Choosing the Right Tool for Cell and Gene Therapy Development: qPCR vs. ddPCR
Cell and gene therapy programs are redefining how sponsors think about bioanalysis. Unlike traditional biologics—where ligand-binding assays or mass spectrometry often dominate—these newer modalities demand tools that can reliably detect and quantify low-abundance DNA and RNA targets. That shift is why conversations around quantitative PCR (qPCR) and droplet digital PCR (ddPCR) come up so frequently, particularly in early scientific planning and regulatory strategy discussions.
At Smithers Pharmaceutical Development Services, qPCR and ddPCR are not viewed as competing technologies, but as complementary tools. The real question is not “which is newer,” but “which platform best answers the scientific and regulatory question at hand.”
Why qPCR and ddPCR Matter More in Cell and Gene Therapy
Modern cell and gene therapy programs are built around nucleic acids—including bioanalysis of vector genomes or transgene mRNA—often present at extremely low levels and embedded in complex biological matrices. These realities require polymerase chain reaction–based platforms that offer sensitivity, specificity, and reproducibility across a wide range of applications, from biodistribution to shedding studies.
While qPCR has long been the workhorse of molecular bioanalysis, ddPCR has gained traction in recent years because of its ability to deliver absolute quantitation with exceptional precision. The increased adoption of these platforms is not about novelty—it’s about necessity as programs move faster and regulatory expectations become more defined.
When qPCR Is the Right Fit
qPCR remains a powerful and highly relevant platform. One of its key advantages is its wide dynamic range, allowing sponsors to quantify DNA or RNA across a broad span of concentrations in a single run. This makes qPCR especially useful for exploratory and screening-focused studies, such as early biodistribution work.
Cost considerations also play a role. qPCR is historically more cost-effective on a per-run basis due to the consumables' lower cost or many biodistribution preclinical programs, qPCR provides the right balance of performance, speed, and scalability.
Where ddPCR Delivers Clear Advantages
ddPCR excels when sensitivity is critical. Its narrower dynamic range is offset by its ability to detect and quantify very low copy numbers with greater precision, even in challenging matrices where interference is expected. Because ddPCR does not rely on a standard curve, it enables absolute quantitation based on Poisson Distribution Statistics —an important advantage.
These strengths make ddPCR particularly valuable for shedding studies involving complex matrices such as feces or urine, as well as for cell therapy applications where high sensitivity is essential. In practice, many sponsors find that ddPCR reduces the need for reanalysis, helping to offset higher consumable costs by streamlining workflows and timelines.
Clearing Up Common Misconceptions
A frequent misconception is that ddPCR is prohibitively expensive compared to qPCR. In reality, while ddPCR may carry slightly higher consumable costs, it is far from an order-of-magnitude increase. When considered within the context of the full molecular workflow—including nucleic acid extraction and sample preparation—the incremental investment often becomes diluted.
More importantly, a well-designed ddPCR assay can deliver higher-confidence data with fewer repeats, ultimately improving the return on investment. The key is working with a partner who understands how to design, validate, and implement these assays correctly from the start.
Guidance Matters as Much as the Technology
Choosing between qPCR and ddPCR is rarely a simple “either/or” decision. It depends on study objectives, matrix complexity, sensitivity requirements, and budget constraints. Sponsors benefit most when they have a partner who not only runs the assay but also helps frame the question being asked.
Smithers PDS approaches molecular bioanalysis as a true partnership. Their teams are composed of scientists—not just operators—who contribute scientific insight at every stage of method development and execution. That expertise is backed by a strong publication record and deep experience in regulated molecular bioanalysis.
Why Sponsors Choose Smithers PDS
Sponsors often come to Smithers after experiencing delays or failed assay development elsewhere. The difference is experience, communication, and execution. Smithers’ approach emphasizes doing it once and doing it right—investing upfront in assay development and validation so programs move forward with confidence.
Equally important is transparency. Smithers maintains proactive communication, sharing both good and bad news early, and working collaboratively with sponsors to resolve challenges before they become roadblocks. Their agile, cross-trained teams also provide the flexibility needed to meet accelerated timelines when programs demand rapid turnaround.
Supporting the Bigger Mission
Cell and gene therapies represent hope for patients facing rare and debilitating conditions. Delivering on that promise requires speed, rigor, and uncompromising quality. qPCR and ddPCR are essential tools in that journey—but choosing the right one, at the right time, with the right partner, makes all the difference.
For sponsors navigating these decisions, Smithers Pharmaceutical Development Services brings not just the technology, but the scientific judgment and partnership needed to move programs forward with confidence.
