Table of Contents
1.INTRODUCTION (4)
2.SCOPE4
3.RESPONSIBILITY (4)
4.GLOSSARY OF TERMS (5)
4.1Validation Tests (5)
4.2Analytical Method (5)
4.3Acceptance Criteria (5)中国游泳队
4.4System Suitability Tests (5)
4.5Specificity (5)
4.5.1Identification (5)
4.5.2Impurity tests (5)
4.5.3Assay (content or potency) (6)
4.6Accuracy (6)
4.7Precision (6)
4.7.1Repeatability (6)
4.7.2Intermediate precision (6)
4.7.3Reproducibility (6)
4.8Detection Limit (DL) (6)
4.9Quantitation Limit (QL) (7)
4.10 Linearity (7)
4.11 Range (7)
4.12 Robustness (7)
4.13 Impurity (7)
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4.14 Degradation Product (7)
4.15 Excipient (7)
4.16 Placebo (Blank Formulation) (7)
中学生必背古诗词4.17 Synthetic Formulation (Spiked Placebo) (8)
4.18 Standard Formulation (8)
4.19 Coefficient of Variation (CV) or Relative Standard Deviation (RSD) (8)
4.20 Peak Area Ratio (PAR) (8)
4.21 Working Concentration (Nominal Concentration) (8)
5.PARAMETERS FOR VALIDATION ACCORDING TO TEST METHOD (9)
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6.SPECIFICITY (10)
7.LINEARITY (11)
8.RANGE (12)
9.ACCURACY (RECOVERY) (13)
10.PRECISION (16)
11.DETECTION LIMIT (18)
12.QUANTITATION LIMIT (20)
13.ROBUSTNESS (21)
14.METHOD VALIDATION GUIDELINE SUMMARIES AND ACCEPTANCE
CRITERIA FOR HPLC ASSAY METHODS (24)
15.EXAMPLE OF A GENERIC METHOD VALIDATION PROTOCOL (30)
AMENDMENT HISTORY (32)
1.INTRODUCTION
君子谋道不谋食This document provides Company standards for validating analytical methods for drug substance and drug product. Its applicability and interpretation are defined in CAP001. This document will ensure that a consistent, acceptable approach is taken throughout the Group companies in confirming that our analytical methods are suitable for their intended u. Concepts prented in this document may be generally applicable to other materials such as blends and raw materials and may be applied to other analytical techniques where appropriate.
This document will follow the guidelines given in ICH documents.
2.SCOPE
This version of the method validation guideline has been written with specific references to HPLC assay, impurity and identity testing for drug substances and drug products. The guidelines in this document may also be applied to other techniques. Additional validation guidelines are referenced in parate CAPs.
The procedures covered in this document are guidelines and can be applied to drug substance and drug product method validation exercis. In the early stages of development of a novel drug or formulation, partial validation will usually be acceptable. The principles also apply to method re-validation, which may be required becau of a change in formulation, a manufacturing process, in an analytical method, or when the regulatory standards change. The acceptance criteria for the parameters described in ctions 6 - 13 can be found in ction 14.
3.RESPONSIBILITY
Performing the appropriate level of validation for an analytical method is the direct responsibility of the validating scientist and their line management. However, a "one-team" approach to method development and validation is highly recommended. The "one-team" approach requires that the method development and validation group, communicate and interact with the end-ur group throughout the development, validation, reporting and transfer of the method.
4.GLOSSARY OF TERMS
4.1Validation Tests
Tests done to show that the method is scientifically sound and adequate for the intended u.
4.2Analytical Method
The analytical method refers to the way of performing the analysis. It should describe in detail the steps necessary to perform each analytical test. This may include but is not limited to the sample, the reference standard and the reagents preparations, u of the
equipment/apparatus, generation of the calibration curve, u of the formulae for the calculation, etc.
4.3Acceptance Criteria
Criteria which validation test results should meet for the method to be acceptable.
4.4System Suitability Tests
Tests performed when a system is t up for a method to ensure that the system meets criteria required for reliable assay. System suitability tests are intended to be carried out each time a system is t up for a particular analysis. They ensure conditions and hence results are reproducible both qualitatively and quantitatively.
4.5Specificity
Note:This document refers to the term specificity, as this is now the preferred ICH terminology and should be ud instead of the term lectivity.
Specificity is the ability to asss unequivocally the analyte in the prence of components that may be expected to be prent. Typically the components might include impurities, degradation products, excipients, 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:
4.5.1Identification
To ensure the identity of an analyte.
什么运动最减肥4.5.2Impurity 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.
4.5.3Assay (content or potency)
To provide an exact result which allows an accurate statement on the content or potency of the analyte in a sample.
4.6Accuracy
The accuracy of an analytical procedure express the cloness of agreement between the value that is accepted either as a conventional true value or an accepted reference value and the value found.
4.7Precision
论文正文格式The precision of an analytical procedure express the cloness of agreement (degree of scatter) between a ries of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions. 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 expresd as the coefficient of variation of a ries of measurements.
雪梨冰糖水的功效Precision may be considered at three levels: repeatability, intermediate precision and reproducibility.
4.7.1Repeatability
Repeatability express the precision of a homogeneous sample under the same operating conditions over a short interval of time by one analyst using one instrument.
4.7.2Intermediate precision
Intermediate precision express the precision of a homogeneous sample within a laboratory on different days, different analysts and different equipment, possibly in the same laboratory.
4.7.3Reproducibility
Reproducibility express the precision between laboratories. Current ICH guidelines suggest that reproducibility is usually determined by inter-laboratory collaborative study. (Reproducibility is not required for NDA and MAA filings and is only required for pharmacopoeial registration).
4.8Detection Limit (DL)
The Detection Limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be reliably detected.
