The challenge of multiple audits and redundant training

The UCLA Health Hematologic Malignancy/Stem Cell Transplant Program has been a pioneer in providing cell therapies to patients with hematologic cancers and disorders. In 2015, UCLA began participating in multisite clinical trials for CAR-T therapy and was one of the first centers in the nation to offer both FDA-approved CAR-T therapies, Kymriah® and Yescarta®. As the organization continues to participate in multiple CAR-T and other immunotherapy clinical trials, its apheresis unit and cell therapy lab continue to experience an increase in the need for their cell collection and processing services. Guest author, Heather Steinmetz, MPH, shares some of the challenges her organization has encountered with this rapid growth, such as multiple cell therapy audits. And she shares how adopting standardized processes can help to overcome these challenges.

New and innovative therapies coming to market, or even in clinical trials, present amazing opportunities for patients in need. While this time is extremely exciting for UCLA Health and our staff, this increase in demand has also created challenges for our apheresis unit and cell therapy lab.

The two most significant challenges we have encountered include:

1. Multiple quality system audits (QSAs) and site initiation visits (SIVs) by cell and gene therapy companies, third parties and other organizations, oftentimes with overlapping results
2. Redundant training on processes completed by staff each day

Challenge #1: Multiple quality system audits with overlapping results

As the number of cell therapies in clinical trials increases, the number of audit requests continues to grow. These audits for compliance to Good Tissue Practice (GTP) and Good Manufacturing Practice (GMP) regulations are necessary to ensure apheresis centers and cell therapy labs meet quality standards for the collection and processing of cellular starting material.

From October 2017 through September 2018 alone, our apheresis unit and cell therapy lab underwent:

• One accreditation inspection
• One Risk Evaluation and Mitigation Strategies (REMS) audit
• Two SIVs
• Three commercial audits

The majority of the clinical trial audits and site visits were related to CAR-T or engineered cell therapies. Each audit and site visit requires a significant amount of staff time for preparation, hosting and follow-up.

With multiple QSAs occurring in short timeframes, we have had instances of overlapping, and sometimes conflicting, findings. We’ve had situations where one company accepts a corrective action, but the next company asks for a different corrective action that impacts a standard operating procedure (SOP). Because of contractual agreements, we must notify the first company about the change and receive approval before we can implement the change for the second company.

For each product thus far, including commercial and non-commercial products, we have been asked to revise between five and 15 SOPs. And we must retrain staff each time an SOP changes. As more products gain FDA approval, the current process will likely become unmanageable.

Challenge #2: Duplicative training

Once our center receives approval to collect and process starting material for a therapy, our staff must be trained on the therapy protocols.

Cell and gene therapy companies often train staff on every aspect of cell collection and processing, including those for which an approved SOP already exists. Multiple companies have trained our cell therapy lab staff on opening a dry shipper and putting cells in a liquid nitrogen storage tank—a process our staff complete every day.

It would be more beneficial and efficient to train staff on the aspects of each protocol that are unique to the therapy, such as a collection based on volume versus cell count. Those variations are critically important and require specialized staff training to decrease the risk for error.

Standardization can help

The experience of our organization demonstrates the pressures on the cell collection and processing infrastructure, particularly due to the duplication of audits and training.

A Quality System Audit Program offering licensed audit results to therapy developers can streamline the audit process, saving apheresis and cell therapy lab staff a significant amount of time, while still ensuring quality cell collection and processing, because the auditing organization is auditing for GTP and GMP compliance.

Industry stakeholders can lead solution development

To have the greatest impact and move the needle towards standardization quickly, key stakeholders across the cell and gene therapy industry must come to the table and work together. By doing so, we can get high-quality therapies to patients faster, which will transform how we treat diseases and ultimately improve patient care.

You need to be able to innovate and leverage your relationships so the allogeneic and autologous therapies you are developing can follow that exciting path towards delivery.