ICH M10 Bioanalytical Method Validation Guideline – Part Two: Key Updates and How Technology Can Help

In our last blog post, we took a dive into the 2019 draft of the ICH M10 Bioanalytical Method Validation Guideline, the changes made, and how they affect scientists working at the bench.

In this follow-up post, we’ll see how our scientific informatics platform, the E-WorkBook Cloud and its associated modules, address any concerns bioanalytical scientists may have about the new draft guidance.

QC Placement during the preparation of quality control samples

In this section, the guidance recommended looking at mid-QC levels, applying geometric means as well as arithmetic means for chromatographic assays and ligand binding assays (LBAs).

For chromatographic assays: “During method validation the QCs should be prepared at a minimum of 4 concentration levels within the calibration curve range: the LLOQ, within three times of the LLOQ (low QC), around 30 – 50% of the calibration curve range (medium QC) and at least 75% of the ULOQ (high QC).”

For ligand binding assays: “The QCs should be prepared at a minimum of 5 concentration levels within the calibration curve range: the analyte should be spiked at the LLOQ, within three times of the LLOQ (low QC), around the geometric mean of the calibration curve range (medium QC), and at least at 75% of the ULOQ (high QC) and at the ULOQ.”

The technology piece?

E-WorkBook and the Advance module enable scientists to collate data across the first few bioequivalence study runs. This is to assess all sample results using charts within the spreadsheet to select an additional QC level that should be placed where the majority of subject data resides.

In addition, using the Advance spreadsheet curve fitting engine, you could use a curve from the previous scenario, enter a response that hits a point on the non-linear curve, and have the concentration value instantly calculated to prepare the new QC.

While most laboratory software performs basic calculations, the Advance spreadsheet can also be used as a tool to extend the initial statistical layer and become a tool to aid in scientific review that is either required by an organization’s SOPs or additional regulatory assessments that drive high quality science.

Dilutional Linearity

The guidelines suggest a minimum of three independent runs, followed by sample analysis. Apart from running up operational costs, this approach is time-consuming. However, E-WorkBook can ease these pressures.

“For each dilution factor tested, at least 3 runs should be performed using the number of replicates that will be used in sample analysis.”

The technology piece?

If labs start to implement three independent runs per ICH M10 guidelines, then E-WorkBook enables cloning of experimental records with the ability to update different reagents/plates for each specific run. While the lab sees an increase in work, the documentation is minimal since the experimental design is the same.

Run Failure Investigation

What’s the cause and how long will it take to make the connection?

“There should be an SOP that directs how investigations are triggered and conducted.”

The technology piece?

Using E-WorkBook and its integration with our Inventory module, in one click, you can see a report of every critical reagent, buffer, plate lot number, lot of matrix, standard and QC prep, analyst, piece of equipment, and sample that was used on the study. And with a simple export, each type is sorted in a list format to assess variety in lots or preps.

Moreover, every material/sample/equipment is accessible by hyperlinks as well as any component used to prepare any of the materials and samples in addition to all the links to see the experimental records. Time spent on investigations is cut significantly using E-WorkBook.

Analytical Run Design

Where the guideline touches on the design of an analytical run, it has slightly different recommendations for chromatographic assays and ligand binding assays, and the E-WorkBook Cloud suite addresses these points.

For chromatographic assays: “An analytical run consists of a blank sample (processed matrix sample without analyte and without IS), a zero sample (processed matrix with IS), calibration standards at a minimum of 6 concentration levels, at least 3 levels of QCs (low, medium and high) in duplicate (or at least 5% of the number of study samples, whichever is higher) and the study samples to be analysed. ICH M10 Guideline 17 The QCs should be divided over the run in such a way that the accuracy and precision of the whole run is ensured. Study samples should always be bracketed by QCs.”

For ligand binding assays: “An analytical run consists of a blank sample, calibration standards at a minimum of 6 concentration levels, at least 3 levels of QCs (low, medium and high) applied as two sets (or at least 5% of the number of study samples, whichever is higher) and the study samples to be analysed. The blank sample should not be included in the calculation of calibration curve parameters. The QCs should be placed in the run in such a way that the accuracy and precision 831 of the whole run is ensured taking into account that study samples should always be bracketed by QCs.”

The technology piece?

With the flexibility of the Advance spreadsheet, enforcing business rules regarding the appropriate number of QCs along with random placement can be pre-configured in a template. Then all the analyst needs to do is select a plate size (48/96/384), enter the number of test samples and points on the curve, and the plates can be designed from a plate map library of common layouts reducing human error and the time for manual designation.

Reporting

The guideline recommends a standardized format for reporting, for which a single location for all the experimental information is the easiest way forward.

If all your method parameters, validation/sample analysis plans, acceptance criteria, analytical run summary, final data tables, and stability information are contained in the same environment and all retrievable by query, would the effort saved versus manually collating that data trump the customer specific report design? And can we mention that final report approvals WITH E-signatures is already available out of the box.

The technology piece?

With the configurability of the Advance Spreadsheet, the ideal report generation tool is not too farfetched. The only question is, what format do you prefer? Word or PDF?

You can read the full 2019 draft ICH M10 Bioanalytical Method Validation Guideline here.

Curious to discover how the E-WorkBook suite can help you implement the draft ICH M10 guideline in your bioanalytical lab? Visit our website here or get in touch with our experts.