Volume 40 Number 3 | June 2026
Summary
Carlo Ledesma, MS, MLS(ASCP)SH, QLS, DLM, Volunteer Contributor
The conversation about where medical laboratory scientists fit in with regenerative medicine often starts too late—after the scientists, the bioengineers, and the clinicians have already built the room. Cell and gene therapies (CGTs) are no longer aspirational. As of late 2024, the FDA had approved more than 34 CGT products, with projections of approximately 20 new approvals per year and over 5,000 clinical trials registered globally.1 The profession responsible for quality control, release testing, identity assays, and compliance infrastructure for these therapies is clinical laboratory sciences. And yet, the field is still being invited in as an afterthought rather than seated at the design table.
The Product Is the Patient’s Cells
In autologous CAR-T therapy, the starting material is a leukapheresis product drawn from a patient who may be days from relapse. What happens in the laboratory between that collection and the reinfusion of genetically modified T-cells determines everything. There is no formulation error that can be caught at dispensing, no buffer swap at the last step. The laboratory is the manufacturing process, and every result is a release decision.
This changes what clinical laboratory competency means. Immunophenotyping in this context is not a reflex panel—it is a primary method for characterizing T-cell subset composition, distinguishing effector from memory phenotypes, and confirming CAR expression. Flow cytometry has become indispensable to CAR-T characterization, with the FDA’s 2024 CAR-T CMC guidance specifically citing flow cytometry, cytokine secretion assays, transduction efficiency measurements, and cell-killing assays as recommended potency test strategies.2 Spectral platforms capable of 50-color immunophenotyping panels are now being deployed to capture the depth of information required for both product release and post-infusion monitoring.3
“The profession has always done its most consequential work quietly, before anyone sees the result. In a CAR-T program, that invisible work has a name—a patient who relapsed, went through apheresis, waited out manufacturing, and came back for reinfusion.”
The molecular repertoire has expanded with equal urgency. Droplet digital PCR (ddPCR) and its successors have become workhorses for critical release assays—vector copy number (VCN) determination, residual plasmid DNA detection, and replication-competent lentivirus or retrovirus screening in CAR-T drug products.4 ddPCR provides absolute quantification without standard curves, a distinct advantage in GMP environments where reproducibility between operators and instruments is not optional.5 Researchers at St. Jude Children’s Research Hospital reported that transitioning from ddPCR to newer digital PCR platforms reduced turnaround time for some release assays from 72 hours to under 24, without compromising accuracy.4 These are not esoteric research applications—they are the infrastructure of safe product release.
Quality Systems Are Scientific Work
There is a persistent tendency to treat quality and regulatory compliance as an administrative burden rather than a scientific discipline. Having worked at the intersection of both, I can say that framing is wrong, and organizations pay for it when they act on it.
Advanced therapy medicinal products (ATMPs) are manufactured within a genuinely complex regulatory architecture. Cellular therapy products are subject to 21 CFR Part 1271 governing human cells, tissues, and cellular and tissue-based products; 21 CFR Parts 600–680 for biologics standards; and, for GMP manufacturing environments, the requirements of 21 CFR Part 211.6 In February 2023, FDA restructured its oversight apparatus by creating the Office of Therapeutic Products (OTP) within CBER—a “super office” composed of six offices, 14 divisions, and 33 branches, built specifically to manage the surge in CGT applications.7 The agency is also moving toward greater flexibility in product release specifications and process validation approaches as the science matures.8
The laboratory professional who understands both what an assay is measuring biologically and what the regulatory expectation is for that measurement is not easy to find. It takes someone who has run the potency assay and written the SOP, who understands why a deviation in VCN testing carries different risk implications than a deviation in sterility hold time. That scientific and compliance fluency, working together, is a defining competency of the modern CGT laboratory professional—and it is not being developed fast enough.
A Workforce Problem the Field Created
The CGT workforce shortage did not emerge suddenly. According to a 2023 gap analysis by the Alliance for Regenerative Medicine, most biotherapy companies carried multiple open positions, with talent searches averaging two to three months.9 The same report found that the proportion of laboratories unable to hire experienced technical and production staff rose from 28 percent in 2018 to 35 percent in 2023.1 That trajectory suggests the shortage will deepen before it narrows.
The problem has roots in foundational clinical laboratory science programs. According to the American Society for Clinical Laboratory Science, the profession is currently educating fewer than half the number of laboratory professionals needed.10 As of 2025, accredited MLS program counts have declined from their peak, in part because these programs are resource-intensive and enrollment pressure has made them targets for institutional budget cuts.10 Congress has taken notice—the Medical Laboratory Personnel Shortage Relief Act of 2025 directs grants to accredited institutions to train additional clinical laboratory staff.11 Necessary, but not sufficient on its own.
The deeper gap in the CGT space is not just numbers—it is curriculum. A 2025 analysis by the International Society for Cell and Gene Therapy’s Laboratory Practices Committee documented the absence of standardization across training programs and concluded that current education and workforce systems have not kept pace with what biomanufacturing now requires.1 MLS programs are still largely built around traditional clinical laboratory disciplines. That foundation matters, but without structured exposure to GMP principles, cellular therapy bioprocessing, potency assay strategy, and 21 CFR Part 11 data integrity requirements, graduates arrive unprepared for what CGT laboratories need.
The Professional Case
For laboratory scientists who choose to pursue this path, the work is substantively different from traditional diagnostic laboratory practice—built around different stakes and different consequences. When a product fails release, a patient may have no alternative. When a potency assay lacks appropriate matrix control, that gap is borne by someone who may already be out of options. Rigorous laboratory work has always mattered; in this context, the cost of getting it wrong is immediate and irreversible.
What the regenerative medicine field needs from medical laboratory scientists is not a polished resume full of transferable skills. It needs professionals who understand what they are releasing and why it matters—who can sit across from a quality auditor, a regulatory affairs director, or a treating physician and speak fluently about the science behind the testing. That is not a narrow niche. As the number of approved CGT products continues to grow and cell therapy programs expand into academic medical centers, community hospitals, and specialty practices across the country, it becomes the next chapter of clinical laboratory practice.
The profession has always done its most consequential work quietly, before anyone sees the result. In a CAR-T program, that invisible work has a name—a patient who relapsed, went through apheresis, waited out manufacturing, and came back for reinfusion. The laboratory’s job is to make sure what returns to that patient is exactly what was promised. Getting that right is the clearest argument for bringing clinical laboratory scientists in earlier, training them better, and paying attention to what they already know how to do.
The views expressed in this article reflect the professional opinions of the author and do not represent the official position of any regulatory agency or institution.
References
- International Society for Cell & Gene Therapy (ISCT) Lab Practices Committee. Shaping the future of cell and gene therapy workforce development: training of cell therapy processing personnel. Cytotherapy. 2025;27(4):417–421.
- Ferretti R, et al. Analysis of the measurements used as potency tests for the 31 US FDA-approved cell therapy products. PMC. 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC11877884/
- Maryamchik E, Gallagher KM, Preffer FI, Kadauke S, Maus MV. Using Spectral Flow Cytometry for CAR T-Cell Clinical Trials: Game Changing Technologies Enabling Novel Therapies. Cytometry B Clin Cytom. 2024. https://pmc.ncbi.nlm.nih.gov/articles/PMC11476793/
- Naeimi Kararoudi M, et al. Enhancing the Release Testing Platform for Cell and Gene Therapies: Shifting from ddPCR to dPCR. Cytotherapy. 2025.
- Lu A, et al. Application of droplet digital PCR for the detection of vector copy number in clinical CAR/TCR T cell products. J Transl Med. 2020;18:191.
- USDM Life Sciences. A Guide to Cellular Therapy Regulations. May 2024. https://usdm.com/resources/blogs/cellular-therapy-regulations
- Riordan R, et al. Cell & Gene Therapies: An Overview of FDA Regulatory Considerations for 2024. Cell & Gene. April 2024. https://www.cellandgene.com/doc/cell-gene-therapies-an-overview-of-fda-regulatory-considerations-for-0001
- FDA/CBER. Flexible Requirements for Cell and Gene Therapies to Advance Innovation. January 11, 2026. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/flexible-requirements-cell-and-gene-therapies-advance-innovation
- Alliance for Regenerative Medicine. Workforce Report: Gap Analysis for the Cell and Gene Therapy Sector. March 2023.
- Cremeans L, cited in: Clinical Lab Worker Shortage: Addressing the Gap. Medical Technology Schools. 2025. https://www.medicaltechnologyschools.com/medical-lab-scientist/interview-clinical-worker-shortage
- The Laboratory Workforce Shortage: A Silent Crisis Impacting Health Care. George Washington University Health Sciences Programs. 2025. https://healthsciencesprograms.gwu.edu/news/biomedical-laboratory-workforce
Carlo Ledesma is the Director of Quality and Regulatory Compliance and Chief Scientific Officer at Cellestiq in Oklahoma City, Oklahoma.