Benefits of a comprehensive quality program for cryopreserved PBMC covering 28 clinical trials sites utilizing an integrated, analytical web-based portal.
The HIV Vaccine Trials Network (HVTN) is a global network of 28 clinical trial sites dedicated to identifying an effective HIV vaccine. Cryopreservation of high-quality peripheral blood mononuclear cells (PBMC) is critical for the assessment of vaccine-induced cellular immune functions. The HVTN PBMC Quality Management Program is designed to ensure that viable PBMC are processed, stored and shipped for clinical trial assays from all HVTN clinical trial sites. The program has evolved by developing and incorporating best practices for laboratory and specimen quality and implementing automated, web-based tools. These tools allow the site-affiliated processing laboratories and the central Laboratory Operations Unit to rapidly collect, analyze and report PBMC quality data. The HVTN PBMC Quality Management Program includes five key components: 1) Laboratory Assessment, 2) PBMC Training and Certification, 3) Internal Quality Control, 4) External Quality Control (EQC), and 5) Assay Specimen Quality Control. Fresh PBMC processing data is uploaded from each clinical site processing laboratory to a central HVTN Statistical and Data Management Center database for access and analysis on a web portal. Samples are thawed at a central laboratory for assay or specimen quality control and sample quality data is uploaded directly to the database by the central laboratory. Four year cumulative data covering 23,477 blood draws reveals an average fresh PBMC yield of 1.45×10(6)±0.48 cells per milliliter of useable whole blood. 95% of samples were within the acceptable range for fresh cell yield of 0.8-3.2×10(6) cells/ml of usable blood. Prior to full implementation of the HVTN PBMC Quality Management Program, the 2007 EQC evaluations from 10 international sites showed a mean day 2 thawed viability of 83.1% and a recovery of 67.5%. Since then, four year cumulative data covering 3338 specimens used in immunologic assays shows that 99.88% had acceptable viabilities (>66%) for use in cellular assays (mean, 91.46% ±4.5%), and 96.2% had acceptable recoveries (50%-130%) with a mean of recovery of 85.8% ±19.12% of the originally cryopreserved cells. EQC testing revealed that since August 2009, failed recoveries dropped from 4.1% to 1.6% and failed viabilities dropped from 1.0% to 0.3%. The HVTN PBMC quality program provides for laboratory assessment, training and tools for identifying problems, implementing corrective action and monitoring for improvements. These data support the benefits of implementing a comprehensive, web-based PBMC quality program for large clinical trials networks.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA; HIV Vaccine Trials Network, Seattle, WA 98109, USA.
Constance
C
Ducar
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA; HIV Vaccine Trials Network, Seattle, WA 98109, USA.
Donna
D
Smith
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA; HIV Vaccine Trials Network, Seattle, WA 98109, USA.
Cris
C
Pinzon
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA; HIV Vaccine Trials Network, Seattle, WA 98109, USA.
Michael
M
Stirewalt
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA.
Cristine
C
Cooper
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA; HIV Vaccine Trials Network, Seattle, WA 98109, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Laboratory Medicine, University of Washington, Seattle, WA 98195, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA.
M Juliana
MJ
McElrath
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, E4-200, PO Box 19024, Seattle, WA 98109, USA; HIV Vaccine Trials Network, Seattle, WA 98109, USA. Electronic address: jhural@fhcrc.org.
John
J
Hural
D016915:AIDS Vaccines / Q000627:therapeutic use*; D002470:Cell Survival; D002568:Certification; D002986:Clinical Trials as Topic / Q000592:standards*; D032921:Consensus; D003299:Cooperative Behavior; D015925:Cryopreservation / Q000592:standards*; D019983:Guideline Adherence / Q000592:standards; D015658:HIV Infections / Q000175:diagnosis / Q000276:immunology / Q000628:therapy* / Q000821:virology; D006801:Humans; D007159:Immunologic Tests / Q000592:standards*; D007318:Inservice Training; D007391:International Cooperation; D020407:Internet; D007753:Laboratories / Q000592:standards*; D059232:Laboratory Personnel / Q000592:standards; D059021:Laboratory Proficiency Testing / Q000592:standards*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D015166:Monitoring, Immunologic / Q000592:standards*; D015588:Observer Variation; D017410:Practice Guidelines as Topic / Q000592:standards; D011237:Predictive Value of Tests; D016730:Program Development; D015397:Program Evaluation; D011786:Quality Control; D015203:Reproducibility of Results; D013048:Specimen Handling / Q000592:standards*; D018511:Systems Integration; D013997:Time Factors; D016896:Treatment Outcome; D057188:Workflow
D016915:AIDS Vaccines
Clinical trials; Cryopreservation; HIV; Immune monitoring; Peripheral blood mononuclear cells; Quality assurance