[PPT PDF] Pharmaceutical Water System Design Validation -SAMPLING CONSIDERATIONS

[PPT PDF] Pharmaceutical Water System Design Validation -SAMPLING CONSIDERATIONS

Pharmaceutical Water System- SAMPLING CONSIDERATIONS

Water systems should be monitored at a frequency that is sufficient to ensure that the system is in control and continues to produce water of acceptable quality. Samples should be taken from representative locations within the processing and distribution system. Established sampling frequencies should be based on system validation data and should cover critical areas including unit operation sites. The sampling plan should take into consideration the desired attributes of the water being sampled. For example, systems for Water for Injection because of their more critical microbiological requirements, may require a more rigorous sampling frequency.

Analyses of water samples often serve two purposes: in-process control assessments and final quality control assessments. In-process control analyses are usually focused on the attributes of the water within the system. Quality control is primarily concerned with the attributes of the water delivered by the system to its various uses. The latter usually employs some sort of transfer device, often a flexible hose, to bridge the gap between the distribution system use-point valve and the actual location of water use. The issue of sample collection location and sampling procedure is often hotly debated because of the typically mixed use of the data generated from the samples, for both in-process control and quality control. In these single sample and mixed data use situations, the worst-case scenario should be utilized. In other words, samples should be collected from use points using the same delivery devices, such as hoses, and procedures, such as preliminary hose or outlet flushing, as are employed by production from those use points. Where use points per se cannot be sampled, such as hard-piped connections to equipment, special sampling ports may be used. In all cases, the sample must represent as closely as possible the quality of the water used in production. If a point of use filter is employed, sampling of the water prior to and after the filter is needed because the filter will mask the microbial control achieved by the normal operating procedures of the system.

Samples containing chemical sanitizing agents require neutralization prior to microbiological analysis. Samples for microbiological analysis should be tested immediately, or suitably refrigerated to preserve the original microbial attributes until analysis can begin. Samples of flowing water are only indicative of the concentration of planktonic (free floating) microorganisms present in the system. Biofilm microorganisms (those attached to water system surfaces) are usually present in greater numbers and are the source of the planktonic population recovered from grab samples. Microorganisms in biofilms represent a continuous source of contamination and are difficult to directly sample and quantify. Consequently, the planktonic population is usually used as an indicator of system contamination levels and is the basis for system Alert and Action Levels. The consistent appearance of elevated planktonic levels is usually an indication of advanced biofilm development in need of remedial control. System control and sanitization are key in controlling biofilm formation and the consequent planktonic population.

Sampling for chemical analyses is also done for in-process control and for quality control purposes. However, unlike microbial analyses, chemical analyses can be and often are performed using on-line instrumentation. Such on-line testing has unequivocal in-process control purposes because it is not performed on the water delivered from the system. However, unlike microbial attributes, chemical attributes are usually not significantly degraded by hoses. Therefore, through verification testing, it may be possible to show that the chemical attributes detected by the on-line instrumentation (in-process testing) are equivalent to those detected at the ends of the use point hoses (quality control testing). This again creates a single sample and mixed data use scenario. It is far better to operate the instrumentation in a continuous mode, generating large volumes of in-process data, but only using a defined small sampling of that data for QC purposes. Examples of acceptable approaches include using highest values for a given period, highest time-weighted average for a given period (from fixed or rolling sub-periods), or values at a fixed daily time. Each approach has advantages and disadvantages relative to calculation complexity and reflection of continuous quality, so the user must decide which approach is most suitable or justifiable.

Pharmaceutical Water System-CHEMICAL CONSIDERATIONS

The chemical attributes of Purified Water and Water for Injection were specified by a series of chemistry tests for various specific and nonspecific attributes with the intent of detecting chemical species indicative of incomplete or inadequate purification. While these methods could have been considered barely adequate to control the quality of these waters, they nevertheless stood the test of time. This was partly because the operation of water systems was, and still is, based on on-line conductivity measurements and specifications generally thought to preclude the failure of these archaic chemistry attribute tests.

USP moved away from these chemical attribute tests to contemporary analytical technologies for the bulk waters Purified Water and Water for Injection. The intent was to upgrade the analytical technologies without tightening the quality requirements. The two contemporary analytical technologies employed were TOC and conductivity. The TOC test replaced the test for Oxidizable substances that primarily targeted organic contaminants. A multistaged Conductivity test which detects ionic (mostly inorganic) contaminants replaced, with the exception of the test for Heavy metals, all of the inorganic chemical tests (i.e., Ammonia, Calcium, Carbon dioxide, Chloride, Sulfate).

Pharmaceutical Water Systems: Pharmaceutical Water Storage & Distribution Systems

Replacing the heavy metals attribute was considered unnecessary because (a) the source water specifications (found in the NPDWR) for individual Heavy metals were tighter than the approximate limit of detection of the Heavy metals test for USP XXII Water for Injection and Purified Water (approximately 0.1 ppm), (b) contemporary water system construction materials do not leach heavy metal contaminants, and (c) test results for this attribute have uniformly been negative—there has not been a confirmed occurrence of a singular test failure (failure of only the Heavy metals test with all other attributes passing) since the current heavy metal drinking water standards have been in place. Nevertheless, since the presence of heavy metals in Purified Water or Water for Injection could have dire consequences, its absence should at least be documented during new water system commissioning and validation or through prior test results records.

Total solids and pH are the only tests not covered by conductivity testing. The test for Total solids was considered redundant because the nonselective tests of conductivity and TOC could detect most chemical species other than silica, which could remain undetected in its colloidal form. Colloidal silica in Purified Water and Water for Injection is easily removed by most water pretreatment steps and even if present in the water, constitutes no medical or functional hazard except under extreme and rare situations. In such extreme situations, other attribute extremes are also likely to be detected. It is, however, the user’s responsibility to ensure fitness for use. If silica is a significant component in the source water, and the purification unit operations could be operated or fail and selectively allow silica to be released into the finished water (in the absence of co-contaminants detectable by conductivity), then either silica-specific or a total solids type testing should be utilized to monitor and control this rare problem.

The pH attribute was eventually recognized to be redundant to the conductivity test (which included pH as an aspect of the test and specification); therefore, pH was dropped as a separate attribute test.

The rationale used by USP to establish its conductivity specification took into consideration the conductivity contributed by the two least conductive former attributes of Chloride and Ammonia, thereby precluding their failure had those wet chemistry tests been performed. In essence, the Stage 3 conductivity specifications (see Water Conductivity  645 ) were established from the sum of the conductivities of the limit concentrations of chloride ions (from pH 5.0 to 6.2) and ammonia ions (from pH 6.3 to 7.0), plus the unavoidable contribution of other conductivity-contributing ions from water (H+ and OH–), dissolved atmospheric CO2 (as HCO3–), and an electro-balancing quantity of either Na+ of Cl–, depending on the pH-induced ionic imbalance (see Table 1). The Stage 2 conductivity specification is the lowest value on this table, 2.1 µS/cm. The Stage 1 specifications, designed primarily for on-line measurements, were derived essentially by summing the lowest values in the contributing ion columns for each of a series of tables similar to Table 1, created for each 5  increment between 0  and 100 . For example purposes, the italicized values in Table 1, the conductivity data table for 25 , were summed to yield a conservative value of 1.3 µS/cm, the Stage 1 specification for a nontemperature compensated, nonatmosphere equilibrated water sample that actual had a measured temperature of 25  to 29 . Each 5  increment table was similarly treated to yield the individual values listed in the table of Stage 1 specifications (see Water Conductivity  645 ).

As stated above, this rather radical change to utilizing a conductivity attribute as well as the inclusion of a TOC attribute allowed for on-line measurements. This was a major philosophical change and allowed major savings to be realized by industry. The TOC and conductivity tests can also be performed “off-line” in the laboratories using collected samples, though sample collection tends to introduce opportunities for adventitious contamination that can cause false high readings. The collection of on-line data is not, however, without challenges. The continuous readings tend to create voluminous amounts of data where before only a single data point was available. As stated under Sampling Considerations, continuous in-process data is excellent for understanding how a water system performs during all of its various usage and maintenance events in real time, but is too much data for QC purposes. Therefore, a justifiable fraction or averaging of the data can be used that is still representative of the overall water quality being used.

Packaged waters present a particular dilemma relative to the attributes of conductivity and TOC. The package itself is the source of chemicals (inorganics and organics) that leach over time into the water and can easily be detected. The irony of organic leaching from plastic packaging is that when the Oxidizable substances test was the only “organic contaminant” test for both bulk and packaged waters, that test’s insensitivity to those organic leachables rendered their presence in packaged water at high concentrations (many times the TOC specification for bulk water) virtually undetectable. Similarly, glass containers can also leach inorganics, such as sodium, which are easily detected by conductivity, but are undetected by the wet chemistry tests for water (other than pH or Total solids). Most of these leachables are considered harmless by current perceptions and standards at the rather significant concentrations present. Nevertheless, they effectively degrade the quality of the high-purity waters placed into these packaging system. Some packaging materials contain more leachables than others and may not be as suitable for holding water and maintaining its purity.

The attributes of conductivity and TOC tend to reveal more about the packaging leachables than they do about the water’s original purity. These “allowed” leachables could render the packaged versions of originally equivalent bulk water essentially unsuitable for many uses where the bulk waters are perfectly adequate.

[PPT PDF] Pharmaceutical Water System Design Validation -SAMPLING CONSIDERATIONS pdf [PPT PDF] Pharmaceutical Water System Design Validation -SAMPLING CONSIDERATIONS

Pharmaceutical Water System-MICROBIAL CONSIDERATIONS

The major exogenous source of microbial contamination of bulk pharmaceutical water is source or feed water. Feed water quality must, at a minimum, meet the quality attributes of Drinking Water for which the level of coliforms are regulated. A wide variety of other microorganisms, chiefly Gram-negative bacteria, may be present in the incoming water. These microorganisms may compromise subsequent purification steps. Examples of other potential exogenous sources of microbial contamination include unprotected vents, faulty air filters, ruptured rupture disks, backflow from contaminated outlets, unsanitized distribution system “openings” including routine component replacements, inspections, repairs, and expansions, inadequate drain and air-breaks, and replacement activated carbon, deionizer resins, and regenerant chemicals. In these situations, the exogenous contaminants may not be normal aquatic bacteria but rather microorganisms of soil or even human origin. The detection of nonaquatic microorganisms may be an indication of a system component failure, which should trigger investigations that will remediate their source. Sufficient care should be given to system design and maintenance in order to minimize microbial contamination from these exogenous sources.

Unit operations can be a major source of endogenous microbial contamination. Microorganisms present in feed water may adsorb to carbon bed, deionizer resins, filter membranes, and other unit operation surfaces and initiate the formation of a biofilm. In a high-purity water system, biofilm is an adaptive response by certain microorganisms to survive in this low nutrient environment. Downstream colonization can occur when microorganisms are shed from existing biofilm-colonized surfaces and carried to other areas of the water system. Microorganisms may also attach to suspended particles such as carbon bed fines or fractured resin particles. When the microorganisms become planktonic, they serve as a source of contamination to subsequent purification equipment (compromising its functionality) and to distribution systems.

Another source of endogenous microbial contamination is the distribution system itself. Microorganisms can colonize pipe surfaces, rough welds, badly aligned flanges, valves, and unidentified dead legs, where they proliferate, forming a biofilm. The smoothness and composition of the surface may affect the rate of initial microbial adsorption, but once adsorbed, biofilm development, unless otherwise inhibited by sanitizing conditions, will occur regardless of the surface. Once formed, the biofilm becomes a continuous source of microbial contamination.

[PPT PDF] Pharmaceutical Water System Design Validation -SAMPLING CONSIDERATIONS

ENDOTOXIN CONSIDERATIONS

Endotoxins are lipopolysaccharides found in and shed from the cell envelope that is external to the cell wall of Gram-negative bacteria. Gram-negative bacteria that form biofilms can become a source of endotoxins in pharmaceutical waters. Endotoxins may occur as clusters of lipopolysaccharide molecules associated with living microorganisms, fragments of dead microorganisms or the polysaccharide slime surrounding biofilm bacteria, or as free molecules. The free form of endotoxins may be released from cell surfaces of the bacteria that colonize the water system, or from the feed water that may enter the water system. Because of the multiplicity of endotoxin sources in a water system, endotoxin quantitation in a water system is not a good indicator of the level of biofilm abundance within a water system.

Pharmaceutical Water System Design Validation – Microbial Testing of Water

Endotoxin levels may be minimized by controlling the introduction of free endotoxins and microorganisms in the feed water and minimizing microbial proliferation in the system. This may be accomplished through the normal exclusion or removal action afforded by various unit operations within the treatment system as well as through system sanitization. Other control methods include the use of ultrafilters or charge-modified filters, either in-line or at the point of use. The presence of endotoxins may be monitored as described in the general test chapter Bacterial Endotoxins Test  85 .

MICROBIAL ENUMERATION CONSIDERATIONS

The objective of a water system microbiological monitoring program is to provide sufficient information to control and assess the microbiological quality of the water produced. Product quality requirements should dictate water quality specifications. An appropriate level of control may be maintained by using data trending techniques and, if necessary, limiting specific contraindicated microorganisms. Consequently, it may not be necessary to detect all of the microorganisms species present in a given sample. The monitoring program and methodology should indicate adverse trends and detect microorganisms that are potentially harmful to the finished product, process, or consumer. Final selection of method variables should be based on the individual requirements of the system being monitored.

It should be recognized that there is no single method that is capable of detecting all of the potential microbial contaminants of a water system. The methods used for microbial monitoring should be capable of isolating the numbers and types of organisms that have been deemed significant relative to in-process system control and product impact for each individual system. Several criteria should be considered when selecting a method to monitor the microbial content of a pharmaceutical water system. These include method sensitivity, range of organisms types or species recovered, sample processing throughput, incubation period, cost, and methodological complexity. An alternative consideration to the use of the classical “culture” approaches is a sophisticated instrumental or rapid test method that may yield more timely results. However, care must be exercised in selecting such an alternative approach to ensure that it has both sensitivity and correlation to classical culture approaches, which are generally considered the accepted standards for microbial enumeration.

Pharmaceutical Water System Design Operation & Validation

Consideration should also be given to the timeliness of microbial enumeration testing after sample collection. The number of detectable planktonic bacteria in a sample collected in a scrupulously clean sample container will usually drop as time passes. 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. The opposite effect can also occur if the sample container is not scrupulously clean and contains a low concentration of some microbial nutrient that could promote microbial growth within the sample container. Because the number of recoverable bacteria in a sample can change positively or negatively over time after sample collection, it is best to test the samples as soon as possible after being collected. If it is not possible to test the sample within about 2 hours of collection, the sample should be held at refrigerated temperatures (2  to 8 ) for a maximum of about 12 hours to maintain the microbial attributes until analysis. In situations where even this is not possible (such as when using off-site contract laboratories), testing of these refrigerated samples should be performed within 48 hours after sample collection. In the delayed testing scenario, the recovered microbial levels may not be the same as would have been recovered had the testing been performed shortly after sample collection. Therefore, studies should be performed to determine the existence and acceptability of potential microbial enumeration aberrations caused by protracted testing delays.

Source : USP

Expert Committee : (PW05) Pharmaceutical Waters 05

USP29–NF24 Page 3056

Pharmacopeial Forum : Volume No. 30(5) Page 1744

Pharmaceutical Water System Ppt,

Pharmaceutical Water Systems,

Purified Water Specification As Per Usp,

Pharmaceutical Water System Design Operation And Validation Pdf,

pharmaceutical water system design operation and validation,

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Pharmaceutical Water Systems: Storage & Distribution Systems,

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Pharmaceutical Water Systems: Types: Water quality specifications,

Pharmaceutical Water System: principles for pharmaceutical water systems

[PPT PDF] Pharmaceutical Water System Design Validation – Microbial Testing of Water

[PPT PDF] Pharmaceutical Water System Design Validation - Microbial Testing of Water

[PPT PDF] Pharmaceutical Water System Design Validation – Microbial Testing of Water is discussed in detail in this article. 

Pharmaceutical Water System: Classical Culture Approach  for microbial testing of water

Classical culture approaches for microbial testing of water include but are not limited to pour plates, spread plates, membrane filtration, and most probable number (MPN) tests. These methods are generally easy to perform, are less expensive, and provide excellent sample processing throughput. Method sensitivity can be increased via the use of larger sample sizes. This strategy is used in the membrane filtration method. Culture approaches are further defined by the type of medium used in combination with the incubation temperature and duration. This combination should be selected according to the monitoring needs presented by a specific water system as well as its ability to recover the microorganisms of interest: those that could have a detrimental effect on the product or process uses as well as those that reflect the microbial control status of the system.

There are two basic forms of media available for traditional microbiological analysis: “high nutrient” and “low nutrient”. High-nutrient media such as plate count agar (TGYA) and m-HPC agar (formerly m-SPC agar), are intended as general media for the isolation and enumeration of heterotrophic or “copiotrophic” bacteria. Low-nutrient media such as R2A agar and NWRI agar (HPCA), may be beneficial for isolating slow growing “oligotrophic” bacteria and bacteria that require lower levels of nutrients to grow optimally. Often some facultative oligotrophic bacteria are able to grow on high nutrient media and some facultative copiotrophic bacteria are able to grow on low-nutrient media, but this overlap is not complete. Low-nutrient and high-nutrient cultural approaches may be concurrently used, especially during the validation of a water system, as well as periodically thereafter. This concurrent testing could determine if any additional numbers or types of bacteria can be preferentially recovered by one of the approaches. If so, the impact of these additional isolates on system control and the end uses of the water could be assessed. Also, the efficacy of system controls and sanitization on these additional isolates could be assessed.

Duration and temperature of incubation are also critical aspects of a microbiological test method. Classical methodologies using high nutrient media are typically incubated at 30  to 35  for 48 to 72 hours. Because of the flora in certain water systems, incubation at lower temperatures (e.g., 20  to 25 ) for longer periods (e.g., 5 to 7 days) can recover higher microbial counts when compared to classical methods. Low-nutrient media are designed for these lower temperature and longer incubation conditions (sometimes as long as 14 days to maximize recovery of very slow growing oligotrophs or sanitant injured microorganisms), but even high-nutrient media can sometimes increase their recovery with these longer and cooler incubation conditions. Whether or not a particular system needs to be monitored using high- or low-nutrient media with higher or lower incubation temperatures or shorter or longer incubation times should be determined during or prior to system validation and periodically reassessed as the microbial flora of a new water system gradually establish a steady state relative to its routine maintenance and sanitization procedures. The establishment of a “steady state” can take months or even years and can be perturbed by a change in use patterns, a change in routine and preventative maintenance or sanitization procedures, and frequencies, or any type of system intrusion, such as for component replacement, removal, or addition. The decision to use longer incubation periods should be made after balancing the need for timely information and the type of corrective actions required when an alert or action level is exceeded with the ability to recover the microorganisms of interest.

The advantages gained by incubating for longer times, namely recovery of injured microorganisms, slow growers, or more fastidious microorganisms, should be balanced against the need to have a timely investigation and to take corrective action, as well as the ability of these microorganisms to detrimentally affect products or processes. In no case, however, should incubation at 30  to 35  be less than 48 hours or less than 96 hours at 20  to 25 .

Normally, the microorganisms that can thrive in extreme environments are best cultivated in the laboratory using conditions simulating the extreme environments from which they were taken. Therefore, thermophilic bacteria might be able to exist in the extreme environment of hot pharmaceutical water systems, and if so, could only be recovered and cultivated in the laboratory if similar thermal conditions were provided. 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. Such chemical/nutritional conditions do not exist in high purity water systems, whether ambient or hot. Therefore, it is generally considered pointless to search for thermophiles from hot pharmaceutical water systems owing to their inability to grow there.

[PPT PDF] Pharmaceutical Water System Design Validation – Microbial Testing of Water

The microorganisms that inhabit hot systems tend to be found in much cooler locations within these systems, for example, within use-point heat exchangers or transfer hoses. If this occurs, the kinds of microorganisms recovered are usually of the same types that might be expected from ambient water systems. Therefore, the mesophilic microbial cultivation conditions described later in this chapter are usually adequate for their recovery.

“Instrumental” Approaches  for microbial testing of water : Pharmaceutical Water System

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. These methods all possess a variety of advantages and disadvantages. Advantages could be their precision and accuracy or their speed of test result availability as compared to the classical cultural approach. In general, instrument approaches often have a shorter lead time for obtaining results, which could facilitate timely system control. This advantage, however, is often counterbalanced by limited sample processing throughput due to extended sample collection time, costly and/or labor-intensive sample processing, or other instrument and sensitivity limitations.

[PPT PDF] Pharmaceutical Water System Design Validation – Microbial Testing of Water

Furthermore, instrumental approaches are typically destructive, precluding subsequent isolate manipulation for characterization purposes. Generally, some form of microbial isolate characterization, if not full identification, may be a required element of water system monitoring. Consequently, culturing approaches have traditionally been preferred over instrumental approaches because they offer a balance of desirable test attributes and post-test capabilities.

Suggested Methodologies : Pharmaceutical Water System

The following general methods were originally derived from Standard Methods for the Examination of Water and Wastewater, 17th Edition, American Public Health Association, Washington, DC 20005. Even though this publication has undergone several revisions since its first citation in this chapter, the methods are still considered appropriate for establishing trends in the number of colony-forming units observed in the routine microbiological monitoring of pharmaceutical waters. It is recognized, however, that other combinations of media and incubation time and temperature may occasionally or even consistently result in higher numbers of colony-forming units being observed and/or different species being recovered.

[PPT PDF] Pharmaceutical Water System Design Validation - Microbial Testing of Water

The extended incubation periods that are usually required by some of the alternative methods available offer disadvantages that may outweigh the advantages of the higher counts that may be obtained. The somewhat higher baseline counts that might be observed using alternate cultural conditions would not necessarily have greater utility in detecting an excursion or a trend. In addition, some alternate cultural conditions using low-nutrient media tend to lead to the development of microbial colonies that are much less differentiated in colonial appearance, an attribute that microbiologists rely on when selecting representative microbial types for further characterization. It is also ironical that the nature of some of the slow growers and the extended incubation times needed for their development into visible colonies may also lead to those colonies being largely nonviable, which limits their further characterization and precludes their subculture and identification.

Methodologies that can be suggested as generally satisfactory for monitoring pharmaceutical water systems are as follows. However, it must be noted that these are not referee methods nor are they necessarily optimal for recovering microorganisms from all water systems. The users should determine through experimentation with various approaches which methodologies are best for monitoring their water systems for in-process control and quality control purposes as well as for recovering any contraindicated species they may have specified.

Pharmaceutical Water System: Drinking Water:

POUR PLATE METHOD OR MEMBRANE FILTRATION METHOD1

Sample Volume—1.0 mL minimum2

Growth Medium—Plate Count Agar3

Incubation Time—48 to 72 hours minimum

Incubation Temperature—30  to 35

Purified Water:

POUR PLATE OR MEMBRANE FILTRATION METHOD1

 

Sample Volume—1.0 mL minimum2

Growth Medium—Plate Count Agar3

Incubation Time—48 to 72 hours minimum

Incubation Temperature—30  to 35

 

Water for Injection:

 

MEMBRANE FILTRATION METHOD

Sample Volume—100 mL minimum2

Growth Medium—Plate Count Agar3

Incubation Time—48 to 72 hours minimum

Incubation Temperature—30 C to 35 C

1  A membrane filter with a rating of 0.45 µm is generally considered preferable even though the cellular width of some of the bacteria in the sample may be narrower than this. The efficiency of the filtration process still allows the retention of a very high percentage of these smaller cells and is adequate for this application. Filters with smaller ratings may be used if desired, but for a variety of reasons the ability of the retained cells to develop into visible colonies may be compromised, so count accuracy must be verified by a reference approach.

2  When colony counts are low to undetectable using the indicated minimum sample volume, it is generally recognized that a larger sample volume should be tested in order to gain better assurance that the resulting colony count is more statistically representative. The sample volume to consider testing is dependent on the user’s need to know (which is related to the established alert and action levels and the water system’s microbial control capabilities) and the statistical reliability of the resulting colony count. In order to test a larger sample volume, it may be necessary to change testing techniques, e.g., changing from a pour plate to a membrane filtration approach. Nevertheless, in a very low to nil count scenario, a maximum sample volume of around 250 to 300 mL is usually considered a reasonable balance of sample collecting and processing ease and increased statistical reliability. However, when sample volumes larger than about 2 mL are needed, they can only be processed using the membrane filtration method.

3  Also known as Standard Methods Agar, Standard Methods Plate Count Agar, or TGYA, this medium contains tryptone (pancreatic digest of casein), glucose and yeast extract.

Source : USP

Expert Committee : (PW05) Pharmaceutical Waters 05

USP29–NF24 Page 3056

Pharmacopeial Forum : Volume No. 30(5) Page 1744

Phone Number : 1-301-816-8353

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Pharmaceutical Water Systems,

Purified Water Specification As Per Usp,

Pharmaceutical Water System Design Operation And Validation Pdf,

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Pharmaceutical Water Systems: Storage & Distribution Systems,

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Pharmaceutical Water Systems: Types: Water quality specifications,

Pharmaceutical Water System: principles for pharmaceutical water systems

Pharmaceutical Water System PPT – What Is Pharmaceutical Water – Principles PDF

Pharmaceutical Water System PPT - What Is Pharmaceutical Water - Principles PDF

Water is the most widely used substance, raw material or starting material in the production, processing and formulation of pharmaceutical products. It has unique chemical properties due to its polarity and hydrogen bonds. This means it is able to dissolve, absorb, adsorb or suspend many different compounds. These include contaminants that may represent hazards in themselves or that may be able to react with intended product substances, resulting in hazards to health.

Pharmaceutical Water System Ppt – What Is Pharmaceutical Water

Water is used as 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.

Pharmaceutical water includes different types of water used in the manufacture of drug products.

THE 8 TYPES OF WATER ARE:

Non-potable
Potable (drinkable) water
USP purified water
USP water for injection (WFI)
USP sterile water for injection
LUSP sterile water for inhalation
USP bacteriostatic water for injection
USP sterile water for irrigation

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. 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.

Pharmaceutical Water System PPT - What Is Pharmaceutical Water - Principles PDF

A single specification for this difficult-to-control attribute would unnecessarily burden some water users with irrelevant specifications and testing. 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 48 to 72 hours to generate results. 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 pass/fail decision on all product lots between the previous sampling’s acceptable test result and a subsequent sampling’s acceptable test result. The technical and logistical problems created by a delay in the result of such an analysis do not eliminate the user’s 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.

Pharmaceutical Water System PPT – What Is Pharmaceutical Water – Principles PDF

Important Notes on Pharmaceutical Water Systems

  1. Control of the quality of water throughout the production, storage and distribution processes, including  microbiological and chemical quality, is a major concern. Unlike other product and process ingredients, water is usually drawn from a system on demand, and is not subject to testing and batch or lot release before use. Assurance of quality to meet the on-demand expectation is, therefore, essential. Additionally, certain microbiological tests may require periods of incubation and, therefore, the results are likely to lag behind the water use.
  2. Control of the microbiological quality of WPU is a high priority. Some types of microorganism may proliferate in water treatment components and in the storage and distribution systems. It is crucial to minimize microbial contamination by proper design of the system, periodic sanitization and by taking appropriate measures to prevent microbial proliferation.
  3. Different grades of water quality are required depending on the route of administration of the pharmaceutical products. Other sources of guidance about different grades of water can be found in pharmacopoeias and related documents.

Pharmaceutical Water System: Principles For Pharmaceutical Water Systems

 

  • Pharmaceutical water production, storage and distribution systems should be designed, installed, commissioned, qualified and maintained to ensure the reliable production of water of an appropriate quality. It is necessary to validate the water production process to ensure the water generated, stored and distributed is not beyond the designed capacity and meets its specifications.
  • The capacity of the system should be designed to meet the average and the peak slow demand of the current operation. If necessary, depending on planned future demands, the system should be designed to permit increases in the capacity or designed to permit modification. All systems, regardless of their size and capacity, should have appropriate recirculation and turnover to assure the system is well controlled chemically and microbiologically.
  • The use of the systems following initial validation (installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ)) and after any planned and unplanned maintenance or modification work should be approved by the quality assurance (QA) department using change control documentation.
  • Pharmaceutical Water System PPT – What Is Pharmaceutical Water – Principles PDF Doc
  • Water sources and treated water should be monitored regularly for chemical, microbiological and, as appropriate, endotoxin contamination. The performance of water purification, storage and distribution systems should also be monitored. Records of the monitoring results, trend analysis and any actions taken should be maintained.
  • Where chemical sanitization of the water systems is part of the biocontamination control programme a validated procedure should be followed to ensure that the sanitizing process has been effective and that the sanitizing agent has been effectively removed.