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6 Pharmaceutical Technology ® | BioPharm International ® Trends in Manufacturing May 2025 PharmTech.com CELL AND GENE THERAPIES tion 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 manu- facturing facilities for true end-to-end scale. It relies on f lexible manufacturing capabilities without re- quiring changes to hardware, meaning process mod- ifications are entirely managed through software. As a result, technology transfer between smart facilities in any geography is streamlined through the lever- age of platform standards. Combined, these aspects will make it easier to scale cell therapies globally and meet total patient demand. Developing the IDMO The tenets of the IDMO concept can be viewed from the top down: manufacturing facilities must be stan- dardized and interconnected, technolog y within each smart factory must ensure end-to-end integra- tion, and the platform technologies themselves must be robust enough to serve multiple functions. Execution starts from the bottom up. From its be- ginnings, 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 thou- sands 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 ap- proved 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. Ma nufac t ur i ng at sca le requi res reduci ng t he footprint, eliminating manual processes, increas- ing 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 re- quire traditional cleanroom spaces because manual process steps are eliminated through robotic orches- tration of streamlined and fully integrated manufac- turing processes. "End-to-end" can be misleading. If a therapeutic de- veloper or CDMO has just purchased multiple units with the intent to scale, they will need to develop all new up- stream 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 factor y approach incorporates multiple ancillar y technologies to enable the f ull value proposition of end-to-end automated manu- facturing. That includes designed-for-pur pose in- frastructure and facilities, requiring a high degree of engineering expertise. Integral pieces A smart cell therapy factory must implement Industry 4.0 concepts across the end-to-end supply chain. Much of the field has yet to grapple with complicating factors outside of manufacturing itself because few have at- tempted deploying manufacturing platforms at scale, but a holistic approach is required for the IDMO model. The biggest ancillary consideration is a quality control (QC) system that incorporates in-process and release as- says, and keeping up with the pace of a fully integrated manufacturing platform will require the system to be automated as well. In fact, for this reason, much of the facility will need to be streamlined and integrated. Upstream, streamlining includes processes such as kitting and media manufacturing. Downstream, integration includes processes such as drug product storage and waste management. Even the cleaning process in materia l accession rooms can be auto- mated through the adoption of vaporized hydrogen peroxide. Everything must be balanced and stream- lined within an IDMO smart factory to match the pro- duction throughput across the end-to-end manufac- turing journey, from the moment apheresis material arrives at the facility to the moment the final drug product is shipped back out for infusion. One key enabler for the IDMO approach is the in- tegration of these automated platforms across unit operations within the pharma software ecosystem. Specifically, the interface and integration of these systems with enterprise resource planning systems for supply chain management, manufacturing exe- cution systems for electronic batch records, and lab- Commercial cell therapies have progressed toward becoming front- line treatments for certain hematological malignancies.