Gene therapy products while a relatively new category with limited approval history nevertheless still requires rigorous characterization and quality control. Potency estimation for gene therapy, especially those using adeno-associated virus (AAV) as a vector to deliver the product is a measure of the therapeutic activity of the drug that also involves measure infection of target cells (DNA, copy number), transcription (RNA measurement), translation (protein expression), protein modifications, proper localization of the protein product (protein function at the targeted location).
The Food and Drug Administration (FDA) describes potency for a gene therapy product as “the specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result.” (21 CFR 600.3(s)). Applied StemCell (ASC) offers a preclinical Bioservice platform that support AAV gene therapy and cell therapy development to meet the fast-growing needs in gene and cell therapy space. ASC has extensive experience in AAV gene therapy products using AAV2, AAV5, AAV, 6, AAV8, AAV100M and other serotypes: titer estimation, infectivity, and potency; serotype assessment for cell line and animal models.
To detect transduction efficiency (infectivity) and potency by measuring protein expression, ASC will develop and validate of ELISA assays to be precise and sensitive enough to detect changes in transgene protein expression levels, as defined in (21 CFR 600.3(s) and 610.10; and 21 CFR 210.3(b)(16)(ii)) and to be able to compare relative potencies of different manufactured lots of AAV9-TK2 for release of the product, as defined in (21 CFR 610.1; 21 CFR 211.165(a)).The assay development phase will also include addressing the FDA guidelines for the ELISA including; accuracy, precision, specificity, linearity and range, system suitability and robustness.