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Analytical Method Validation Introduction.pptx
Introduction and Guidance for Method Development
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Analytical Method Validation Introduction.pptx
- 1. Analytical Method Validation MS. NEHAS. RAUT ASSISTANT PROFESSOR SMT. KISHORITAI BHOYAR COLLEGE OF PHARMACY, KAMPTEEE
- 2. CONTENTS INTRODUCTION ANALYTICALMETHOD DEVELOPMENT METHOD VALIDATION OBJECTIVES OF VALIDATION HIGH PERFORMANCE LIQUID CHROMATOGRAPHY UV SPECTROPHOTOMETRY CONCLUSION REFERENCES
- 3. INTRODUCTION Analytical chemistrydeals with the separation, quantification and chemical components identification of natural and artificial materials constituted with one or more compounds or elements Categories: Qualitative Analysis; Quantitative Analysis The examination of pharmaceutical formulations and bulk drugs regarding the quality control and assurance. Rapid increase in pharmaceutical industries and production of drug in and around the world cause increase in demand to seek novel and systematic analytical techniques in the pharmaceutical industries Analytical method development has become the basic activity of analysis
- 4. Development inscientific and concrete analytical methods has been resulted from the advancements of analytical instruments The improvements of the analytical method development and analytical instruments have reduced the time and cost of analysis and enhanced precision and accuracy Techniques applicable to analysis are developed and validated for active pharmaceutical ingredients, excipients, related substances, drug products, degradation products and, residual solvents, etc
- 5. ANALYTICAL METHOD DEVELOPMENT To test and ensure the Quality of Drug substances/ Drug products. To analyze the existing either pharmacopoeial or non-pharmacopoeial products, novel methods are developed to reduce the cost besides time for better precision and ruggedness These methods are optimized and validated through trial runs. Purpose of analytical method development… When there is no official drug or drug combination available in the pharmacopoeias When there is no decorous analytical process for the existing drug in the literature due to patent regulations When there are no analytical methods for the formulation of the drug due to the interference caused by the formulation excipients Analytical methods for the quantitation of the analyte in biological fluids are found to be unavailable The existing analytical procedures may need costly reagents and solvents.
- 6. Steps forthe development of the method Analyte standard characterization Method requirements Literature search and prior methodology Choosing a method Instrumental setup and initial studies Optimization Documentation Evaluation of development method with real samples Estimation of percent recovery of real samples and demonstration of quantitative sample analysis
- 7. Guidance for MethodValidation CDER : “Analytical Procedures and Method Validation” Draft guidance August 2000 ICH: Validation Of Analytical Procedures: Text And Methodology Q2(R1) 2005. USP 41: General Chapter Validation of Compendial Methods
- 8. Types of AnalyticalProcedures to be Validated Identification tests; Eg. FTIR spectrum Quantitative tests for impurities' content; Eg. 10ppm to 2% Limit tests for the control of impurities; Eg. < 100ppm Quantitative tests of the active moiety in samples of drug substance or drug product or other selected component(s) in the drug product. Eg. 99-101%
- 9. VALIDATION Validation isa documented evidence of the consistency of the any process OR system. The process of validation of analytical method is adopted to confirm that the employed analytical procedure for a specific tests meet the intended requirements. Guidelines from the USP, ICH, FDA etc., can provide a framework for validations of pharmaceutical methods. Results from the method validation can be considered to judge its quality, reliability as well consistency applicable to analytical results.
- 10. METHOD VALIDATION Parametersof Analytical Method Validation Analytical methods have been validated in pursuance of ICH guidelines of Q2 (R1). Accuracy Precision Repeatability Intermediate Precision Specificity Detection Limit (LOD) Quantitation Limit (LOQ) Linearity Range System suitability Robustness Ruggedness Furthermore, revalidation may be necessary in the following circumstances: changes in the synthesis of the drug substance; changes in the composition of the finished product; changes in the analytical procedure
- 11. Analytical procedure Characteristics IDENTIFICATION TESTINGFOR IMPURITIES ASSAY - dissolution - content/potency Quantitative Limit test Accuracy No Yes No Yes Precision- Repeatability No Yes No Yes Intermediate precision No Yes No Yes Interm.Precision No Yes No Yes Specificity Yes Yes Yes Yes Detection Limit No Yes Yes No Quantitation Limit No Yes No No Linearity No Yes No Yes Range No Yes No Yes
- 12. Specificity Specificity isthe ability to assess unequivocally the analyte in the presence of components which may be expected to be present. Typically, these might include impurities, degradants, matrix, etc. Lack of specificity of an individual analytical procedure may be compensated by other supporting analytical procedure(s). This definition has the following implications: Identification: to ensure the identity of an analyte. Purity Tests: to ensure that all the analytical procedures performed allow an accurate statement of the content of impurities of an analyte, i.e. related substances test, heavy metals, residual solvents content, etc. Assay (content or potency): to provide an exact result which allows an accurate statement on the content or potency of the analyte in a sample.
- 13. ACCURACY: Trueness The accuracy of an analytical procedure expresses the closeness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found. PRECISION: The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. Precision may be considered at three levels: repeatability, intermediate precision and reproducibility. Precision should be investigated using homogeneous, authentic samples. However, if it is not possible to obtain a homogeneous sample it may be investigated using artificially prepared samples or a sample solution. The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements.
- 14. Repeatability: Repeatabilityexpresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision. Intermediate precision: Intermediate precision expresses within-laboratories variations: different days, different analysts, different equipment, etc. Reproducibility: Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology).
- 15. DETECTION LIMIT: The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value. QUANTITATION LIMIT: The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products.
- 16. LINEARITY: The linearityof an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. RANGE: The range of an analytical procedure is the interval between the upper and lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity. ROBUSTNESS: The robustness of an analytical procedure is a measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage.
- 17. Objectives of Validation Chromatography is the most widely used laboratory technique for separation, identification and quantification of components of liquid and gaseous mixtures. Solid mixtures are also analyzed by first converting them to a liquid or gaseous state, using suitable sample preparation techniques. Principle High performance liquid chromatography (HPLC) is separation technique utilizing differences in distribution of compounds to two phases; called stationary phase and mobile phase. The stationary phase designates a thin layer created on the surface of fine particles a mobile phase designates the liquid flowing over particles. Under a certain dynamic condition, each component in a sample has difference distribution equilibrium depending on solubility in the phases and or molecular size. As a result, the components move at different speed over the stationary phase and thereby separated from each other.
- 18. Calibration “The demonstrationthat a particular instrument or device produces results within specified limits by comparison with those produced by a reference or traceable standard over an appropriate range of measurements”. Calibration of HPLC: Parameters are: Flow rate accuracy Injector accuracy Wavelength accuracy Injector linearity System Precision Detector linearity Column oven temperature accuracy
- 19. Types of detectors A detector gives specific response for the components separated by the column and also provides the required sensitivity. It has to be independent of any changes in mobile phase composition. Majority of the applications require UV-VIS detection though detectors based on other detection technique are also popular these days • UV-VIS detector • Photo diode array detector • Fluorescence detector y detector • Mass spectroscopic detector • Refractive index detector • Electrochemical detector • Light scattering detectors
- 20. CONCLUSION When analyticalmethod 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
Editor's Notes
- #1 Method validation is the process to confirm that the analytical procedure employed for a specific test is suitable for its intended use. Methods need to be validated or revalidated as follows: Before their introduction into routine use Whenever the conditions change for which the method has been validated (e.g., instrument with different characteristics) Whenever the method is changed, and the change is outside the original scope of the method When quality control indicates an established method is changing with time In order to demonstrate the equivalence between two methods (e.g., a new method and a standard) Method validation has received considerable attention
- #5 When no authoritative methods are available, new methods are being developed for analysis of novel products.