Learning from issues in assay cross-validation / method transfersPeter van Amsterdam
Examples of successful and failed method transfers from the innovator lab to a CRO plus reflections on factors which may or may not be of importance when off-shoring methods.
This document discusses a proficiency testing program for laboratories that analyze used oil. The program sends quarterly samples of real used oils to participating laboratories to test for various parameters like metals, sulfur, and flash point. It evaluates the laboratories' results using z-scores to identify any outliers or potential errors. Nearly 50 U.S. and international laboratories have participated over 6 rounds. The results show better agreement for bulk properties like heating value than for minor constituents like metals, and accurately measuring arsenic at low levels is difficult. The program aims to assess laboratory performance and compliance with regulations for used oil analysis.
All for one, one for all - The Chinese BMV guidance in perspective to other g...Peter van Amsterdam
The presentation discusses the evolution and harmonization of bioanalytical method validation guidance documents from various regulatory agencies around the world. It finds that the EMA, MHLW, and CFDA guidelines are very similar in structure and content, and can be considered the "Eurasian standard" for bioanalytical method validation. Several other regions reference or are aligned with this standard. While guidelines from regions like the Americas have some additional local requirements, the overall principles are essentially the same. The presentation concludes that further harmonization on detailed requirements may not be necessary if new or revised guidelines follow the main principles of the "Eurasian standard".
1) The document describes the development of a fully automated purification platform using preparative liquid chromatography/mass spectrometry (LC/MS) to streamline the process of purifying crude synthetic compounds from receipt to biochemical screening.
2) The platform includes six integrated workstations controlled by a central program to automatically dissolve, analyze, purify, collect fractions, weigh, and distribute compounds for assay and quality control.
3) The program was designed to minimize errors, automatically select purification methods, generate purification sequences, and track samples and data from start to finish to decrease the time required to get compounds into screening.
Thad Yousey has over 12 years of experience developing and validating assays for clinical studies in the pharmaceutical industry. He has worked at Quintiles, Bristol-Meyers Squibb, and Prevalere developing methods for analyte extraction and detection using LC/MS/MS and other techniques. His responsibilities included optimizing extraction methods, mass spectrometry parameters, and chromatography to support drug discovery, clinical trials, and FDA submissions. He is proficient in various software and instrumentation used in bioanalytical method development and validation.
The document summarizes the results of testing to identify extractables and leachables from a nylon syringe filter. Multiple analytical techniques were used, identifying several oligomers of nylon 6 in leachables and additional compounds like methyl esters, glycerol esters, and alkanes in exhaustive extracts. The major polymer antioxidant Irgafos 168 was also detected.
This document provides guidance on developing and optimizing a regulated bioanalytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). It discusses important considerations for method development including choosing a detection technique, optimizing sample extraction and chromatography conditions, and validating the final method. The goal is to develop a selective, sensitive and reproducible method for quantifying biological samples in a regulated setting.
Learning from issues in assay cross-validation / method transfersPeter van Amsterdam
Examples of successful and failed method transfers from the innovator lab to a CRO plus reflections on factors which may or may not be of importance when off-shoring methods.
This document discusses a proficiency testing program for laboratories that analyze used oil. The program sends quarterly samples of real used oils to participating laboratories to test for various parameters like metals, sulfur, and flash point. It evaluates the laboratories' results using z-scores to identify any outliers or potential errors. Nearly 50 U.S. and international laboratories have participated over 6 rounds. The results show better agreement for bulk properties like heating value than for minor constituents like metals, and accurately measuring arsenic at low levels is difficult. The program aims to assess laboratory performance and compliance with regulations for used oil analysis.
All for one, one for all - The Chinese BMV guidance in perspective to other g...Peter van Amsterdam
The presentation discusses the evolution and harmonization of bioanalytical method validation guidance documents from various regulatory agencies around the world. It finds that the EMA, MHLW, and CFDA guidelines are very similar in structure and content, and can be considered the "Eurasian standard" for bioanalytical method validation. Several other regions reference or are aligned with this standard. While guidelines from regions like the Americas have some additional local requirements, the overall principles are essentially the same. The presentation concludes that further harmonization on detailed requirements may not be necessary if new or revised guidelines follow the main principles of the "Eurasian standard".
1) The document describes the development of a fully automated purification platform using preparative liquid chromatography/mass spectrometry (LC/MS) to streamline the process of purifying crude synthetic compounds from receipt to biochemical screening.
2) The platform includes six integrated workstations controlled by a central program to automatically dissolve, analyze, purify, collect fractions, weigh, and distribute compounds for assay and quality control.
3) The program was designed to minimize errors, automatically select purification methods, generate purification sequences, and track samples and data from start to finish to decrease the time required to get compounds into screening.
Thad Yousey has over 12 years of experience developing and validating assays for clinical studies in the pharmaceutical industry. He has worked at Quintiles, Bristol-Meyers Squibb, and Prevalere developing methods for analyte extraction and detection using LC/MS/MS and other techniques. His responsibilities included optimizing extraction methods, mass spectrometry parameters, and chromatography to support drug discovery, clinical trials, and FDA submissions. He is proficient in various software and instrumentation used in bioanalytical method development and validation.
The document summarizes the results of testing to identify extractables and leachables from a nylon syringe filter. Multiple analytical techniques were used, identifying several oligomers of nylon 6 in leachables and additional compounds like methyl esters, glycerol esters, and alkanes in exhaustive extracts. The major polymer antioxidant Irgafos 168 was also detected.
This document provides guidance on developing and optimizing a regulated bioanalytical method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). It discusses important considerations for method development including choosing a detection technique, optimizing sample extraction and chromatography conditions, and validating the final method. The goal is to develop a selective, sensitive and reproducible method for quantifying biological samples in a regulated setting.
The document discusses reference standards which are substances used to ensure the identity, strength, quality and purity of medicines. Reference standards are obtained from organizations like USP and used to support various measurements in chemical, biological, clinical and physical areas. The document outlines the process of preparation, characterization, storage and utilization of reference standards. It provides guidelines on properties like purity, stability and intended use of reference standards.
HPLC Method Development & Method Validation (mr.s)22suresh
This document describes the development and validation of an HPLC method for estimating drugs. It discusses the principles of HPLC, steps in method development including selecting the method, column, mobile phase and detector. Method validation parameters like accuracy, precision, specificity, linearity and robustness are also summarized. The document provides details on the optimization process and validation procedures to ensure the method is suitable for its intended use.
Understanding Bioanalytical Method Validation in a Regulatory PerspectiveDr. Ishaq B Mohammed
The document provides an overview of bioanalytical method development and validation. It discusses key aspects of the process including sample preparation techniques, calibration curves and quality control standards, method validation parameters such as selectivity, specificity, carryover, precision and accuracy, and acceptance criteria. The goal of bioanalytical method validation is to demonstrate that the analytical method is reliable and reproducible for its intended use in quantitatively measuring analytes in a biological matrix.
Diteba is a cGMP/GLP pharmaceutical laboratory located near Toronto, Canada that offers analytical R&D services including method development and validation, bioanalytical testing, quality control release testing, stability testing, and in vitro release testing. The company has over 10,000 square feet of laboratory space equipped with state-of-the-art instrumentation. Diteba's team of senior scientists have extensive experience across various therapeutic areas and analytical techniques.
This document describes the development and validation of an RP-HPLC method for the quantification of verapamil in drug substances and products. It involves selecting the optimal chromatographic conditions, such as the column, mobile phase, flow rate, and developing the method according to ICH guidelines. The method development steps include selecting the HPLC method and conditions, optimizing the selectivity and system parameters, and validating the method parameters like accuracy, precision, specificity, linearity and range. The goal is to develop a simple, accurate and precise RP-HPLC method for the analysis of verapamil that can be validated as per regulatory requirements.
Analytical method development and validation for simultaneous estimationProfessor Beubenz
The document discusses analytical method development and validation for the simultaneous estimation of active pharmaceutical ingredients (APIs). It covers topics such as the need for method development, the steps involved, parameters for validation as outlined in ICH guidelines, and the use of high performance liquid chromatography (HPLC). The key objectives of validation are to demonstrate that the developed method is suitable for its intended purpose and can reliably quantify the APIs.
Development and Validation of a RP-HPLC methodUshaKhanal3
The document describes the process of developing and validating a reverse phase high performance liquid chromatography (RP-HPLC) method. It involves determining method goals and analysis requirements based on the sample properties, conducting research on existing methods, selecting an analysis technique, optimizing the separation conditions through a systematic approach, and validating the method. Key steps include choosing the detector and mobile phase, optimizing variables like column type, temperature, flow rate and solvent composition to improve resolution and separation time, and testing the method's accuracy, precision, specificity and robustness.
This document presents information on HPLC method development and validation. It begins with an introduction to analytical chemistry and chromatography. It then discusses the principles, types, and modes of HPLC, as well as factors to consider in method development such as column selection and mobile phase selection. The document concludes with a discussion of method validation parameters such as system suitability, specificity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness. References on the topic are also provided.
The document discusses Good Laboratory Practices (GLP), which are standards that provide a framework for conducting and reporting laboratory studies. It notes that GLP was developed in response to cases of fraud and poor practices found by the FDA in the 1970s. Key aspects of GLP include standardized operating procedures, trained personnel, appropriate facilities and equipment, meticulous record-keeping, and reporting of study results. GLP is intended to ensure reliability and integrity of nonclinical safety data submitted to regulatory authorities.
The document discusses the development of monographs for the Indian Pharmacopoeia. It outlines the Indian Pharmacopoeia Commission's vision of promoting high drug quality standards for medicines used in India. It describes the objectives in creating monographs that reflect India's pharmaceutical industry capabilities while safeguarding smaller manufacturers. The document provides guidance on the formats, contents and quality standards considered for monographs in different categories like active pharmaceutical ingredients, excipients, dosage forms and other drug products.
The presence of Per- and Polyfluorinated Alkyl Substances (PFAS) in drinking water is being thoroughly studied due to the persistence of these compounds in the environment and their potential health effects. However, there is limited knowledge about the occurrence of these chemicals in bottled water, despite the increasing concerns about PFAS in the food supply. This poster shows results from a fast and simple direct injection method similar to draft EPA method 8237, using the Shimadzu triple quad LCMS-8050 to analyze seven commercially available samples of bottled water for 24 PFAS.
The document provides guidance on developing an analytical method for determining assay and related substances in new drug formulations using HPLC-UV. It outlines the key steps, including selecting the detector and chromatographic conditions based on the drug's properties; forced degradation studies to identify degradation products; method validation including linearity, accuracy and comparison to pharmacopeial methods; and establishing system suitability criteria and finalizing the method. The goal is to develop a robust stability-indicating method for routine quality control testing according to ICH guidelines.
The third inter-laboratory analytical quality control exercise was conducted for surface water laboratories in India. 35 laboratories participated by analyzing standard samples for 9 parameters. The performance of laboratories varied widely across parameters. Only 16 laboratories reported results for all 9 parameters. 4 laboratories could not analyze any parameter accurately. The highest performance was for conductivity and sodium analysis while the lowest was for boron. Systematic errors affected results more than random errors for most laboratories and parameters as indicated by result clusters in specific quadrants of Youden plots. Overall, the exercise revealed opportunities to improve accuracy for many laboratories and parameters.
Good Laboratory Practices Mubashir MaqboolMUBASHIR WANI
GLP (Good Laboratory Practice) is a quality system for managing non-clinical laboratory studies to ensure reliability and integrity of test data. It outlines requirements for facility organization, personnel responsibilities, quality assurance programs, standard operating procedures, and retention of records and reports. GLP aims to ensure studies are well-designed, conducted and documented according to all principles to allow for traceability and reproducibility of results.
Basic skills training guide hplc method development and validation- an over...bmarkandeya
This document provides an overview of HPLC method development and validation. It focuses on optimizing HPLC conditions and discusses various critical steps in analytical method development and validation. These include developing a stability-indicating HPLC method to analyze degradation products during stability studies and validating the method to demonstrate its suitability for intended use. Key aspects of method development and validation covered are sample preparation, HPLC analysis, standardization, and quantitative measures of column efficiency.
Guidelines for Preparing Laboratory Information FileMD. SELIM REZA
This document provides guidelines for preparing a Laboratory Information File (LIF) to describe the operations of pharmaceutical quality control laboratories. The LIF should include 13 sections that describe: general laboratory information; quality management systems; documentation control; personnel; premises; equipment; materials; subcontracting; sample handling; validation; out-of-specification investigations; stability testing; and microbiological testing, if applicable. The LIF is intended to be a concise yet comprehensive reference of approximately 30 pages that outlines all relevant aspects of the laboratory's quality system and operations.
High performance liquid chromatography (HPLC) is a technique used to separate compounds in a liquid mixture. An HPLC system consists of a solvent reservoir, pump, injector, separation column, and detector. The mixture is injected and the components separate as they pass through the column at different rates depending on how they partition between the mobile and stationary phases. HPLC is used for research, quality control, and regulatory purposes to separate, analyze, purify, and quantify complex mixtures like drugs, metabolites, polymers, proteins, lipids, and environmental pollutants.
This poster describes analytical operating conditions for analysis of US EPA Method 8260C1, Revision 3, August 2006, and includes BFB tune parameters, calibration details, and a complete MDL and Precision and Accuracy study for almost 100 target compounds at multiple concentrations.
Nilesh Dashrath Kamble presented a seminar on method development and validation in HPLC. The presentation discussed the steps involved in HPLC method development including column selection, mobile phase composition, pH range selection, and optimization of separation conditions. It also covered validation parameters such as accuracy, precision, specificity, limit of detection, and limit of quantification as per ICH guidelines. The presentation included an example method development for the simultaneous estimation of atorvastatin and telmisartan from a tablet formulation.
Multiple Federal and State Agencies (e.g. EPA, DOD, DEQs and DEPs) in the United States as well as international organizations (e.g. ASTM) are quickly publishing new analytical methodologies for PFAS monitoring and establishing more stringent limits. Liquid Chromatography with Mass Spectrometry-based detection is established as the most suitable technology for meeting the requirements from official methods released up to date for monitoring PFAS. A comparison of instruments’ performance was conducted in this work.
This document provides a summary of the content areas and competencies tested on the Medical Laboratory Technician (MLT) certification examination. It is organized into six main sections: Blood Bank, Chemistry, Hematology, Microbiology, Urinalysis/Other Body Fluids, and Laboratory Operations. Each section lists the specific topics covered, such as blood typing and crossmatching in Blood Bank or electrolyte and protein testing in Chemistry. Competencies involve technical skills like performing laboratory tests, problem solving abnormal results, verifying quality control, and communicating with clinicians. The examination evaluates knowledge, interpretation, and problem-solving skills through multiple choice questions.
The document discusses reference standards which are substances used to ensure the identity, strength, quality and purity of medicines. Reference standards are obtained from organizations like USP and used to support various measurements in chemical, biological, clinical and physical areas. The document outlines the process of preparation, characterization, storage and utilization of reference standards. It provides guidelines on properties like purity, stability and intended use of reference standards.
HPLC Method Development & Method Validation (mr.s)22suresh
This document describes the development and validation of an HPLC method for estimating drugs. It discusses the principles of HPLC, steps in method development including selecting the method, column, mobile phase and detector. Method validation parameters like accuracy, precision, specificity, linearity and robustness are also summarized. The document provides details on the optimization process and validation procedures to ensure the method is suitable for its intended use.
Understanding Bioanalytical Method Validation in a Regulatory PerspectiveDr. Ishaq B Mohammed
The document provides an overview of bioanalytical method development and validation. It discusses key aspects of the process including sample preparation techniques, calibration curves and quality control standards, method validation parameters such as selectivity, specificity, carryover, precision and accuracy, and acceptance criteria. The goal of bioanalytical method validation is to demonstrate that the analytical method is reliable and reproducible for its intended use in quantitatively measuring analytes in a biological matrix.
Diteba is a cGMP/GLP pharmaceutical laboratory located near Toronto, Canada that offers analytical R&D services including method development and validation, bioanalytical testing, quality control release testing, stability testing, and in vitro release testing. The company has over 10,000 square feet of laboratory space equipped with state-of-the-art instrumentation. Diteba's team of senior scientists have extensive experience across various therapeutic areas and analytical techniques.
This document describes the development and validation of an RP-HPLC method for the quantification of verapamil in drug substances and products. It involves selecting the optimal chromatographic conditions, such as the column, mobile phase, flow rate, and developing the method according to ICH guidelines. The method development steps include selecting the HPLC method and conditions, optimizing the selectivity and system parameters, and validating the method parameters like accuracy, precision, specificity, linearity and range. The goal is to develop a simple, accurate and precise RP-HPLC method for the analysis of verapamil that can be validated as per regulatory requirements.
Analytical method development and validation for simultaneous estimationProfessor Beubenz
The document discusses analytical method development and validation for the simultaneous estimation of active pharmaceutical ingredients (APIs). It covers topics such as the need for method development, the steps involved, parameters for validation as outlined in ICH guidelines, and the use of high performance liquid chromatography (HPLC). The key objectives of validation are to demonstrate that the developed method is suitable for its intended purpose and can reliably quantify the APIs.
Development and Validation of a RP-HPLC methodUshaKhanal3
The document describes the process of developing and validating a reverse phase high performance liquid chromatography (RP-HPLC) method. It involves determining method goals and analysis requirements based on the sample properties, conducting research on existing methods, selecting an analysis technique, optimizing the separation conditions through a systematic approach, and validating the method. Key steps include choosing the detector and mobile phase, optimizing variables like column type, temperature, flow rate and solvent composition to improve resolution and separation time, and testing the method's accuracy, precision, specificity and robustness.
This document presents information on HPLC method development and validation. It begins with an introduction to analytical chemistry and chromatography. It then discusses the principles, types, and modes of HPLC, as well as factors to consider in method development such as column selection and mobile phase selection. The document concludes with a discussion of method validation parameters such as system suitability, specificity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness. References on the topic are also provided.
The document discusses Good Laboratory Practices (GLP), which are standards that provide a framework for conducting and reporting laboratory studies. It notes that GLP was developed in response to cases of fraud and poor practices found by the FDA in the 1970s. Key aspects of GLP include standardized operating procedures, trained personnel, appropriate facilities and equipment, meticulous record-keeping, and reporting of study results. GLP is intended to ensure reliability and integrity of nonclinical safety data submitted to regulatory authorities.
The document discusses the development of monographs for the Indian Pharmacopoeia. It outlines the Indian Pharmacopoeia Commission's vision of promoting high drug quality standards for medicines used in India. It describes the objectives in creating monographs that reflect India's pharmaceutical industry capabilities while safeguarding smaller manufacturers. The document provides guidance on the formats, contents and quality standards considered for monographs in different categories like active pharmaceutical ingredients, excipients, dosage forms and other drug products.
The presence of Per- and Polyfluorinated Alkyl Substances (PFAS) in drinking water is being thoroughly studied due to the persistence of these compounds in the environment and their potential health effects. However, there is limited knowledge about the occurrence of these chemicals in bottled water, despite the increasing concerns about PFAS in the food supply. This poster shows results from a fast and simple direct injection method similar to draft EPA method 8237, using the Shimadzu triple quad LCMS-8050 to analyze seven commercially available samples of bottled water for 24 PFAS.
The document provides guidance on developing an analytical method for determining assay and related substances in new drug formulations using HPLC-UV. It outlines the key steps, including selecting the detector and chromatographic conditions based on the drug's properties; forced degradation studies to identify degradation products; method validation including linearity, accuracy and comparison to pharmacopeial methods; and establishing system suitability criteria and finalizing the method. The goal is to develop a robust stability-indicating method for routine quality control testing according to ICH guidelines.
The third inter-laboratory analytical quality control exercise was conducted for surface water laboratories in India. 35 laboratories participated by analyzing standard samples for 9 parameters. The performance of laboratories varied widely across parameters. Only 16 laboratories reported results for all 9 parameters. 4 laboratories could not analyze any parameter accurately. The highest performance was for conductivity and sodium analysis while the lowest was for boron. Systematic errors affected results more than random errors for most laboratories and parameters as indicated by result clusters in specific quadrants of Youden plots. Overall, the exercise revealed opportunities to improve accuracy for many laboratories and parameters.
Good Laboratory Practices Mubashir MaqboolMUBASHIR WANI
GLP (Good Laboratory Practice) is a quality system for managing non-clinical laboratory studies to ensure reliability and integrity of test data. It outlines requirements for facility organization, personnel responsibilities, quality assurance programs, standard operating procedures, and retention of records and reports. GLP aims to ensure studies are well-designed, conducted and documented according to all principles to allow for traceability and reproducibility of results.
Basic skills training guide hplc method development and validation- an over...bmarkandeya
This document provides an overview of HPLC method development and validation. It focuses on optimizing HPLC conditions and discusses various critical steps in analytical method development and validation. These include developing a stability-indicating HPLC method to analyze degradation products during stability studies and validating the method to demonstrate its suitability for intended use. Key aspects of method development and validation covered are sample preparation, HPLC analysis, standardization, and quantitative measures of column efficiency.
Guidelines for Preparing Laboratory Information FileMD. SELIM REZA
This document provides guidelines for preparing a Laboratory Information File (LIF) to describe the operations of pharmaceutical quality control laboratories. The LIF should include 13 sections that describe: general laboratory information; quality management systems; documentation control; personnel; premises; equipment; materials; subcontracting; sample handling; validation; out-of-specification investigations; stability testing; and microbiological testing, if applicable. The LIF is intended to be a concise yet comprehensive reference of approximately 30 pages that outlines all relevant aspects of the laboratory's quality system and operations.
High performance liquid chromatography (HPLC) is a technique used to separate compounds in a liquid mixture. An HPLC system consists of a solvent reservoir, pump, injector, separation column, and detector. The mixture is injected and the components separate as they pass through the column at different rates depending on how they partition between the mobile and stationary phases. HPLC is used for research, quality control, and regulatory purposes to separate, analyze, purify, and quantify complex mixtures like drugs, metabolites, polymers, proteins, lipids, and environmental pollutants.
This poster describes analytical operating conditions for analysis of US EPA Method 8260C1, Revision 3, August 2006, and includes BFB tune parameters, calibration details, and a complete MDL and Precision and Accuracy study for almost 100 target compounds at multiple concentrations.
Nilesh Dashrath Kamble presented a seminar on method development and validation in HPLC. The presentation discussed the steps involved in HPLC method development including column selection, mobile phase composition, pH range selection, and optimization of separation conditions. It also covered validation parameters such as accuracy, precision, specificity, limit of detection, and limit of quantification as per ICH guidelines. The presentation included an example method development for the simultaneous estimation of atorvastatin and telmisartan from a tablet formulation.
Multiple Federal and State Agencies (e.g. EPA, DOD, DEQs and DEPs) in the United States as well as international organizations (e.g. ASTM) are quickly publishing new analytical methodologies for PFAS monitoring and establishing more stringent limits. Liquid Chromatography with Mass Spectrometry-based detection is established as the most suitable technology for meeting the requirements from official methods released up to date for monitoring PFAS. A comparison of instruments’ performance was conducted in this work.
This document provides a summary of the content areas and competencies tested on the Medical Laboratory Technician (MLT) certification examination. It is organized into six main sections: Blood Bank, Chemistry, Hematology, Microbiology, Urinalysis/Other Body Fluids, and Laboratory Operations. Each section lists the specific topics covered, such as blood typing and crossmatching in Blood Bank or electrolyte and protein testing in Chemistry. Competencies involve technical skills like performing laboratory tests, problem solving abnormal results, verifying quality control, and communicating with clinicians. The examination evaluates knowledge, interpretation, and problem-solving skills through multiple choice questions.
Countries’ presentation on internal quality control: China 1ExternalEvents
The second lab managers’ meeting of the South-East Asia Laboratory NETwork (SEALNET) took place on 19 - 23 November 2018 in ICAR-IISS (Indian Institute of Soil Science), Bhopal, India.
Ms. Liping Yang , China National Center for Quality Supervision and Test of Chemical Fertilizers, Beijing, 2nd Day
According to Quality by Design (QbD) concept, quality should be built into product/method during pharmaceutical/analytical development. Recently, Design of Experiments (DoE) have been widely used to understand the effects of multidimensional and interactions of input factors on the output responses of pharmaceutical products and analytical methods.
Chris Impellitteri: EPA's update on PFAS analytical methodsOECD Environment
On 11 June 2020, the OECD hosted a webinar on the latest developments in analytical and monitoring methods for PFASs. It is important to understand the levels and trends of PFASs in the global environment, biota and in products so as to take relevant measures to reduce environmental and human exposure.
The webinar featured the following speakers:
Introduction by Eeva Leinala, Principal Administrator, Environment Directorate, OECD
Shoji Nakayama, Centre for Health and Environmental Risk Research, National Institute for Environmental Studies, Japan presented work on worldwide trends in tracing PFAS in the environment;
Chris Impellitteri, EPA’s Office of Research and Development, United States presented an update on EPA’s Analytical Methods for PFAS;
Stefan Posner, Independent researcher, presented work on the development of CEN and ISO test methods for the analysis of PFAS in textile and leather.
The webinar video recording is available at: https://youtu.be/O9s4qvD9i_c
Webinar: How to Develop a Regulatory-compliant Continued Process Verificatio...MilliporeSigma
Participate in the interactive webinar now: http://bit.ly/CPVWebinar
Product life cycle consists of 3 phases: Process Design, Process Performance Qualification and the last and the lengthiest Continued Process Verification (CPV). As more and more biomanufacturing processes enter commercial phases, the critical need to understand how to efficiently perform CPV programs arises.
Explore our webinar library: www.emdmillipore.com/webinars
Webinar: How to Develop a Regulatory-compliant Continued Process Verification...Merck Life Sciences
Participate in the interactive webinar now: http://bit.ly/CPVWebinar
Product life cycle consists of 3 phases: Process Design, Process Performance Qualification and the last and the lengthiest Continued Process Verification (CPV). As more and more biomanufacturing processes enter commercial phases, the critical need to understand how to efficiently perform CPV programs arises.
Explore our webinar library: www.merckmillipore.com/webinars
Plenary talk at ISPAC conference on the use of polycyclic aromatic hydrocarbons (PAHs) in environmental forensics. Covers basics of what enviromental forensics investigations (EFIs) are and how PAHs can be used to help determine sources of releases (creosote, railway ties), oil sands development and oil spill releases (Macondo oil spill, gulf oil spill).
This document is an ISO/IEC17025:2017 assessment checklist report for a laboratory. It lists the clause requirements from the standard and the comparable laboratory documents that meet each requirement. For each clause, it provides the relevant procedure names or documents and notes on implementation. The checklist covers all aspects of the management system, including structural requirements, resource management, process requirements, and management system documentation as required by the standard.
1) Standard analytical methods often require minor adjustments when transferred between laboratories or instruments. Method adjustments do not require revalidation if system suitability criteria are still met.
2) Standard methods must be verified when implemented in a new laboratory to demonstrate the laboratory's ability to successfully perform the method. Verification typically involves system suitability tests and repetition of one to three critical validation experiments.
3) If standard method parameters must be changed beyond established tolerance limits, or if new analytes or matrices are introduced, the method requires revalidation. All method changes and verifications should follow a documented process.
This document discusses Good Laboratory Practice (GLP) standards, which are federal regulations in the United States mandated by the FDA and EPA to ensure quality and integrity in laboratory studies submitted for regulatory approval. GLP standards were established in the 1970s after cases of laboratory malpractice and fraudulent research studies were uncovered. GLP regulations provide requirements for facilities, personnel, equipment calibration and maintenance, recordkeeping, and standard operating procedures to improve oversight of laboratory research. Compliance with GLP principles, even if not formally required, can improve research quality.
The document discusses Good Laboratory Practice (GLP) standards which were mandated by the FDA and EPA in the 1970s after cases of laboratory malpractice and fraudulent research studies surfaced. GLP standards establish rules for conducting non-clinical safety studies submitted to regulatory agencies and help assure the quality and integrity of study data. Key aspects of GLP compliance include requirements for documentation, equipment calibration and maintenance, proper labeling and use of reagents and chemicals.
The document discusses Good Laboratory Practices (GLP). It provides background on GLP, noting that it is an FDA regulation created in 1978 in response to cases of poor laboratory practices and fraudulent activities. GLP provides a framework for planning, performing, monitoring, recording, and reporting laboratory studies. Key aspects of GLP include requirements for facilities, equipment, test systems, standard operating procedures, personnel responsibilities, quality assurance programs, and record keeping. Adherence to GLP aims to ensure the quality and integrity of data submitted to regulatory agencies.
Stephan Krause discusses opportunities to accelerate analytical method validation for biosimilars using analytical platform technology (APT) methods. APT methods are analytical methods used for multiple products without modification that may not require full validation for each new product. Krause outlines how APT methods can be applied to product and process characterization methods as well as routine testing methods to reduce validation requirements. He also discusses the need for increased analytical method performance to address differences between biosimilars and reference products and acceptance criteria for various tiers of analytical similarity.
Points to Consider in QC Method Validation and Transfer for Biological ProductsWeijun Li
The document discusses considerations for analytical method validation and transfer for biological products. It provides three case studies as examples:
1) Creating spiking materials for size exclusion chromatography (SEC) validation by inducing chemical reactions to form aggregates and low molecular weight species for use in spiking studies.
2) Conducting a practice run with mock samples prior to an analytical method transfer to identify potential issues. The practice run failed equivalence testing, indicating differences between the labs.
3) Troubleshooting the practice run by examining potential differences in stock standards and standard curves between labs. Analysis found a less than 1% difference in stock standards but differences in standard curve slopes and intercepts between labs.
1) Researchers developed a UV-Vis predictive model to estimate phenolic measurements from Adams-Harbertson assays using only UV-Vis spectroscopy data as input.
2) An experiment was conducted to analyze measurement error in the Adams-Harbertson assays, finding operator contribution to be 3.3-34.4%.
3) A standardized operating procedure for the Adams-Harbertson assays is being created and validated to reduce variability and runtime of the assays.
The document discusses good manufacturing practices (GMP) for excipient suppliers. It provides guidance on qualifying excipient suppliers, ensuring traceability of excipients throughout their lifecycle, assessing supplier GMP conformance, and evaluating significant changes in excipients. The document also summarizes International Pharmaceutical Excipients Council (IPEC) guides on GMP auditing practices for excipient manufacturers and distributors.
This poster describes a GCMS purge-and-trap (P&T) method validation study conducted to evaluate operating conditions for the existing US EPA Method 624 VOC list, using updated technology and advanced GCMS instrumentation.
For more information, go to www.ssi.shimadzu.com and follow Shimadzu on Twitter at @ShimadzuSSI. Thanks for viewing.
The document summarizes the student's industrial work experience at the Central Drug Control Laboratory of NAFDAC. It describes the various testing units of the laboratory including the High Performance Liquid Chromatography (HPLC) unit. It explains the components and working of HPLC, the system suitability test conducted on the HPLC machine, and the procedures to analyze acetaminophen tablet samples using HPLC. The student concludes that the industrial training improved their practical understanding and recommends that SIWES students should be paid to motivate learning.
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The incorporation of a 3DCSM and completion of HRSC provided a tool for enhanced, data-driven, decisions to support a change in remediation closure strategies. Currently, an approved pilot study has been obtained to shut-down the remediation systems (ISCO, P&T) and conduct a hydraulic study under non-pumping conditions. A separate micro-biological bench scale treatability study was competed that yielded positive results for an emerging innovative technology. As a result, a field pilot study has commenced with results expected in nine-twelve months. With the results of the hydraulic study, field pilot studies and an updated risk assessment leading site monitoring optimization cost lifecycle savings upwards of $15MM towards an alternatively evolved best available technology remediation closure strategy.
Improving the viability of probiotics by encapsulation methods for developmen...Open Access Research Paper
The popularity of functional foods among scientists and common people has been increasing day by day. Awareness and modernization make the consumer think better regarding food and nutrition. Now a day’s individual knows very well about the relation between food consumption and disease prevalence. Humans have a diversity of microbes in the gut that together form the gut microflora. Probiotics are the health-promoting live microbial cells improve host health through gut and brain connection and fighting against harmful bacteria. Bifidobacterium and Lactobacillus are the two bacterial genera which are considered to be probiotic. These good bacteria are facing challenges of viability. There are so many factors such as sensitivity to heat, pH, acidity, osmotic effect, mechanical shear, chemical components, freezing and storage time as well which affects the viability of probiotics in the dairy food matrix as well as in the gut. Multiple efforts have been done in the past and ongoing in present for these beneficial microbial population stability until their destination in the gut. One of a useful technique known as microencapsulation makes the probiotic effective in the diversified conditions and maintain these microbe’s community to the optimum level for achieving targeted benefits. Dairy products are found to be an ideal vehicle for probiotic incorporation. It has been seen that the encapsulated microbial cells show higher viability than the free cells in different processing and storage conditions as well as against bile salts in the gut. They make the food functional when incorporated, without affecting the product sensory characteristics.
Kinetic studies on malachite green dye adsorption from aqueous solutions by A...Open Access Research Paper
Water polluted by dyestuffs compounds is a global threat to health and the environment; accordingly, we prepared a green novel sorbent chemical and Physical system from an algae, chitosan and chitosan nanoparticle and impregnated with algae with chitosan nanocomposite for the sorption of Malachite green dye from water. The algae with chitosan nanocomposite by a simple method and used as a recyclable and effective adsorbent for the removal of malachite green dye from aqueous solutions. Algae, chitosan, chitosan nanoparticle and algae with chitosan nanocomposite were characterized using different physicochemical methods. The functional groups and chemical compounds found in algae, chitosan, chitosan algae, chitosan nanoparticle, and chitosan nanoparticle with algae were identified using FTIR, SEM, and TGADTA/DTG techniques. The optimal adsorption conditions, different dosages, pH and Temperature the amount of algae with chitosan nanocomposite were determined. At optimized conditions and the batch equilibrium studies more than 99% of the dye was removed. The adsorption process data matched well kinetics showed that the reaction order for dye varied with pseudo-first order and pseudo-second order. Furthermore, the maximum adsorption capacity of the algae with chitosan nanocomposite toward malachite green dye reached as high as 15.5mg/g, respectively. Finally, multiple times reusing of algae with chitosan nanocomposite and removing dye from a real wastewater has made it a promising and attractive option for further practical applications.
Optimizing Post Remediation Groundwater Performance with Enhanced Microbiolog...Joshua Orris
Results of geophysics and pneumatic injection pilot tests during 2003 – 2007 yielded significant positive results for injection delivery design and contaminant mass treatment, resulting in permanent shut-down of an existing groundwater Pump & Treat system.
Accessible source areas were subsequently removed (2011) by soil excavation and treated with the placement of Emulsified Vegetable Oil EVO and zero-valent iron ZVI to accelerate treatment of impacted groundwater in overburden and weathered fractured bedrock. Post pilot test and post remediation groundwater monitoring has included analyses of CVOCs, organic fatty acids, dissolved gases and QuantArray® -Chlor to quantify key microorganisms (e.g., Dehalococcoides, Dehalobacter, etc.) and functional genes (e.g., vinyl chloride reductase, methane monooxygenase, etc.) to assess potential for reductive dechlorination and aerobic cometabolism of CVOCs.
In 2022, the first commercial application of MetaArray™ was performed at the site. MetaArray™ utilizes statistical analysis, such as principal component analysis and multivariate analysis to provide evidence that reductive dechlorination is active or even that it is slowing. This creates actionable data allowing users to save money by making important site management decisions earlier.
The results of the MetaArray™ analysis’ support vector machine (SVM) identified groundwater monitoring wells with a 80% confidence that were characterized as either Limited for Reductive Decholorination or had a High Reductive Reduction Dechlorination potential. The results of MetaArray™ will be used to further optimize the site’s post remediation monitoring program for monitored natural attenuation.
Lessons from operationalizing integrated landscape approaches
2019 AEHS San Diego Internation Conference
1. Presentation Title
Subtitle / Author
Which Method
Should/Did You Use
for PFAS?
AEHS
29th Annual International
Conference
March 21, 2019
David A. Gratson, CEAC
Rock J. Vitale, CEAC
David R. Blye, CEAC
Meg A. Michell
2. Agenda
Issues
Chemistry
Methods of Analysis
Variations on a theme
that impact data comparability
ISO
DoD
Strict US
EPA
ASTM
Modified
Method
Availability of
Standards
Calibration
Sample
Performance
Monitoring
Extraction Analysis Reporting
3. PFAS Issues – Big Picture
Laboratories are being requested to analyze for
per/polyfluoroalkyl substances (PFAS) in matrices that
have no approved US EPA methodology.
Laboratory accreditation/oversight is lacking.
These differences lead to poor data comparability.
Industries and agencies are under pressure for
information.
US EPA has been slow to develop/validate methods.
US EPA Action Plan
Decisions are being made using data of unknown
quality.
6. PFAS Structures
Sulfonamido Substances
(+ & -, aka FOSA), (D)
Other (E)
PFOSA
More at: https://www.atsdr.cdc.gov/pfas/and https://www.itrcweb.org/Team/Public?teamID=78
7. World of Methods
ISO 25101, aqueous (2009)
Rarely used in the U.S.
ASTM D7968-17a
Soil, single laboratory only
ASTM D7979 – 17
Water, Sludge, Influent, Effluent and Wastewater
single laboratory only
Department of Defense (DoD)
Quality Systems Manual (QSM)
aqueous
soil/solids
ASTM
DoD
ISO
8. World of Methods (Cont.)
US EPA Method 537 – Drinking Water,
just revised November 2018
Coming (Q1 2019?)
US EPA 8327
water only, direct injection, screening
US EPA 8328
water/soil/sediment, solid-phase extraction (SPE),
isotopic dilution
US EPA 8329
Air, biota, food: no published/validated methods
Modified
Method
Strict US
EPA
9. PFAS Analytes vs. Method
PFAS Class 537.1
Drinking Water Only
537
Modified*
DoD QSM 5.2
Number of Analytes 18 18-50+ Per laboratory
A (Carboxylates) 9 (C4-C14) Yes Yes
B (Sulfonates) 5 (2 with ether
group)
Yes Yes
C (Fluorotelomer) 0 Likely Likely
D (Sulfonamido
Substances)
2 Likely Likely
E (Other) 2 ? ?
Notes Attempted to
include more
analytes, poor SPE
recovery
As a standard
becomes
available
Prescribed QC Table B.15
Other: ADONA, HFPO-DA (GenX component)
10. PFAS Analytes vs. Method (Cont.)
PFAS Class ASTM D7968-17a ASTM D7979-17
Number of Analytes 21 + 21 +
A (Carboxylates) 11 (C4-C14) 11 (C4-C14)
B (Sulfonates) 3 (C4, C6, C8), + 1 cyclic 3 (C4, C6, C8), + 1 cyclic
C (Fluorotelomer) 6 6
D (Sulfonamido
Substances)
0* 0*
E (Other) 0 0
Notes Performance based, could add
compounds
Performance based, could add
compounds
* Listed as likely applicable analytes
14. Standards
US EPA Method 537 and DoD QSM indicate that
standards should include linear and branched
isomers unless unavailable.
ASTM methods do not specify linear and branched
isomers in the calibration standard section
(assumed later in methods).
Majority of standards will include linear, methyl
isomers, and dimethyl isomers only.
Standards are not available with branched isomers
for a number of PFAS target compounds.
15. Standards (Cont.)
Limited number of isotope-labeled compounds are
available.
Laboratories do not always utilize all available
standards.
Mass transitions that are monitored are variable.
Some monitor one transition mass.
Fewer monitor two transition masses.
16. Calibration Technique Variability
External standard
Target response ratio with target concentration
Internal standard
Target internal response ratio with target/internal concentration
Internal added post sample extraction and concentration
Isotope dilution
Isotope standard added prior to sample extraction
Isotope/internal standard response ratio with isotope/internal
standard concentration, or maybe external standard calibration
for isotope
Target/isotope response ratio with target/isotope concentration
17. Calibration Models
Calibration models vary:
Average response factor (RF) or relative response factor (RRF)
Relative standard deviation (RSD) ≤ 20%, or 30%, or other
Linear equation with or without weighting
R2 ≥ 0.99, or 0.98, or other
Quadratic equation with or without weighting
R2 ≥ 0.99 or other
Force curve through origin or not
Comparability
18. Calibration Check Variability
Some laboratories will utilize just the re-fit recovery
for acceptance.
Continuing calibration verifications
Daily
Beginning and closing of sequence, every 30 analyses
± 20% recovery, ± 30% recovery, or other
Calibration model and acceptance criteria impact
the calculated result
19. Extraction Techniques
• US EPA Method 537 – SPE
(drinking water only)
• ASTM Method D7979-16 and
D7979-17 (aqueous and sludge)–
methanol shake/vortex
• ASTM Method D7968-17 (soil) methanol vortex
• DoD QSM 5.1.1 and 5.2, SPE for aqueous, not specified
for other matrices
• Laboratory-specific modified methods – anything goes
SPE Schematic: https://separationmethods.com/product-category/sample-preparation/spe-cartridges/
20.
21. Extraction Techniques
Solid or other matrices being tested include:
Shake/vortex or sonication
Automated solvent extraction (not common)
Automated Soxhlet extraction (not common)
Microwave (not common)
Image: https://www.chemistryworld.com/opinion/classic-kit-soxhlet-extractor/3004940.article
22. Extraction Techniques (Cont.)
Extraction solvents vary (reagent water, methanol,
acetonitrile)
Cleanups for extracts may or may not be performed
Extracts may be:
Concentrated to dryness, then transferred into
solvent
Concentrated, but not to dryness
Not concentrated at all
23. Variability So Far
Availability of
Standards
• Linear, branched,
isotopes
Calibration
• Approach, frequency,
acceptance criteria
Extraction (chain
length, polarity, pKa)
• SPE, Liquid-liquid, shake,
sonicate
24. Sample-specific Performance Monitoring
External standard technique
Surrogate compounds added prior
to extraction monitors extraction
performance
No separate instrument monitor
Internal standard technique
Internal standard added immediately
prior to instrument analysis
monitors instrument
Surrogates + internal standards
Batch
Check Standards
On-Instrument
Internal Standards
Extraction
Surrogates
25. Sample-specific Performance Monitoring
Isotope dilution technique
Labeled compounds added prior to extraction for
isotope dilution compensate for extraction efficiency.
Labeled compounds are used to calculate target
results.
Internal standard added prior to analysis to
quantitate labeled compounds (well, not all
laboratories).
Internal standard monitors instrument performance.
26. Reporting and Analyte List Variability
Various state and federal agencies have inconsistent
analyte lists.
Laboratories will report fewer or more PFAS analytes
than included in Method 537 (e.g., include 6:2
fluorotelomer sulfonic acid, PFBA, PFPA, etc.).
The variability in PFAS lists between facilities makes data
comparisons more difficult.
Chemical Abstracts Service (CAS) number use has been
variable (e.g., sulfonic acid, sulfate, or salt) and is many
times wrong.
27. How to Build Quality Data
Due to modified methods, you must first understand
the laboratory’s approach.
Obtain the SOPs, then review and thoroughly
understand them.
Set up method-specific technical requirements.
Start a performance testing (PT) sample program.
Ensure laboratory can provide a Full data package
deliverable.
Many laboratories performing M537 don’t have experience in
generating Full data packages.
Verify and validate data.
28. Web www.envstd.com | Email solutions@envstd.com
Thank You “Setting the Standards for Innovative
Environmental Solutions”
dgratson@envstd.com 505-660-8521