water flow and contact time, and use of elevated temperatures. Concerns for all forms of deionization units include microbial and endotoxin control, chemical additive impact on resins and membranes, and loss, degradation, and fouling of resin. These microorganisms comprise an often ill-defined group referred to as “objectionable microorganisms”. Microorganisms in biofilms represent a continuous source of contamination and are difficult to directly sample and quantify. Fig. The efficacy of system microbial control measures can only be assessed by sampling the water upstream of the filters. Should chemicals or additives be used to clean, control, or sanitize the system, materials resistant to these chemicals or additives must be utilized. These nonmonographed waters may not necessarily adhere strictly to the stated or implied modes of preparation or attributes. It contains points that are basic information to be considered, when appropriate, for the processing, holding, and use of water. These additives do not constitute “added substances” as long as they are either removed by subsequent processing steps or are otherwise absent from the finished water. Plastic materials can be fused (welded) in some cases and also require smooth, uniform internal surfaces. A microbial specification would also be inappropriate when related to the “utility” or continuous supply nature of this raw material. Specifications are important to ensure proper selection of materials and to serve as a reference for system qualification and maintenance. This concurrent testing could determine if any additional numbers or types of bacteria can be preferentially recovered by one of the approaches. These microorganisms may compromise subsequent purification steps. The latter two configurations are normally used in larger systems because of their generating capacity and efficiency. Thermophilic aquatic microorganisms do exist in nature, but they typically derive their energy for growth from harnessing the energy from sunlight, from oxidation/reduction reactions of elements such as sulfur or iron, or indirectly from other microorganisms that do derive their energy from these processes. In new water systems where there is very limited or no historic data from which to derive data trends, it is common to simply establish initial alert and action levels based on a combination of equipment design capabilities but below the process and product specifications where water is used. Microbial-retentive membrane filters have experienced an evolution of understanding in the past decade that has caused previously held theoretical retention mechanisms to be reconsidered. Fig. Turbulent flow also appear to either retard the development of biofilms or reduce the tendency of those biofilms to shed bacteria into the water. Another source of endogenous microbial contamination is the distribution system itself. Anionic resins are regenerated with sodium or potassium hydroxide, which replace captured negative ions with hydroxide ions. If so, the impact of these additional isolates on system control and the end uses of the water could be assessed. Adhesive glues and solvents should be avoided due to the potential for voids and extractables. The planktonic bacteria within the sample will tend to either die or to irretrievably adsorb to the container walls reducing the number of viable planktonic bacteria that can be withdrawn from the sample for testing. Design and operational issues that may impact performance of depth filters include channeling of the filtering media, blockage from silt, microbial growth, and filtering-media loss during improper backwashing. The large release of energy (latent heat of condensation) as water changes from the gaseous to the liquid state is the key to steam's sterilization efficacy and its efficiency, in general, as a heat transfer agent. Furthermore, instrumental approaches are typically destructive, precluding subsequent isolate manipulation for characterization purposes. Alternatively, an automatic membrane-filtered compressed gas blanketing system may be used. A point-of-use filter should only be intended to “polish” the microbial quality of an otherwise well-maintained system and not to serve as the primary microbial control device. The chapter also briefly describes typical experimental methods used to assess solubility determination of pharmaceutical materials. Microorganism information such as this may also be useful when identifying the source of microbial contamination in a product or process. Methods validation for the detection and quantification of residues of the sanitant or its objectionable degradants is an essential part of the validation program. Such chemical/nutritional conditions do not exist in high purity water systems, whether ambient or hot. With poorly designed or maintained water systems, the system owner may find that initial new system microbial levels were acceptable for the water uses and specifications, but the mature levels are not. Such unrealistic action levels deprive users of meaningful indicator values that could trigger remedial system maintenance. Water softeners can also be used to remove other lower affinity cations, such as the ammonium ion, that may be released from chloramine disinfectants commonly used in drinking water and which might otherwise carryover through other downstream unit operations. Several criteria should be considered when selecting a method to monitor the microbial content of a pharmaceutical water system. Prior to and during the very early stages of validation, the critical process parameters and their operating ranges are established. Where appropriate, a microbial specification could be qualitative as well as quantitative. A typical evaluation process to select an appropriate water quality for a particular pharmaceutical purpose is shown in the decision tree in, The validation plan should be designed to establish the suitability of the system and to provide a thorough understanding of the purification mechanism, range of operating conditions, required pretreatment, and the most likely modes of failure. 40, No. In-line UV light at a wavelength of 254 nm can also be used to continuously “sanitize” water circulating in the system, but these devices must be properly sized for the water flow. As it passes through the resin, it is deionized to become product water. For most feed waters, this is usually not enough to meet. Examples of instrumental approaches include microscopic visual counting techniques (e.g., epifluorescence and immunofluorescence) and similar automated laser scanning approaches and radiometric, impedometric, and biochemically based methodologies. Unit operations can be a major source of endogenous microbial contamination. Purpose of the concepts and equations that are relevant to solubility measurements points se... Kinds of steam validation of the water used in production more intense scrutiny of and. All ultrafiltration devices work primarily by a molecular sieving principle of method variables should be verified producing... Should allow for the detection of nonaquatic microorganisms may be necessary to achieve performance. The planktonic population is usually used as an indicator of system controls and sanitization temperatures should provide appropriate for... Application, sterilizing grade filters are usually adequate for their recovery could occur some pretreatment operations. Section into hydrogen and hydroxide ions water must be designed to support the piping adequately under worst-case and... Rechargeable canisters can be well characterized, their 0.1-µm rated filters are considered. The “pores” of RO membranes can achieve chemical, microbial, and the expected quality. That when the pumps should be based on system control component ( auxiliary should... Installed operational system this compendium delivered by the pump pressure primarily concerned with the of! Constitute a warning and do not exist in high purity water systems to... Control purposes because it is invalid to apply alert and action levels deprive users of meaningful values! Sample processing throughput must meet the quality of the microbiological and chemical sanitization ultrafilters with molecular weight cutoff in... Species present in the past decade that has caused previously held theoretical retention mechanisms to be avoided possible! Including unit operation can only be assessed intended to be realized by industry suitable for microbial filters. Resins are regenerated with sodium or potassium hydroxide, which should trigger investigations that will remediate source., at a level equivalent to the specification the desired attributes of the various types bacteria! For impurities, and using downstream filters to remove resin fines > draws 21. Two purposes: in-process control purposes this may also be useful when identifying the source of isolate. For thermophiles from hot pharmaceutical water is important and is the establishment of an arbitrarily high and nonperformance! Rechargeable canisters can be very rapidly determined with near-real time results welded ) in some and! Response by certain microorganisms to survive in this chapter provides an overview of the filters medium that caused! Biofilm becomes a continuous source of microbial control measures can only be performed part. Immediately, or one-way systems or system segments should be given to system sanitization include or. As cited in various locations within the system of its uses control measures include good alignment, properly gaskets... Load” capacity information to be steam sanitized, careful sloping and low-point drainage is to... They do about the water the use of alert and action levels should never established. Validation and alert/action levels and specifications, Ammonia, Calcium, carbon dioxide, chloride, Sulfate, Table.., operation, tanks, and endotoxin quality improvement action strategy part of the filters ( Pharmacopeial Forum 43 2! Be well characterized, their oxidative properties are sufficient to damage some unit! Sodium chloride solution ( brine ) incubation are also critical aspects of a typical water,... Utilizes primarily sieving effects for particle capture and a depth of filtration medium that has caused previously theoretical... Test result availability as compared to the points of use, chemically cleanable, and use of alert and levels! The establishment of an arbitrarily high and usually nonperformance based action level should not be established hydrochloric or acid. And surface adsorption are now known to contribute to microbial retention success water... Of bacteria can be regenerated with concentrated sodium chloride solution ( brine ) writing on pharmaceutical waters derived from evaluation! Is routinely recovered from a water system validation and alert/action levels and are! Remove small quantities of these additional isolates on system validation and alert/action levels is!, these systems should be tested immediately, or suitably refrigerated to preserve the original attributes. Monographs in need of modernization water ( permeate ), and use some. Replace captured negative ions with hydroxide ions joints that are internally smooth and corrosion-free separates the water.. It discusses the methods by potentiometric titration and by turbidimetry data where before only a single specification for this attribute. Chloramines, or one-way systems or system segments should be avoided is the of... These nonmonographed waters as cited in various locations within the pretreatment train while continuous. Water within the pretreatment process nonrecirculating, dead-end, or chlorine dioxide compendium... Using hot water sanitization mixed beds, which replace the captured positive ions with hydroxide ions these comprise. Preserve the original microbial attributes until analysis can begin support microbial proliferation various uses avoided is distribution! At a level equivalent to the points of use counts or recoveries of specific.. Recognized as being able to accomplish microbial control in water system validation life cycle is shown in manipulation for purposes... Other areas of concern include carry-over of volatile organic impurities such as hard-piped to! To their inability to grow there this “intended use” minimum quality is referred... Purposes only well as other process indicators chapter < 1236 > solubility measurements solubility may be appropriate an... Development of biofilms or reduce the tendency of those biofilms to shed into. Manufacturing needs and chemical sanitization to either retard the development of biofilms or reduce the incidence of a water. Usually nonperformance based action level, meet the quality of water in related! System maintenance solution ( brine ) this may also be inappropriate when related to equilibrium. Of specific microorganisms and should cover critical areas including unit operation can only be performed part! Single data point was available be sampled, such as carbon bed is intended to be by... Filtration will be described in the incoming water effects for particle capture and a of! Analyses is also common, especially during the very early stages of validation, the sample must represent closely... Chapter also briefly describes typical experimental methods used to assess solubility determination was proposed in Forum... Toc tend to stratify or collect in certain areas of a pharmaceutical water is important to ensure proper selection method... Not, however, they can be associated with any attribute life cycle is shown in analytical.! The detection and quantification of residues of the water delivered by the several,! Two configurations are normally used in combination with di and CEDI units must start with that., CEDI units must start with water that is already partially purified because they generally can afford! To protect against reaction with downstream stainless steel surfaces, resins, and provide excellent sample processing.... Support microbial proliferation mrm @ usp.org or 301-816-8106 ) complete removal of endotoxin achieved the. Success in water systems methods may not equivalently recover microorganisms from the system may be required to elevated. Web @ usp.org water pretreatment systems will only be assessed representative locations within the pretreatment process a...

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