Streamlining Vaccine Process Characterization Using an Automated Reactor System

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During a September 2022 webinar, Kyle Deluca (a senior scientist in engineering at Merck) highlighted bottlenecks in his group’s workflow for characterizing production of a pneumonia vaccine. In that process, purified components undergo chemical modification in a synthesis reactor, followed by buffer exchange, size-based separation, additional chemical modification, and final purification. Because the modification steps were time and labor intensive, Merck automated them. With support from Mettler Toledo, Deluca and Felix Milman (a specialist in engineering at Merck) described how their group implemented the EasyMax 102 thermostat system and associated software tools, improving process consistency and robustness while reducing time and labor requirements.

The Presentation
Deluca explained that both chemical-modification steps involve precision dilution and dosing of buffers and reagents, incubation within a narrow temperature range over a long period, and subsequent cooling of reaction products. Initial workflows for those steps involved considerable hands-on time for recipe generation, calculation of dilution volumes, reagent preparation and application, and process monitoring. Because the second modification requires addition of reagents within an inert atmosphere, manual work also introduced risks for disrupting the gases and reactants.

The Merck team sought to automate, miniaturize, and digitalize such activities. They selected the EasyMax 102 system because it enables precise, automated control over reaction temperatures and regulates inert-gas flow over reaction vessels. The system also provides for connection of dosing pumps. Thus, it can be programmed to perform complex reagent-addition procedures.

Using EasyMax 102 technology and iControl software, the team established semiautomated processes for both chemical-modification steps. For the first step, operators still must prepare a couple of key reagents by hand. But after that, manual handling is minimized. Operators can load materials into the system, develop an experiment template, upload it to the iControl program, prime dosing pumps, and initiate the experiment, removing the reaction product after the system has cooled it. The updated workflow takes two rather than four hours, which saves ~350 operator hours per year.

The team implemented a similar process for the second chemical modification. A key advantage of using EasyMax 102 system for that step, Deluca noted, is that temperature monitoring and reagent addition are executed under inert-gas overlay without operator intervention, minimizing disruption to reactants.

Merck facilitated implementation of the EasyMax 102 system and iControl software by developing a program for recipe building. Milman pointed out that each chemical-modification step involves multiple and sometimes repeating procedures. Generating a complex recipe from scratch is time consuming and susceptible to transcription errors. The team needed a recipe-generation program that could interface with iControl software, create repeatable but adjustable “blocks” of procedures, and ensure consistent application of process-specific and calculated parameters.

Milman’s group adapted an iControl experiment template to write an R-based programming script that replaces variable process parameters with user-defined, calculated, and/or database values. Upon completion, the script exports an .xml experiment template that can be uploaded into iControl software for execution.

The team incorporated the script into a web application to facilitate access for provisioned users. RStudio’s Shiny framework for R was particularly useful for building the user interface (UI), Milman explained. RStudio offers free downloads for prebuilt functions that are conducive to data-science applications, including data storage, wrangling, and plotting. Such features simplified UI development, enabling the Merck team to engineer functions for easy selection of process inputs.

The web application has helped Merck to accelerate the journey from experimental design to execution by automating some aspects of recipe generation. Together, the EasyMax 102 system, iControl program, and recipe-writing application are reducing time and labor needed to characterize the chemical-modification steps in Merck’s vaccine production process.

Questions and Answers
How scalable are results generated by the EasyMax 102 system? Merck has used it for chemical modification at 1/40 of a commercial-scale process. Slight differences in mixing behavior have been observed across scales, but results have been comparable. The system also enables users to adjust parameters to help ensure scalability.

How might the automated workflow described herein be applied to other processes? Such a workflow can be developed for most any application involving operator transcription or data collection and storage.

Find the full webinar online at