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CLIA Requirements for Gene and Cell Therapy Programs

It is a common misconception that all aspects of cell and gene therapy research and development are excluded from Clinical Laboratory Improvement Amendments (CLIA) oversight. While it may not be necessary for the intermediate phases of a clinical trial, CLIA certification is needed to conduct testing for patient enrollment and post-marketing surveillance purposes since patient-specific results may be reported. Because of this, it will be most efficient to place your gene or cell therapy program’s bioanalytical work with a CLIA-certified CRO laboratory – that way the developed assays will be verified as in compliance with CLIA regulations from the start and can be carried through all stages of development and past market approval.

Below are several areas of testing needed throughout the gene and cell therapy development process that fall under CLIA oversight and what to look for in a CRO partner to ensure they not only uphold CLIA compliance, but can also deliver the most accurate and robust results for your study needs:

Immunoassays for Clinical Trial Inclusion/Exclusion
Immunoassays, such as ADAs and NAbs, involve patient-specific testing to identify those who could benefit most from new gene-targeted therapies and are therefore subject to regulation by CLIA. For immunoassays, this patient-specific testing may involve identification of pre-existing antibodies to a viral vector used in a biotherapeutic. An example of this can be seen in a recent study conducted by BioAgilytix in which we developed an NAb assay to measure the prevalence of pre-existing antibodies against the AAV9 serotype in patients for a gene therapy clinical trial.

Molecular Testing
Results from various molecular testing methods can guide the establishment of inclusion and exclusion criteria for patient enrollment in gene or cell therapy clinical trials. The objective of any one of these assays is to match the patient’s molecular profile with the appropriate targeted therapy. Biomarker assays may be used to quantify levels of specific analytes to provide an individualized treatment that will maximize efficacy and mitigate side effects, and this testing has broad applicability across disease states including oncology, autoimmune, metabolic, and neurology. Other molecular methods to detect and quantify nucleic acids, such as digital droplet PCR (ddPCR), can be leveraged to test for rare cellular mutations, single-nucleotide polymorphisms (SNPs), and other variants such as cancer.

Immunophenotyping via flow cytometry, or FACS analysis, can derive relevant information for disease diagnosis and classification, and this technology is often used in the study of rare diseases as well as for multiple types of cancer. Again, if testing generates individual patient results, particularly when used for disease diagnosis or classification, this work falls under CLIA oversight. Flow cytometry is leveraged to analyze the ratio of various cellular populations specific to a disease state, and well as for genotyping for variants, and can help to stratify patients with diseases of different classifications to guide targeted treatment plans. To ensure accuracy, it requires a platform that is able to generate reliable, repeatable, and detailed data on cell count, properties, and classification on a cell-by-cell basis.

Patient-Specific Monitoring Throughout Treatment
Testing to evaluate and monitor the success of a delivered therapy in a patient must also comply with CLIA regulations. This can include assays for gene transcript analysis, identifying development of post-treatment mutations, and for monitoring tumor burden. CLIA-compliant NAb assays are also essential for monitoring host immune response to a vector used in gene or cell therapy, to understand the gene or cell therapy’s immunogenic profile and to monitor for adverse events. Your CRO partner will not only need CLIA certification but also an arsenal of expertise in PK/PD, biomarker, cell-based assay, and immunogenicity testing in order to effectively support delivery of patient-specific monitoring results.

Patient-specific reporting is a critical component in the development of personalized medicines, and BioAgilytix is able to provide the individualized data that will help you make pivotal decisions regarding drug safety, dosing, and inclusion/exclusion criteria for patient enrollment in your gene or cell therapy clinical trial. Our advanced laboratories in Durham, NC and Boston, MA are CLIA certified and we maintain in-house all of the state-of-the-art platforms discussed above. Speak with our scientists to learn how we can support your cell and gene therapies at various stages of their development and ensure their regulatory compliance.

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