The ICH guidelines provide validation requirements for analytical procedures including accuracy, precision, specificity, linearity, range, limit of detection, and limit of quantification. Accuracy and precision should be established across the specified range and determined using multiple concentration levels in triplicate. Precision has three levels - repeatability under short-term conditions, intermediate precision over longer time periods and varied conditions, and reproducibility between laboratories. The limits of detection and quantification establish the lowest levels that can be detected and quantified. Linearity is evaluated across several concentration levels and statistical measures. The range demonstrates performance within the intended concentrations. Specificity ensures no interference from impurities or matrix.

1. Topic- ICH Guidelines for Validation of Equipments
Institute of Pharmaceutical Research
Presented by- Sakshi Singh
Subject- Modern Pharmaceutics (MPH103T)
M.Pharm Ist year (Sem I)
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2. ICH GUIDELINES OF VALIDATION OF EQUIPMENT
ICH Q2 Guidelines are followed for validation of equipment which
define the objective of validation of an analytical procedure to demonstrate
that it is suitable for its intended purpose.
• It includes
1. Accuracy
2. Precision
 Repeatability
 Intermediate
 Reproducibility

3. Cont..
3. Limit of detection
4. Limit of Quantization
5. Linearity
6. Range
7. Specificity

4. ACCURACY
• 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. This is sometimes termed trueness.
• Accuracy should be established across the specified range of the analytical
procedure
• Should be assessed using a minimum of 3 concentration levels, each in triplicate
(total of 9 determinations)

5. PRECISION
• The precision of an analytical procedure expresses the closeness of agreement
between a series of measurements obtained from multiple sampling of the same
homogeneous sample under the prescribed conditions.
• Precision considered at three levels
i. Repeatability
ii. Intermediate precision
iii. Reproducibility

6. i. REPEATABILITY
• Express the precision under the same operating conditions such as same
measurements, same procedures, same equipment etc. over a short interval of
time.
• Also referred to as Intra-assay precision
• Should be assessed using minimum of 9 determinations (3 concentrations/ 3
replicates) or
• Minimum of 6 determinations at the 100% level.

7. ii INTERMEDIATE PRECISION
• Intermediate precision expresses within-laboratories variations: the precision
obtained within a single laboratory over a longer period of time (generally at least
several months) and takes into account more changes than repeatability. different
days, different analysts, different equipment, etc.
• These factors are constant within a day (i.e. behave systematically within day
timescale) but are not constant over a longer time period and thus behave as
random in the context of intermediate precision.
• It is not considered necessary to study these effects individually. The use of an
experimental design (matrix) is encouraged

8. iii REPRODUCIBILITY
• Reproducibility expresses the precision between laboratories OR inter-laboratory
trial
• It is beneficial when an analytical method is standardized or is going to be used in
more than one laboratory (e.g. method developed in R&D departments).
• It is not always needed for single lab validation

9. LIMIT OF DETECTION (LOD)
• 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.
• Several approaches for determining the detection limit are possible.
a. Based on visual evaluation: 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.
b. Based on Signal-to-Noise Approach: This approach can only be applied to
analytical procedures which exhibit baseline noise. Estimated by Signal to
Noise Ratio of 3:1.

10. LIMIT OF QUANITIATION (LOQ)
• 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. There are two types-
a. Based on visual evaluation-Visual evaluation may be used for non-
instrumental methods but may also be used with instrumental methods.
b. Based on Signal to Noise - This approach can only be applied to analytical
procedures which exhibit baseline noise. Estimated by Signal to Noise Ratio of
10:1

11. 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.
• Linearity should be evaluated
i. By Visual Inspection of plot of signals vs analyte concentration
ii. By Appropriate statistical methods :
 Linear Regression (y = mx + b)
 Correlation Coefficient, y-intercept (b), slope(m)
iii. Acceptance criteria: Linear regression r2 >0.95
• Requires a minimum of 5 concentration levels

12. 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.
• Acceptable range having linearity, accuracy, precision.
a. For Drug Substance & Drug product Assay
 80 to 120% of test Concentration
b. For Content Uniformity Assay
 70 to 130% of test Concentration
c. For Dissolution Test Method
 +/- 20% over entire Specification Range
d. For Impurity
 From MDL to 100% of Impurity Specification Limit

13. SPECIFICITY
•Ability of an analytical method to measure the analyte free from interference due
to other components which include impurities, degradants, matrix, etc.
•An investigation of specificity should be conducted during the validation of :
•Identification tests- suitable identification tests should be able to discriminate
between compounds of closely related structures which are likely to be present.
•Determination of impurities -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 -to provide an exact result which allows an accurate statement on the content
or potency of the analyte in a sample.