 is senior vice-president and general manager (IDMO Business), Cellares.

John Tomtishen

3d rendering of Human cell or Embryonic stem cell microscope background. | Image Credit: © Anusorn - stock.adobe.com

Despite the tremendous therapeutic prom­ise of cell and gene therapies (CGTs) for pa­tients globally, the space is at a crossroads. Long-standing issues around patient acces­sibility have contributed to investor pullback, biotech companies shuttering, and even a few life-saving therapies being pulled from markets.

The industry needs to do better to support all pa­tients in need. The biggest obstacle to accessibility has been pharma’s need to effectively reinvent manufacturing for living drugs made from human cells. It has not been possible to develop large-batch man­ufacturing as is done for most other therapeutic mo­dalities, meaning commercial-scale manufacturing has until now been unrealistic. Finally, the industry is beginning to incorporate Industry 4.0 concepts that have worked well for other types of manufac­turing, including automation.

Industry 4.0 is more than just the types of tech­nology that are deployed. Rather, these approaches underscore integration across the end-to-end patient journey. Many biopharmaceutical companies are still thinking about a black box (or several) to swap in for specific manufacturing processes, but that won’t enable the kind of scale most therapies will need to meet total patient demand. Still others are relying on contract development and manufacturing organiza­tions (CDMOs) to enable scale through next-generation end-to-end platforms, which can still be capacity constrained by upstream and downstream processes.

A new model is the integrated development and manufacturing organization (IDMO). As the name implies, this includes fully integrated smart manu­facturing facilities for true end-to-end scale. It relies on flexible manufacturing capabilities without re­quiring changes to hardware, meaning process modifications are entirely managed through software. As a result, technology transfer between smart facilities in any geography is streamlined through the lever­age of platform standards. Combined, these aspects will make it easier to scale cell therapies globally and meet total patient demand.

The tenets of the IDMO concept can be viewed from the top down: manufacturing facilities must be stan­dardized and interconnected, technology within each smart factory must ensure end-to-end integra­tion, and the platform technologies themselves must be robust enough to serve multiple functions.

Execution starts from the bottom up. From its be­ginnings, the biggest choke point in the cell therapy space has been manufacturing, which makes that the first place to start.

Today, commercial cell therapies have progressed toward becoming front-line treatments for certain hematological malignancies, meaning tens of thou­sands of additional patients may soon be eligible for these therapies. However, that number of batches haven’t even been manufactured yet in aggregate. It likely will not be long before cell therapies are also ap­proved in other indications, including autoimmune diseases. Even with heavy investment from pharma companies and the CDMO sector in new facilities and streamlined processes, traditional manufacturing is years away from meeting total patient demand.

Manufacturing at scale requires reducing the footprint, eliminating manual processes, increas­ing throughput, and lowering cost of goods. The most robust approach to address these issues is the deployment of fully closed and automated end-to-end manufacturing platforms. These platforms do not require traditional cleanroom spaces because manual process steps are eliminated through robotic orches­tration of streamlined and fully integrated manufac­turing processes.

“End-to-end” can be misleading. If a therapeutic de­veloper or CDMO has just purchased multiple units with the intent to scale, they will need to develop all new up­stream and downstream systems to match the system’s throughput. Even the best manufacturing system, in isolation, might just mask a bottleneck, rather than fix it.

The IDMO smart factory approach incorporates multiple ancillary technologies to enable the fullvalue proposition of end-to-end automated manu­facturing. That includes designed-for-purpose in­frastructure and facilities, requiring a high degree of engineering expertise.

John Tomtishen is senior vice-president and general manager (IDMO Business), Cellares.

Pharmaceutical Technology®/Pharmaceutical Technology® Europe/BioPharm International

When referring to this article, please cite it as Tomtishen, J. Ushering in Industry 4.0 with the IDMO Model to Solve the CGT Manufacturing Bottleneck. 

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Global scale-up requires developing replicable processes that work the same no matter where they are performed. This can be accomplished with smart factories that utilize fully automated manufacturing platforms.