Analytical method validation

Analytical Method Validation [ICH Q2(R1)]:

Analytical Method Validation [ICH Q2(R1)] By Mr. kunal C Mehta Department of quality assurance Shree devi college of pharmacy mangalore

Analytical Methods - Introduction:

Analytical Methods - Introduction Methods involved in the analysis of a drug substance/drug product. Analytical methods are broadly: Physical methods Chemical methods In chemical methods: Qualitative methods Quantitative methods

Types of Analytical Procedures to be Validated :

Identification tests Testing for impurities Assay Procedures, dissolution, CU etc.. Types of Analytical Procedures to be Validated

Typical validation characteristics :

Typical validation characteristics Accuracy Precision Repeatability Intermediate Precision Specificity Detection Limit Quantitation Limit Linearity Range

Accuracy:

Accuracy 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. A study of recovery was conducted

Precision:

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. The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements.

Precision - Repeatability:

Precision - Repeatability Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision By calculating the assay of six individual samples Precision – Intermediate precision Intermediate precision expresses within-laboratories variations: different days, different analysts, different equipment, etc. Analyst to analyst variability, System to system variability etc Precision - Reproducibility Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology). Covered under analytical method transfer.

Specificity:

Specificity Specificity is the 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. An investigation of specificity should be conducted during the validation of identification tests, determination of impurities (RS) and Assay. Specificity was covered with i) Placebo Interference ii) Impurity interference (By spiking the impurity standards) iii) Interference from degradation products (Forced degradation samples)

Detection Limit:

Detection Limit It is the lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value. Based on Visual Evaluation The detection limit is determined by the analysis of samples with known concentrations of analyte and by establishing the minimum level at which the analyte can be reliably detected. Based on Signal-to-Noise Determination of the signal-to-noise ratio is performed by comparing measured signals from samples with known low concentrations of analyte with those of blank samples and establishing the minimum concentration at which the analyte can be reliably detected. A signal-to-noise ratio between 3 or 2:1 is generally considered acceptable for estimating the detection limit. Based on the Standard Deviation of the Response and the Slope Based on the Standard Deviation of the Blank or Based on the Calibration Curve

Quantitation Limit:

Quantitation Limit It is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy. Validation procedures same as the detection limits.

Linearity:

Linearity The linearity of 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. For the establishment of linearity, a minimum of 5 concentrations is recommended.

Range:

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 :

ROBUSTNESS It 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.

SYSTEM SUITABILITY TESTING :

SYSTEM SUITABILITY TESTING System suitability testing is an integral part of many analytical procedures. The tests are based on the concept that the equipment, electronics, analytical operations and samples to be analyzed constitute an integral system that can be evaluated as such. System suitability test parameters to be established for a particular procedure depend on the type of procedure being validated.

Slide 15:

THANK YOU