Application of HACCP for development of quality risk management in a water purification system

Abstract The present work reports the implementation of the Hazard Analysis Critical Control Point (HACCP) methodology to analyze the water purification system of a pharmaceutical site, in order to assure the system quality and prevent failures. As a matter of fact, the use of HACCP for development and implementation of Quality Risk Management (QRM) is not usual in pharmaceutical plants and it is applied here to improve the performance of the water purification system of a polymerization pilot plant used to manufacture pharmaceutical grade polymer microparticles. Critical Control Points (CCP) were determined with the aid of a decision tree and questions were made to characterize whether identified hazards constitute actual CCPs and should be monitored. When deviations were detected, corrective actions were performed and action plans were used for following-up and implementation of corrective actions. Finally, microbiological and physicochemical parameters were analyzed and the obtained results were regarded as appropriate. Therefore, it is shown that HACCP constitutes an effective tool for identification of hazards, establishment of corrective actions and monitoring of the critical control points that impact the process and the quality of the final pharmaceutical product most significantly.

Cálculo da estimativa da incerteza de medição associada ao ensaio de contagem de bactérias heterotróficas em matriz água purificada através da técnica de detecção por fluorescência / Measurement uncertainty calculation associated with heterotrophic bacterial count in purified water matrix using the fluorescence detection technique

A incerteza de medição representa o nível de confiança no resultado. Para a estimativa da incerteza de medição foi empregado o cálculo do desvio padrão da reprodutibilidade intralaboratorial de 48 ensaios de contagem de bactérias heterotróficas pela técnica da membrana filtrante com detecção por fluorescência pelo uso de substrato fluorogênico em amostras de água purificada contaminadas artificialmente entre 10 e 100 UFC/mL. O valor obtido, 1,3 x 10-3 (log10), indica que a técnica utilizada pode ser uma alternativa para a estimativa da incerteza de medição em ensaios microbiológicos quantitativos de contagem de bactérias heterotróficas em amostras de água purificada. (AU)

Measurement uncertainty represents the confidence level in the result. To estimate the expanded measurement uncertainty, the standard deviation of intra-laboratory reproducibility of 48 heterotrophic bacterial count assays by fluorescence detection by the use of fluorogenic substrate on artificially contaminated purified water samples between 10 and 100 CFU/mL was used. The value obtained, 1.3 x 10-3 (log10), indicates that the technique used can be an alternative to estimate measurement uncertainty in quantitative microbiological heterotrophic bacterial count assays in purified water samples using fluorogenic substrate. (AU)

Cálculo da estimativa da incerteza de medição associada ao ensaio de contagem de bactérias heterotróficas em matriz água purificada através da técnica de detecção por fluorescência / Measurement uncertainty calculation associated with heterotrophic bacterial count in purified water matrix using the fluorescence detection technique

A incerteza de medição representa o nível de confiança no resultado. Para a estimativa da incerteza de medição foi empregado o cálculo do desvio padrão da reprodutibilidade intralaboratorial de 48 ensaios de contagem de bactérias heterotróficas pela técnica da membrana filtrante com detecção por fluorescência pelo uso de substrato fluorogênico em amostras de água purificada contaminadas artificialmente entre 10 e 100 UFC/mL. O valor obtido, 1,3 x 10-3 (log10), indica que a técnica utilizada pode ser uma alternativa para a estimativa da incerteza de medição em ensaios microbiológicos quantitativos de contagem de bactérias heterotróficas em amostras de água purificada.

Measurement uncertainty represents the confidence level in the result. To estimate the expanded measurement uncertainty, the standard deviation of intra-laboratory reproducibility of 48 heterotrophic bacterial count assays by fluorescence detection by the use of fluorogenic substrate on artificially contaminated purified water samples between 10 and 100 CFU/mL was used. The value obtained, 1.3 x 10-3 (log10), indicates that the technique used can be an alternative to estimate measurement uncertainty in quantitative microbiological heterotrophic bacterial count assays in purified water samples using fluorogenic substrate.

Physical and chemical quality, biodiversity, and thermodynamic prediction of adhesion of bacterial isolates from a water purification system: a case study

ABSTRACT The objective of this study was to evaluate the quality of water purification system and identify the bacteria this system, predict bacterial adherence according to the hydrophobicity of these microorganisms and of the polypropylene distribution loop for purified water. The assessment of drinking water that supplies the purification system allowed good-quality physical, chemical, and microbiological specifications. The physicochemical specifications of the distributed purified water were approved, but the heterotrophic bacteria count was higher than allowed (>2 log CFU mL-1).The sanitation of the storage tank with chlorine decreased the number of bacteria adhered to the surface (4.34 cycles log). By sequencing of the 16SrDNA genes, six species of bacteria were identified. The contact angle was determined and polypropylene surface and all bacteria were considered to be hydrophilic, and adhesion was thermodynamically unfavorable. This case study showed the importance of monitoring the water quality in the purified water systems and the importance of sanitization with chemical agents. The count of heterotrophic bacteria on the polypropylene surface was consistent with the predicted thermodynamics results because the number of adhered cells reached approximate values of 5 log CFU cm-2.

Discussion on the purified water inspection methods in the Chinese Pharmacopoeia of edition 2010 / 药学实践杂志

Objective To modify the purified water analysis methods in the Chinese Pharmacopoeia (Vol .Ⅱ ,Edition 2010) ,and mainly focus on the pH value determination ,analysis of nitrate and nitrite ,and the inspection of microorganism . Methods The usage of regents and colorimetric tubes in the analysis of nitrate and nitrite were inquired ,the feasibility of plat-ing culture used in the inspection of microorganism were proposed ,and the suggestion of using more instrumental analysis in-stead of titrimetric analysis in the purified water inspection wasraised .Results The choice of colormetric apparatus and the precision of the regents were explicit .The plating method was better in convenience and reliability than membrane-filter proce-dure during the microorganism inspection .Instrumental analysis is the trend of purified water inspection and deserved to be rec-ommended .Conclusion Based on our own and others′studies ,the methods of impurity analysis are improved ,which might be accepted in the revision of Chinese Pharmacopoeia in future .

Determinación bacteriológica de la calidad del agua para consumo humano obtenida de filtros ubicados dentro del campus central de la Universidad de San Carlos de Guatemala / Bacteriological determination of the quality of drinking water obtained from filters located in the central campus of the University of San Carlos of Guatemala

"Purified water" is described as having organoleptic, physical, chemical and microbiological characteristics that does not represent any risk for human health. The present study was based in the determination of water quality from 21 ozone and sedimentation water filters form the Faculties of Agronomy, Architecture, Chemical Sciences and Pharmacy, Economic Sciences, Enginery and Odontology; The School of History, Social Work; The University Gym and The Center of Sea Studies (CEMA) (Spanish acronyms); located in the central campus of Universidad de San Carlos de Guatemala. The main purpose of the study to determine if the water samples extracted from the filters a qualified for human intake. This evaluation is based on the quantity of total and fecal coliforms according to the most probable number method (MPN) and the presence of Escherichia coli (E. coli), both evaluated under [COGUANOR NTG 29001],2010 standards. The results indicate that the filters located in the Faculties of Chemical Sciences and Pharmacy, Economical Sciences, Social Work, Dentistry are over the safety limits for total coliforms established for potable water under COGUANOR standards. Also the samples taken in the Faculties of Economical Sciences and Chemical Sciences and Pharmacy show a positive result in the presence of E. coli too, means that the water extracted from those filters is not qualified for human intake. Keywords: purified water, ozone filters, sedimentation

Avaliação da qualidade de águas purificadas utilizadas em farmácias de manipulação / Assessing the quality of purified water used in compounding pharmacies

The Brazilian Food, Drug and Sanitary Agency (ANVISA) published a Resolution (RDC 67) in 2007, repealing RDC 33 of 2000, which established a legally required monthly analysis of a number of microbiological and physicochemical variables in the purified water used in compounded pharmaceutical preparations, which were not specified in the preceding RDC. In view of the amendment, the aim of this study was to assess the quality of purified water used in compounding pharmacies in the region of Araraquara (SP, Brazil) and review the impact of the most recent regulation (RDC 67 of 2007) on this quality. In the study, 744 samples of purified water were collected from 30 pharmacies in the course of four years (2008 to 2011). The variables recorded were: presence of total coliforms and fecal coliforms/E. coli, pH, color, turbidity, total dissolved solids, fluoride and residual free chlorine. The methods used were pharmacopeial standards for water analysis, published by the Brazilian National Health Foundation (FUNASA) and the American Public Health Association (APHA). Among the samples, 78.90% were in compliance with the required standards. No sample contravened the rules for color and fecal coliforms/E. coli. However, 0.54%, 7.80%, 10.75%, 0.54% and 4.56% of the samples were unacceptable in terms of turbidity, fluorides, pH, free residual chlorine and total coliforms respectively. There was a variation in the number of irregular samples by comparing the years of 2008 and 2009 (20.26% and 26.71%, respectively) and the years of 2010 and 2011 (18.33% and 19.91%, respectively). Four years after the RDC n°. 67 of 2007, manipulation pharmacies are still adjusting to the rules, and it is important that ANVISA and others agencies continue monitoring to ensure the quality of purified water...

A RDC n° 67 de 2007, que revogou a RDC nº 33 de 2000, regulamentou análises mensais que avaliam parâmetros microbiológicos e físico-químicos em águas purificadas utilizadas em preparações magistrais, antes não especificados pela RDC n° 33 de 2000. Diante dessas alterações, o objetivo do trabalho foi avaliar a qualidade de águas utilizadas em farmácias de manipulação em Araraquara e região e verificar o impacto da legislação mais recente (RDC nº 67 de 2007) nessa qualidade. Foram analisadas 744 amostras de água purificada em 30 farmácias no decorrer de quatro anos (2008 a 2011). Os parâmetros avaliados foram: presença de coliformes totais e coliformes termotolerantes/E.coli, pH, cor, turbidez, sólidos totais dissolvidos, fluoreto e cloro residual livre. Os métodos utilizados seguiram padrões de farmacopeias, da FUNASA e da APHA. Dentre as amostras analisadas 78,90% estavam em conformidade com os padrões estabelecidos. Não foram encontradas amostras irregulares quanto aos parâmetros cor e coliformes termotolerantes/E. coli. No entanto, 0,54%, 7,80%, 10,75%, 0,54% e 4,56% das amostras estavam irregulares para turbidez, fluoretos, pH, cloro residual livre e coliformes totais, respectivamente. Foi observada uma variação do número de amostras irregulares ao compararmos os anos de 2008 e 2009 (20,26% e 26,71% respectivamente) com os anos de 2010 e 2011 (18,33% e 19,91% respectivamente). Quatro anos após a RDC n° 67 de 2007, as farmácias de manipulação ainda estão se adequando às normas e é importante que a ANVISA e outros órgãos continuem a fiscalização para garantir a qualidade da água purificada...

Effect of Replacement of New Reverse Osmosis Film of Water Purification System to Clinical Biochemistry / 现代检验医学杂志

Objective To test if the quality of produced water could come up to the standards of clinical biochemistry,and e-valuate the effect of the produced water after replacement of a new reverse osmosis film of the laboratory water purification system.Methods The ion concentration of the produced water was tested by ohmmeter in Beckman Coulter supporting TianChuang water purification system TCHS-RO/100A and HM COM-100 conductivity meter.The biochemical index ALT,AST,TBIL,ALP,GGT,TP,ALB,BUN,CR,UA,GLU,TC,TG,HDL,LDL,CK,LDH,P,Ca of mixed serum were tested 20 times by AU680 under the condition of normal purified water(control group),and the same operation were repeat-ed after changing to newly produced water(experimental group)to evaluate the effect of newly produced water to biochemi-cal analysis.The triglyceride (TG)reagent blank was tested 3times/d for 5 days to evaluate the glycerin level in the pro-duced water.Results The conductivity of purified water was reduced to (0.1±0.0)μS/cm 30 min after starting up by HM COM-100,and the electric resistance of purified water remained stable at 18.25MΩcm 50min after starting up.During the bi-ochemical analysis by AU680,the value of TG in control group=1.04 mmol/L,in experimental group=21.39 mmol/L,the differences showed statistical significance (P0.05).The reagent blank was stable at A660nm=0.015 6±0.000 4 in the fifth day.Conclusion After produced approximately 2 800 L purified water in the system,glycerine could be cleaned up in produced water.It is needed to continuously test the quality of produced water to evaluate the effect of which to clinical bio-chemistry after replacement of a new reverse osmosis film.

A processor of multifunctional truck-mounted water for disaster medical rescue / 局解手术学杂志

Objective To develop a equipment of vehicular multifunctional water,and the problem of water in disaster medical rescue was solved. Methods According to the features of the field water in earthquakes,floods and other disasters,a kind of disaster relief in the wild integrated production,supplying softening water and water purification technology was created,and a system by the pretreatment system, ion exchange,reverse osmosis systems,and storage and transportation system and other parts of the small truck-mounted multifunctional water treatment equipment was developed. Results The vehicular prototypes of multifunctional water treatment machine was developed,the pond water and river water were tested to prove that the throughput of the equipment in production and supply in the land of disaster relief,the puri-fied water and softening water reached 2 080 L/day and 12 100 L/day,which could meet the conducted large-scale medical treatment de-mand. Conclusion The successful design of the vehicular multifunctional water processor carried out the medical rescue with water prob-lem,and provided a new method and new equipment,which was worthy of popularization and application.

Avaliação da qualidade da água purificada em farmácias magistrais da região de São José do Rio Preto, SP / Quality assessment of purified water used in pharmacies in São José do Rio Preto, SP

A água é a matéria-prima mais utilizada na produção de várias formas farmacêuticas, sendo um constituinte da própria formulação e exigindo para tal uma série de especificações físico-químicas e microbiológicas. Além disso, é um insumo de utilização imprescindível para testes laboratoriais e procedimentos de limpeza de equipamentos e utensílios. O presente trabalho teve como objetivo verificar o grau de contaminação química e microbiana em água purificada utilizada em farmácias magistrais da região de São José do Rio Preto, SP. As coletas foram realizadas segundo recomendações da USP Pharmacopeia, com os devidos cuidados de assepsia, e as amostras encaminhadas imediatamente ao laboratório de controle de qualidade. Foram analisados vários parâmetros físico-químicos, tais como aspecto, pH, condutividade, resíduo por evaporação, amônia, cálcio, cloreto, metais pesados, sulfato e substâncias oxidáveis, além de parâmetros microbiológicos, como contagem total de aeróbios e pesquisa de coliformes totais e termotolerantes e Pseudomonas aeruginosa. Os resultados indicaram alguns parâmetros de não conformidade: em 10% das amostras analisadas para o pH e pesquisa de impurezas inorgânicas, em 17% para condutividade, em 14% para substâncias oxidáveis e em 20% para análise microbiológica, ressaltando a necessidade de maior rigor na produção e qualidade da água purificada produzida e/ou armazenada nesses estabelecimentos farmacêuticos.

Water is the raw material used most in the production of diverse pharmaceutical forms and, being a constituent of the formulation itself, is subject to a number of physico-chemical and microbiological specifications. In addition, it is indispensable for laboratory tests and the cleaning of equipment and apparatus. The aim of this study was to ascertain the degree of physicochemical and microbiological contamination of purified water used in compounding pharmacies in the city of São José do Rio Preto, SP, Brazil. Samples were taken as recommended in the USP Pharmacopeia, with careful aseptic technique, and sent immediately the to quality control laboratory. Physicochemical properties were analyzed, including appearance, pH, conductivity, residue after evaporation, ammonia, calcium, chloride, heavy metals, sulfate and oxidizable substances, and microbiological tests were performed: total aerobic microbial count and detection of total and thermotolerant coliforms and Pseudomonas aeruginosa. Results showed that some parameters did not conform to the standards, especially pH, conductivity, inorganic impurities, oxidizable substances and microbiological test data, in 10%, 17%, 10%, 14% and 20% of the analyzed samples, respectively, This points to the need for greater care in the production and/or storage of purified water in these pharmaceutical establishments.

Synergistic Effect of Purified Water and Magnesium Deficiency Food on Learning and Memory of Offspring of Rats / 环境与健康杂志

Objective To study the effect of purified water on the neurobehavioral development of the offspring and the synergistic effect of the magnesium deficiency in food. Methods SD rats were divided into four groups,control food plus control water (control group),control food plus purified water,magnesium deficiency food plus control water,magnesium deficiency plus purified water,from five weeks of age of the F0 generation to five weeks of the F1 generation respectively. Morris water maze (MWM) was used to test the spatial learning and memory ability of offspring of rats. Results In the early training days of the place navigation,control group offspring of rats showed a shorter swimming time than the other groups. There were no significant differences among all experimental groups in the later training days of the place navigation,spatial probe test and visible platform trial,however the tendency was still to remain. Conclusion Purified water can damage the learning ability of offspring of rats and the learning ability delay will be more obviously when magnesium is deficient in food.

Evaluation of3Kinds of Water for Pharmaceutical Purposes Processing Techniques / 中国药房

OBJECTIVE:To introduce water processing treatment technology and equipment for hospital manufacturing laboratory.METHODS:According to the relevant standards recorded in China Pharmacopoeia and electric conductivity,water quality of purified water manufactured by3kinds of techniques were evaluated.The advantages and disadvantages of these techniques were compared with regard to the utilization of source water,convenience of operation,environmental pollution,and so on.RESULTS:Purified water manufactured by these3kinds of techniques all met the standards recorded in China Phar?macopoeia,best quality was obtained by the technique of combining ion exchange with first order reverse osmosis,the next in order is obtained through the combination of second order reverse osmosis with electrode ionization(EDI).The purified water could be distilled to be water for injection which meets the standard in China Pharmacopoeia.CONCLUSION:Combination of second order reverse osmosis with EDI is the optimal water processing technique considering quality of purified water,utiliza?tion of source water,convenience of operation,environmental pollution and so on.Multiple distillation technology is the main artwork to prepare water for injection.

Detection of Heavy Metals in Purified Water by Non - interference Method / 中国药房

OBJECTIVE:To scientifically control the limit of heavy metals in purified water .METHODS:Heavy metals in the purified water were detected by the refined testing water specifically for detection in accordance with Chinese Pharmacopoeia .RESULTS: Interference could be removed by using the refined testing water in the detection of heavy metals in the purified water .CONCLUSIONS: Limiting the contents of heavy metals of refined testing water to a minimum range can reduce interference to a large degree, thus making the detection results more accurate.

Maintenance of RO processing system used in hemodialysis machine / 医疗卫生装备

The operating principle,system structure and influencing factors for water quality are expounded and the maintenance of RO processing system is introduced.

Design of separate water service system according to quality in hospital / 医疗卫生装备

A design of a kind of separate water service system according to quality in hospital is introduced in this paper.The functions of the system and the standards for quality of every types of water are discussed.Its technological process of water treatment covers several kinds of membrane separation technology and the different demands for water quality in hospital are met by separate distribution.It is energy-saving,water-saving and easy to manage.

Study on Contents of Elements and Mutagenecity of Organic Extracts of Drinking Water in Different Processes of Deep Water Treatment / 环境与健康杂志

0.05) . Significant decreases of contents of 14 kinds of macro-elements and trace elements in purified water were found compared with those in water samples after activated carbon filtration (t = 2.496 9-5.261 7, F2 and showed significant dose-response relationship respectively (r = 0.980, P

Rapid Determination of Arsenic in Water by Graphite Furnace Atomic Absorption Spectrometry / 环境与健康杂志

Objective To establish a method for direct determination of arsenic in water by graphite furnace atomic absorp-tion spectrometry.Methods The contents of arsenic in water samples were directly determined by graphite furnace atomic ab-sorption spectrometry under given conditions of wavelength,ashing and atomization temperature after adding an appropriate amount of nickel sulfate to water samples without enrichment,extraction or transformation of arsenic into hydrogen arsenide of the samples.Results The linear range of the method was0.005-0.200mg /L with a correlation coefficient of0.9996.The re-covery rate,relative standard deviation and detection limit were95.0%-105.0%,4.0%-7.5%and0.005mg /L respectively.Con clu sion Compared with the silver salt method and hydride generation-atomic absorption spectrometry,this method had many advantages such as simplicity of operation,rapidity and suitability for the analysis of batch samples.

Effects of Long-term Consumption of Purified Water on Lead Accumulation in Organs of Rats / 环境与健康杂志

Objective To understand whether long term consumption of purified water can cause lead accumulation and enhance lead toxicity in the rats with chronic lead exposure. Methods 104 male SD weaned rats were randomly divided into eight groups,tap water,purified water,tap water plus lead (lead acetate,Pb2+: 50 mg/L ),purified water plus lead (Pb2+: 50 mg /L),tap water plus lead (Pb2+: 200 mg/L ),purified water plus lead (Pb2+: 200 mg/L),tap water plus lead (Pb2+: 800 mg/L),purified water plus lead (Pb2+: 800 mg/L). All were fed with normal food and kept in the same environmental conditions. The blood samples were collected after 4,6,8,10,24 and 28 weeks of lead exposure. The brain,heart,liver,kidney,bone were sampled at the experimental endpoint and the lead concentration was determined with graphite furnace atomic absorption spectrometric method,zinc protoporphyrin (ZPP) level was measured by using surface fluorescence method. Results At the same lead exposure level,no difference of blood lead level was observed between the groups of drinking purified water and tap water,however,the lead level in the organs tissue,including brain,heart,liver,kidney,bone,was significantly higher in the group drinking purified water compared with drinking tap water. The blood ZPP level in rats drinking purified water was also higher than the rats drinking tap water,the significant difference were occurred at low lead level exposure (P

Research of EDI Technology and Its Application in Field Pharmaceutical Water Preparation / 医疗卫生装备

Objective To apply the EDI technology to the field pharmaceutical water preparation, thus improve the ability to prepare pharmaceutical water. Methods The EDI pharmaceutical water production technics was studied, and different kinds of technics were analyzed. The resistance value and TOC content of product water by EDI system were checked. The compact field purified water apparatus was developed, for which self-developed EDI was core technology. Results EDI system had advanced performance, for which the resistance value was high level, and the content of TOC was low. The produced water accorded with the criterion of purified water of Chinese Pharmacopoeia 2005. Conclusion EDI technology adapts to field pharmaceutical water production, and improves the quality of produced water and the adaptability of the system.