Quality Control Testing Laboratory

The GMP Quality Control Testing Laboratory (QCTL) is a core housed in the Institute for Regenerative Cures and is licensed by the state of California for clinical patient testing with a maintained CLIA certificate of compliance.  The staff consists of two California licensed Clinical Laboratory Scientists, a hospital lab technician III, and a Medical/Laboratory Director.  The QCTL provides clinical CD34+ cell analysis utilizing the International Society of Hematotherapy and Graft Engineering (ISHAGE) gating strategy.   

In addition to clinical CD34 analysis, the QCTL provides clinical trial product release testing for the GMP Facility and other university researchers. The tests available for release testing are endotoxin performed utilizing the Endosafe®- PTS systems by Charles River Laboratories, sterility culture prescribed in the Code of Federal Regulation Title 21 Part 610, and gram stain. 

As prescribed by CLIA, the QCTL participates in peer proficiency testing through the College of American Pathologists.  The lab is enrolled in stem cell and umbilical cord blood surveys which encompass CD34 stem cell analysis and a gram stain survey.  Additionally, the QCTL participates in proficiency testing for endotoxin through Charles River Laboratories.  Participation in peer comparison is part of the ongoing quality system of the laboratory.  In addition to the proficiency testing component of quality, all patient and research results are reviewed for quality control and quality assurance. 

Test Menu

Sterility Culture (compendial method)– Per USP <71>, 1mL of final formulation is inoculated into each of two media (thioglycollate and soybean-casein digest).  Total submission volume is a minimum of 2.5mL; if this volume is not available, alternatives will need to be discussed.  Sample is incubated for 14 days to conclude a result of “no growth.”  If the sample is turbid, it will be subcultured for a final read no less than 4 days later.  Why culture?  Examining final products for contamination is a practical measure for patient safety.  Inhibition Testing is needed for new products.

Inhibition Testing (Bacteriostasis/Fungistasis) – Per USP <71>, all products submitted for sterility culture need to be assessed for inhibition, in order to reach a valid result of “no growth.”  This testing is only needed once per product. This testing requires a minimum of 6.5mL of final formulation to be parsed into 1mL aliquots that will each be inoculated with a suspension of microorganism (S. aureus, B. vulgatis, P. aeruginosa, C. albicans, A. brasiliensis, B. subtilis).  Each inoculation is less than 100 CFU.  An acceptable results is “growth.”  Testing is typically complete within five days.  Please notify the QCTL three days before sample submission. 

Gram Stain – This testing is available as STAT depending on staff availability for an extra fee.  Please allow up to four hours for results after STAT sample submission.  This testing requires 500uL sample volume.

Endotoxin – This testing is available as STAT depending on staff availability for an extra fee.  Please allow up to two hours for results after STAT sample submission.  This testing requires at least 500uL sample volume.  The Endosafe PTS Reader is used.  Results are typically released on the same certificate of analysis if both gram stain & endotoxin are ordered.  Please provide an endotoxin limit calculated for your product; calculation guidance is available in USP 85.  Inhibition & Enhancement Testing is needed for new products.

Endotoxin Inhibition and Enhancement Testing – This is a one-time test for agents that enhance or inhibit endotoxin detection in the product sample submitted.  At least 500uL are needed for this test; ideally more sample is better in the event that multiple sample preparations need to be tested.  The Endosafe PTS Reader is used.

CD34 Flow Cytometry – This test is validated for whole blood in EDTA tubes, apheresis product with heparin or ACDA, and bone marrow with heparin or ACDA.  STAT testing is available for this test depending on staff availability for an additional fee.  Other sample types require test development and validation.

CD3 Flow Cytometry – This test is validated for apheresis product with heparin or ACDA.  STAT testing is available for this test depending on staff availability for an additional fee.  Other sample types require test development and validation.

Viability Flow Cytometry – We perform viability as a part of all of our flow cytometry testing using 7AAD viability dye.

Automated Cell Count – Typically white blood cells only are reported on a test report for this test, but an entire complete blood cell count can be provided upon request.  Testing is performed with a Sysmex XN-330 and requires at least 500uL.

Custom Test – Other testing may be performed in the QCTL after development.  These tests are typically flow cytometry panels that have been developed after collaboration with the client and tested with final formulation in parallel with another lab before becoming a test of record. Our clinical testing is required to follow the Clinical Laboratory Improvement Amendments (CLIA) of 1988, as outlined in 42 CFR 493.  Validation of clinical trial product testing may be in progress during the trial with the goal of complete validation.  It is necessary to provide additional final formulation to perform studies on antibody titrations, sample stability, linearity, precision, accuracy, sensitivity, and/or correlation.

Contact: QCTL@ucdavis.edu