The document provides guidance on inspecting water purification systems used in pharmaceutical applications, outlining key areas to review such as schematics, sample procedures, test results, maintenance logs, and validation documents, and recommends verifying systems by walking through and checking components, instrumentation, and records.
This document discusses water purification and engineering for pharmaceutical use. It examines requirements for water treatment systems, storage and distribution, sampling and testing, and sanitization. Key points include selecting suitable contact materials, maintaining turbulent flow and avoiding dead legs to control biocontamination, and using techniques like continuous circulation, UV radiation, and periodic sanitization to prevent microbial growth.
A brief summary of Water System in pharmaceuticals including its production and distribution with regulatory and qualification requirements. This presentation gives a basic layout to non-engineering people a basic understanding of Water System in Pharmaceutical.
The document discusses water systems and purification methods used in pharmaceutical manufacturing. It introduces different grades of water quality (e.g. purified water, water for injections) and their applications. Common water contaminants are outlined. Water purification systems may use various pretreatment steps and methods like filtration, softening, and disinfection. Proper design, operation, and maintenance of water systems is required to reliably produce water of the necessary quality.
The document discusses pharmaceutical water systems. It begins by defining various types of high purity water like purified water, sterile purified water, water for injection, and sterile water for injection. It then discusses how purified water and water for injection are produced, typically through processes like distillation, ion exchange, or reverse osmosis. The document also covers considerations for storing and distributing high purity water, such as using stainless steel materials, minimizing dead legs, and sanitizing distribution systems through heat, ozone, or chemicals. Finally, it presents different options for setting up hot and cold storage and distribution systems.
This document discusses pharmaceutical validation and process validation. It begins with an introduction to process validation, describing it as the analysis of data gathered throughout product design and manufacturing to confirm a process can reliably output products to a determined standard. It then covers the documentation of process validation, including validation master plans, protocols, and reports. The rest of the document discusses specific types of process validation and provides examples of validating different pharmaceutical dosage forms and processes.
The document discusses the validation of a water supply system for a pharmacy college. It outlines the objectives of validation to ensure consistent production of water meeting quality specifications. The validation process includes design qualification, installation qualification, operation qualification, and performance qualification to test the system under all expected operating conditions. Key steps involve defining quality attributes, developing a validation protocol and acceptance criteria, conducting testing and data collection, and documenting the validation results.
The document provides an overview of validation requirements in the pharmaceutical industry. It defines validation and traces its origins back to the 1970s where it began with sterilization processes and has now expanded to all product, process, and facility matters. Validation is important as it assures quality, is a regulatory requirement, reduces costs, and is legally required. The document outlines the various stages of validation from user requirement specification to process validation and continuous process verification. It provides details on what each stage involves and its goals.
This document discusses the process validation of capsules. It begins by providing background on validation and defining process validation according to the FDA. It then describes the three main types of process validation: prospective, concurrent, and retrospective. Key documents used in validation like the validation master plan, validation protocols and reports, and standard operating procedures are also outlined. The validation process for capsules is then detailed, including evaluating the capsule composition, selecting the encapsulation process and equipment, and testing the encapsulation step. Critical factors considered during encapsulation like the technique used and encapsulation speed are also summarized.
This document discusses water purification and engineering for pharmaceutical use. It examines requirements for water treatment systems, storage and distribution, sampling and testing, and sanitization. Key points include selecting suitable contact materials, maintaining turbulent flow and avoiding dead legs to control biocontamination, and using techniques like continuous circulation, UV radiation, and periodic sanitization to prevent microbial growth.
A brief summary of Water System in pharmaceuticals including its production and distribution with regulatory and qualification requirements. This presentation gives a basic layout to non-engineering people a basic understanding of Water System in Pharmaceutical.
The document discusses water systems and purification methods used in pharmaceutical manufacturing. It introduces different grades of water quality (e.g. purified water, water for injections) and their applications. Common water contaminants are outlined. Water purification systems may use various pretreatment steps and methods like filtration, softening, and disinfection. Proper design, operation, and maintenance of water systems is required to reliably produce water of the necessary quality.
The document discusses pharmaceutical water systems. It begins by defining various types of high purity water like purified water, sterile purified water, water for injection, and sterile water for injection. It then discusses how purified water and water for injection are produced, typically through processes like distillation, ion exchange, or reverse osmosis. The document also covers considerations for storing and distributing high purity water, such as using stainless steel materials, minimizing dead legs, and sanitizing distribution systems through heat, ozone, or chemicals. Finally, it presents different options for setting up hot and cold storage and distribution systems.
This document discusses pharmaceutical validation and process validation. It begins with an introduction to process validation, describing it as the analysis of data gathered throughout product design and manufacturing to confirm a process can reliably output products to a determined standard. It then covers the documentation of process validation, including validation master plans, protocols, and reports. The rest of the document discusses specific types of process validation and provides examples of validating different pharmaceutical dosage forms and processes.
The document discusses the validation of a water supply system for a pharmacy college. It outlines the objectives of validation to ensure consistent production of water meeting quality specifications. The validation process includes design qualification, installation qualification, operation qualification, and performance qualification to test the system under all expected operating conditions. Key steps involve defining quality attributes, developing a validation protocol and acceptance criteria, conducting testing and data collection, and documenting the validation results.
The document provides an overview of validation requirements in the pharmaceutical industry. It defines validation and traces its origins back to the 1970s where it began with sterilization processes and has now expanded to all product, process, and facility matters. Validation is important as it assures quality, is a regulatory requirement, reduces costs, and is legally required. The document outlines the various stages of validation from user requirement specification to process validation and continuous process verification. It provides details on what each stage involves and its goals.
This document discusses the process validation of capsules. It begins by providing background on validation and defining process validation according to the FDA. It then describes the three main types of process validation: prospective, concurrent, and retrospective. Key documents used in validation like the validation master plan, validation protocols and reports, and standard operating procedures are also outlined. The validation process for capsules is then detailed, including evaluating the capsule composition, selecting the encapsulation process and equipment, and testing the encapsulation step. Critical factors considered during encapsulation like the technique used and encapsulation speed are also summarized.
This document discusses various water treatment processes used in the pharmaceutical industry, including reverse osmosis (RO), demineralization (DM), and ultrafiltration. RO uses semipermeable membranes to remove dissolved solids, particles, and microorganisms from water. DM removes mineral salts using ion exchange resins. Ultrafiltration uses membranes to retain suspended solids and high molecular weight substances. The document also describes different types of treated water used in pharmaceutical applications, such as water for injection and sterile water, and their production processes.
This document discusses the need for high-quality water in pharmaceutical manufacturing. It notes that water is used directly and indirectly in products and cleaning. It then outlines the goals of understanding water quality systems, sources, and validation/qualification requirements. Various water treatment techniques are explained including filtration, softening, reverse osomosis and more. Validation involves proving the engineering design, operating procedures and maintenance plans. The presentation covers installation qualification, operational qualification, and performance qualification testing over multiple phases to verify long-term control of water systems.
This document provides an introduction to water systems for pharmaceutical use. It discusses the importance of water quality for pharmaceutical processes and products. It outlines various water types like purified water, highly purified water, and water for injections. It emphasizes that water systems must be properly designed, installed, operated and maintained according to GMP to ensure consistent production of water meeting quality specifications. It also discusses common water contaminants and the need to monitor water sources and treat water appropriately based on its chemistry and contaminants.
This document outlines Good Manufacturing Practices (GMP) for producing sterile pharmaceutical products. It discusses that GMP ensures products are consistently manufactured and controlled to quality standards for their intended use. Specific requirements are provided for facilities, equipment, environmental controls, personnel hygiene and sanitation practices when manufacturing sterile injectables, ophthalmic preparations and other sterile products to minimize risks of contamination. Production must follow documented procedures and strict aseptic techniques to ensure the sterility and quality of manufactured medicines.
Description of Effluent treatment plant ,its process,types of waste water discharge , Regulations And Guideline Overview , Designing of ETP , special test for tretment of water , etc
This document provides information on cleaning validation and analytical method validation. It discusses key aspects of cleaning validation including protocols, sampling methods, acceptance criteria, and reports. It emphasizes that cleaning validation is important to prevent contamination between products manufactured using the same equipment. It also covers parameters that are important to validate analytical methods such as selectivity, precision, accuracy, linearity, and calibration curves. The document is a reference for professionals on best practices for cleaning validation and analytical method validation.
Cleaning validation is a critical process in pharmaceutical operations to ensure clean environments and equipment. It helps assure the safety, purity and quality of pharmaceutical products by demonstrating contaminated residues have been adequately removed. The document discusses the importance of cleaning validation and outlines factors to consider like equipment, facilities, cleaning methods, agents, and establishing acceptance criteria through sampling and testing. Proper standard operating procedures and documentation of cleaning validation is necessary to comply with cGMP regulations.
This document provides an overview of air handling systems (AHUs) and HVAC qualification for pharmaceutical facilities. It contains sections on introduction, types of clean rooms, principles of clean rooms, HVAC components, regulatory requirements, contamination control, air flow patterns, and HVAC qualification steps including user requirement specification, design qualification, and installation qualification. The objective is to understand the need for pharmaceutical air handling systems and their technical and qualification requirements.
The document discusses auditing of a critical system called an effluent treatment plant (ETP). It begins with definitions of key terms related to ETPs like effluent, influent, and sludge. It then covers the advantages of wastewater systems, the need for ETPs, and factors to consider in ETP design. The document outlines the treatment levels and processes in an ETP from preliminary to tertiary. It provides examples of physical, chemical, and biological processes. Finally, it discusses audit checklists and procedures for ETPs and considerations for environmental impact assessments.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
Water system , IMPORTANCE OF WATER & Water Treatment ICHAPPS
Water system, IMPORTANCE OF WATER.Water is widely used as a raw material, ingredient and solvent in the processing formulation and in the manufacture of pharmaceutical products, Active pharmaceutical ingredients and in intermediates.Water is widely used as a raw material, ingredient and solvent in the processing formulation and in the manufacture of pharmaceutical products, Active pharmaceutical ingredients and in intermediates.
This document provides guidance for the preparation and submission of veterinary master files to the FDA's Center for Veterinary Medicine. It defines six types of master files, including Veterinary Master Files (VMFs) and Public Master Files. The guidance eliminates Type I VMFs, which contained information on manufacturing sites, facilities, procedures and personnel. Holders with existing Type I VMFs can request transferring information to other VMF types. The guidance describes the remaining VMF types and provides instructions for submissions, reviews, confidentiality and other procedures.
Water auditing involves analyzing water consumption to identify ways to reduce, reuse, and recycle water. It is important for efficient water management in India due to increasing water scarcity issues. A water audit quantifies water inputs and outputs to determine water losses. This allows utilities to reduce leakage and non-revenue water. Water audits have benefits like financial savings, public awareness of conservation, and identifying unauthorized water uses.
This document discusses process validation. It defines process validation as establishing documented evidence that a process will consistently produce a product meeting its predetermined specifications. The key aspects of process validation are to obtain consistent and reliable data, demonstrate that the process remains in control, and show the process works as intended. There are different types of process validation including prospective, retrospective, and concurrent validation. Process validation involves multiple phases from process design and qualification to process verification and monitoring. It is important for quality, safety, efficacy and compliance with global regulatory agencies.
The document discusses validation in pharmaceutical manufacturing. It defines validation and equipment qualification, which includes design qualification, installation qualification, operational qualification, and performance qualification. The goals of equipment qualification are to ensure equipment works correctly and produces accurate results through documentation and control of any changes. Specific validation processes for an autoclave used in stem sterilization are also outlined.
This document summarizes a presentation on pharmaceutical waters from the USP chapter 1231. It discusses various types of bulk and sterile waters used in pharmaceutical applications, including their sources, uses, and quality standards. Purified water and water for injection are produced in large volumes on-site for use in non-parenteral and parenteral preparations, respectively. Source water is treated and purified to meet chemical, microbial, and endotoxin limits defined in pharmacopeial monographs. Water systems must be validated to reliably produce water meeting all specified quality attributes.
There are two types of pharmaceutical water: bulk forms and packaged forms. Bulk forms include purified water and water for injection, which are produced on-site for immediate use. Packaged forms include bacteriostatic water for injection, sterile water for injection, sterile water for irrigation, sterile water for inhalation, and sterile purified water. These are pre-packaged, sterilized, and shelf-stable to maintain purity. Common packaged waters are bacteriostatic water, which contains benzyl alcohol as a preservative, sterile water for injection in single-dose containers, and sterile water for irrigation intended for short procedures.
This document discusses various water treatment processes used in the pharmaceutical industry, including reverse osmosis (RO), demineralization (DM), and ultrafiltration. RO uses semipermeable membranes to remove dissolved solids, particles, and microorganisms from water. DM removes mineral salts using ion exchange resins. Ultrafiltration uses membranes to retain suspended solids and high molecular weight substances. The document also describes different types of treated water used in pharmaceutical applications, such as water for injection and sterile water, and their production processes.
This document discusses the need for high-quality water in pharmaceutical manufacturing. It notes that water is used directly and indirectly in products and cleaning. It then outlines the goals of understanding water quality systems, sources, and validation/qualification requirements. Various water treatment techniques are explained including filtration, softening, reverse osomosis and more. Validation involves proving the engineering design, operating procedures and maintenance plans. The presentation covers installation qualification, operational qualification, and performance qualification testing over multiple phases to verify long-term control of water systems.
This document provides an introduction to water systems for pharmaceutical use. It discusses the importance of water quality for pharmaceutical processes and products. It outlines various water types like purified water, highly purified water, and water for injections. It emphasizes that water systems must be properly designed, installed, operated and maintained according to GMP to ensure consistent production of water meeting quality specifications. It also discusses common water contaminants and the need to monitor water sources and treat water appropriately based on its chemistry and contaminants.
This document outlines Good Manufacturing Practices (GMP) for producing sterile pharmaceutical products. It discusses that GMP ensures products are consistently manufactured and controlled to quality standards for their intended use. Specific requirements are provided for facilities, equipment, environmental controls, personnel hygiene and sanitation practices when manufacturing sterile injectables, ophthalmic preparations and other sterile products to minimize risks of contamination. Production must follow documented procedures and strict aseptic techniques to ensure the sterility and quality of manufactured medicines.
Description of Effluent treatment plant ,its process,types of waste water discharge , Regulations And Guideline Overview , Designing of ETP , special test for tretment of water , etc
This document provides information on cleaning validation and analytical method validation. It discusses key aspects of cleaning validation including protocols, sampling methods, acceptance criteria, and reports. It emphasizes that cleaning validation is important to prevent contamination between products manufactured using the same equipment. It also covers parameters that are important to validate analytical methods such as selectivity, precision, accuracy, linearity, and calibration curves. The document is a reference for professionals on best practices for cleaning validation and analytical method validation.
Cleaning validation is a critical process in pharmaceutical operations to ensure clean environments and equipment. It helps assure the safety, purity and quality of pharmaceutical products by demonstrating contaminated residues have been adequately removed. The document discusses the importance of cleaning validation and outlines factors to consider like equipment, facilities, cleaning methods, agents, and establishing acceptance criteria through sampling and testing. Proper standard operating procedures and documentation of cleaning validation is necessary to comply with cGMP regulations.
This document provides an overview of air handling systems (AHUs) and HVAC qualification for pharmaceutical facilities. It contains sections on introduction, types of clean rooms, principles of clean rooms, HVAC components, regulatory requirements, contamination control, air flow patterns, and HVAC qualification steps including user requirement specification, design qualification, and installation qualification. The objective is to understand the need for pharmaceutical air handling systems and their technical and qualification requirements.
The document discusses auditing of a critical system called an effluent treatment plant (ETP). It begins with definitions of key terms related to ETPs like effluent, influent, and sludge. It then covers the advantages of wastewater systems, the need for ETPs, and factors to consider in ETP design. The document outlines the treatment levels and processes in an ETP from preliminary to tertiary. It provides examples of physical, chemical, and biological processes. Finally, it discusses audit checklists and procedures for ETPs and considerations for environmental impact assessments.
Fluidized Bed Dryer
Principle of FBD
Construction of FBD
Working of FBD
Steps of Fluidization
Qualification of FBD
Design Qualification
Installation Qualification
Operational Qualification
Performance Qualification
References
Water system , IMPORTANCE OF WATER & Water Treatment ICHAPPS
Water system, IMPORTANCE OF WATER.Water is widely used as a raw material, ingredient and solvent in the processing formulation and in the manufacture of pharmaceutical products, Active pharmaceutical ingredients and in intermediates.Water is widely used as a raw material, ingredient and solvent in the processing formulation and in the manufacture of pharmaceutical products, Active pharmaceutical ingredients and in intermediates.
This document provides guidance for the preparation and submission of veterinary master files to the FDA's Center for Veterinary Medicine. It defines six types of master files, including Veterinary Master Files (VMFs) and Public Master Files. The guidance eliminates Type I VMFs, which contained information on manufacturing sites, facilities, procedures and personnel. Holders with existing Type I VMFs can request transferring information to other VMF types. The guidance describes the remaining VMF types and provides instructions for submissions, reviews, confidentiality and other procedures.
Water auditing involves analyzing water consumption to identify ways to reduce, reuse, and recycle water. It is important for efficient water management in India due to increasing water scarcity issues. A water audit quantifies water inputs and outputs to determine water losses. This allows utilities to reduce leakage and non-revenue water. Water audits have benefits like financial savings, public awareness of conservation, and identifying unauthorized water uses.
This document discusses process validation. It defines process validation as establishing documented evidence that a process will consistently produce a product meeting its predetermined specifications. The key aspects of process validation are to obtain consistent and reliable data, demonstrate that the process remains in control, and show the process works as intended. There are different types of process validation including prospective, retrospective, and concurrent validation. Process validation involves multiple phases from process design and qualification to process verification and monitoring. It is important for quality, safety, efficacy and compliance with global regulatory agencies.
The document discusses validation in pharmaceutical manufacturing. It defines validation and equipment qualification, which includes design qualification, installation qualification, operational qualification, and performance qualification. The goals of equipment qualification are to ensure equipment works correctly and produces accurate results through documentation and control of any changes. Specific validation processes for an autoclave used in stem sterilization are also outlined.
This document summarizes a presentation on pharmaceutical waters from the USP chapter 1231. It discusses various types of bulk and sterile waters used in pharmaceutical applications, including their sources, uses, and quality standards. Purified water and water for injection are produced in large volumes on-site for use in non-parenteral and parenteral preparations, respectively. Source water is treated and purified to meet chemical, microbial, and endotoxin limits defined in pharmacopeial monographs. Water systems must be validated to reliably produce water meeting all specified quality attributes.
There are two types of pharmaceutical water: bulk forms and packaged forms. Bulk forms include purified water and water for injection, which are produced on-site for immediate use. Packaged forms include bacteriostatic water for injection, sterile water for injection, sterile water for irrigation, sterile water for inhalation, and sterile purified water. These are pre-packaged, sterilized, and shelf-stable to maintain purity. Common packaged waters are bacteriostatic water, which contains benzyl alcohol as a preservative, sterile water for injection in single-dose containers, and sterile water for irrigation intended for short procedures.
Validation of water systems used to produce demineralized, distilled, and water for injection is important in the pharmaceutical industry to ensure water quality. The document discusses the objectives, types, design, operation, and monitoring of water systems. Key aspects of validation include design qualification, installation qualification, operational qualification, and performance qualification to demonstrate systems consistently produce water meeting quality specifications under all operating conditions. Ongoing maintenance and revalidation if changes are made helps maintain system performance over time.
Bacteriological analysis of drinking water by MPN method.prakashtu
This document describes the MPN (Most Probable Number) method for analyzing drinking water bacteriologically. The MPN method involves inoculating water samples in multiple dilutions into lactose broths to detect coliform bacteria presence. Positive samples are then cultured on EMB agar to isolate and identify E. coli. Confirmed E. coli colonies produce acid and gas when cultured in lactose broth at 44.5°C. The number of positive samples at each dilution level is used with statistical tables to estimate the MPN of coliform bacteria per 100ml of water. This provides a statistical analysis of bacteria levels in drinking water samples.
The document discusses India's efforts to provide safe drinking water to its population. It notes that in 1975, over 1 billion people globally lacked access to safe water. In response, India developed various five-year plans from 1980-1997 to expand access, with the goal of supplying safe water to all rural villages. Key aspects of ensuring water safety discussed include water quality standards, testing for contaminants, monitoring programs, and strategies like water treatment and sanitation inspections. The document also examines health impacts of contaminated water and international targets for access to improved water sources.
This document discusses different types of pharmaceutical water used in manufacturing and packaging medications. There are two main categories - bulk forms produced on-site for immediate use, including purified water and water for injection, and packaged sterile forms with preservatives or single-dose containers to maintain sterility over time, such as bacteriostatic water, sterile water for injection, irrigation, and inhalation. The document provides details on the intended uses and specifications of each type of pharmaceutical water.
Investigation into Sappi Enstra sewage water qualityMegan Rose
Treated water from Ancor sewage works is used at Sappi Enstra. Corruseal.
Megan Rose, Pr.Sci.Nat.
Materials Scientist
Neopak Research and Development
South Africa
Lean Clean - Total Organic Carbon Analysis for Cleaning Validation in Pharmac...nvasoya
This document discusses using design of experiments to evaluate combining the analysis of cleaning agents and drug products using total organic carbon analysis. A factorial design of experiments was conducted varying pH, volume, and oxidizer flow rate during analysis of cleaning agents. The results showed little to no variation between factors, indicating parameters can be changed without affecting results. Additionally, even the worst variation was small compared to the permitted residue limit. Therefore, cleaning agents and drug products can be analyzed together in one sample to streamline the process without increasing risk.
The document discusses freeze drying and lyophilizer maintenance. It begins with an introduction to freeze drying and its importance. It then covers the freeze drying process sequence, calibration of lyophilizers, types of maintenance including preventative and corrective, and maintenance of lyophilizer components. Key aspects of maintenance discussed include calibration, cleaning, leak testing, and ensuring proper operation of systems like refrigeration, vacuum pumps and more. Routine maintenance is emphasized as important for reliable performance and quality results from freeze drying.
Applications for Water Activity and Sorption Isotherms in PharmaceuticalsLabFerrer LabFerrer
The pharmaceutical industry has been measuring moisture for decades.
Why? Because most people think water is the enemy of API stability. Turns out they're only partly right.
FDA Form 483 (Inspectional Observations) - Top Violations 2013Marc Sanchez
FDA Attorney Marc Sanchez discusses the Top FDA Form 483 (Inspectional Observations) from fiscal year 2013. The top observations provide a foundation for preparing for a pre-inspection, for-cause inspection, or routine surveillance inspection.
1) The document outlines the validation process for a tablet compression machine, including installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).
2) The IQ establishes that the machine is installed correctly according to specifications. The OQ tests that the machine operates as intended at different speeds and settings.
3) The PQ evaluates the machine's compression capabilities by producing tablets and testing for characteristics like content uniformity, thickness, hardness, and friability. The validation protocol brings all stages together in a report.
validation of solid presentation by ahsan khanDRx Ahsan Khan
This document discusses validation of solid dosage forms such as tablets and capsules. It covers the key aspects of validation including validation of raw materials, analytical methods, equipment, and manufacturing processes. The manufacturing process involves various unit operations for tablets such as mixing, granulation, drying, lubrication, compression, and coating. In-process and finished product testing are also important parts of validation. Validation ensures a reproducible product that meets specifications.
This document outlines the process of validation for non-sterile pharmaceutical products. It discusses prospective validation, which involves validating the production process prior to releasing finished product for sale, concurrent validation during routine production, and retrospective validation which involves reviewing historical data. The key steps are identifying critical process parameters, conducting validation protocols with predetermined acceptance criteria, and documenting results in a validation report.
3 top ten fda warning letter findings by theShirley Roach
The document outlines the top ten most common Good Manufacturing Practice (GMP) findings by the FDA in fiscal year 2003 based on Form 483 observations. The most frequent finding was a failure to follow and/or document written production and process control procedures, which was referenced on 317 Form 483s. Other top findings included responsibilities of the quality control unit, written procedures for production and process controls, testing and release for distribution, and validation. The document also provides examples of common GMP violations found during inspections, such as dirty facilities, unqualified equipment, and lack of corrective and preventative action procedures.
Formurex is a contract research organization that provides drug formulation development services, analytical testing, GMP manufacturing, and stability studies to support clinical trials for pharmaceutical companies. Its mission is to advance medicine using cutting-edge drug formulation and delivery technologies. Services include preformulation studies, formulation development through various processes like granulation and coating, analytical testing through methods like HPLC and dissolution, and GMP manufacturing of tablets and capsules to support early-stage clinical trials.
This document discusses commissioning, qualification, validation, monitoring and maintenance of water systems for pharmaceutical use. It recommends a three-phase approach to performance qualification over an extended period to prove system reliability and robustness. Phase 1 involves intensive initial monitoring, phase 2 further monitoring using standard operating procedures, and phase 3 demonstrates performance over one year including seasonal variations. Ongoing system monitoring and a controlled maintenance program are also recommended, along with regular system reviews.
The document discusses the validation of water supply systems for pharmaceutical use. It outlines the need to validate water systems due to water being the most commonly used raw material. The validation process includes design qualification, installation qualification, operation qualification and performance qualification to ensure appropriate design, installation, and operation of the system. Regular monitoring and maintenance is also required to guarantee continued production of water meeting quality specifications.
The document discusses the validation of water supply systems for pharmaceutical use. It outlines the need to validate water systems due to water being the most commonly used raw material. The validation process includes design qualification, installation qualification, operation qualification and performance qualification to ensure appropriate design, installation, and operation of the system. Regular monitoring and maintenance is also required to guarantee continued production of water meeting quality specifications.
The document discusses the validation of water supply systems for pharmaceutical use. It outlines the validation process, which includes design qualification to verify the system design, installation qualification to confirm proper installation, operation qualification to test system functionality under static conditions, and performance qualification to demonstrate consistent performance over time under normal operating conditions. Routine monitoring, maintenance, and change control procedures are also required to ensure continued system operation and water quality as specified.
This document provides an overview of water treatment systems for pharmaceutical use. It discusses the various types of water (e.g. purified water, water for injections) and their specifications. It also outlines common water contaminants and the principles of water purification systems. The document reviews pretreatment processes like filtration and softening as well as downstream treatments such as reverse osmosis, deionization, and distillation. It emphasizes that water systems must be properly designed, installed, and maintained according to GMP to ensure a reliable supply of high quality water.
Validation of pharaceutical water system and pure steamJp Prakash
This document discusses the validation of pharmaceutical water systems and pure steam. It covers the validation sequences of design qualification, installation qualification, operational qualification, and performance qualification. Design qualification involves validating components like piping, tanks, filters, and distillation stills. Installation qualification ensures proper installation. Performance qualification demonstrates the system can reliably produce water and steam meeting quality requirements over extended use. Validation is necessary to assure safety, efficacy and quality according to regulations.
Water for Pharmaceutical Use........pptxNazim Hussain
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.for pharmaceutical water systems.
Annex 1: Development of monographs for The International Pharmacopoeia Annex 2: WHO good manufacturing practices: water for pharmaceutical use Annex 3: Pharmaceutical development of multisource (generic) pharmaceutical products - point to consider
Annex 4: Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Programme: quality part.
Annex 5: Development of paediatric medicines: points to consider in formulation
Annex 6: Recommendations for quality requirements for artemisinin as a starting material in the production of antimalarial active pharmaceutical ingredient.
Inspection of water systems
8.2 The following list identifies items and a logical sequence for a WPU system inspection or audit:
– a current drawing of the water system showing all equipment in the system from the inlet to the points of use along with sampling points and their designations;
– approved piping drawings (e.g. orthographic and/or isometric);
– a sampling and monitoring plan with a drawing of all sample points;
– training programme for sample collection and testing;
– the setting of monitoring alert and action levels;
– monitoring results and evaluation of trends;
– inspection of the last annual system review;
– review of any changes made to the system since the last audit and a check that the change control has been implemented;
– review of deviations recorded and their investigation;
– general inspection of system for status and condition;
– review of maintenance, failure and repair logs;
– checking calibration and standardization of critical instruments
This document discusses water for pharmaceutical use. It covers water system requirements, water quality specifications for different grades of water, common water purification methods like distillation and reverse osmosis, and the application of specific water grades in processes and dosage forms. It emphasizes that water systems must be properly designed, installed, and maintained according to GMP to ensure consistent production of water meeting quality standards.
Water quality can impact diagnostic instrument performance and patient results. Contaminants like bacteria, ions, and organics can interfere with assays. Purification technologies like reverse osmosis, ultrafiltration, and electro-deionization are used to produce high purity water for clinical analyzers. Strict quality standards help ensure water does not introduce errors, but biofilms can still form within instruments. Technicians must carefully monitor quality controls, troubleshoot issues, and maintain water purification systems.
1) The document discusses validation of water systems for pharmaceutical use, including water quality specifications, purification methods, and commissioning, qualification, operation and maintenance of the systems.
2) It outlines various water grades including drinking water, purified water, highly purified water, and water for injections, and describes methods for producing each grade including distillation, ion exchange, ultrafiltration and reverse osmosis.
3) Validation of water systems aims to demonstrate the capability of the systems to consistently supply water meeting predetermined quality criteria through qualification testing over extended periods and under varying conditions.
The document discusses water purification engineering for pharmaceutical use. It covers water treatment systems including filtration, reverse osmosis, distillation, and ultrafiltration. It also addresses water storage, sampling, testing limits for bacteria and chemicals, and types of water used in pharmaceuticals like water for injections and final rinse. The objectives are to examine basic technology and requirements for water purification systems used in pharmaceutical manufacturing.
Bs water-treatment-presentation-1-1 finalsDaphne Tan
Water treatment is crucial for safe consumption and usage. It removes contaminants like chlorine, fluoride, parasites and dioxins that can be hazardous to health. For haemodialysis patients who use large volumes of water, treatment is essential to avoid health complications. Reverse osmosis is commonly used as it removes bacteria, endotoxins and dissolved solids. Strict water quality monitoring and disinfection is needed, as contaminated water could be life threatening for haemodialysis patients. Proper equipment, storage and process design are important to ensure safe, effective water treatment.
Bs water-treatment-presentation-1-1 finalsDaphne Tan
Water treatment is important for haemodialysis patients who are exposed to large volumes of water directly through their bloodstream. Reverse osmosis (RO) is commonly used to treat water for haemodialysis as it removes contaminants, bacteria and endotoxins. Proper design, monitoring and maintenance of the RO system is required. Storage tanks must be designed to prevent bacterial growth and reject water can be recycled to reduce wastage. Regular testing is needed to ensure water quality meets Association for the Advancement of Medical Instrumentation standards to protect patient safety.
Water system validation by- Akshay kakdeAkshay Kakde
This presentation discusses the validation of water systems used in pharmaceutical manufacturing. It covers the need for high quality water and purification systems, as well as the various qualification activities involved in validating such systems, including design qualification, installation qualification, operational qualification, and performance qualification. The presentation provides details on regulatory requirements and specifications for purified water and water for injection. It emphasizes that validation is necessary to ensure water systems consistently produce water meeting quality standards to avoid contamination of pharmaceutical products.
This document discusses the validation of dissolution test apparatus. It begins with a brief history of validation and reasons for validating equipment. Validation ensures equipment operates consistently and accurately. The document then discusses various types of dissolution test apparatus and the qualification process, including design, installation, operational, and performance qualification. It also addresses sources of error and concludes that acceptable qualification demonstrates the apparatus is validated for use in dissolution testing.
The document discusses water purification for pharmaceutical use. It describes various types of water (e.g. purified water, highly purified water, water for injection) and their specifications. The purification process involves multiple validation phases to demonstrate the system can consistently produce water meeting specifications. Quality must be controlled during production, storage and distribution to prevent microbial or chemical contamination.
This document discusses validation of critical utilities in the pharmaceutical industry. It covers validation of various systems including purified water systems, compressed air systems, HVAC systems, and clean steam systems. It describes the FDA requirements for validation which includes installation qualification, operational qualification and performance qualification. It provides specifications for purified water and discusses environmental monitoring programs for validated utilities.
The document discusses principles and approaches to cleaning validation for pharmaceutical manufacturing. It covers topics such as cleaning validation protocols and reports, personnel and equipment, use of detergents, microbiology, sampling, analytical methods, acceptable limits, and bracketing of products for validation. The objectives of cleaning validation are to demonstrate that cleaning procedures adequately remove product, detergent, and microbial residues to prevent contamination and cross-contamination. Written standard operating procedures and documentation of validation studies are required.
This document provides regulatory guidance on processing intermediate, bulk, and packaged pharmaceutical products according to good manufacturing practices (GMP). It discusses three key stages of manufacturing: (1) intermediate products that undergo processing from raw materials to near-final formulation; (2) bulk products that are final formulation ready for primary packaging; and (3) packaging of bulk products. The document outlines GMP guidelines from WHO on cleaning equipment, environmental controls, process validation, and packaging operations to minimize risks like cross-contamination. It emphasizes keeping detailed records of production processes and environmental monitoring to ensure quality and traceability.
1. Supplementary Training Modules on
Good Manufacturing Practice
Water for
Pharmaceutical Use
Part 3:
Inspection of water
purification systems
WHO Technical Report Series
No 929, 2005. Annex 3
Water | Slide 1 of 30 January 2006
2. Water for Pharmaceutical Use
Objectives
To understand:
The specific requirements when inspecting water systems,
including associated documentation
Water system inspection techniques and approaches
Water | Slide 2 of 30 January 2006
3. Water for Pharmaceutical Use
Prepare an aide-memoire for items to inspect:
Schematic drawing review
Changes to system since installation
Sampling procedure and plan
Specifications, results and trends
Out-of-specification results
Annual system review
Deviations 8.
Water | Slide 3 of 30 January 2006
4. Water for Pharmaceutical Use
Prepare an aide-memoire for items to inspect (2):
Results of system performance monitoring
Out of limit results, failure investigations and alarms recorded
Sanitization procedures and records
Maintenance and repairs logs/records
Instrument calibration and standardization
Qualification and validation including DQ, IQ, OQ, PQ
Requalification when appropriate, etc.
8.
Water | Slide 4 of 30 January 2006
5. Water for Pharmaceutical Use
Where to start:
What is the water to be used for?
– sterile products
– non-sterile products, e.g. oral liquid products, external
applications
– solid dosage forms
– washing and rinsing
Start: Document review – site verification – followed by additional
document review
Water | Slide 5 of 30 January 2006
6. Water for Pharmaceutical Use
Verification:
Start with document review (e.g. schematic drawing of the
system, "water quality manual" if available)
Review change control (in case of changes after qualification
and validation)
On site verification (system in accordance with the drawing)
Start source water supply
Pre-treatment and treatment systems
Water | Slide 6 of 30 January 2006
7. Water for Pharmaceutical Use
Documentation should reflect information on:
Pipeline
Valves (non-return type)
Breather points
Couplings
Pipe slope
Velocities
Sampling points
Drain points
Instrumentation
Flow rates
Water | Slide 7 of 30 January 2006
8. Water for Pharmaceutical Use
Documentation should reflect information on (2):
Specification for each system element
Standard procedures for use
System changes
Routine and non-routine maintenance
Investigations and corrective action
Validation studies
Chemical and microbiological specifications
Sampling instructions
Test procedures
Responsible persons
Training requirements
Water | Slide 8 of 30 January 2006
9. Water for Pharmaceutical Use
On site review and verification:
Walk through the system, verifying the parts of the system
as indicated in the drawing
Review procedures and "on site" records, logs, results
Verify components, sensors, instruments
Inspect the finishing, state, calibration status, labels, pipes,
tanks etc as discussed in previous parts of this module
Start with source water supply – follow whole system "loop"
Water | Slide 9 of 30 January 2006
10. Water for Pharmaceutical Use
Well water
Inspect exposed parts of the well, depth of well
Check for nearby septic systems, hazardous materials
usage (pesticides, fertilizers, etc.)
Well maintenance
Water | Slide 10 of 30 January 2006
11. Water for Pharmaceutical Use
Raw water storage
May be required prior to pre-treatment
Check material of construction
– Concrete, steel are acceptable but check corrosion
– Plastics or plastic linings may leach
Check cover
– To keep out insects, birds and animals
Check disinfection practices
Water | Slide 11 of 30 January 2006
12. Water for Pharmaceutical Use
Water treatment system inspection (1)
Checks may include:
– dead legs
– filters
– pipes and fittings
– Ionic beds
– storage tanks
– by-pass lines
Water | Slide 12 of 30 January 2006
13. Water for Pharmaceutical Use
Water treatment system inspection (2)
Checks may include:
– pumps
– UV lights
– sample points
– reverse osmosis
– valves
– heat exchangers
– Instruments, controls, gauges, etc.
Water | Slide 13 of 30 January 2006
14. Water for Pharmaceutical Use
Other checks (1)
Stainless steel – PVC and most plastics not recommended
Weld quality
Hygienic couplings
Passivation
Air breaks or “Tundish”
Water | Slide 14 of 30 January 2006
15. Water for Pharmaceutical Use
Other checks (2)
Pipes and pumps
– hygienic couplings
– welded pipes
– hygienic pumps
– hygienic
sampling points
– acceptable floor
– no leaks
Water | Slide 15 of 30 January 2006
16. Water for Pharmaceutical Use
Other checks (3)
Check condition of equipment
Staining on
water storage
tanks
Corrosion on plates of heat exchangers
indicates possible contamination
Water | Slide 16 of 30 January 2006
17. Water for Pharmaceutical Use
Other checks (4)
Maintenance records, maintenance of pump seals and O rings
Water | Slide 17 of 30 January 2006
18. Water for Pharmaceutical Use
Other checks (5)
Air filters
Integrity testing, sterilization
and replacement frequency
Check burst discs
Water | Slide 18 of 30 January 2006
19. Water for Pharmaceutical Use
Other checks (6)
Softened water
out to deionizer By-pass lines
By-pass valve
Carefully check by-pass
valves and lines
These sometimes leak or are
inadvertently left open
A blanking piece is better
during operation phase
Zeolite water softener
exchanges Ca and Mg for Na
Water | Slide 19 of 30 January 2006
20. Water for Pharmaceutical Use
Other checks (7)
Activated carbon bed sanitization
Temperature-compensated conductivity meters
Influence of plastic pipe adhesive on TOC
Non-condensable gases in pure steam
Water | Slide 20 of 30 January 2006
21. Water for Pharmaceutical Use
Other checks (8)
Polypropylene welding inspection
– checking pin holes
Retrospective validation of WFI system
Rouging of WFI storage systems
Spray ball efficacy
Water | Slide 21 of 30 January 2006
22. Water for Pharmaceutical Use
Other checks (9)
UV light – monitoring performance and lamp life and
intensity
Validating ozone dosage
Specifications for acids, alkalis for DI and sodium chloride
for water softener
“Normally open” and “normally closed” valves
Water | Slide 22 of 30 January 2006
23. Water for Pharmaceutical Use
Then review additional documentation
Qualification protocols and reports
Change control request (where applicable)
Requalification (where applicable)
QC and microbiology laboratory:
SOP for sampling
Procedures and records
Water | Slide 23 of 30 January 2006
24. Water for Pharmaceutical Use
Sampling (1)
There must be a sampling procedure
Sample integrity must be assured
Sampler training
Sample point
Sample size
Water | Slide 24 of 30 January 2006
25. Water for Pharmaceutical Use
Sampling (2)
Sample container
Sample label
Sample transport and storage
Arrival at the laboratory
Test method
When is the test started?
Water | Slide 25 of 30 January 2006
26. Water for Pharmaceutical Use
Testing
Review method verification
Chemical testing
Microbiological testing
– test method
– types of media used
– incubation time and temperature
– objectionable and indicator organisms
– manufacturer must set specifications
Water | Slide 26 of 30 January 2006
27. Water for Pharmaceutical Use
Suggested bacterial limits (CFU /mL)
Sampling location Target Alert Action
Raw water 200 300 500
Post multimedia filter 100 300 500
Post softener 100 300 500
Post activated carbon filter 50 300 500
Feed to RO 20 200 500
RO permeate 10 50 100
Points of Use 1 10 100
Water | Slide 27 of 30 January 2006
28. Water for Pharmaceutical Use
Pyrogens and endotoxins
Any compound injected into mammals which gives rise to fever is
a “Pyrogen”
Endotoxins are pyrogenic, come from Gram negative bacterial
cell wall fragments
Detect endotoxins using a test for lipopolysaccharides (LPS)
– rabbit test detects pyrogens
– LAL test detects endotoxins
Ultrafiltration, distillation and RO may remove pyrogens
Water | Slide 28 of 30 January 2006
29. Water for Pharmaceutical Use
Group Session
You are given a schematic drawing of a water system to discuss. List any
problems and their solutions
IN C O R R E C T W A T E R T R E A T M E N T PL A N T
Water | Slide 29 of 30 January 2006
30. Water for Pharmaceutical Use
Group Session
M O D IFIE D W A T E R T R E A T M E N T PL A N T
Water | Slide 30 of 30 January 2006
Editor's Notes
दिसंबर 4, 2012
दिसंबर 4, 2012
दिसंबर 4, 2012 8 . Inspection of water systems WPU (PW, HPW and WFI) systems are likely to be the subject of regulatory inspection from time to time. Users should consider conducting routine audit and self-inspection of established water systems . This GMP guidance can be used as the basis of inspection. The following list identi.es items and a logical sequence for a WPU system inspection or audit : — a sampling and monitoring plan with a drawing of all sample points ; — the setting of monitoring alert and action levels ; — monitoring results and evaluation of trends ; — inspection of the last annual system review ; — review of any changes made to the system since the last audit and check that the change control has been implemented ; — review of deviations recorded and their investigation ; — general inspection of system for status and condition ; — review of maintenance, failure and repair logs; and — checking calibration and standardization of critical instruments . For an established system that is demonstrably under control, this scope of review should prove adequate. For new systems, or systems that display instability or unreliability, the following should also be reviewed : — performance quali.cation ; — operational quali.cation; and — installation quali.cation .
दिसंबर 4, 2012
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दिसंबर 4, 2012 Well water: Some pharmaceutical manufacturers need to draw water from wells or bore holes. Some manufacturers feel they have better control of water from their own wells than from a municipal source. The aquifer that the well taps into may be contaminated, or the construction materials of the well could contribute to contamination. The exposed parts of the well should be inspected periodically for cracked, corroded, or damaged casing , broken or missing well caps , and settling and cracking of surface seals . The depth of the well should also be determined – the shallower the well the greater is the chance of contamination from surface contaminants. Check: The use of nearby septic systems (which could contribute coliforms or faecal bacteria). If there are hazardous materials used nearby. Sometimes these are disposed of in nearby septic system s . Hazardous materials include: Pesticides – farmers in areas near the well could use pesticides, which can permeate through the aquifer. Fertilizers , such as nitrates and phosphates, can be troublesome to remove and can encourage the proliferation of micro-organisms, especially algae if there is any light available. Herbicides – organophosphates can enter the aquifer. F uels , such as diesel and petrol spills can also be problematic. Testing records to show water is “potable”. Records of well maintenance. The manufacturer must have procedures such as disinfection procedures or sediment removal , together with the use of any chemicals in the well . Chemicals that can leach include the oils used to lubricate the pumps.
दिसंबर 4, 2012 Large scale storage: Raw water storage may be required according to local circumstances, such as intermittent water supplies. Storage can be typically in cisterns or reservoirs made of concrete or tanks made of steel. Sometimes plastic or rubber bladders are used but these can cause significant problems with leachates and odours. Check the material of construction: - Concrete and steel are acceptable, but check corrosion; - Plastics or plastic linings may leach plastizisers such as phthalates. The storage must have adequate cover to keep out insects, birds and animals. However, an air filter is not usually necessary. The quality of the raw water in this type of storage needs to be periodically checked and a physical inspection carried out. Disinfection of the water is required. This is usually with chlorine at concentrations of 1 – 2 ppm. The chlorine levels need to be checked periodically. The storage tanks should be covered because the chlorine may have a life of only a few hours, and algal blooms may be encouraged if water is exposed to sunlight. UV lights suspended in these tanks are not effective bactericides. Periodically the tank should be emptied and cleaned.
दिसंबर 4, 2012
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दिसंबर 4, 2012 Inspection: (Contd.) Check pipes and pumps. The photograph shows a good example of a neatly laid-out water treatment room with good equipment and pipes. There are hygienic couplings (Ladish® or Tri-Clover ® clamps), welded pipes and hygienic pumps. Note also hygienic sampling points.
दिसंबर 4, 2012 Inspection: (Contd.) Assess physical condition of equipment. Look for stains and leaks that could indicate problems. Check to make sure heat exchangers are double tube or double shell. If not, there should be continuous pressure monitoring to ensure the heating or cooling liquid does not contaminate the pure water through any pinholes. For single plate heat exchangers, the pressure of the heating or cooling liquid must be LOWER than the purified water at all times. An exception may be where the liquid is of a higher purity than the water being produced. Note from the heat exchanger example above that even high grade stainless steel, such as 318SS, can be subject to pit corrosion!
दिसंबर 4, 2012 Inspection: (Contd.) Check maintenance of the entire system by examining the maintenance procedure and records. For example, check the “O” rings of connections and the maintenance of the pump seals. The pump on the left shows good connections and a good standard of engineering. The one on the right shows a threaded coupling, called a milk coupling or sanitary coupling . Threaded couplings and couplings in general should be avoided whenever possible. Where welding is impossible, hygienic couplings should be used or milk (sanitary) coupling, which are acceptable since the threaded fitting is not part of the fluid pathway, and so should not contaminate the water. The inspector must be satisfied that hidden seals and “O” rings have actually been removed, examined and/or replaced during maintenance.
दिसंबर 4, 2012 Inspection: (Contd.) Check air filters which should be hydrophobic (otherwise, they can be blocked by a film of water condensate) and should be able to be sanitized. Those on WFI plants should be be able to be sterilized and integrity-tested. Check replacement frequency, which the pharmaceutical manufacturer should determine with assistance from the filter supplier. Check burst discs because if they have ruptured without being noted the storage system can become contaminated.
दिसंबर 4, 2012 Inspection: (Contd.) By-pass valves and by-pass lines are often used for maintenance procedures. In critical situations there may be, for example, two pumps in parallel, in case one breaks down. Additionally, engineers like to be able to replace a pump or a filter without dismantling large sections of the system. However, valves in by-pass lines can leak, be left open, or be contaminated, and so they are undesirable. A “blanking” piece is often better during operation of the system, so that there is no physical connection.
दिसंबर 4, 2012 Inspection: ( Contd.) Further points to check: Activated carbon bed sanitization – these can become overgrown with bacteria quite quickly. Check sanitization frequency to ensure the AC remains uncontaminated. Calibration of temperature-compensated conductivity meters is often overlooked or not done properly. Influence of plastic pipe adhesive on Total Organic Carbon (TOC) compliance - some adhesives will leach into the water and these can be volatile. Non-condensable gases in pure steam – for example nitrogen and oxygen. They affect the apparent pressure of sterilization processes, lowering their effectiveness.
दिसंबर 4, 2012 Inspection: (Contd.) Further points to check: Polypropylene welding inspection. If polypropylene pipe is used and welded, has the manufacturer checked for pin holes? Retrospective validation of WFI system. Many water plants are 10 – 20 years old and may not have been properly validated. Can they be properly retrospectively validated? Rouging of WFI Systems. The high temperatures of these storage and distribution systems seem to lead to a build up of a deposit known as rouge . Check to see if the manufacturer carries out a periodic physical check for this effect, and what steps are taken to remove the rouge. Sometimes re-passivation is effective. Spray ball efficacy. This is not easy to determine and must be assessable. If the spray ball is jammed it will not work properly, but because it cannot be seen it is not easy to check. There are non-rotating or fixed spray balls or spray cones which may be better in small systems.
दिसंबर 4, 2012 Inspection: (Contd.) Further points to check: UV light – monitoring performance and lamp life. The lethal radiant energy from UV lights drops off quickly, so many have to be replaced approximately every 6 months. Does the manufacturer have an hour meter and is the lamp replaced according to the supplier’s recommendations? Can the intensity of the light be measured? Validating ozone dosage is difficult. It may be possible for the manufacturer to get the supplier’s validation studies showing worst case lethal effects. Water softener sodium chloride specifications. Like any ancillary material, the salt, acids and alkalis used as consumables in water treatment plant should have purchase specifications. Note: testing is not required unless for trouble shooting purposes. Check the drawings to see if valves are marked as “Normally Open” or “Normally Closed”, then physically check the valve position. It is surprising sometimes that valves are not returned to the correct operating position; for example, after de-ionizer regeneration.
दिसंबर 4, 2012
दिसंबर 4, 2012 Sampling: There must be a sampling procedure. The sample integrity must be assured. The sample received in the laboratory must reflect the bulk water’s physical, chemical, and biological quality. Because of water’s solvent properties and the nature of micro-organisms, this can change very quickly. For example, the microbe population in ideal circumstances can double or triple every hour. Microbes can grow at very low temperatures and in extremely low nutrient levels. Even distilled water may have enough nutrients to support organisms such as some of the pseudomonas species. The persons who take the sample should also have training on aseptic handling practices, to ensure that they do not contaminate the sample while it is being taken. The sample point should be hygienic and the practice of flushing it, or not, should follow manufacturing practice. Sample points for subsystems, such as de-ionizers and RO’s, should be as close to the downstream side as possible in order to reflect the quality of the water being fed to the next subsystem. All water outlets in the factory should also be checked periodically. This should be done unannounced, if possible, so that water can be sampled through any attachments to the outlet, such as hoses or pumps. Sample sizes of at least 100 – 500mL are required; samples of 1 or 2 mL are unacceptable.
दिसंबर 4, 2012 Sampling: (Contd.) The sample container should be sterile, inert, and able to be securely closed. Plastic containers that are re-sterilized sometimes distort in the autoclave, so that the quality of recycled containers should be carefully checked. Some plastics may leach and thus affect tests such as the TOC test. Single-use, sterile, inert plastic bags are available. However, these could prove too expensive for some manufacturers to consider. The container must be properly labeled. The label should have the date, time and location sampled as well as the sampler’s name or initials. It must be attached firmly to the container. Felt tip permanent markers are satisfactory but may leach solvent if used on plastics, and may thus affect the TOC test. It is important for the label to be properly removed should the container be recycled. Unless tested within a few hours, the sample should be chilled to less than 8 o C, but not frozen. Samples from heated water systems should be rapidly cooled. If a sample is to be transported to a remote laboratory, refrigerated packing must be allowed for to ensure that the sample stays cool. Inclusion of a temperature data logger is good practice. On arrival at the laboratory the condition and temperature of the sample should be noted, as this may be important if an out of specification result needs to be investigated. It is good practice to have a sample registration and tracking system. The laboratory should record the time at which microbial testing started.
दिसंबर 4, 2012 Testing: Method Verification - The methods must be validated or verified in the laboratory, even if they are pharmacopoeial methods. Chemical testing - Chemical testing follows normal laboratory practices. However, TOC requires sophisticated, expensive equipment and trained technicians, which may put it beyond the reach of some manufacturers. Microbiological testing - It is important that microbiological testing be conducted in a well-equipped laboratory with adequate resources. Method : The common methods for microbial total count are Most Probable Number Test (not reliable for low numbers), Spread or Pour Plate (can only test only 1 or 10mL respectively; not reliable for low counts) or membrane filtration, which is preferred. Media : There are various types of test media that can be used. Incubation time and temperature : Preferably 32 o C or lower (higher temperatures than this inhibit aquatic microflora) and up to 5 days (sub-lethally damaged organisms may not revive quickly). Objectionable and indicator organisms: Any organism which can grow in the final product, or can cause physical and chemical changes to the product, or is pathogenic, is unacceptable in purified water. Indicator organisms, such as Escherichia coli or coliforms, point to faecal contamination. They “indicate” possible contamination by other pathogenic organisms. The manufacturer must set specifications for total count and absence of objectionable and indicator organisms. The USP recommends a limit of 100 total aerobic microbial colony-forming units (CFU) per mL for purified water.
दिसंबर 4, 2012 Sampling locations and limits for microbiological testing: The limits are not from any official literature and are thus intended merely as a guide. The table is a suggested list of sampling locations and limits (for total aerobic microbial plate count). Note that in some countries, the “Action” required if out of specification results are detected may well include recall of therapeutic goods even if they meet finished goods specification. This is because the water treatment system is seen to be out of control. Prudent manufacturers should react promptly to “alert” limits so that the system remains in control. CFU = colony forming units
दिसंबर 4, 2012 Pyrogens and endotoxins: Any compound giving rise to fever when injected into mammals is a “Pyrogen”. Even sterile water can be pyrogenic. Endotoxins are pyrogenic, and they come from Gram negative bacterial cell wall fragments. Esc h erichia coli appears to be the main culprit. Endotoxins are highly toxic to mammalian cells and are one of the most potent modulators of the immune system. If injected into mammals they cause fever. Endotoxins can be detected using a test for lipopolysaccharides . The Rabbit test detects pyrogens, and the LAL test detects endotoxins. Ultra-filtration, distillation, and RO may remove pyrogens.
दिसंबर 4, 2012 In this group session, you are given a schematic of a water system ( See handout 2-3-24) . Discuss the drawing and list any problems and their solutions. (Note to trainer: The following handout 2-3-25, giving correct answers, should not be distributed until after discussion.)
दिसंबर 4, 2012 This slide indicates the modified water schematic. (See handout 2-3-25.)