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What Impacts Starting Material Quality? Part 3: Defining the Balance Between Purity and Yield

Nov 12, 2019 10:07:00 AM / by Nancy Andon, MSc

Hand holding balance_AdobeStock_93896353-1During the previous segment of this blog series, cell collection experts at HemaCare reviewed apheresis best practices in donor recruitment, apheresis technology, and cell handling techniques. This week, we define the difference between purity and yield, and examine their contribution to starting material quality.

Defining Quality

Optimizing leukapheresis collection quality is a balance between total cell yield and sample purity. Although white blood cell counts occur within a predictable range in healthy donors, there is variability within that range. Total white blood cell (leukocyte) counts, as well as differential cell counts, vary from donor to donor, and from one collection to the next. The total number of leukocytes collected during an apheresis session can be increased by collecting a greater volume of material, either by collecting at higher flow rates or for a longer duration. However, this is naturally limited by donor safety considerations related to age, BMI, or other factors, as well as cell viability concerns since higher flow rates can potentially damage cells or alter leukocyte function.

Quality, however, is not necessarily defined by the total cell yield, but rather by the yield of the target cell type that will be used for research or therapeutic process development. In the case of CAR-T development, for example, the goal would be to have a leukapheresis unit with low red blood cell and granulocyte count and high lymphocyte count. Optimizing yield may increase the probability of collecting a greater number of target cells, but often at the cost of also collecting a greater number of contaminating cell types. Higher volume yields may necessitate additional processing steps to remove contaminating cell types, often at the expense of target cell yield and process development efficiency.

Apheresis Sample Purity

Rather than yield, one can optimize collection with the goal of sample purity. In this case, collection parameters are focused on maximizing target cell counts, and by extension, the functional efficacy of the apheresis material. Optimizing separation of blood components and cell types, while it may yield a lower volume leukapheresis product, can help guarantee higher target cell purity from the start, and result in lower target cell loss due to a minimized need for further separation steps. In collections where the donor’s physiology results in a naturally lower volume but high-quality product, it is inadvisable to change collection parameters in an attempt to get a higher cell yield, since this may simply serve to increase the number of contaminating cell types.

Narrowing selection parameters too far in hopes of higher purity, however, has the potential drawback of losses in the total number of target cells collected. Moreover, in spite of ideal collection conditions, apheresis units from an apparently healthy donor can sometimes contain a significantly higher percentage of granulocytes than average. This is not often due to inefficient collection, but may, in some cases, indicate an underlying condition or undiagnosed disease, such as cancer. [1] In fact, high percentage of granulocytes are frequently observed in disease-state patient material, thus consideration should be given to these challenges prior to translation of processes to a clinical setting.


The best strategy is not to be overly focused on either yield or purity, but rather to strive for the best balance between the two. “Collection efficiency” is defined by the ratio of the target cell population to contaminating cell types in the collected volume, as well as the total number of target cells collected via leukapheresis compared to those calculated to be present in the circulation. High collection efficiency makes for high-quality apheresis material, which results in high-quality data downstream.

Optimizing leukapheresis efficiency requires expertise in the contribution of many different predictive factors such as collection timing, pre-apheresis cell counts, demographics, and disease-related factors. It also requires specialized training and hands-on experience in donor selection and management, apheresis best practices, and cell collection equipment.

Post-collection handling affects starting material quality as well. Precise temperature regulation and optimized cryopreservation, storage, and shipping procedures all positively impact cell viability and cell function. It takes a well-trained, experienced team to reliably produce high-quality cell therapy starting material; careful consideration of the need for high-quality material will give cell therapy products their best chance for success.

Click here to view HemaCare’s Finding the Balance in Your Starting Material: Purity and Yield infographic.


  1. Forget P. et al. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 10: 12. Jan 2017.


Nancy Andon, MSc

Written by Nancy Andon, MSc

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