Robust Validation Studies: Ensuring Quality and Reliability

The importance of validating your method

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:

Demonstrate with a documented evaluation that their MoA is suitable for its intended use, according to the guidelines specified by the regulatory bodies that govern the approval of drugs for human use
Be assured of the quality of the analytical results that they receive from an MoA that is established specifically for their product
Facilitate internal QA/QC reviews and to expedite audits from clients or regulatory bodies, through the full traceability between the MoA and the procedures, systems, and facilities on which its design is based on
Be assured that Vironova offers high quality expertise in method validation, which can be invaluable during the development of the validation study

The method of analysis (MoA)

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.

Why should the method of analysis be validated?

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.

Validating the method of analysis with Vironova

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.

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Preparing a cryoTEM sample in our GMP-certified transmission electron microscopy laboratory

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Validate your method

Contact us to discuss your specific project with our experts. Our experience in the field will be invaluable when validating your method!

Steps in a validation study at Vironova

Establish a method of analysis for the specific product
Perform pre-validation tests, and determine which samples to use in the validation study
Establish a validation plan, considering the following parameters:

- Define the purpose and scope of the validation study
- Define the sample attributes to be tested
- List the materials, equipment, and facilities to be used
- Outline a framework for various validation tests
- Define the acceptance criteria for the various validation tests

4. Perform the validation tests

5. Generate a validation report, which can be submitted to the regulatory authorities

6. Update the validation status of the client-specific MoA

Steps in a validation study at Vironova copy-3

Steps leading to a validated MoA

Contents of a validation plan

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.

Contents of a validation plan copy

What the validation report consists of

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.

Download an example of an AAV batch release report (cryoTEM)

Validation study outline

Request a validation study for your project through the link, and we will contact you to schedule a telephone conference meeting.
In this meeting, we will discuss the tests to be performed as well as timelines and costs of the study. Usually, we recommend performing a small initial feasibility study with your product before the full validation study. The feasibility study takes the same duration as a normal project, approximately ten working days after imaging.
You will be assigned a validation team from Vironova, including a project leader who will maintain communication between all relevant parties during the validation, a validation leader, and QA representative who are responsible for setting up the project plan.
The first draft of the validation plan and the method of analysis will be sent to you for comments, and we recommend that your QA department revise it. This communication takes 3 – 4 weeks.
After the revision, both documents will be approved by Vironova and you. This communication takes around 1 week.
After all the paperwork is approved, a quotation is sent to you and your finance department for approval. All the instructions for sample shipment are also provided and the timeslot allocation will be defined. For regular validations, imaging takes 6 – 8 weeks.
Image analysis and reporting are performed and sent to you. If any questions are raised, they are addressed by a telephone conference or email. You will need to revise and approve the validation reports. This process takes approximately 3 – 4 weeks.
The validation report is approved, and the validation study is finalized. From now on, this specific method will be used to analyze your specific product.

When to perform a re-validation

According to ICH guidelines, re-validation of Analytical Procedures is necessary when there is a change in:

the synthesis of the drug substance
the composition of the finished product
the analytical procedure

Validation studies