The Translational Trial Development and Support Laboratory (TTDSL) was established in 2002 to provide the facilities and expertise to support clinical assay development from technology developed in academic laboratories.
We also provide assay development and testing support for early phase clinical trials with a focus on cell and gene therapy. We work with investigators locally, nationally and internationally and from both academia and industry.
The core is CAP / CLIA certified and has a diverse portfolio of high complexity assays that are not offered by traditional labs. Our tests are SOP-driven, highly controlled, and we also have an assigned quality assurance staff to ensure data integrity and compliance with CAP / CLIA, GxP, and other applicable regulations.
Clinical Assay Development
One of our mandates is to help investigators bring their specialized laboratory-developed tests to the clinic. We provide support in optimizing a standard operating procedure (SOP), validating the assay at a level congruent with CAP regulations, and then offering the test through the TTDSL or in conjunction with another Cincinnati Children's clinical laboratory. Previous examples of this process include our Fanconi anemia complementation assay (now offered at the research level) and the VEGF-D assay.
Clinical Trial Monitoring
The TTDSL has effectively supported 11 Phase I/II gene therapy clinical trials by designing tailored analytical assays and acquiring sponsor-developed assays via technology transfer. We have extensive experience in providing the following services:
- Central laboratory coordination
Peripheral blood leukocyte isolation, lineage sorting, and analysis by flow cytometry
Vector copy number by qPCR
Hematopoietic cell colony forming unit (CFU) assay
Gene expression by qPCR or flow cytometry
Replication competent vector testing by qPCR (inquire for availability)
Although these techniques have been utilized primarily for lentiviral/retroviral vector monitoring, they can be developed for any vector system or even non-gene therapy clinical trials. Testing for Phase III clinical trials is possible if satisfied by compliance with CAP regulations.
Gene Therapy Product Testing
The TTDSL performs these assays at an SOP-driven level with QA review to align with current FDA guidance for Phase I/II studies and the needs of the Sponsor. The following assays are offered:
In vitro immortilization (IVIM) assay to assess genotoxicity of integrating viral vectors (based on Modlich et al, PMCID: PMC2835038)
Lentiviral vector physical titer assay by p24 or viral RNA
Lentiviral / retroviral vector infectious titer determination using HT1080 cells and qPCR analysis of integrated vector
Lentiviral vector toxicity of human CD34+ cells with optional CFU assay or qPCR copy number determination
Endotoxin by the LAL method
Mycoplasma by PCR (Roche MycoTOOL or Agilent MycoSensor)
The TTDSL holds a Type 5 Master File (BB-MF) that may be used as a cross-reference in support of IND submissions. We can also assist in developing customized testing assays. The TTDSL has a broad expertise in qPCR, ELISA, protein HPLC, cell culture, and flow cytometry-based assay development. Importantly, management has several years of experience in gene therapy product testing and manufacturing.