This document discusses analytical method validation. It begins by explaining why method validation is important, such as ensuring consistent, reliable, and accurate data from analytical measurements. It then provides background on regulatory requirements for method validation from agencies like the FDA. The document outlines the key steps in method validation, including qualification of instruments, materials, analysts, developing validation protocols, performing validation experiments, and documenting results. It also discusses ICH and USP guidelines for method validation characteristics like accuracy, precision, specificity, linearity, range, and more. Finally, it provides details on specificity testing and criteria for different analytical procedure types.
1. ICH Q7 provides guidance for good manufacturing practices for manufacturing active pharmaceutical ingredients. It is intended to help ensure APIs meet quality and purity requirements.
2. The guidelines apply to all stages of API manufacturing, including receiving, production, packaging, testing and distribution. It covers APIs made through chemical synthesis, extraction, fermentation and other processes.
3. The guidelines address requirements for facilities, equipment, personnel, documentation, materials management, production controls, validation, complaints and recalls to ensure quality management.
Validation is defined as establishing documented evidence that a process will consistently produce a product meeting specifications. Analytical methods must be validated for identification tests, quantitative tests for impurities, limit tests, and assays. Key parameters for validation include linearity and range, specificity, precision, accuracy, limits of detection and quantification, robustness, and system suitability. Validation demonstrates a method is suitable for its intended use by proving the method is accurate, precise, specific, robust, and capable of detecting analytes at low concentrations.
This document discusses validation of analytical procedures. It is divided into two parts. Part I provides definitions and discusses typical validation characteristics such as accuracy, precision, specificity, detection limit, and quantitation limit. Part II provides more detailed methodology guidance on how to validate these characteristics. It describes how to validate specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, and robustness of analytical procedures. The goal of validation is to demonstrate that analytical procedures are suitable for their intended purpose in identifying, quantifying, and testing impurities in drug substances and products.
The document discusses guidelines for controlling elemental impurities in pharmaceutical products according to ICH Q3D. It provides information on:
- Common sources of elemental impurities in drug products
- Classification of elements into categories based on their toxicity and likelihood of occurrence
- Methods for establishing permitted daily exposures (PDEs) for elements
- A risk-based approach to assessing and controlling elemental impurities that includes identifying potential sources, evaluating levels compared to PDEs, and documenting control plans
- Options for converting PDEs into concentration limits in drug products or components
The guidelines aim to replace qualitative heavy metal limits with quantitative control of specific elemental impurities shown to have no therapeutic benefit. Manufacturers must
Analytical method validation, ICH Q2 guidelineAbhishek Soni
Analytical Method Validation, ICH Q2 Guideline.
General principles related to the analytical method validation.
Validation of analytical method as per International Council for Harmonisation(ICH) guidelines and the United States Pharmacopeia(USP).
Glossary.
Useful in understanding the terms :
Specificity
Linearity
Range
Accuracy
Precision
Detection limit
Quantitation limit
Robustness
Ruggedness
System suitability testing
Analytical methods validation as per ich & uspGANESH NIGADE
This document discusses analytical method validation as per ICH and USP guidelines. It defines validation as establishing documentary evidence that a procedure maintains compliance. Method validation involves demonstrating that an analytical procedure is suitable for its intended purpose by testing parameters such as accuracy, precision, specificity, detection limit, quantitation limit, linearity, range, ruggedness and robustness. It also discusses the different types of analytical procedures that require validation including identification tests, quantitative impurity tests, limit tests and assays.
The document describes a post graduate diploma program in Pharmaceutical Quality Assurance and Quality Control offered by the Institute of Good Manufacturing Practices India (IGMPI). The 12-month program covers topics like quality assurance, quality control, validation, documentation, and case studies. It aims to provide knowledge on quality issues, industry needs, and techniques. Graduates can work as QA/QC managers or officers in pharmaceutical and healthcare industries. IGMPI also offers other programs in areas like GMP, regulatory affairs, and clinical research.
This presentation was made to solely for students to make them aware/ understand basics of “Validation”. These slides are part of lectures delivered in M. Pharmacy Curriculum & taken up from various books and websites
1. ICH Q7 provides guidance for good manufacturing practices for manufacturing active pharmaceutical ingredients. It is intended to help ensure APIs meet quality and purity requirements.
2. The guidelines apply to all stages of API manufacturing, including receiving, production, packaging, testing and distribution. It covers APIs made through chemical synthesis, extraction, fermentation and other processes.
3. The guidelines address requirements for facilities, equipment, personnel, documentation, materials management, production controls, validation, complaints and recalls to ensure quality management.
Validation is defined as establishing documented evidence that a process will consistently produce a product meeting specifications. Analytical methods must be validated for identification tests, quantitative tests for impurities, limit tests, and assays. Key parameters for validation include linearity and range, specificity, precision, accuracy, limits of detection and quantification, robustness, and system suitability. Validation demonstrates a method is suitable for its intended use by proving the method is accurate, precise, specific, robust, and capable of detecting analytes at low concentrations.
This document discusses validation of analytical procedures. It is divided into two parts. Part I provides definitions and discusses typical validation characteristics such as accuracy, precision, specificity, detection limit, and quantitation limit. Part II provides more detailed methodology guidance on how to validate these characteristics. It describes how to validate specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, and robustness of analytical procedures. The goal of validation is to demonstrate that analytical procedures are suitable for their intended purpose in identifying, quantifying, and testing impurities in drug substances and products.
The document discusses guidelines for controlling elemental impurities in pharmaceutical products according to ICH Q3D. It provides information on:
- Common sources of elemental impurities in drug products
- Classification of elements into categories based on their toxicity and likelihood of occurrence
- Methods for establishing permitted daily exposures (PDEs) for elements
- A risk-based approach to assessing and controlling elemental impurities that includes identifying potential sources, evaluating levels compared to PDEs, and documenting control plans
- Options for converting PDEs into concentration limits in drug products or components
The guidelines aim to replace qualitative heavy metal limits with quantitative control of specific elemental impurities shown to have no therapeutic benefit. Manufacturers must
Analytical method validation, ICH Q2 guidelineAbhishek Soni
Analytical Method Validation, ICH Q2 Guideline.
General principles related to the analytical method validation.
Validation of analytical method as per International Council for Harmonisation(ICH) guidelines and the United States Pharmacopeia(USP).
Glossary.
Useful in understanding the terms :
Specificity
Linearity
Range
Accuracy
Precision
Detection limit
Quantitation limit
Robustness
Ruggedness
System suitability testing
Analytical methods validation as per ich & uspGANESH NIGADE
This document discusses analytical method validation as per ICH and USP guidelines. It defines validation as establishing documentary evidence that a procedure maintains compliance. Method validation involves demonstrating that an analytical procedure is suitable for its intended purpose by testing parameters such as accuracy, precision, specificity, detection limit, quantitation limit, linearity, range, ruggedness and robustness. It also discusses the different types of analytical procedures that require validation including identification tests, quantitative impurity tests, limit tests and assays.
The document describes a post graduate diploma program in Pharmaceutical Quality Assurance and Quality Control offered by the Institute of Good Manufacturing Practices India (IGMPI). The 12-month program covers topics like quality assurance, quality control, validation, documentation, and case studies. It aims to provide knowledge on quality issues, industry needs, and techniques. Graduates can work as QA/QC managers or officers in pharmaceutical and healthcare industries. IGMPI also offers other programs in areas like GMP, regulatory affairs, and clinical research.
This presentation was made to solely for students to make them aware/ understand basics of “Validation”. These slides are part of lectures delivered in M. Pharmacy Curriculum & taken up from various books and websites
Understanding of Analytical Method Validation Approach in Pharmaceutical Industry. Analytical method validation Verification is a wide chapter and a huge scope of applicability. In different types of methods, instrument, measurement approach all can effect the validation effort. However the basic fundamental will remains same, the parameters, acceptance criteria, functionality may vary depending upon the type of method, instrument etc.
ISO 10993-5 Biological Evaluation of Medical Devices - Tests for In Vitro Cyt...NAMSA
ISO 10993-5 presents test methods for evaluating the acute adverse effects of extractables from medical device materials. Testing cytotoxicity is a requirement for all medical devices. Different cytotoxicity methods include qualitative elution assays, agar overlay tests, direct contact tests, and quantitative assays like MTT and colony formation that allow endpoint evaluation. Controls include negative articles like HDPE tubing and positive references like latex and chemicals containing ZDEC and ZDBC.
This document provides a summary of the key steps to implement ICH Q3D Guideline for Elemental Impurities:
1. Collect baseline information on potential elemental impurity sources from suppliers.
2. Define the risk assessment strategy to use, such as the component-based Options 1, 2A, 2B or finished-product Option 3.
3. Develop an analytical plan using techniques like ICP-MS to test for elemental impurities.
4. Establish a control strategy where impurities below 30% of the PDE are acceptable.
5. Manage the implementation as a continuous process, reassessing for product or supplier changes.
POTENTIAL SOURCES OF ELEMENTAL IMPURITIESMehulJain143
INTRODUCTION
INDENTIFICATION OF POTENTIAL ELEMENTAL IMPURITIES
FACTORS AFFECTING
EVALUATION
RISK ASSESSMENT AND CONTROL OF ELEMENTAL IMPURITIES
GENERAL PRINCIPLES
This document discusses blend uniformity analysis (BUA), which tests the adequacy of mixing active pharmaceutical ingredients with other drug product components. BUA is recommended for dosage forms requiring content uniformity testing. Under good manufacturing practices, each commercial batch must be tested to validate uniform mixing. Sample size for BUA is typically 6-10 points, with samples less than 3 times an individual dose. Acceptance criteria for BUA assays is 90-110% of the mean with an RSD of no more than 5%. Stratified sampling targets locations with higher failure risks. The Product Quality Research Institute recommends additionally testing stratified dosage unit samples throughout production.
Related Substances-Method Validation-PPT_slideBhanu Prakash N
This document provides an overview of analytical method validation. It defines validation as demonstrating a method is suitable for its intended purpose. Key validation characteristics discussed include precision, accuracy, specificity, linearity, range, detection limit, quantitation limit, ruggedness and robustness. The document describes the methodology for evaluating each characteristic, such as spiking known concentrations of analytes and establishing acceptance criteria. It emphasizes that validation confirms a method consistently produces results meeting pre-defined standards of quality.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
Calibration is the process of establishing the relationship between measurements indicated by an instrument and known standard values. It involves identifying instruments and sources of standards, following calibration procedures, documenting results, and accounting for sources of error. Key steps include calibrating against certified reference materials and national standards to minimize uncertainty and ensure traceability. Instruments are calibrated using single-point, multi-point or other procedures depending on the instrument type.
The document summarizes the ICH Q2 R1 guideline on the validation of analytical procedures. It discusses the objective of validation, which is to demonstrate that an analytical procedure is suitable for its intended purpose. It describes the types of analytical procedures that should be validated, including identification tests, quantitative impurity tests, limit tests for impurities, and assay procedures. It then goes into detail describing the validation parameters that should be tested, including specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, robustness, and system suitability. The document provides information on how to validate both compendial and non-compendial analytical procedures, as well as the concept of verification for compendial methods
This document provides information on the preparation and potency determination of oxytocin and human antihaemophilic vaccine. It describes that oxytocin is obtained from pituitary glands and stimulates uterine contraction and milk ejection. Its potency is determined by comparing its activity to a standard preparation in assays measuring blood pressure depression in chickens. The document also describes that human antihaemophilic vaccine is prepared from human plasma to be rich in clotting factor VIII. Its potency is determined by comparing the amount needed to reduce clotting time to that of a standard preparation in an assay using citrated plasma.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
This document discusses guidelines for validating analytical methods from the International Council for Harmonisation (ICH). It defines method validation as demonstrating that analytical procedures are suitable for their intended use. Key parameters of method validation discussed include specificity, linearity, range, accuracy, precision, detection and quantitation limits, ruggedness and robustness. The guidelines provide criteria for acceptance in each parameter area to ensure analytical methods are suitable to support the quality and potency of pharmaceutical products.
This document provides guidance on bioanalytical method validation. It discusses validation parameters such as selectivity, accuracy, precision, recovery, calibration curves, and stability. Full validation is recommended when developing a new bioanalytical method or validating a revised method. Partial validation may be done for modifications like changes in matrix, reagents, or instrumentation. Cross-validation between methods and labs is also addressed. Recommendations are provided for chemical and microbiological/ligand-binding assay validation.
Qualification of analytical instrumentsFaris ameen
This document provides guidelines for qualifying analytical instruments including electronic balances, pH meters, and UV-Visible spectrophotometers. It discusses the various levels of qualification including: Level I which involves selecting instruments and suppliers; Level II which involves installation and releasing instruments for use; Level III which involves periodic checks; and Level IV which involves in-use checks. Specific guidelines are provided for qualifying balances, pH meters, and UV-Visible spectrophotometers, including recommended tolerance limits for various parameters, calibration procedures, and qualification frequencies.
Method Validation - ICH /USP Validation, Linearity and Repeatability labgo
1. The document provides an overview of method validation requirements from various regulatory bodies and guidelines. It discusses key validation parameters such as specificity, linearity, range, accuracy, precision, detection limit, and quantitation limit.
2. Validation is required to demonstrate that analytical methods are suitable for their intended purposes. It identifies potential sources of error and quantifies errors in the method. Validation includes parameters like linearity, range, accuracy, and precision.
3. The document provides details on establishing various validation parameters according to regulatory guidelines from ICH, FDA, and USP. It also discusses considerations for validating methods like instrument qualification and defines method life cycles.
This document discusses analytical method validation. It provides definitions and guidelines for validating analytical methods from regulatory agencies. Key aspects of method validation discussed include accuracy, precision, specificity, range, linearity, limits of detection and quantification. Validation parameters are described for different types of analytical tests including identification, quantitative impurity tests and assays. Guidelines are provided for qualifying analytical instrumentation and categorizing instruments based on complexity.
ANALYTICAL METHOD VALIDATION BY P.RAVISANKAR Dr. Ravi Sankar
This document discusses analytical method validation. It begins with an introduction that defines validation and discusses its importance and regulatory requirements. The document then covers specific validation parameters such as specificity, linearity, accuracy, precision, limit of detection, limit of quantification and more. For each parameter, the document provides definitions, procedures for evaluation, and acceptance criteria. It emphasizes that validation demonstrates a method is suitable for its intended purpose and supports the identity, quality, purity and potency of drug substances and products. The overall summary is that analytical method validation is critical to ensure quality and compliance in the pharmaceutical industry.
Understanding of Analytical Method Validation Approach in Pharmaceutical Industry. Analytical method validation Verification is a wide chapter and a huge scope of applicability. In different types of methods, instrument, measurement approach all can effect the validation effort. However the basic fundamental will remains same, the parameters, acceptance criteria, functionality may vary depending upon the type of method, instrument etc.
ISO 10993-5 Biological Evaluation of Medical Devices - Tests for In Vitro Cyt...NAMSA
ISO 10993-5 presents test methods for evaluating the acute adverse effects of extractables from medical device materials. Testing cytotoxicity is a requirement for all medical devices. Different cytotoxicity methods include qualitative elution assays, agar overlay tests, direct contact tests, and quantitative assays like MTT and colony formation that allow endpoint evaluation. Controls include negative articles like HDPE tubing and positive references like latex and chemicals containing ZDEC and ZDBC.
This document provides a summary of the key steps to implement ICH Q3D Guideline for Elemental Impurities:
1. Collect baseline information on potential elemental impurity sources from suppliers.
2. Define the risk assessment strategy to use, such as the component-based Options 1, 2A, 2B or finished-product Option 3.
3. Develop an analytical plan using techniques like ICP-MS to test for elemental impurities.
4. Establish a control strategy where impurities below 30% of the PDE are acceptable.
5. Manage the implementation as a continuous process, reassessing for product or supplier changes.
POTENTIAL SOURCES OF ELEMENTAL IMPURITIESMehulJain143
INTRODUCTION
INDENTIFICATION OF POTENTIAL ELEMENTAL IMPURITIES
FACTORS AFFECTING
EVALUATION
RISK ASSESSMENT AND CONTROL OF ELEMENTAL IMPURITIES
GENERAL PRINCIPLES
This document discusses blend uniformity analysis (BUA), which tests the adequacy of mixing active pharmaceutical ingredients with other drug product components. BUA is recommended for dosage forms requiring content uniformity testing. Under good manufacturing practices, each commercial batch must be tested to validate uniform mixing. Sample size for BUA is typically 6-10 points, with samples less than 3 times an individual dose. Acceptance criteria for BUA assays is 90-110% of the mean with an RSD of no more than 5%. Stratified sampling targets locations with higher failure risks. The Product Quality Research Institute recommends additionally testing stratified dosage unit samples throughout production.
Related Substances-Method Validation-PPT_slideBhanu Prakash N
This document provides an overview of analytical method validation. It defines validation as demonstrating a method is suitable for its intended purpose. Key validation characteristics discussed include precision, accuracy, specificity, linearity, range, detection limit, quantitation limit, ruggedness and robustness. The document describes the methodology for evaluating each characteristic, such as spiking known concentrations of analytes and establishing acceptance criteria. It emphasizes that validation confirms a method consistently produces results meeting pre-defined standards of quality.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
Calibration is the process of establishing the relationship between measurements indicated by an instrument and known standard values. It involves identifying instruments and sources of standards, following calibration procedures, documenting results, and accounting for sources of error. Key steps include calibrating against certified reference materials and national standards to minimize uncertainty and ensure traceability. Instruments are calibrated using single-point, multi-point or other procedures depending on the instrument type.
The document summarizes the ICH Q2 R1 guideline on the validation of analytical procedures. It discusses the objective of validation, which is to demonstrate that an analytical procedure is suitable for its intended purpose. It describes the types of analytical procedures that should be validated, including identification tests, quantitative impurity tests, limit tests for impurities, and assay procedures. It then goes into detail describing the validation parameters that should be tested, including specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, robustness, and system suitability. The document provides information on how to validate both compendial and non-compendial analytical procedures, as well as the concept of verification for compendial methods
This document provides information on the preparation and potency determination of oxytocin and human antihaemophilic vaccine. It describes that oxytocin is obtained from pituitary glands and stimulates uterine contraction and milk ejection. Its potency is determined by comparing its activity to a standard preparation in assays measuring blood pressure depression in chickens. The document also describes that human antihaemophilic vaccine is prepared from human plasma to be rich in clotting factor VIII. Its potency is determined by comparing the amount needed to reduce clotting time to that of a standard preparation in an assay using citrated plasma.
Dissolution procedure development and validation, USP 1092Md. Saddam Nawaz
This document discusses the development and validation of dissolution procedures according to USP<1092>. It provides general comments on the purpose of dissolution testing and discusses key aspects of developing a discriminating and reproducible method, including choice of medium, apparatus, study design, sampling, and validation. The document outlines factors to consider for various dosage forms and provides examples of typical dissolution conditions and acceptance criteria.
This document discusses guidelines for validating analytical methods from the International Council for Harmonisation (ICH). It defines method validation as demonstrating that analytical procedures are suitable for their intended use. Key parameters of method validation discussed include specificity, linearity, range, accuracy, precision, detection and quantitation limits, ruggedness and robustness. The guidelines provide criteria for acceptance in each parameter area to ensure analytical methods are suitable to support the quality and potency of pharmaceutical products.
This document provides guidance on bioanalytical method validation. It discusses validation parameters such as selectivity, accuracy, precision, recovery, calibration curves, and stability. Full validation is recommended when developing a new bioanalytical method or validating a revised method. Partial validation may be done for modifications like changes in matrix, reagents, or instrumentation. Cross-validation between methods and labs is also addressed. Recommendations are provided for chemical and microbiological/ligand-binding assay validation.
Qualification of analytical instrumentsFaris ameen
This document provides guidelines for qualifying analytical instruments including electronic balances, pH meters, and UV-Visible spectrophotometers. It discusses the various levels of qualification including: Level I which involves selecting instruments and suppliers; Level II which involves installation and releasing instruments for use; Level III which involves periodic checks; and Level IV which involves in-use checks. Specific guidelines are provided for qualifying balances, pH meters, and UV-Visible spectrophotometers, including recommended tolerance limits for various parameters, calibration procedures, and qualification frequencies.
Method Validation - ICH /USP Validation, Linearity and Repeatability labgo
1. The document provides an overview of method validation requirements from various regulatory bodies and guidelines. It discusses key validation parameters such as specificity, linearity, range, accuracy, precision, detection limit, and quantitation limit.
2. Validation is required to demonstrate that analytical methods are suitable for their intended purposes. It identifies potential sources of error and quantifies errors in the method. Validation includes parameters like linearity, range, accuracy, and precision.
3. The document provides details on establishing various validation parameters according to regulatory guidelines from ICH, FDA, and USP. It also discusses considerations for validating methods like instrument qualification and defines method life cycles.
This document discusses analytical method validation. It provides definitions and guidelines for validating analytical methods from regulatory agencies. Key aspects of method validation discussed include accuracy, precision, specificity, range, linearity, limits of detection and quantification. Validation parameters are described for different types of analytical tests including identification, quantitative impurity tests and assays. Guidelines are provided for qualifying analytical instrumentation and categorizing instruments based on complexity.
ANALYTICAL METHOD VALIDATION BY P.RAVISANKAR Dr. Ravi Sankar
This document discusses analytical method validation. It begins with an introduction that defines validation and discusses its importance and regulatory requirements. The document then covers specific validation parameters such as specificity, linearity, accuracy, precision, limit of detection, limit of quantification and more. For each parameter, the document provides definitions, procedures for evaluation, and acceptance criteria. It emphasizes that validation demonstrates a method is suitable for its intended purpose and supports the identity, quality, purity and potency of drug substances and products. The overall summary is that analytical method validation is critical to ensure quality and compliance in the pharmaceutical industry.
This document discusses guidelines for analytical method validation. It outlines types of analytical methods that require validation including chromatographic, spectroscopic, and dissolution methods. Key analytical performance characteristics used in validation are described such as specificity, linearity, range, accuracy, precision, detection/quantitation limits, robustness, and system suitability testing. The document provides details on determining these characteristics and validating methods. It also addresses revalidation and references for further information.
Calibration and validation of analytical instrumentsSolairajan A
This document discusses the calibration and validation of various analytical instruments used in pharmaceutical analysis. It provides details on calibrating UV-Vis spectrophotometers, IR spectrophotometers, spectrofluorimeters, HPLC, and GC. Calibration ensures instrument readings are accurate against standards, while validation confirms the instrument is correctly installed and operating as intended. The document outlines tests and acceptance criteria for evaluating characteristics like wavelength accuracy, resolution, noise, baseline flatness, sensitivity, flow rate, and linearity during calibration and validation of different analytical instruments.
The document discusses analytical method validation. It defines validation as establishing evidence that a process will consistently produce a product meeting predetermined specifications. The objectives are to discuss aspects of validation including principles, approaches, and characteristics. Key steps in validation are establishing accuracy, precision, specificity, linearity, range, limits of detection and quantification, and robustness of analytical procedures used for identification, quantification of impurities and active ingredients.
The dissolution test is an important means of assuring the continuing performance of non-solution orally administered drug products. The development of a dissolution test procedure is briefly discussed in USP general information chapter In Vitro and In Vivo Evaluation of Dosage Forms 1088, whereas general information chapter Validation of Compendial Procedures 1225 gives limited validation information for dissolution testing. Neither of these two chapters provides a level of detail and focus sufficient for dissolution testing. In 2001, a Stimuli article provided an initial rationale and discussion of content for a new general information chapter. The new chapter, The Dissolution Procedure: Development and Validation 1092, was intended to supplement the information in 1088 and 1225 and provided step-by-step detail for development and validation as well as offering information on new technology and equipment. In 2006, the chapter became official with the Second Supplement to USP 29–NF 24 (2–4).
The General Chapters—Dosage Forms Expert Committee 2010–2015 placed the review and possible revision of The Dissolution Procedure: Development and Validation 1092 on its work plan for the 2010–2015 revision cycle (2011) .
Drug Regulations has prepared this presentation based on the proposed chapter.
The document discusses analytical method validation, including defining method validation as ensuring an analytical method provides acceptable data for its intended use. It outlines the common steps in method development and validation and the validation parameters that should be assessed, including accuracy, precision, specificity, linearity, range, and robustness. The document provides details on how each of these parameters should be evaluated during the validation process.
Method Development and Validation-Solid Phase Extraction-Ultra Performance Li...Partha Ray
This method validates a solid phase extraction-ultra performance liquid chromatography-tandem mass spectrometry (SPE-UPLC-MS/MS) method for quantifying the antibiotic pirlimycin in bovine feces and urine. The method was sensitive, accurate, and precise for quantifying pirlimycin at low nanogram per gram and nanogram per milliliter levels. The method was applied to samples from dairy cows administered pirlimycin intramammarily, detecting pirlimycin in feces at 40.5-287 ng/g and in urine at 46.1-254 ng/mL over 120 hours. This validated method can be used to study the environmental impact of antibiotic excretion from livestock
CNP EXPO _ Payvision Landing in Europe a regulatory approachPayvision
In his presentation Ignacio Gonzalez-Paramo, VP Global Compliance PAYVISION, will try to provide the audience with an insight on why EU regulation is strategically key for those willing to establish in the EU or to strengthen their market positioning there.
On top of that, he will also walk the attendees through the key actors in the European policy making process, as well as the most important pieces of legislation to be borne in mind by potential or existing EU CNP players. Ignacio will also underscore the regulatory issues that might imply hurdles for running a CNP business.
And, to end with, he will provide some pieces of advice on how to successfully address those issues.
• Understand why a regulatory strategy is needed.
• Get familiar with:
o Main actors in the EU Policy making process.
o Types of EU legal and regulatory instruments.
o Key pieces of legislation (for the payments business).
o Specific issues to overcome.
• Provide guidance on how to minimize regulatory business implications.
o Strategic alliances & partnerships, licensing options).
To compare filing process of NDA of different countries of India, US and Euro...Aakashdeep Raval
To compare filing process of NDA of different countries of India, US and Europe.
B) Preparation of global list documents of registration of IND and NDA as per USFDA and Europe.
This document discusses various types of antibiotics including beta-lactams, aminoglycosides, macrolides, fluoroquinolones, and tetracyclines. It provides details on specific antibiotics like cefixime, clarithromycin, ciprofloxacin, levofloxacin, and moxifloxacin including their mechanisms of action, indications, dosages, pharmacokinetics, adverse effects, and contraindications. The document also discusses antibiotic classification and safety in pregnancy.
This document summarizes guidelines for analytical method validation from various regulatory agencies. It discusses the purpose of validation to verify method suitability for submissions. Key validation characteristics covered include specificity, linearity, range, accuracy, precision, detection/quantitation limits, robustness, and system suitability testing. It notes that revalidation may be necessary if the analytical method or drug product is changed.
This document discusses the key aspects of analytical method validation including specificity, linearity, range, accuracy, precision, detection limit, quantitation limit, robustness, and system suitability testing. It provides detailed descriptions and recommendations for establishing each validation characteristic to demonstrate that an analytical procedure is suitable for its intended use.
ANALYTICAL METHOD VALIDATION -A PREDICAMENT OF SERVICE PROVIDERanezlin
This document discusses analytical method validation and outlines the challenges faced when outsourcing these services. It notes that while full validation according to ICH guidelines may not always be necessary, methods should still be scientifically sound. Some ways to reduce validation efforts discussed include adjusting the scope based on development stage, establishing method feasibility early on, and employing a risk-based approach. The responsibilities of both service providers and sponsors are examined, with the importance of alignment on quality expectations through a detailed agreement emphasized.
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.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
This document outlines the key steps in method validation for clinical chemistry laboratories. It defines method validation and discusses when methods should be validated. The key aspects that must be validated include calibration, precision, accuracy, linearity, limit of detection, analytical range, sensitivity, specificity, ruggedness and robustness. Thorough documentation of the validation study is also required. Validating a method involves experimentally testing these parameters and documenting the results to provide objective evidence that the method is suitable for its intended use.
Risk-based Analytical Method Validation and Maintenance Strategies SK-Sep13Stephan O. Krause, PhD
This document discusses risk-based analytical method validation and maintenance strategies. It covers topics such as risk assessment processes for analytical method validation readiness, risk-based study designs and acceptance criteria, analytical method replacement, analytical method maintenance, and analytical method transfer. The presentation provides examples and considerations for each topic.
Raaj Global Pharma Regulatory Affairs Consultants Thane-mumbai profile-updat...Rajashri Survase Ojha
Raaj-GPRAC is a Thane-Mumbai (India) based agency.
Our offerings includes but not limited to making Regulatory filing strategy, Preparation of pharmaceutical product registration dossier, filing assistance, response to regulatory queries, life cycle management, regulatory compliance audit and Training.
We offer flexible and need based services to meet customer/client requirements so as to save time and cost.
This presentation from the Institute of Validation Technology's 7th Annual Method Validation covers regulatory expectations for deviations and out-of-specification results and protocol exceptions, change control, handing investigations and CAPAs, and avoiding common pitfalls.
The document discusses phase appropriate method validation. It provides guidelines for validating analytical methods based on the intended use and stage of product development. Validation requirements become more extensive in later phases, from proof of concept in Phase I to full validation in Phase III. Key validation characteristics discussed include specificity, selectivity, range, accuracy, precision, detection limit, quantitation limit, linearity and robustness. The document also covers stress studies, system suitability criteria, and the differences between stability indicating and specificity methods.
CCK Discussion Forum on Impurity Emergence: A Wake Up Call for Drug Safety & Quality - 13 Oct 2019 at ICCBS, University of Karachi. Session largely participated by qualified and experienced pharmaceutical professionals having diversified educational background and experience.
Validation of analytical methods involves establishing documented evidence that a process will consistently produce results meeting predetermined specifications. It is necessary to ensure customer satisfaction, comply with regulations, and control costs. Proper documentation of validation activities includes validation master plans, protocols, and reports. Types of validation include process, cleaning, equipment, and validation of analytical methods itself. Method validation parameters that must be checked include selectivity, precision, accuracy, linearity, range, limit of detection, limit of quantification, and robustness. Validation ensures process efficiency and quality for the pharmaceutical industry.
Validation of analytical methods involves establishing documented evidence that a process will consistently produce results meeting predetermined specifications. It is necessary to ensure customer satisfaction, comply with regulations, and control costs. Proper documentation of validation activities includes validation master plans, protocols, and reports. Types of validation include process, cleaning, equipment, and validation of analytical methods itself. Method validation parameters that must be checked include selectivity, precision, accuracy, linearity, range, limit of detection, limit of quantification, and robustness. Validation ensures process efficiency and quality for the pharmaceutical industry.
Validation of analytical methods involves establishing documented evidence that a process will consistently produce results meeting predetermined specifications. It is necessary to ensure customer satisfaction, comply with regulations, and control costs. Proper documentation of validation activities includes validation master plans, protocols, and reports. Types of validation include process, cleaning, equipment, and validation of analytical methods itself. Method validation parameters that must be checked include selectivity, precision, accuracy, linearity, range, limit of detection, limit of quantification, and robustness. Validation ensures process efficiency and quality for the pharmaceutical industry.
Validation and verification of immunoassay methods dr. ali mirjalili Dr. Ali Mirjalili
This document discusses validation and verification of immunoassay methods. It begins with an introduction to immunoassays and classifications. It then discusses standards, terminology, steps in method validation including performance characteristics like precision, accuracy, recovery and qualitative test validation. It also covers test verification. Specific topics covered in depth include precision, accuracy, recovery, linearity, analytical sensitivity, and establishing the reportable range.
This document discusses validation in the pharmaceutical industry. It defines validation as confirming that a process, procedure, or system achieves the desired results. There are various types of validation including process, equipment, facility, analytical method, and computer system validation. Process validation involves establishing scientific evidence that a process is capable of consistently producing quality products. The key stages of process validation are process design, process qualification, and continued process verification. Common validation parameters discussed include accuracy, precision, specificity, linearity, range, limit of detection, limit of quantification, ruggedness, and robustness.
The document discusses the development, optimization, and validation of HPLC methods. It begins by outlining reasons why new HPLC methods may need to be developed, such as when existing methods are not suitable for a new drug or formulation. The document then describes the general steps in HPLC method development, including defining separation goals based on the sample properties, choosing sample pretreatment and detection methods, optimizing the separation conditions, and checking for any problems. Key parameters that require optimization are also outlined, such as the stationary and mobile phases, column, and detector. The document concludes by discussing the process of validating the method, including evaluation of accuracy, precision, linearity, range, specificity, limits of detection and quantification, robustness
Validation of Analytical and Bioanalytical methodssarikakkadam
Guidelines for Validation of Analytical and Bioanalytical methods as per ICH (Q2R1) and USFDA respectively with an example of Bioanalytical method validation.
This document summarizes the ICH Q2 R1 Guideline on validation of analytical procedures. It discusses the objective of validation, which is to demonstrate that an analytical procedure is suitable for its intended purpose. It outlines the types of analytical procedures that should be validated, including identification tests, quantitative impurity tests, limit tests for impurities, and assay procedures. It also describes the key validation characteristics that should be tested, such as specificity, accuracy, precision, detection limit, quantitation limit, linearity, range, robustness, and system suitability. The document provides details on these validation parameters and recommends the type of data that should be collected for each parameter. It also discusses related topics like method verification versus validation and re
The document discusses analytical method validation for good manufacturing practices. It covers validation of pharmacopoeial and non-pharmacopoeial methods, and characteristics that should be considered during validation including accuracy, precision, robustness, specificity, linearity, range, detection limit and quantitation limit. The objectives are to validate analytical methods to demonstrate suitability for their intended purpose and ensure results are reliable, accurate and reproducible.
The document provides guidelines on validation of analytical procedures from the International Conference on Harmonisation (ICH) and the World Health Organization (WHO). It discusses validation characteristics like accuracy, precision, specificity, linearity, range, detection limit and quantitation limit that should be considered when validating identification tests, assays, and tests for impurities. It provides definitions for key terms and recommendations on how validation of these characteristics should be performed.
This document summarizes guidelines for validating analytical methods as outlined by the International Council for Harmonisation (ICH). It discusses key aspects of method validation that should be considered, including specificity, linearity, range, accuracy, precision, detection limit, quantitation limit, robustness, and ruggedness. Specific procedures for establishing each parameter are provided. The objective of validation is to demonstrate that the analytical method is suitable for its intended purpose by consistently producing reliable results. Validation helps ensure the quality, safety, and efficacy of pharmaceutical products.
The document defines method validation and discusses its importance for developing confidence in analytical methods and meeting regulatory requirements. It describes when validation is necessary, such as for compendial or non-compendial methods. Key validation characteristics are discussed, including accuracy, precision, specificity, linearity, range, detection and quantification limits, and robustness. The document provides guidance on testing for these characteristics and establishing acceptance criteria to ensure analytical methods are suitable for their intended purposes.
Laboratory Validation Methods system pptxdanielmwandu
The document summarizes the presentation on validation of laboratory tests given by Daniel Mwandu. It discusses the importance of method validation for ensuring accurate and reliable test results. It outlines the key steps in validation including pre-validation, establishing validation parameters to measure trueness, accuracy, precision, etc. and post-validation monitoring. Method validation is important for conforming to standards like ISO 15189 and helps troubleshoot any issues. The presentation used examples to illustrate validation of a new pregnancy test kit.
This presentation include general introduction to validation of analytical method . analytical method validation include following points such as :
Introduction
Objective ,Types of analytical procedures to be validated,Validation parameters as per ICH and USP , cleaning validation , procedure , validation data, accuracy , range , precision, LOD, LOQ ,linearity, ruggedness , robustness
A practical guide to analytical method validation, including measurement unce...Victor Huamaní León
This document provides a practical guide to analytical method validation using a holistic approach. It discusses four key aspects of validation:
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This document provides a summary of key concepts for developing bioanalytical methods in a statistically sound manner. It discusses the importance of understanding assay variability through statistical analysis in order to control methods and ensure reliability. The document recommends a quality by design approach involving scoping experiments, design of experiments, and method optimization to build understanding and control. It emphasizes involving a statistician from the start and using statistical process control charts to monitor methods and manage risk on an ongoing basis. The overall message is that a data-driven method development strategy incorporating statistical principles can improve bioanalytical method performance and control.
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2. Why Method Validation is Important?
1. The purpose of analytical measurement is to get consistent,
reliable and accurate data.
Incorrect measurement results can lead to tremendous costs.
2. Equal importance for those working in a regulated and in an
accredited environment.
U.S. FDA, EMEA, EPA, AOAC, ISO
Analytical Method Validation 2
3. Background
NDA and ANDA must include the analytical procedures necessary
to ensure:
Identity, Strength, Quality, Purity, and Potency of the Drug
Substances and Drug product [21CFR 314.50(d)(l) and
314.94(a)(9)(i)]
Data to establish and reliability [21CFR 211.169(e) and
211.194(a)(2)]
Analytical Method Validation 3
4. Validation is an Old Concept
But There are Many Problems
Lack of documented procedures and documented validation results
Sampling or Sample preparation step contribute to overall error.
Accessories and materials used for equipment qualification are not
qualified.
Limits for Operational Qualification
Lack of software validation and computer system validation
Qualification and validation are done at just one particular point in time.
Adaptation of acceptance criteria for qualification of new system
Analytical Method Validation 4
5. Validation Activity Including
the Complete Analytical Procedure
Sampling
Sample Preparation
Analysis
Data Evaluation Reporting
Analytical Method Validation 5
7. Considerations Prior to
Method Validation
Suitability of Instrument
Status of Qualification and Calibration
Suitability of Materials
Status of Reference Standards, Reagents, Placebo Lots
Suitability of Analyst
Status of Training and Qualification Records
Suitability of Documentation
Written analytical procedure and proper approved protocol with
pre-established acceptance criteria
Analytical Method Validation 7
8. Validation Step
Define the application, purpose and scope of the
method.
Analytes? Concentration? Sample matrices?
Develop a analytical method.
Develop a validation protocol.
Qualification of instrument.
Qualify/train operator
Analytical Method Validation 8
9. Validation Step
Qualification of material.
Perform pre-validation experiments.
Adjust method parameters and/or
acceptance criteria if necessary.
Perform full validation experiments.
Develop SOP for executing the method in routine analysis.
Document validation experiments and results in the
validation report.
Analytical Method Validation 9
10. System Suitability
Validation
Calibration
Pump Injector
Detector Data System
Analyst Method
Sample
Analytical Method Validation 10
11. Verification vs. Validation
Compendial vs. Non-compendial Methods
Compendial methods-Verification
Regulatory analytical procedure in USP/NF
Non-compendial methods-Validation
Alternative analytical procedure proposed by the applicant for
use instead of the regulatory analytical procedure
Analytical Method Validation 11
12. Regulations and Guidelines of
Validation
US FDA 21 CFR (Code of Federal Regulations) Part 210 and 211
Part 210: cGMP in Manufacturing, Processing, Packaging, or Holding of
Drugs; General
Part 211: cGMP for Manufacturing Practice for Finished Pharmaceuticals
ICH Guidelines
Q2A, Text on Validation of Analytical procedures
(March 1995)
Q2B, Validation of Analytical Procedures: Methodology (May 1997)
USP Chapter <1225>
Validation of Compendial Methods
Analytical Method Validation 12
13. The accuracy, sensitivity, specificity, and reproducibility of test methods
employed by the firm shall be established and documented. Such
validation and documentation may be accomplished in accordance with
211.194(a)(2). 21 CFR PART 211 - CURRENT GOOD
MANUFACTURING PRACTICE FOR FINISHED
PHARMACEUTICALS
Subpart I-Laboratory Controls
211.165 Testing and release for distribution (e)
Methods validation means establishing, through documented evidence,
a high degree of assurance that an analytical method will consistently
yield results that accurately reflect the quality characteristics of the
product tested.
21 CFR PART 210 - CURRENT GOOD MANUFACTURING
PRACTICE IN MANUFACTURING, PROCESSING, PACKING,
OR HOLDING OF DRUGS
210.3 Definitions (b) (25)
Analytical Method Validation 13
14. The objective of validation of an analytical procedure is to
demonstrate that it is suitable for its intended purpose
ICH Guideline for Industry Q2A
In practice, it is usually possible to design the experimental work such
that the appropriate validation characteristics can be considered
simultaneously to provide a sound, overall knowledge of the capabilities
of the analytical procedure, for instance: Specificity, Linearity, Range,
Accuracy, and Precision.
ICH Guideline for Industry Q2B
Analytical Method Validation 14
15. ICH/USP Validation Requirements
Precision
Specificity Repeatability
Linearity Intermediate Precision
Range Limit of Detection
Accuracy Limit of Quantitation
Robustness
Analytical Method Validation 15
16. USP Data Elements Required For Assay Validation
Analytical Assay Category 2
Assay
Performance Assay Category 1
Quantitative Limit Tests Category 3
Parameter
Accuracy Yes Yes * *
Precision Yes Yes No Yes
Specificity Yes Yes Yes *
LOD No No Yes *
LOQ No Yes No *
Linearity Yes Yes No *
Range Yes Yes * *
Ruggedness Yes Yes Yes Yes
* May be required, depending on the nature of the specific test.
Category 1: Quantitation of major components or active ingredients
Category 2: Determination of impurities or degradation products
Category 3: Determination of performance characteristics Analytical Method Validation 16
17. ICH Validation Characteristics vs.
Type of Analytical Procedure
Type of Analytical Impurity testing
Identification Assay
Procedure Quantitative Limit Tests
Accuracy No Yes No Yes
Precision
Repeatability No Yes No Yes
Interm. Prec. No Yes No Yes
Specificity Yes Yes Yes Yes
LOD No No Yes No
LOQ No Yes No No
Linearity No Yes No Yes
Range No Yes No Yes
Analytical Method Validation 17
18. Specificity
Ability of an
analytical method
to measure the
analyte free from
interference due to
Selectivity
other components. Bias
Analytical Method Validation 18
19. Specificity: ICH/USP
An investigation of specificity should be conducted
during the validation of an identification test, an
impurities assay, and a potency assay.
Procedures used will depend on the intended
objective of the analytical procedure.
If a method can not completely discriminate, two
of more procedures are recommended.
Analytical Method Validation 19
20. Specificity: Identification
Should be able to discriminate between compounds
closely related in structure.
Confirmed by obtaining negative results for samples
with spiked related compounds and positive results
for samples with analyte.
Choice of potential interfering substances should be
based on sensible scientific judgment considering
substances that could likely occur.
Analytical Method Validation 20
21. Specificity: Impurities/Assay
Chromatographic Methods
Demonstrate Resolution
Impurities/Degradants Available
Spike with impurities/degradants
Show resolution and a lack of interference
Impurities/Degradants Not Available
Stress Samples
For assay, Stressed and Unstressed Samples should be
compared.
For impurity test, impurity profiles should be compared.
Analytical Method Validation 21
22. Pure and Impure HPLC peaks
Peak purity tests can also be evaluated with
The spectra of Photodiode array detectors
Mass spectrometry
Analytical Method Validation 22
23. Specificity: Potential Interference
Placebo
Drug Substance Degradants
Drug Product Degradants
Related Substances
Packaging Extractables
Analytical Method Validation 23
24. Forced Degradation Studies
Heat High Temperature (50 to 60 oC)
Humidity Humidity (70 to 80%)
Acid Hydrolysis Acid Hydrolysis (0.1 N)
Base Hydrolysis Base Hydrolysis (0.1 N)
Oxidation Peroxide Oxidation (3 to 30%)
Light Intense UV/Visible Light
Intent is to create 10 to 30 % Degradation
Analytical Method Validation 24
26. Linearity
Ability of an assay
to elicit a direct and
proportional
response to
changes in analyte
concentration.
Analytical Method Validation 26
27. Linearity Should be Evaluated
By Visual Inspection of plot of signals vs. analyte
concentration
By Appropriate statistical methods
Linear Regression (y = mx + b)
Correlation Coefficient, y-intercept (b), slope (m),
residual sum of squares
Requires a minimum of 5 concentration levels
Analytical Method Validation 27
28. Linearity Example
R square = 0.999
Slope = 0.97
y-intercept = 0.233
Line Eq.: Y = 0.97X + 0.233
Std. Error = 1.319
Std. Deviation of Slopes = 0.0079
Analytical Method Validation 28
29. Range
The interval between the
upper and lower
concentrations of analyte
in the sample that have
been demonstrate to have
a suitable level of
precision, accuracy, and
linearity.
Analytical Method Validation 29
30. Range
Normally derived from Linearity studies.
Established by confirming that the method provides
acceptable degree of linearity, accuracy, and
precision.
Specific range dependent upon intended
application of the procedure.
Analytical Method Validation 30
31. Minimum Specified Range:
For Drug Substance & Drug product Assay
80 to 120% of test Concentration
For Content Uniformity Assay
70 to 130% of test Concentration
For Dissolution Test Method
+/- 20% over entire Specification Range
For Impurity Assays
From Reporting Level to 120% of Impurity Specification for
Impurity Assays
From Reporting Level to 120% of Assay Specification for
Impurity/Assay Methods
Analytical Method Validation 31
32. Accuracy
Closeness of the test
results obtained by the
method to the true value.
Analytical Method Validation 32
33. Accuracy
Should be established across specified range of analytical
procedure.
Should be assessed using a minimum of 3 concentration
levels, each in triplicate (total of 9 determinations)
Should be reported as:
Percent recovery of known amount added (reference material) or
The difference between the mean assay result and the accepted
value
Analytical Method Validation 33
34. Accuracy Data Set (1 of 3)
% Recovery % Recovery
Amount
Amount Percent 99.2 98.9
Found Recovery
Added (mg)
(mg) 99.3 99.3
0.0 0.0 ---
99.4 99.7
50.2 50.4 100.5
Mean 99.3 99.3
79.6 80.1 100.6
Std.dev. 0.1 0.4
99.9 100.7 100.8
95%C.I 99.3±0.25 99.3±0.99
Analytical Method Validation 34
35. Analyte recovery at different
concentration
Analyte Ingred. (%) Analyte ratio Unit Mean recovery (%)
100 1 100 % 98-102
≥ 10 10-1 10 % 98-102
≥1 10-2 1% 97-103
≥ 0.1 10-3 0.1% 95-105
0.01 10-4 100 ppm 90-107
0.001 10-5 10 ppm 80-110
0.0001 10-6 1 ppm 80-110
0.00001 10-7 100 ppb 80-110
0.000001 10-8 10 ppb 60-115
0.0000001 10-9 1 ppb 40-120
AOAC manual for the Peer-Verified Methods program
Analytical Method Validation 35
36. Precision
Ball Ball Strike Strike
Ball Strike
Ball Ball Ball StrikeStrike
The closeness of agreement Ball Ball Strike
(degree of scatter) between a
series of measurements obtained
from multiple samplings of the
same homogeneous sample.
Should be investigated using
homogeneous, authentic samples.
Analytical Method Validation 36
37. Precision… Considered at 3 Levels
Repeatability
Intermediate Precision
Reproducibility
Analytical Method Validation 37
38. Repeatability
Express the precision Should be assessed
under the same using minimum of 9
operating conditions determinations
over a short interval (3 concentrations/ 3
of time. replicates) or
Also referred to as Minimum of 6
determinations at the
Intra-assay precision
100% level.
Analytical Method Validation 38
39. Intermediate Precision
Express within-laboratory Depends on the
variations. circumstances under which
Expressed in terms of standard the procedure is intended
deviation, relative standard to be used.
deviation (coefficient of variation) Studies should include
and confidence interval. varying days, analysts,
Known as part of Ruggedness in equipment, etc.
USP
Analytical Method Validation 39
40. Repeatability & Intermediate Precision
Day 1 Day 2
100.6 99.5
100.8 99.9
100.1 98.9
100.3 99.2
100.5 99.7
100.4 99.6
Mean = 100.5 Mean = 99.5
RSD = 0.24% RSD = 0.36%
CI = 100.5 ± 0.24 CI = 99.5 ± 0.36
Grand
Mean = 100.0
RSD = 0.59%
Analytical Method Validation 40
41. Reproducibility
Definition: Ability reproduce data within the
predefined precision
Determination: SD, RSD and confidence interval
Repeatability test at two different labs.
Note: Data not required for BLA/NDA
Analytical Method Validation 41
42. Reproducibility Study
Lab 1 Lab 2 Lab 3
Day 1 Day 2 Day 1 Day 2 Day 1 Day 2
Analyst Analyst Analyst Analyst Analyst Analyst
1 2 1 2 1 2
3 Preps 3 Preps 3 Preps 3 Preps 3 Preps 3 Preps
Analytical Method Validation 42
44. Detection Limit (DL) Quantitation Limit (QL)
Lowest amount of analyte in a Lowest amount of analyte in a
sample that can be detected sample that can be quantified
but not necessarily quantitated. with suitable accuracy and
precision.
Estimated by Signal to Noise
Estimated by Signal to Noise
Ratio of 3:1.
Ratio of 10:1.
Analytical Method Validation 44
45. Detection Limit (DL) and Quantitation
Limit (QL) Estimated by
1. Based in Visual Evaluations
- Used for non-instrumental methods
2. Based on Signal-to Noise-Ratio
- 3:1 for Detection Limit
- 10:1 for Quantitation Limit
3. Based on Standard Deviation of the Response
and the Slope
Analytical Method Validation 45
47. Detection Limit (DL) and
Quantitation Limit (QL)
3.3s 10s
DL = QL =
S S
S = slope of calibration curve
s = standard deviation of blank readings or
standard deviation of regression line
Validated by assaying samples at DL or QL
Analytical Method Validation 47
48. Robustness
Definition: Capacity to remain unaffected by small
but deliberate variations in method parameters
Determination: Comparison results under differing
conditions with precision under normal conditions
Variations may include: stability of analytical solution,
variation of pH in a mobile phase, different column
(lot/supplier), temperature, flow rate.
Analytical Method Validation 48
52. Robustness-Mobile Phase Change
MeOH/ Retention Retention
Resolution
Water Time 1 Time 2
75:25 11.94 16.41 7.39
80:20 8.47 11.17 6.17
85:15 7.81 10.18 5.93
Analytical Method Validation 52
53. ICH/USP System Suitability
ICH USP 23 <621>
System Suitability Requirements
Definition: evaluation of
equipment, electronic, Parameters Recommendations
analytical operations and
K’ In general k’ ≥ 2.0
samples as a whole
R > 2, between the peak of
Determination: repeatability, interest and the closest
R potential interferent
tailing factor (T), capacity (degradant, internal STD,
impurity, excipient, etc…..)
factor (k’), resolution (R), and
T T≤2
theoretical Plates (N)
N In general N > 2000
Repeatability RSD ≤ 2.0% (n ≥ 5)
Analytical Method Validation 53
54. Guidance on Re-Validation
“When sponsors make changes in the analytical
procedure, drug substance, drug product, the
changes, may necessitate revalidation of the
analytical procedures.”
“The degree of revalidation depends on the nature
of the change.”
“FDA intends to provide guidance in the future on
post-approval changes in analytical procedures.”
Analytical Method Validation 54
55. References
‘Analytical Methods Validation for FDA Compliance’ 교육교재 The Center for
Professional Advancement 2003. 3.12-14.
Guideline for submitting samples and analytical data for kethods validation
(Feb. 1987)
ICH Q2A
ICH Q2B
21 Code of Federal Registrations Part 210 and 211
Michael E. Swatrz and Ira S. Krull, Analytical method development and
validation. Mrcel Dekker, Inc. New York, 1997.
USP 23 <1225>
http://www.waters.com
Ludwig Huber, Validation and Qualification in Analytical Laboratories,
Interpharm Press Inc. Buffalo Grove, Illinois, 1999.
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