Dr Pramod Kumar Pandey BSc (Hons), MSc, PhD, founder of PharmaGuru.co, is a highly experienced Analytical Research Expert with over 31 years in the pharmaceutical industry. He has played a key role in advancing innovation across leading Indian and global pharmaceutical companies. He can be reached at admin@pharmaguru.co
Validation of pharmacopoeial methods should be performed using minimal analytical parameters, focusing primarily on specificity, detection limit, and quantification limit. Pharmacopoeial methods is presumed to be validated and therefore only requires verification or partial validation. What is a Pharmacopoeial Method? Pharmacopoeial methods are analytical procedures published in recognised pharmacopoeias like: These methods are widely accepted […]
Validation of Pharmacopoeial Methods: How to Perform It Properly
Validation of pharmacopoeial methods should be performed using minimal analytical parameters, focusing primarily on specificity, detection limit, and quantification limit.
Pharmacopoeial methods is presumed to be validated and therefore only requires verification or partial validation.
What is a Pharmacopoeial Method?
Pharmacopoeial methods are analytical procedures published in recognised pharmacopoeias like:
United States Pharmacopoeia (USP)
European Pharmacopoeia (EP)
British Pharmacopoeia (BP)
Japanese Pharmacopoeia (JP)
These methods are widely accepted standards. However, despite their official status, they are not “plug and play”—you still need to demonstrate that the method works reliably under your specific laboratory conditions and as per your process requirements.
Validation of Pharmacopoeial Methods: Validation or Verification
Pharmacopoeial methods are presumed to be validated, and should only be verified/validated to be appropriate for the pharmaceutical needs:
Verification is required when:
You adopt a pharmacopoeial method without modification.
You use a method on your own instrument with your specific sample matrix.
Validation is required when:
You modify the pharmacopoeial method.
You use it for a different sample type, concentration range, or formulation.
The method is applied outside of its original scope (e.g., different dosage form).
In case you do not modify the pharmacopoeial method.
At lease the following 3 prameters should be performed:
Specificity
Detection limit
Quantification Limit
Expert Tips: Additional parameters can be considered based on method requirements
In case you modify the pharmacopoeial method.
The follwing validation parameters should be perforomed:
1. Accuracy
How close is your result to the true value?
Typically assessed by recovery studies at different concentrations (e.g., 80%, 100%, 120%).
2. Precision
Repeatability (intra-day): Same analyst, instrument, and day.
Intermediate precision (inter-day): Different analysts, instruments, or days.
3. Specificity
Ability to assess the analyte clearly in the presence of other components (e.g., excipients, impurities).
4. Linearity
The method should show a linear response over a specified concentration range.
5. Range
The interval between the upper and lower concentration of analyte where the method has been shown to be accurate, precise, and linear.
6. Limit of Detection (LOD) and Limit of Quantitation (LOQ)
LOD: Lowest amount that can be detected but not necessarily quantified.
LOQ: Lowest amount that can be quantitatively measured.
7. Robustness
A measure of method reliability under small, deliberate variations (e.g., changes in pH, flow rate, column temperature).
Validation of Pharmacopoeial Methods: Step-by-Step
Step 1: Review the Method Thoroughly
Understand its scope, sample matrix, instrument settings, and limitations.
Step 2: Develop a Validation Protocol
Define the purpose, scope, parameters to be tested, acceptance criteria, and responsibilities.
Step 3: Conduct Experiments
Prepare standards and samples.
Perform trials based on your protocol.
Record all data meticulously.
Step 4: Analyse Data Statistically
Use regression analysis, %RSD, recovery percentage, etc.
Compare results with acceptance criteria.
Step 5: Document Everything
Generate a validation/verification report with:
Summary of results
Deviations (if any)
Conclusion on method suitability
Step 6: Get QA Approval
Submit documentation for QA review and approval before routine use.
Expert Tips: Common Mistakes to Avoid
Skipping robustness studies.
Not documenting instrument calibration.
Assuming USP methods don’t need any verification.
Using unqualified analysts or instruments.
Conclusion
While pharmacopoeial methods carry the weight of authority, their application in your lab must be proven through validation or verification. Regulatory agencies like the FDA and EMA expect proof that methods perform reliably under your conditions, regardless of their origin.
Investing time in proper method validation ensures data integrity, regulatory compliance, and ultimately, patient
Is it necessary to validate a method if it’s already in the USP or other pharmacopoeia?
Not always. If the method is used exactly as described for the same sample type, only method verification is needed to confirm it performs reliably under your laboratory conditions. However, validation is required if any modifications are made or if the method is applied outside its intended scope.
