Validating a method of analysis (MoA) for a given product is an integral part of good manufacturing practice (GMP), assuring quality, reliability, and consistency in analytical testing. A validated MoA assures the reliability of the analytical results by demonstrating that the analytical method is suitable for its intended purpose with documented evidence.
Validating the method of analysis with Vironova’s EM Services enables our clients to:
The MoA is an analytical procedure that is established to analyze a critical quality attribute in the product. Vironova’s EM Services specializes in the application of cryogenic transmission electron microscopy (cryoTEM) and negative stain transmission electron microscopy (nsTEM) for the direct visualization of nanosized particles and their subsequent analysis using Vironova’s proprietary software, Vironova Analyzer Software (VAS).
In our GMP-certified transmission electron microscopy (TEM) laboratory, our qualified personnel conduct cryoTEM and nsTEM analyses according to standard operating procedures (SOPs). The SOPs are general documents to which we follow closely in the laboratory. However, for certain client products, Vironova designs specific MoA that are compliant with the guidelines defined by the regulatory authorities (e.g., FDA, EMA). For these client-specific methods of analysis, Vironova offers validation studies that are performed according to the principles of Validation of Analytical Procedures, ICH Q2 (R1). A validated MoA assures that the chosen TEM method is a suitable analytical technique for evaluating specific attributes of a certain product.
It is important to demonstrate that the results generated using the MoA are reliable and repeatable, with an acceptable precision. Moreover, it is crucial to assure that the analytical results are reproducible under different conditions and are not affected by external factors. For this reason, different tests (e.g., specificity, precision, robustness) are performed in a validation study as applicable per the guidelines.
In a method validation, several tests are performed to evaluate the performance of the MoA in terms of, for instance, the precision of results it generates, and thereby, its suitability for analyzing critical quality attributes of a specific product.
As an example, a MoA based on cryoTEM can be established to determine the ratio of filled and empty adeno-associated virus (AAV) vectors. The performance of the MoA can be demonstrated in a validation study by performing several applicable validation tests. Some of these tests may be performed by different personnel on separate occasions. After testing, the results are compared to predefined acceptance criteria and registered in a validation report. Based on the results, a conclusion on the suitability of the MoA for that specific product can be made.
Preparing a cryoTEM sample in our GMP-certified transmission electron microscopy laboratory
Steps leading to a validated MoA
Vironova has developed procedures referring to the ICH Q2 (R1) Guideline on Validation of Analytical Procedures, to ensure that the method validation fulfils the requirements.
A validation report provides a summarized overview of tests, results, comments, and deviations observed during the validation study. Moreover, it concludes if the proposed method of analysis is suitable for its intended purpose and if there are any limitations of the method. This document may be submitted by the client to regulatory authorities when required to confirm that the use of cryoTEM or nsTEM is suitable as an analytical method for that specific product.
According to ICH guidelines, re-validation of Analytical Procedures is necessary when there is a change in: