Q&A ON VALIDATION OF ANALYTICAL PROCEDURES – ICH Q2 GUIDELINE PART -9
Question 1:
What is robustness, and when should its evaluation be considered?
Answer 1:
Robustness is the measure of an analytical procedure’s reliability with respect to deliberate variations in method parameters. Its evaluation should be considered during the development phase of the procedure.
Question 2:
What should be done if measurements are susceptible to variations in analytical conditions?
Answer 2:
If measurements are susceptible to variations in analytical conditions, the analytical conditions should be suitably controlled, or a precautionary statement should be included in the procedure.
Question 3:
What are some examples of typical variations that may be considered during the evaluation of robustness?
Answer 3:
Examples of typical variations include stability of analytical solutions, extraction time, variations in pH and composition of mobile phase (for liquid chromatography), different columns, temperature, and flow rate (for both liquid and gas chromatography).
Question 4:
What is the purpose of system suitability testing?
Answer 4:
System suitability testing is conducted to ensure that the equipment, electronics, analytical operations, and samples to be analyzed constitute an integral system that can be evaluated as such. It helps ensure the validity of the analytical procedure whenever it is used.
Question 5:
What factors determine the system suitability test parameters for a particular procedure?
Answer 5:
The system suitability test parameters for a particular procedure depend on the type of procedure being validated. Additional information on these parameters can be found in Pharmacopoeias.
Question 6:
What determines the degree of revalidation required for an analytical procedure?
Answer 6:
The nature of the changes determines the degree of revalidation required for an analytical procedure.
Question 7:
What does specificity refer to in the context of an analytical procedure?
Answer 7:
Specificity refers to the ability to assess the analyte unequivocally in the presence of other components that may be expected to be present, such as impurities, degradants, or matrix.
Question 8:
How can lack of specificity in an individual analytical procedure be compensated?
Answer 8:
Lack of specificity in an individual analytical procedure can be compensated by other supporting analytical procedures.
Question 9:
What are the implications of specificity in analytical procedures?
Answer 9:
The implications of specificity are:
Identification: Ensuring the identity of an analyte.
Purity Tests: Ensuring that all analytical procedures allow for an accurate statement of the content of impurities of an analyte, such as related substances tests, heavy metals, residual solvents content, etc.
Assay (content or potency): Providing an exact result that allows for an accurate statement on the content or potency of the analyte in a sample.
Question 10:
Why is it important to clearly understand the objective of an analytical procedure during its validation?
Answer 10:
Understanding the objective of an analytical procedure is crucial because it governs the validation characteristics that need to be evaluated. This understanding ensures that the validation process aligns with the intended purpose of the analytical procedure.
Question 11:
What are some typical validation characteristics that should be considered during the validation of an analytical procedure?
Answer 11:
Some typical validation characteristics include accuracy, precision, repeatability, intermediate precision, specificity, detection limit, quantitation limit, linearity, and range.
Question 12:
Why is it important to consider validation characteristics during the development of an analytical procedure?
Answer 12:
Considering validation characteristics during the development of an analytical procedure ensures that the procedure is designed to meet the necessary standards for accuracy, precision, and reliability. It helps in identifying potential areas of improvement and ensures that the procedure is fit for its intended purpose.
Question 13:
Why is robustness not listed in the table of important validation characteristics?
Answer 13:
Robustness, although an important aspect of analytical procedure development, is not listed in the table of validation characteristics because it should be considered at an appropriate stage in the development process. Unlike accuracy, precision, and other listed characteristics, robustness is more closely associated with method development and optimization rather than validation.
Question 14:
How should occasional exceptions to the typical validation characteristics be addressed?
Answer 14:
Occasional exceptions to the typical validation characteristics should be dealt with on a case-by-case basis. This means that specific considerations should be made for individual analytical procedures based on their unique requirements, challenges, and intended applications.
