Kit Temperature During Cord Blood Shipments

Any temperature extremes that would threaten the life of a child or a pet - being left in a parked car for more than a few minutes, traveling in the cargo hold of an airplane, etc. - also kills cord blood stem cells. The key to shipping fresh cord blood to the laboratory with maximum cell survival is to keep the temperature stable inside the shipping kit. But this simple requirement can be very challenging to implement.

Research has shown that blood-forming stem cells lose their viability when exposed to temperature extremes, either too hot or too cold (1-6). Based on this well established knowledge, regulatory authorities have always recommended that fresh cord blood be maintained at temperatures between 4 and 30 degrees Celsius during transport (7-9).

When cord blood is collected from a birth and must be shipped across countries or even oceans to reach the laboratory, there are numerous opportunities for temperature excursions. What type of vehicle is used to transport the cord blood to the airport, and where in the vehicle is the cord blood held? How long does the cord blood wait to board a plane, and where does it wait? Where does the cord blood travel in the plane? Finally, on the receiving end, how is the cord blood off-loaded from the plane and delivered to the laboratory?

Once upon a time, before the devastating events of Sept. 11, 2001 ("9/11"), the Parent's Guide to Cord Blood used to advise parents to hire a medical courier to carry their baby's cord blood with a "secure chain of custody". Those couriers would insure that cord blood was hand-carried from the inside of a temperature-controlled vehicle into the passenger compartment of an airplane, so that the shipping kit was always in a temperature-controlled environment.

In the post-9/11 world, airports have drastically increased their security, and medical transport procedures have had to adapt to this new reality. It is no longer possible for parents to hire a medical courier. Now couriers only work on contracts for companies that have been approved by national transportation authorities. Hence, the only way for parents to ship cord blood with a courier is to hire a cord blood bank that has a contract with a courier. Even so, the couriers no longer have the freedom to walk cord blood onto a boarding airplane. The cord blood must be delivered to the boarding ramp agents, who will load it on the plane. If the flight is delayed or cancelled, it is the ramp agents and not the courier who have discretion over where the cord blood package is held.

Under today's circumstances, it is more important than ever that the collection kits used to ship cord blood must have good temperature stability, because it is possible that the life of the blood cells will depend on the kit insulation for hours at a time. More insulation is always better, and more insulation usually means bigger kits.

In the United States, there are two very different scenarios in which parents ship cord blood. One is if the parents are donating the cord blood to a public bank that accepts donations by mail. Figure 1 in the accompanying photo gallery of cord blood collection kits displays the shipping kits used by mail-in donation programs. To keep costs down, these programs ship cord blood with FedEx, a transport service that provides no temperature guarantee whatsoever. Consequently, it is imperative that the shipping kits used by public banks must have enough insulation to maintain their internal temperature for the full 48 hour time window allowed for transport to a public bank. These kits are big square boxes that are so sturdy they can be sterilized and reused multiple times.

The more common scenario is one where parents have hired a private company to store their baby's cord blood for the family, and they receive a kit for collection and shipping that is more compact. Figure 2 in the accompanying photo gallery of cord blood collection kits displays the kits used by some of the family banks in the United States (each photo links to the bank web site). They are usually 9 to 14 inches wide but may only be 2.5 to 3 inches deep. Most of these kits represent a compromise: Most have less temperature stability than public bank kits, but they are intended to be carried by courier transport.

This leads to the question of how kit temperature stability is measured. Ideally, any claims that a cord blood bank makes for their shipping kit should be based upon standardized testing by an independent third party. The vast majority of claims that US family banks currently make for the temperature stability of their shipping kits are based upon their own validation tests (10-11). Instead, the banks should have a third party test their kits. Examples of standards agencies that certify and accredit package performance testing are International Safe Transit Association (ISTA) and International Air Transport Association (IATA).

If the temperature inside a cord blood shipping kit exceeded suggested limits during transit, is there any way to know? In fact yes, there is: if the kit contains a temperature logger or simply an out-of-range temperature detector, there will be a record. While temperature loggers are routinely used by family banks in the EU and Canada, very few family banks in the US market have temperature sensors in their kits. However, the 5th edition FACT accreditation standards issued in July 2013 (12) require family bank kits to measure whether the temperature has gone out of range.

To conclude, the Parent's Guide to Cord Blood recommends that parents who are selecting a family cord blood bank ask the following questions about their kits:

1. Ask the bank if their contract includes courier transport, and check that the transport company they name actually provides medical courier service.

2. Ask the bank if their shipping kit was tested by an independent third party.

3. Ask the bank how their shipping kit performs under standardized testing protocols for summer and winter.

4. Ask the bank if their kit contains a method to monitor the temperature once the cord blood is placed in the kit for shipment.

The more parents that ask these questions and demand reassuring answers, the more pressure there will be on US family banks to uniformly adopt high quality practices for cord blood transport.

Dr. Verter acknowledges invaluable assistance with the research behind this article from Greg Davis of First International Courier Systems, Richard Jennings of FamilyCord, Dr. Linda Kelley of Cryo-Cell International, and Dr. Ed Guindi of CORD:USE.

References

1. Yamaguchi M, Fujihara M, Wakamoto S, Sakai H, Takeoka S, Tsuchida E, Hamada H, Azuma H, Ikeda H (2009) Biocompatibility study of hemoglobin vesicles, cellular-type artificial oxygen carriers, with human umbilical cord hematopoietic stem/progenitor cells using an in vitro expansion system. ASAIO J. 55(3):200-205.
2. Wierenga, PK, Setroikomo, R, Kamps, G, Kampinga, HH and Vellenga, E (2003) Differences in heat sensitivity between normal and acute myeloid leukemic stem cells: feasibility of hyperthermic purging of leukemic cells from autologous stem cell grafts. Exp Hematology 31(5):421-7.
3. Wierenga, PK, Brenner, MK and Konings, AWT (1998) Enhanced selectivity of hyperthermic purging of human progenitor cells using Goralatide, an inhibitor of cell cycle progression. Bone Marrow Transplantation 21:73-78.
4. Symonds, RP, Wheldon, TE , Clarke, B and Bailey, G (1981) A comparison of the response to hyperthermia of murine haemopoietic stem cells (CFU-S) and L1210 leukaemia cells: enhanced killing of leukaemic cells in the presence of normal marrow cells. Br. J. Cancer 44:682-691.
5. Elkon, D, Sabio, H, Pinizzotto, M, Sigurdsson, M and Baker, DG (1984) Effect of hyperthermia on murine myeloid precursors. Cancer 54(9):1973-1976.
6. Elkon, D, Sabio, H, McGrath, E and Baker, D. (1981) Temperature dependent inhibition of murine granulocyte-monocyte precursors. Cancer Research 41:1812-1816.
7. Food and Drug Administration. Guidance for industry: minimally manipulated unrelated allogeneic placental/umbilical cord blood intended for hematopoietic reconstitution for specified indications. Rockville, MD: CBER Office of Communication, Outreach, and Development; 2009.
8. AABB Cellular Therapy Standards 6th edition effective July 1, 2013.
9. Foundation for the Accreditation of Cellular Therapy FACT Cord Blood Bank Standards 5th edition effective July 1, 2013.
10. St. Jour, L, Popp, D, Robbins, P and Kelley, L (2013) Development of a Cost-effective, Single-use Container to Maximize Protection from High Temperature for Transportation of Fresh Umbilical Cord Blood. poster at 11th International Cord Blood Symposium, San Francisco, June 2013.
11. Wolfson, RN (2013) Ob.Gyn. News, Supplement, July 2013 issue
12. From FACT: "The standards that address transportation of cord blood units from the collection site to the processing facility are the C7 standards in the 5th edition NetCord-FACT Standards. C7.5 specifically deals with the temperature, however, it does not state the temperature that must be maintained but instead requires that the appropriate temperature range be determined by the bank and specified in the appropriate SOPs (see also C6.7.2- storage temperature). Standard C7.5.2 requires that the temperature inside the outer container be continuously monitored."