AABB News: Managing Apheresis Unit Demand

This article originally appeared in AABB News, a benefit of AABB membership. Join AABB today to read the rest of this month’s issue.

The field of regenerative medicine is growing. Forecast data estimates there could soon be a threefold increase in apheresis collection demand in the United States – from approximately 43,000 annual collections in 2021 to 132,000 by 2025.¹

There are now two U.S. Food and Drug Administration-approved gene therapies for rare diseases and six chimeric antigen receptor (CAR) T-cell therapies in use as treatment for six difference cancers. In the research pipeline, there are hundreds more cell and gene therapy products being studied, many already in phase 3.² With this growing demand, many apheresis centers are left struggling to adapt.

“In the past four to five years, there have been two growth areas that have made it difficult to keep up,” said Jeffrey L. Winters, MD, chair of the Division of Transfusion Medicine and director of the Therapeutic Apheresis Unit at the Mayo Clinic College.

The first is increased utilization of photopheresis to treat graft-versus-host disease (GVHD), he said. Growth of the stem cell transplant program has meant more and more patients with GVHD. The apheresis unit has had to add significantly more pieces of equipment and additional slots for patients to handle what Winters estimated to be 75-85% growth in these procedures in the past 5 years.

“The thing that has been even bigger for us has been all the CAR T-cell therapies and the collection of peripheral mononuclear cells that get manufactured into CAR T-cell therapies,” Winters said. “That is the current challenge for us.”

CAR T-cell therapies have been an exciting advance in the treatment of cancer, specifically in hematologic malignancies. All currently available CAR T-cell therapies are customized for individual patients. T cells are collected from each patient at an apheresis center and re-engineered by a manufacturer to bind to specific proteins on cancer cells and kill them.³

“Obviously we like to see these advances for patients, but the development of more and more cell therapies has created a challenge with apheresis units because we don’t always have the capacity to meet this growing demand,” said Federico Rodriguez Quezada, SBB, Collections and Processing Lab Facility Manager at University of Florida Health Shands Cancer Hospital.

Pressure Points

The two pressure points associated with meeting this growing demand are related to staff and scheduling.

Each person undergoing cell collection, whether they are a healthy donor or a patient, must be connected with a machine, Rodriguez Quezada said, and apheresis centers need qualified individuals to operate those machines.

“This is a big issue because these people need to be under continuous surveillance to make sure they are ok… no changes in blood pressure, no adverse reactions, etc.,” Rodriguez Quezada said.

In most centers, the person monitoring patients, donors, and machines are nurses. “Apheresis nurses are highly skilled,” said Patricia A.R. Brunker, MD, DPhil, medical director of patient services on the Blood Transfusion Service at Massachusetts General Hospital.

“Even if we are getting nurses coming from other complex areas, like the intensive care unit, or who are familiar with handling complex machines like dialysis nurses, it still takes a full year for us to train them to be independent operators of these apheresis machines.”

These nurses have to be trained not only in cellular therapy collections, but also in collection for therapeutic apheresis procedures. Hospitals running apheresis centers have to provide thorough resources in both areas.

Winters said that his unit has been struggling to fill nursing positions and the long training times mean that, until training is complete, two nurses are often assigned to one procedure. Winters said he has had one full-time equivalent nursing position open for about six months without interest from potential candidates.

Beyond having a sufficient volume of staff, mononuclear cell collections complicate staffing further because of workflow issues.

“It is harder for us to attempt to staff a procedure list that includes a substantial chunk of very last-minute add-ons that are time sensitive,” Brunker said.

Much of mononuclear cell collection is dictated by the availability of drug manufacturers’ processing slots, whether for an approved product or one being tested in a clinical trial. “These manufacturers have limited manufacturing slots,” Winters said. “They don’t work on weekends. They can’t accept shipment after a certain time of day. They don’t accept shipments on Fridays.”

From a space standpoint, there are times in the day when many beds in his unit are not being utilized, Winters said. That is because everybody wants the same time slots: the morning, when beds are in short supply.

“If you look at beds at 3 PM on a Friday, though, all 17 might be open,” Winters said. Additionally, each unit may only have one or two nurses trained in a specific manufacturer’s collection protocol. “I may not have all my nurses trained to do every product,” Winters said. “That spins into issues from scheduling, especially if the manufacturer tells us that we have to collect to fill a specific manufacturing slot and the two nurses I have trained on that product are scheduled to be off at that time. Then we are stuck rearranging schedules, and that ripples out.”

Protocols/Manufacturers

Complicating things further, each CAR T-cell manufacturer has its own protocols in place for cell collection.

“There are slight, or maybe not-so-slight, differences in how they want collections done – all of which deviate from our standard operating procedures,” Winters said.

Each manufacturer has its own protocols for documentation and its own computer portal for data entry. Each portal is similar to the others, but may have a number of small differences.

“These differences may include something as simple as the unit things are entered in as,” Brunker said. “One portal may want a temperature entered in Fahrenheit and one in Celsius.” Each portal will have a different URL, a different firewall, a different user ID. Some might require a different pre-procedure lymphocyte count. Some may define a procedure based on time on machine or on volume processed.

“All of these differences open up the possibility for error and inefficiencies, slowing down workflow,” Brunker said.

The American Society for Apheresis (ASFA) Clinical Applications Committee (IEC Therapy Subcommittee) developed a white paper in collaboration with AABB and other organizations to provide leukapheresis guidance for the collection of mononuclear cells from adults and pediatric patients undergoing immune effector cell therapies for commercial or research applications.⁴

The paper discussed several key questions related to leukapheresis collection and provided consensus recommendations. The paper stressed the importance of collection and cell therapy facilities being involved early on in the development and onboarding of any clinical trial involving immune effector cell therapies for which leukapheresis is required. This involvement allows the facility to determine if the study protocol is feasible, in terms of budget and resources.

“Among other things, the paper is a guide for manufacturers about things that they may not have considered,” Winters said.

The hope in the field is that manufacturers can be persuaded to standardize some of the processes involved in leukapheresis collection for these new therapies.

“We understand that a company is not going to want to standardize everything when they are trying to develop something new, and that we have to be nimble and adapt to that,” Brunker said. “But having some standardization, for example in things like data entry, would be helpful for everyone. Even if it is limiting things to just three or four options. Increased standardization would help us all operationally.”

The situation has gotten somewhat better, Winters said, especially in terms of research products, but there is still room for improvement. The hope is that increased standardization will increase capacity, extending the availability of these new treatments to more patients.

Strategies to Mitigate

The growing demand for apheresis unit services does not appear to be abating. As such, these units must begin to put in places strategies to meet this demand.

To start, Rodriguez Quezada recommended putting in place guidance for how to prioritize patients and procedures, and to make this prioritization known to partners. “We have to prioritize based on the severity of the patient and our workflow,” Rodriguez Quezada said. “For apheresis there has to be a schedule and we have to run by that schedule in order to be sufficiently prepared.”

In some apheresis centers in the U.S. and elsewhere, there is a shift to the use of apheresis technicians, who are monitored or supervised by apheresis nurses. “If for any reason there is something going on clinically with that patient or donor then the nurses are there to take care of it, but this has obvious advantages and disadvantages,” Rodriguez Quezada said.

Winters said Mayo Clinic has started to schedule some nurses on eight-hour shifts and some on ten-hour shifts to allow for some flexibility in scheduling. If nurses are on schedule for hours over and above overtime hours, they receive an additional percentage pay. “We know though that people can only get so much more money before they are burnt out,” Winters said. “This is more of a short-term solution until we can fill positions.”

Mayo has been supportive of the challenges the apheresis unit has seen in recent years, Winters said. An Immune Effector Cell Program was created that gives the unit additional equipment, additional expansion of FTEs, and additional space, including space for beds and storage. Brunker said there has been a slow shift in awareness at her institution. Establishing a cellular therapy compliance officer has been an important part of that.

“You have to begin engaging stakeholders outside of your division and department,” Brunker said. “That has been critical for us to make changes.” For example, Brunker’s apheresis unit has established a request for services form that is required when a research protocol is submitted. Now colleagues seeking to start a new protocol have to call and discuss it with the apheresis unit prior to initiation. This allows the departments to work together to establish a protocol that is viable for everyone, instead of involving apheresis after the protocol has already been established.

As a consequence, the medical and administration leadership at Massachusetts General now knows more about apheresis, Brunker said. “They didn’t understand how highly skilled our staff needs to be, how long it takes to recruit them, and how important it is to retain them after training,” Brunker said.

The Massachusetts General apheresis unit also has a nursing lead who is responsible for creating a nursing job aide. This is a practical guide for nurses that details for protocol X, Y, or Z, the procedures that need to be done, or the computer interface required by the manufacturer.

Brunker said collaboration is key to addressing supply and demand issues. “One of the things I stress is that, unlike some laboratory physicians, I am not an MBA,” Brunker said. “When I was just an attending physician taking care of apheresis patients, I didn’t feel the need to learn that type of economics.”

Now, she said she can frequently be found reading business books. She is self-training in order to be able to better pitch what is needed to the people who need to hear it. Managers need to learn strategies to be able to talk to administration about building a system that has excess capacity at the bottleneck.

This type of work within institutions, and wider collaboration between apheresis units and drug manufacturers will be key for future growth and successfully bringing these dynamic innovations to a larger group of patients.

REFERENCES

1. Be The Match BioTherapies. Effect of rapid cell therapy growth on collection capacity. https://bethematchbiotherapies.com/celllines-blog/rapid-cell-therapy-growth-collection-capacity/. Accessed September 19, 2022.

2. Alliance for Regenerative Medicine. Regenerative Medicine in 2021: A Year of Firsts & Records. https://alliancerm.org/sector-report/ h1-2021-report/. Accessed September 19, 2022.

3. National Cancer Institute. CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers. https://www.cancer.gov/ about-cancer/treatment/research/car-t-cells. Accessed September 19, 2022.

4. Liu HD, Su L, Winters JL, et al. Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis. Cytotherapy.2022;24(9):916-922.