S88 XML Recipe Round Trip via the Dynochem Mixing Web App

Just when you thought you knew why the coolest link on the Internet was the Dynochem Mixing Web App, something even cooler has come along, thanks to collaboration between Scale-up Systems and the wider Autochem business unit of Mettler Toledo.

Used correctly, iControl can export an XML file containing the detailed recipe and trends for your experiments in the EasyMax, OptiMax or using RX-10.  That means the actual amounts charged and the timing, which may differ from the intended experiments set up in your ELN or elsewhere.  

Using iControl 6.2, you can now export that recipe and drag it into the Mixing Web App.  The App then reads the entire procedure, breaks out the relevant operations, calculates material properties for each operation using the Scale-up Suite Materials system, reads equipment information from the Scale-up Equipment Data Service and presents the results for Vessels 1 and 2 in the browser.

You can select Vessel 2 from your equipment network and agitation conditions are then automatically scaled at constant power per unit mass.  You can adjust fill volumes and recalculate conditions.  You can save the results for later re-use, generate a PDF report and share the results with colleagues using the URL for the page.  

If your Vessel 2 selection is from the Mettler ecosystem, you can even export the scaled recipe and drag that into iC Data Center using the new integration with Scale-up Suite.  Your designed experiment will appear moments later in iControl, ready for execution.

That's scale-up of a complex lab procedure with just a few clicks, saving time and tedium compared to current workflows, now fast and easy enough to de-risk any project.

Take a look at the video here (free Scale-up account required) to see the "S88 XML Recipe Round Trip" in action.  To learn more, take the training exercise.

This has a pretty big impact in it's own right.  Even better though, it lays a foundation for other round trips and automations, including workflows that include kinetic models and machine learning applications.  Watch this space!

Dynochem mixing web app now features mixing time, heat transfer and automated scale-up calculations

Thanks to our web development team, the Dynochem mixing web app continues to deliver new capabilities and the latest enhancements include mixing time, heat transfer and automated scaling calculations based on constant power per unit mass:

Get access and make calculations on your own equipment by signing up here.

New: Dynochem Equipment Data Service (EDS) puts equipment data at your fingertips

This month we delivered our new equipment data service (EDS) capability to more than 150 customer organizations globally.  Leading customers adopted the system shortly after release of Scale-up Suite 2 in July 2021; now we are formally going live for everyone.

This SQL database backed approach to managing your equipment data has many advantages compared to the old system of requiring users to find and import our industry-standard Excel-based template, in use since 2011.  It is also the only supported way to retrieve your equipment data into the latest version of our mixing and heat transfer toolbox after 30 June 2022.  

Features include secure user account based access control, easy access from any device and a change log for traceability.

We have made the administrators of your EDS the same people who are administrators of your Dynochem license.  We have sent your admins (custodians of your database) simple instructions to populate the service with your equipment information and make it available to you.  For users, as this capability is rolled out, you will start to see the Vessel Update button becoming active in your Dynochem 6 ribbon.  Other benefits of adoption include:

• Your continued ability to use the latest version of the mixing toolbox with your equipment data after 30 June.  The toolbox will no longer have an Excel file Import button, so the only way to include your organization's equipment in the toolbox will be using the EDS (Vessel Update button in the ribbon)
• The latest version of the toolbox (30 June) will include a fuller range of Mettler Toledo lab  vessels you can easily choose, apply or edit for your applications
• Users no longer need to know ‘where the vessel database file is’, to copy and paste it's web address or to browse to locate it on the network
• Users can access equipment information in any Excel workbook, using the Catalist and Properties buttons on the DC Excel ribbon
• Users on any device can access and view your equipment through a simple web browser interface; they do not need Scale-up Suite installed to do this; they need only to have a scale-up account and be listed on a current valid Dynochem license
• The EDS is a foundation for future enhancements that leverage access to equipment data for many other everyday applications
• The EDS will support a greater number of database fields, requested by customers to better describe your broad range of equipment types, including biologics set-ups.

You can click here to see if your EDS has already been populated by your administrator(s).

Otherwise, contact support@scale-up.com to find out who your admin is and here's a 1-minute (silent) YouTube video showing the EDS in action:

Dynochem: Secure access to equipment info, for users of your Equipment Data Service

Additional useful resources include:

• Help page on Vessel Update
• KB Article on Equipment Data Service
• 30-minute webinar on Equipment Data Service

Scale-up Suite 2 released! Plus news on Dynochem Biologics

It's been even busier than usual at Scale-up Systems recently and here's a catch-up in case you haven't seen it elsewhere yet.

We're delighted to have released Scale-up Suite 2 today (big thanks to Steve Hearn and all of our Development team!) and look forward to customers rolling this out over the next little while.  There are a host of enhancements as covered in our previous post and some new product options, notably RunScript Automation:

• This exposes calls to the Dynochem and Reaction Lab APIs so that customers in our Digitalization Pilot Program can apply our scripts to create autonomous workflows and build their own scripts to implement high-throughput modeling alongside experimentation. Check out a preview video here [5 minutes].

Dynochem 6 has been released as a component of Scale-up Suite 2.

We've also separated the Dynochem model library for biologics into its own dedicated Resources site and created a new product option around this functionality:

• It's called Dynochem Biologics and is focused on the development and manufacturing of large molecule therapeutics using cell culture (USP), downstream purification (DSP) and fill/finish operations.  
• We've built in all of the usual supports you expect from us, including self-paced training and KB articles.  
• Dynochem Biologics already works with Scale-up Suite 1 and we'll be moving all biologics users across to this platform at the end of July.

Actions for you:

• Visit our Installer page to upgrade to Scale-up Suite 2 or have your IT colleagues do so if that's necessary in your organization.  Remember, our cloud licensing means you don't need any on-premise license server and Suite 2 works immediately with the cloud licenses (and content) you already use.
• Contact your Scale-up Systems representative to find out more about our Digitalization Pilot Program or to explore Dynochem Biologics.

Get ready for Dynochem 6 and Scale-up Suite 2: Modeling for Everyone

Last week, Peter Clark gave a preview of new features coming with Scale-up Suite 2.  If you missed the event live, as usual you can catch the recoding in the resources site here.

Peter showed there is something for everyone in the new release.  Whatever modality of drug/ active ingredient you develop or make, whether a small or large molecule or somewhere in between, whether made with cell culture or synthetic organic chemistry, your teams and your enterprise can obtain value daily from our tools.  That takes us several steps closer to our vision to positively impact development of every potential medicine.

Scale-up Suite 2 includes:

• Powerful equipment calculators for scale-up, scale-down and tech transfer, leveraging our industry standard vessel database format
• Rigorous material properties calculators for pure components, mixtures and your proprietary molecules
• Empirical / machine learning tools, to build and use regression models from your data with just a few clicks; including support for DRSM
• Mechanistic modeling of any unit operation, in user-friendly authoring and model development environments
• Hybrid modeling, combining the best of both worlds
• Interactive data visualization, including parallel coordinates and animated contour plots for multidimensional datasets
• New features to make modeling faster, more productive and more enjoyable, incorporating ideas suggested by customers and from our own team
• New capabilities for autonomous creation of models, parameter fitting and process optimization 'headless' on the fly, as well as incorporation of real time data and access from any device.

We believe that:

• Interdisciplinary collaboration accelerates process development and innovation
• Models facilitate collaboration and knowledge exchange
• Interactive, real-time simulations save days and weeks of speculation
• Models are documents with a lifecycle extending from discovery to patient
• Model authoring tools must be convenient and easy to use
• Teams needs models that are easily shared
• Enterprises need tools that embed a modeling culture and support wide participation.

In other words, modeling should be an option for Everyone.  To make that a reality for you, we support our software tools with:

• an Online Library, containing hundreds of templates, documentation and self-paced training
• Free 1-hour on-line training events monthly
• Half-day and full day options for face to face training, available globally
• A free certification program to formally recognize your progress and skills
• Outstanding user support from PhD qualified experts with experience supporting hundreds of projects like yours
• A thriving user community, with round tables and regular customer presentations sharing knowledge and best practices.

We're celebrating 21 years serving the industry this year, supporting more than 20,000 user projects annually, for more than 100 customers all over the world, including 15 of the top 15 pharma companies.

If you're an industry, academic or regulatory practitioner, we invite you to join our user community and start to reap the benefits for your projects.

Bioreactor mass transfer: kLa (O2) versus kLa (CO2)

kLa is an emotive term for many in process development.  It evokes a certain mystery for those whose background is not chemical engineering, a 'TLA' they hear over and over again.  Obtaining values for this scale-dependent 'mass transfer' parameter can be a significant undertaking, whether by experiments, empirical correlations or even CFD.  We provide purpose-designed tools to support fitting kLa to experimental data and for estimation using established correlations.  The experimental approach is the subject of this post.

The dominant experimental technique is the dynamic gassing out method, where dissolved gas concentration is followed versus time using a probe in the liquid phase.  A shortcut method allows kLa to be backed out from a semi-log plot; an implicit assumption here is that there is an abundance of gas.  A more rigorous approach that we advocate fits kLa to a model tracking multi-component mass and composition in both the liquid and gas phases.

The shortcut method contributes to confusion about kLa(O2) versus kLa(CO2), two important gases in cell culture.  Dissolved CO2 can be followed using pH probes.  Practitioners sometimes report separate values for kLa(O2) and kLa(CO2), with kLa(CO2) typically lower and insensitive to agitation.

CO2 is much more soluble than O2 and the two mass transfers are usually in opposite directions in a bioreactor: O2 from gas to liquid and CO2 from liquid to gas.  Incoming air bubbles become saturated with CO2 after a relatively short period of contact, whereas they continue to liberate O2 for most or all of their contact time.  That leads to different sensitivities of dissolved O2 and CO2 to agitation and gas flow rate; and therefore different abilities to measure something close to kLa.  A very nice study of the gas phase in bioreactors by Christian Sieblist and colleagues from Roche bears out this trend.

Practitioners report that successful bioreactor operation and adequate control over both O2 and CO2 (and hence pH) depends strongly on agitation in the case of O2 and gas flow rate in the case of CO2.  In fact, it's a spectrum and kLa and gas flow rate may both be somewhat important for both responses and the particular combination of kLa and gas flow (Qgas) determines the sensitivities for both gases.

We made some response surface plots from a series of gassing out simulations to illustrate.  These show the final amount of dissolved gas in solution at the end of each experiment, when kLa and Qgas are varied systematically in a 'virtual DOE'.  The initial liquid contained no O2 and some dissolved CO2 that was stripped during the experiment; the gas feed was air, so that dissolved O2 increased during the experiment.

Dissolved O2 at the end of a set of kLa measurement experiments in which kLa and Qgas were varied. The final O2 concentration is always sensitive to kLa and only sensitive to Qgas at very low gas flow rates. 

Dissolved CO2 at the end of a set of kLa measurement experiments in which kLa and Qgas were varied. The final CO2 concentration depends only on Qgas at low gas flows; and is sensitive to kLa only at relatively high gas flows. 

Transient concentrations of O2 and CO2 at low gas flow respond differently to changes in kLa.  In this illustration kLa has been increased between runs from 7 1/hr (dashed line) to 21 1/hr (solid line). The dissolved oxygen profile responds but the CO2 profile remains unchanged (click to enlarge).  Clearly, kLa(CO2) cannot be inferred from these data.

Dynochem biologics model library released

Many thanks to customers who engaged with Scale-up Systems as we "built, broke and bettered" our biologics model library in the run-up to release late last year.

More than one hundred biopharmaceutical companies in the Scale-up Suite global user community can now access the tools for immediate use here (https://dcresources.scale-up.com/?q=bio).  An overview of the biologics library is available here.

We expect each tool to grow and be refined by the repeated use that is typical of customer activity and we look forward to supporting more users in taking up the tools in their daily work.

Much like the small molecule opportunity, mechanistic modeling has great potential to accelerate the development of large molecules by shortening development time, making best use of experiments and anticipating manufacturing challenges.  Ours is the first fit-for-purpose and comprehensive mechanistic model library to be built and released in this space, another first of which we are very proud.

Using the Dynochem biologics library delivers daily benefits in development and scale-up while creating digital twins to support your digitalization strategy

Training opportunities using the new tools will be available at regular intervals this year.  Let us know if you'd like a dedicated session for your company or site.

Feel free to share this post with anyone you think may benefit.