Drug shortages seem to be increasingly in the news, most recently, with focus put on several of the standard oncology products which appear to be at near-critical levels of shortage. FDA is logically encouraging manufacturers to increase manufacturing and improve the advance notice of pending shortages, and is considering ways to utilize temporary importation of drugs not approved for use in the U.S. As discussed in a recent post, another option directed at minimizing unnecessary drug wastage relates to developing programs for extending expiration dates beyond those demonstrated by the manufacturer.

A similar question might be raised about how to extend expiration of another critical class of therapeutic products which are constantly in short supply: blood products. Plasma and cryoprecipitate fractionated portions of whole blood can be frozen, but platelets have a very short shelf-life (5 days at room temperature) and red cells (unless frozen in a somewhat complicated and expensive process) must be used within 42 days. These shelf-life legal requirements have been selected as the limits of storage to ensure that the products are of adequate biological activity for their intended purposes, and to ensure that the risk of microbial contamination overgrowth during storage and the subsequent risk of transfusion-transmitted infection is minimized. However, blood product usage is unpredictable, driven by constantly changing clinical need, and substantial fractions of donated fractionated products are discarded due to expiry.

What can be done about blood product shortages? The time-honored approach is a frantic call for emergency donation via the media and personal calls to trusted repeat donors. This is often successful to stabilize community supplies of blood products, although one or two transfusion-heavy medical cases can virtually wipe out the reserves of a smaller community. Improvements in “holding solutions,” the storage conditions under which blood products are maintained to keep their desired biological properties at useful levels, have unfortunately shown only limited capability to significantly extend shelf-life.

However, another potential approach, which has been gaining considerable attention is that of “sterilizing” transfusion products. Technologies exist, and are in continued development, to ensure that any microbial contamination present at donation has been neutralized. Pathogen inactivation procedures appear to be capable of neutralizing virtually any class of microbial contamination that might slip by the standard donor screening procedures. Recent experience with such approaches has demonstrated impressive outcomes for obtaining safer blood products (for review, see Corash et al. 2011. Expert Rev Hematol 4:509-525). With multiple log-10 fold decreases in microbial content, treated blood products become essentially infection-risk free. However, in addition to the production of safer blood, it also has been demonstrated in those countries in which pathogen-inactivation technology has been approved and is employed in blood banks that product shelf-life can be safely extended. If infection risks can be essentially negated and storage conditions established solely to maximally extend product potency, it may be possible to extend the mandatory expiry limits enough to reduce the incidence of critical blood product shortages.

Posted by Bob Roth, Vice President and Worldwide Medical Director. For more information, please contact Bob at bob.roth@weinberggroup.com.