2024-03-26 ChromSword AQbD Manager Specification

Product description and key features

AQbD manager is a software package to organize the workflow and information on HPLC analytical lab work process in accordance with AQbD principles and ICH guidelines and customer existing workflow. Provide the analytical team a SINGLE POINT OF TRUTH for all information and data about samples, project targets, and results. Generate a complete report customizable for every customer's requirements.

AQbD manager software package will be created to manage and organize the work of HPLC analysts to perform analyses and organize data by following AQbD principles and under ICH guidelines. The target of the software package is to help analysts to organise data, define critical parameters and manage the workflow in accordance with requirements and industry standards.

Program components configuration

The program can be used as a stand-alone application or as a part of ChromSword Client Server 5.5. In both cases, it will use ChromSword Client Server 5.5 to store and retrieve data. ClientServer is FDA 21 CFR Part 11 compliant, and all changes in AQbD Project Group will be logged in the Audit Trail of ChromSword 5.5 Client Server. The new version will store more data in database format rather than in files. AQbD Project groups will only exist in a Database and will be stored in ChromSword 5.5 Client Server. Database will be the same as in ChromSword 5.5 Client Server and will be based on PostgreSQL. It will be possible to deploy Client Server on same machine as AQbD Manager or on remote machine. Remote machine could be deployed in internal network. It is also possible to import ChromSword Offline and ColumnViewer data formats which are not part of ChromSword Client Server 5.5 at this moment.

New features that will be specific to AQbD Manager, but can also be used in ChromSword are:

• Export to Chromeleon (Import is already implemented in ChromSword ReportViewer)

• Export to Empower (Import is already implemented in ChromSword ReportViewer)

• Export to OpenLab (Import is already implemented in ChromSword ReportViewer)

Imports and exports will include exporting methods and chromatograms in between Client Server and Empower, OpenLab and Chromeleon. It will be managed through AQbD Manager.

Functional requirements

First screen showed when opening program. Program requires user login of ChromSword Auto client server 5.5 and then only user can access any AQBD workspaces, existing projects runs and also import and export runs to data systems like Empower, OpenLab and Thermo Chromeleon. For Empower it will be implemented using MilleniumToolkit and for OpenLab it will be implemented using OpenLab SDK. For Chromeleon it will be implemented using Chromeleon SDK.

In top of the screen there are wizard steps that user can follow to create new AQBD project group. Each project group can have multiple projects and each project can have multiple runs that are stored in reports and can be exported or imported to Empower, OpenLab and Chromeleon.

Project Groups in AQbD Manager are the same as Project Groups in ChromSword 5.5.

Usually project will be used for each sample, but there might be other use cases where project is used for multiple samples.

All steps of AQbD wizard can be exported and saved as Excel or Word document. When exporting to Excel or Word document user can choose to export only specific steps or all steps and also to export only specific fields or all fields and also to export only specific runs or all runs.

There should be three-step process with dialogs for exporting data:

1. Select which steps to export

2. Select which fields to export

3. Select which runs to export

Selected settings should be possible to save as template and then later to load from template. Also last settings should be saved and then later to be loaded when opening AQbD Manager.

Percentage of completion of each stage is calculated by the filled fields in the form.

AqbdStepChooseProjectGroup

In order to access project groups user must login into ChromSword 5.5 Client Server. Client Server can be located on local machine or on remote machine. Remote machine could be deployed in internal network. All changes in AQbD Project Group will be logged in Audit Trail of ChromSword 5.5 Client Server. AQbD Project Group is the same as ChromSword 5.5 Project Group. Plan is to reuse existing data structures from ChromSword 5.5 and add on top of that specific data structures that are needed for AQBD Manager. In this step user chooses or creates project group, and it will be loaded from ChromSword 5.5 Client Server.

AqbdStepDefinition

Under each Project Group there will be multiple Samples and each sample will have multiple compound, each compound optionally will have chemical structure. Chemical structure can be also loaded from ChemDraw or MarvinSketch. Editing of samples, compounds and chemical structures will be done in popup windows.

With the information from ChemDraw or MarvinSketch or popup (as in CSO2), the structure should contain additional information, such as molecular volume (at least). Hydrophobicity, ec. . Also, basic popup screen should guarantee that drawing was done according to chemical rules.

Initially software will import molecular weight from the structure and then user can edit it, later it will be possible to import structure itself from ChemDraw or MarvinSketch.

In text editors should be possible to paste HTML formatted text and images.

Next there are sample preparation steps and then compound preparation steps that optionally need to be executed before running the method.

In sample preparation it will be possible to also upload and attach images and documents.

Finally, there are attachments that can be added to the project group. Attachments can be added from local file system or added as internet links.

Chemical structure editor is based on

https://web.chemdoodle.com/tutorial/2d-structure-canvases/sketcher-canvas https://partridgejiang.github.io/Kekule.js/demos/demoLauncher.html?id=composer

Chemical structure table like this:

AqbdStepRiskAssestment

Risk mitigation plan (Development plan) is not sequential execution of steps but rather a set of steps that are executed in parallel. Each step can have multiple risk mitigation plans and each risk mitigation plan can have multiple steps. In then end it will produce matrix of runs in full factorial design.

Must have function to add multiple experiment trees/tables in sequence. Each tree/table can have different variables and values.

Development plan each branch can be chosen form predefined list of parameters and each parameter can have multiple values to be tested. After changes in fishbone chart user can re-generate matrix of runs and it will keep as much as possible of previous runs.

After adding all leafs to the tree, user can generate matrix of runs and then export it to Empower, OpenLab or Chromeleon as a methods.

Before export user can choose to export only specific runs or all runs using checkboxes.

Then later can import runs that support specific set of parameters and values.

Highlighted in matrix are runs that have not been executed. Also in fishbone chart invalid parameters are highlighted.

Columns should be loaded from ChromSword Column Database. Also there should be possibility to type in manually parameters and values of columns.

It is also possible to generate ChromSword Scout Project files and import Runs from ChromSword usiing ChromSword Client Server 5.5 without need to have direct access to files. If user is using ChromSword Auto then import will be done using ChromSword User Interface and Client Server 5.5. It will not be possible to import data from RPTX, PRJX files directly as it is intended to be used only with ChromSword Auto 5.5 or ChromSword Client Server 5.5. With AQbD Manager it will now be possible to use Client Server 5.5 without need to have ChromSword Auto 5.5 installed.

Before defining fishbone chart user sets Instruments that will be used in the project. Instruments are loaded from ChromSword 5.5 Client Server. If not using ChromSword Auto then user can type in manually parameters and values.

User also must define Solvent Concentration gradients that will later be used in combination with other parameters to generate matrix of runs.

There is also option to add Automated method development using ChromSword Developer.

AqbdStepScreening

Scouting runs are synchronized with previous step and can be imported from ChromSword Client Server 5.5 or directly form Empower, OpenLab or Chromeleon. It is also possible to type in manually results of scouting runs.

The main feature of this step is to store experimental data with analyst comments on all results reached, review results and define the Rating of each run and then to generate a report of the best runs to proceed for future development with possibility to easy track back results and decisions made to find final method.

As the final step of this screening stage is the choice of method main conditions for future optimization to reach initially set Analytical Target.

Here we should have just a table with all the method variables to see. When we choose to extend a line of screening we will se chromatogram and more basic information, when choosing to open the result fully then we should be able to see all the conditions, put analyst comments, put rating and proceed with this method to Fine optimization as most promising. Also should be a process with coming back to the screening stage if most promising method after future development does not deliver expected results and does not meet initial Analytical Target.

To determine how close we are to the target user uses rating for each run.

After screening there are options to extend experiments to Optimization or Robustness using ChromSword Auto.

Each run with Chromatogram should have a list of conditions used:

1. Buffer

2. Solvent (should adapt if there are more than one on both buffer or solvent level).

3. Column

4. Temperature

5. Injection volume

Also, user should have opportunity to review gradient table so it is possible to check percentages and etc.

ComponentWorkflowStepOptimization

Exclusive page for ChromSword Auto users.

Optimization page is used to optimize the method to reach the Analytical Target. It is used to store results of optimization runs and to generate reports of best runs. Page allows to export ChromSword Developer Project files and import runs from ChromSword using ChromSword Client Server 5.5 without need to have direct access to files.

ComponentWorkflowStepDesignSpace

Exclusive page for ChromSword Auto users.

Design Space page is used to store results of robustness runs and to generate reports of best runs.

Page allows to export ChromSword AutoRobust Project files and import runs from ChromSword using ChromSword Client Server 5.5 without need to have direct access to files.

Data structures

Project will reuse existing data structures from ChromSword Client Server 5.5 and add on top of that specific data structures that are needed for AQBD Manager.

aqbd_runs are used both in risk assessment and in screening. In risk assessment it is used to generate matrix of runs and in screening it is used to store results of scouting runs. In risk assestment runs are template for methods that are exported to Empower, OpenLab and Chromeleon. In screening runs are used to store results of scouting runs and to generate reports of best runs.

Development timeline

Development timeline is as follows:

FAQ - Frequently asked questions

1. Regarding Empower and Openlab import / export this is not a problem. Problem is to control Empower runs. We will implement these functions if necessary step by step.

AQbD Manager will not control Empower runs or any other data systems. It will only import and export methods and chromatograms. Only ChromSword Auto will control runs using supported data systems.

2. AQbD Project Group is the same as ChromSword 5.5 Project Group. Plan is to reuse existing data structures from ChromSword 5.5 and add on top of that specific data structures that are needed for AQBD Manager.

Yes they are the same. AQbD Project Group will be stored in ChromSword 5.5 Client Server.

3. Is it possible to get AI generated summary? > we can generate summary text, but we need to understand how good summary looks like - what facts actually are needed in summary to it be useful?

Can be done, but we need to understand what is needed in summary. Need examples of such summaries that are useful.

4. With AQbD Manager it will now be possible to use Client Server 5.5 without need to have ChromSword Auto 5.5 installed.

Yes

5. What if the information is already gathered by user (older projects). How can they add information without generating matrix (it is already there)? Will it have simple import runs function without unnecessary generating/exporting?

Yes, it will be possible to import runs without generating matrix, but System is NOT intended to be used with older method developement project groups, because it is specifically designed to force user to fill information in each step and follow AQbD process.

6. In some points I see too much connection with CS 5.5 (should be only admin console and additional benefit of better integration with CSA) as AQbD manager should be received as separate application that could work in any requirement even without any instance of CSA.

Yes, but you will need ChromSword 5.5 Client Server to operate AQbD Manager, and it is a separate application that can work without ChromSword Auto 5.5.