Analytical method validation reports form an integral part of product dossiers for the approval of pharmaceutical products and pharmaceutical substances.
Nowadays all countries require that analytical method validation reports with complete chromatograms and raw data must be be submitted along with the dossiers for evaluation and approval of the products.
Method validation is defined as the generation of documented evidence which establishes the suitability of the method for its intended use.
As part of the method validation a number of parameters are required to be established and must meet the globally acceptable acceptance criteria is laid down under the ICH guidelines and in various pharmacopoeia.
Why Method Validation Is Important?
The primary objective of analytical method validation is to ensure overall effectiveness, which is required to be seen through its shelf life; this is done with specific emphasis on the various specifications that were produced during the developmental phase.
With validation, there will be a sure-shot way of determining that the selective method yields results that are reproducible, reliable, and consistent. Hence it must also be ensured that the procedure to be used should be defined with absolute clarity.
There are a few objectives of the method validation study:
- Keeping in mind the acceptance criteria, extensive testing must be done to ensure and guarantee a certain level of consistency.
- Post defining the operating limits, variables must be assessed depending on the effect they have on the testing method.
- It is also essential to find ways to increase productivity and quality while identifying any issues faced during the testing phase.
Method Validation Protocols
Among the method validation protocols, we see the two types; pharmacopoeial and non-pharmacopoeial.
Pharmacopoeial Method: Put in simple words, this type of testing is essential when it comes to analysing the materials used in pharmaceuticals. When this method is used, it must be initially tested thoroughly to see if it can adapt to being routinely used in the laboratory.
Another key aspect that needs to be followed is to be specific with the content present in certain substances strictly without the presence of a placebo.
Non-pharmacopoeial Method: The only rule with this method is that it needs to be validated appropriately.
With most valid testing techniques, the high-pressure liquid chromatography (HPLC) method is known to be one of great efficiency. The simplest way of understanding the HPLC method is that it is a procedure used to separate and identify different components that are present in a certain chemical mixture.
There are certain characteristics that need to be observed during this analysis.
Accuracy: With most test results, there will be an acceptable or true result. Accuracy is explained as getting results as close and agreeable to the true result as possible.
Precision: This is described as the degree of agreement among the various individual test results. It is ideally measured as a bunch of individual results from the mean, which is expressed as the relative standard deviation.
There is also an intermediate precision which talks about the variations that are existent within laboratories.
But if reproducibility has been assessed then there is no reason for the intermediate precision to be executed. In terms of reproducibility, it is viewed as the precision seen between different laboratories.
Repeated Assessment: Nine determinants encompassing a specific range must be assessed to get the optimum results.
Robustness or Rigidity: This describes the ability of a certain procedure to be able to churn out consistent and accurate results despite condition (operational and environmental) changes.
Testing for Robustness: There are specific factors that influence the rigidity of a testing method.
- Stability of the test
- Extraction time
- Temperature and flow rate
- Variations of the pH in a mobile phase and mobile phase composition
Validation in the pharmaceutical laboratory is critical to ensure that they are suitable for the analysis being carried out. In this aspect, there are a few general rules or criteria that can be followed for fruitful execution.
- A clear demarcation and specifications must be laid out for products and materials. Every test performed must be explained in the documentation on standard test methods.
- The standard test methods to be used must be in accordance with the specifications set by regulatory bodies in the case of pharmacopoeial methods and non-pharmacopoeial methods.
- The validation of the study must contain clear reference material, documented in a concise manner.
- An important aspect of the method validation is that the results should be accurate, reliable and, crucially, reproducible.
- Re-validations must be attempted only when there are procedural changes in the synthesis of the substance, when the final product has changed in composition, a change in the analysis method, or when there is a need for the equipment to be modified.
- It must also be ensured that stringent checks are done on the qualifications of the analysts responsible for certain tests.
Why Choose Arbro for Method Validation?
Our laboratory has carried out hundreds of method validation studies for leading pharmaceutical companies in India and around the world helping them successfully register their products in various countries.
We follow a systematic process for conducting validation studies so that the correct data can be submitted in a time bound manner.
We follow these steps –
- The exact analytical method to be followed is shared in the form of a standard testing procedure for approval.
- After the approval of the standard testing procedure a draft method validation protocol is developed.
- The draft method validation protocol is submitted to the client for approval.
- If there are any recommendations from the client these are incorporated into the method validation protocol.
- A final method validation protocol is issued.
- Method validation studies are initiated and carried out as per the protocol.
- After completion of the method validation or draft method validation report is prepared and submitted to the client along with the raw data.
- Once the client gives the go-ahead for preparation of final report the final report incorporating any suggestions a correction this prepared.
- The final report along with all raw data as well as soft copy of the chromatographic data is submitted to the client.
- If there are any queries from the regulatory bodies on the method validation is data submitted we help our clients answer these queries and also carry out additional experiment work if there is a need.
The table below provides a list of some of the common parameters along with their acceptance criteria which are evaluated as part of a method validation exercise.
|S. No||Validation Parameters||Acceptance Criteria|
|% RSD||NMT 10.0|
|2.0||Limit of Detection(Signal to Noise Ratio)||NLT 3:1|
|3.0||Limit of Quantification(Signal to Noise ratio)||NLT 10:1|
|4.0||Specificity||There should not be any interference between the responses of blank, sample and standard.|
|5.1||System Precision||RSD NMT 10.0%|
|5.2||Method Precision||RSD NMT 10.0%|
|5.3||Intermediate Precision||Overall RSD NMT 10.0%|
|6.0||Linearity||Coefficient Correlation NLT 0.99|
(Between 50 to 150 % of the specification limit)
|50 – 150 %|
|9.1||Dilution Integrity |
|NMT 15.0 %|
|NMT 10.0 %|
If you have any requirement for method validation on HPLC, GC, ICP MS or any other technique including microbiology please feel free to contact us by using the quick query form on the right or you can even call us now on +91 – 11 – 45754575 and our team of experts will be happy to help you.