The rapid expansion of advanced therapies has transformed how medicines are designed, manufactured, and evaluated. Unlike traditional pharmaceuticals, advanced therapy products, such as those for gene and cell therapy, function through biological mechanisms that modify cellular behavior or genetic expression, creating new regulatory and analytical challenges. Ensuring consistent product quality requires analytical strategies capable of characterizing highly complex biological systems while meeting evolving global regulatory expectations. As development programs mature, analytical characterization becomes central to demonstrating safety and efficacy in addition to enabling scalable manufacturing and long-term clinical reliability.
Why gene and cell therapy complexity demands specialized analytical characterization
The defining feature of modern gene therapy products and cellular medicines is biological complexity. These therapies may involve viral vectors, genetically modified cells, nucleic acid constructs, or combinations of biological components that interact dynamically with patient tissues. Regulatory guidance recognizes that advanced therapy medicinal products differ fundamentally from conventional drugs because variability may arise from living systems, manufacturing environments, and delivery mechanisms.
For example, Adeno-Associated Virus (AAV) gene therapy platforms rely on viral capsids carrying therapeutic sequences. Small changes during the manufacturing process can alter potency, safety, or biodistribution, making deep analytical characterization essential throughout gene therapy development.
Analytical characterization of these advanced therapies must therefore address multiple dimensions simultaneously:
- Structural and genetic identity of vectors or engineered cells
- Biological activity and functional potency
- Impurity and contaminant profiling derived from host cells or production systems
- Stability and consistency across manufacturing batches
This complexity explains why individualized analytical strategies are often required. Biological therapies demand tailored quality assessment plans aligned with product design, purification workflows, and intended clinical application. Specialized analytical development supports reliable translation from exploratory research to scalable clinical manufacturing, particularly across emerging gene therapy applications such as oncology, rare diseases, and regenerative medicine.
Regulatory landscape: EMA, FDA, and global expectations for analytical characterization
Regulatory agencies increasingly position analytical characterization as a central requirement for the development of gene therapy and cell therapy products. Because advanced therapies involve complex biological systems, both the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) guidance emphasize detailed analytical understanding to demonstrate product quality, consistency, and safety throughout development.
In Europe, analytical expectations are outlined primarily in the Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials, which requires a comprehensive characterization of active substances, manufacturing processes, analytical procedures, and specifications supporting clinical trial applications. In addition, there are other more specific guides, such as the Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products, which defines the analytical requirements for vector design, impurity evaluation, biological activity assessment, and method validation for gene-based products
In the United States, FDA expectations are communicated through the Center for Biologics Evaluation and Research (CBER) guidance for human gene and cellular therapies, which outlines chemistry, manufacturing, and control (CMC) requirements covering identity, purity, and potency testing. FDA guidance on post-approval monitoring further highlights the need for analytical systems capable of supporting long-term safety and effectiveness evaluation.
Across regions, regulators align on a lifecycle, risk-based approach in which analytical characterization supports gene therapy development, manufacturing comparability, and ongoing cell therapy regulatory compliance.
Advanced analytical methods for quality control and characterization
Modern cell and gene therapy analytical methods combine molecular biology, biochemical analysis, and cell-based testing to provide a multidimensional understanding of product quality. Because therapeutic performance depends on biological function, analytical workflows must evaluate both molecular structure and biological activity.
Common analytical approaches include:
- High-performance mass spectrometry and chromatography for impurity profiling.
- Quantitative PCR (qPCR) and digital PCR for gene therapy vector quantification and genome integrity.
- Next-generation sequencing for transgene confirmation and impurity detection.
- Flow cytometry and immunophenotyping for cellular identity in cell therapy analytical development.
- Functional gene therapy potency assays measuring transduction efficiency or biological response.
For viral vectors and genetically modified cells, potency cannot be inferred from concentration alone. Functional assays are required to confirm therapeutic activity, reflecting regulatory expectations that biological efficacy must be demonstrated at the cellular level. Potency testing often integrates multiple orthogonal assays when a single method cannot fully capture biological function.
Advanced analytical laboratories increasingly implement integrated workflows combining molecular characterization with functional testing. This approach supports consistent cell therapy quality control, enabling developers to monitor variability introduced during expansion, cryopreservation, or transport, critical considerations for personalized or autologous therapies.
Analytical challenges in gene and cell therapy product development
One of the most persistent hurdles in advanced therapies development is the management of impurities. Process-related impurities, such as host cell proteins, residual host DNA, and leachables, must be minimized to avoid negative impacts on efficacy and unintended immunogenicity.
Furthermore, bioanalysis must address the unique instabilities of somatic gene therapy candidates. For instance, in gene inhibition therapy, the integrity of the RNA or DNA sequences must be verified through sensitive methods like UPLC-MS/MS to ensure sequence identity and site-specific modifications are preserved throughout the workflow.
For cell-based therapies, analytical testing must often evaluate viability, differentiation status, and functional response simultaneously. Similarly, viral vector products may contain empty or partially filled particles that standard assays cannot easily differentiate, requiring complementary analytical methods to ensure accurate dosing.
Reliable analytical characterization ultimately enables linking gene and cell therapy products’ attributes with clinical outcomes, strengthening confidence in therapeutic performance, but it also requires analytical strategies that evolve alongside product development and regulatory expectations.
Selecting a partner who understands the nuance of advanced biological systems, regulatory-driven analytical requirements, and the variability inherent to complex manufacturing processes is vital as the molecular complexity of therapeutic pipelines increases. At AMSbiopharma, we offer specialized support in designing and implementing “fit-for-purpose” quality control protocols tailored to the unique challenges of advanced therapies.
Contact us today to learn how our analytical expertise can accelerate your development timeline.
References
European Medicines Agency. Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials – Scientific guideline [Internet]. Amsterdam: EMA; 2025 [cited 2026 Feb 12]. Available from: https://www.ema.europa.eu/en/guideline-quality-non-clinical-clinical-requirements-investigational-advanced-therapy-medicinal-products-clinical-trials-scientific-guideline
European Medicines Agency. Quality, preclinical and clinical aspects of gene therapy medicinal products – Scientific guideline [Internet]. Amsterdam: EMA; 2018 [cited 2026 Feb 12]. Available from: https://www.ema.europa.eu/en/quality-preclinical-clinical-aspects-gene-therapy-medicinal-products-scientific-guideline
U.S. Food and Drug Administration. Cellular and gene therapy products [Internet]. Silver Spring, MD: FDA; [cited 2026 Feb 12]. Available from: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products
Yang QE, Lee N, Johnson N, Hong J, Zhao JQ, Sun X, Zhang J. Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy. BBA Adv. 2025 Feb 19;7:100151. doi: 10.1016/j.bbadva.2025.100151