Expert Insight: Exclusive Webinar Highlights: Increasing Efficiency of Method Validation with Waters Empower 3® Method Validation Manager (MVM)Validated analytical methods are vital to achieve consistent, accurate and reliable results. In addition to being an integral part of Good Laboratory Practice (GLP), method validation is a legal requirement to meet the standards of most regulatory bodies. There are multiple challenges during the validation process, from planning the analytical testing in the protocol, to the calculation of results and comparison with acceptance criteria.
In this webinar, the validation of a UPLC® method for related substances of Metoclopramide HCl, using the Empower® 3 Method Validation Manager (MVM),
is discussed. Margaret Maziarz, a Senior Scientist at Waters, highlights how you can streamline your workflow throughout the entire validation process. Watch the on-demand webinar
here; download the associated application note
or read on for highlights from the webinar Q&A session. 1. Can Empower MVM be used to calculate recovery of multiple analytes in the spiked samples?
Percent recovery of multiple analytes can be calculated against the bracket standard injections or a calibration curve. From the Alter Sample Set window, an analyst enters the amounts for each component in the standard injections or in a calibration curve. Using menu bar, click Edit > Amounts. Next, the analyst would enter target amounts for the spiked samples. Finally, the analyst processes the sample set. Empower MVM will then compare the calculated amount of each analyte in the spiked sample over the target amount to calculate the percent of recovery. 2. Is MVM built into Empower or do we purchase it from Waters?
MVM is an option for Empower software, which needs to be purchased from Waters. Click here
to view the MVM
product page. 3. Is this version of MVM compatible with Empower 3 FR1 and/ FR2? Does MVM have to be downloaded to the client server or can it be made available to individual projects? Are individual licenses required?
MVM is available with all versions of Empower 3 and Empower 2. However, the functionality has improved between versions and Empower 2 might not have all capabilities you saw in the webinar. The Method Validation Manager is activated on the server as an Enterprise option, and then licensed by the individual number of users that need to use it. When the MVM option is activated, you can then create specific validation projects at the server level. 4. In the Empower 2 MVM, for the design of experiments (DOE) analyst there are only two options: Analyst A and Analyst B. Quite often there are more than two analysts. For Empower 3, is there an option to extend this list for the DOE Analyst?
For DOE Analysts, the default choices in Empower 2 and 3 are Analyst A and Analyst B. You cannot modify the entries for default factors in an MVM protocol. However, you can create your own factors to evaluate using custom fields within the MVM project to record more and different values, as needed for your laboratory. For example, you can create your own factor for ‘Analyst’ with as many different entries as you need. These tailored factors can be investigated in the DOE and displayed in all the reports. Another example for DOE study - you can create your own factor for ‘column’ to include the name and the serial number for different columns. 5. Do you provide validation data to support the software? Does validation need to be done again at installation?
MVM software is validated by our software validation group and extensively tested by our evaluation group prior to release. It does not need to be validated but should always be qualified upon installation. Waters can provide qualification services for MVM along with the Empower qualification or afterwards, if MVM is activated later. Additionally, most regulated laboratories will perform their own validation against their own user requirements to ensure that the software works as intended in their laboratory. Waters can provide validation consultants to assist this process if you do not have your own validation resources in house. 6. How are validation results handled if Out of Specification (OOS) is encountered? Can the created sample sets be repeated. What will happen to the protocol if there are some deviations?
As with any regulated work, OOS results and repeat tests should be investigated and evaluated by the performer and the management before tests are repeated according to your own quality standard operating procedures (SOPs).
If the results from a validation test fail the acceptance criteria, MVM will identify and flag the OOS results. With Empower MVM, you can add the same validation test multiple times. Hence, you can add the same test to the study and re-run the same sample set. Modifications to the protocol and test results will have to be reviewed and approved by authorized personal. 7. Can Empower MVM be used for validation of methods run on other than Waters instrumentation such as Shimadzu? Can you use it for GC method validation?
Empower MVM can be used to validate any chromatographic methods run on instrumentation controlled by Empower software. The validation tests available in Empower MVM were designed for LC methods, but may also be suitable to GC method validation. The validation tests available within Empower 3 MVM software include linearity, linearity comparison, accuracy, repeatability, intermediate precision, intermediate precision DOE, reproducibility, limit of detection and quantitation determination, robustness, specificity, stability, and filter validation.
Empower supports a large number of third party systems. 8. Is there any predefined acceptance criteria stored in the Empower MVM software for each validation element?
No, the acceptance criteria for each validation test are defined by each laboratory. 9. Is there a list of the available calculations built into the MVM?
Formulas for calculating validation results are built into Empower MVM project and are not visible to the user. 10. Can Empower 3 MVM software be used to generate RRF's?
In Empower 3 FR2, MVM can calculate the Relative Response Factor (RRF) in a linearity test relative to a main component's response factor, as well as to the target response factor. In previous releases of the software, Method Validation calculates RRF relative to the target response factor. 11. How will the validation protocol be approved by authorized persons if the protocol is prepared under the EMPOWER 3 environment? What is the approval and archiving process if another department, like Quality Assurance (QA), does not have access to Empower?
Approvals of MVM protocols are performed through Empower. The authorized persons will use their Empower user accounts to approve the validation protocol and results via electronic signatures. With Empower 3 software, different privileges are assigned to users to control level of access to specific functions. If you would like to learn more about compliance of Empower 3 software with the FDA regulations on electronic records and electronic signatures please read this white paper on The Role of Empower 3 Chromatography Data Software in Assisting with Electronic Records Regulation Compliance
. 12. How often do companies evaluate three different batches of HPLC columns during method validation?
The three batches are often evaluated during validation to ensure that the method continues to be robust across three different column batches.