Abstract
Background
Packed red blood cells (PRBC) are stored at 2°C–6°C to ensure quality. Improper temperature control during PRBC transport reduces the quality of downstream blood products and wastes PRBC units. This study evaluated the suitability of the BioBox LAB10 for in‐hospital PRBC transport.
Methods
Temperatures of the box interior and simulated formulation were measured to assess cooling capabilities. Quality was evaluated by measuring red blood cell count, haemoglobin concentration, haematocrit, pH, potassium concentration, and ATP concentration of PRBC samples. The storage capacity, size, weight, and cost of the BioBox was compared with that of the ATR700.
Results
The BioBox cooled to ≤6°C within 14 min. PRBC temperature remained ≤6°C for approximately 19 h. None of the quality parameters, including ATP concentration, differed significantly between samples stored in the BioBox or in a refrigerator. The BioBox is smaller, lighter, and 84% less expensive than the ATR700, with an equivalent storage capacity.
Conclusions
The BioBox effectively maintains temperature and PRBC quality during transport and provides a practical solution for in‐hospital transport of blood for transfusion owing to its compact, lightweight design, and affordability.
1. INTRODUCTION
Packed red blood cells (PRBCs) must be stored at 2°C–6°C to maintain quality and prevent bacterial growth. 1 While their transport temperature is not regulated in Japan, PRBC exposed to uncontrolled temperatures for >60 min must be discarded. 2 Consequently, PRBC are typically dispensed one unit at a time. However, in emergencies or when the required volume is uncertain, multiple PRBC units may be dispensed, increasing the risk of units being discarded due to prolonged exposure to uncontrolled temperature.
Recently, in Japan, the BioBox LAB10 (BioBox; SUGIYAMA‐GEN Co., Ltd., Tokyo, Japan) was introduced for the temperature‐controlled transport of pharmaceutical products (Figure 1A). A BioBox containing frozen ice packs can maintain temperatures of ≤6°C for several hours under the test conditions. In our hospital, the BioBox is used to transport and temporarily store PRBC when multiple units are dispensed.
FIGURE 1.
(A) Exterior view of the BioBox. Dimensions: 335 (W) × 235 (D) × 295 mm (H). (B) Interior view of the BioBox. The interior dimensions of the partitions holding the product are 217 (W) × 120 (D) × 176 mm (H). When in use, the Cool Lab Ice +3 packs are placed in the five locations indicated by the arrows. (C) Exterior view of an ice pack. (D) Blood bag containing simulated formulation and temperature data logger. (E) Temperature transition of the simulated formulation, measured three times. The grey‐shaded area represents the acceptable PRBC storage temperature range (2°C–6°C).
Widely used in Japan, the Active Transport Refrigerator (ATR700, Toho Pharmaceutical Co., Ltd., Tokyo, Japan) is a portable device developed in 2012 to transport blood products to remote islands. 3 The ATR700 operates on alternating current power or an internal battery. In a previous study, the ATR700 maintained a stable interior temperature between 2°C and 6°C regardless of external conditions and the quality of the stored PRBC was comparable to that stored in blood centres. 4
This study evaluated the efficacy of the BioBox by validating its cold storage function and assessing the quality of the stored PRBC. Additionally, we compared the storage capacity, external dimensions, weight, and cost of the BioBox with those of the ATR700.
2. METHODS
2.1. BioBox LAB10
The BioBox has a capacity of up to five packs of PRBC (one pack containing 280 mL = 2 units, based on the standard PRBC specifications in Japan). The BioBox was cooled as designed by the manufacturer. Ice packs (Cool Lab Ice +3; SUGIYAMA‐GEN Co., Ltd.) were pre‐frozen at ≤−20°C for at least 24 h before being placed at the sides and top of the BioBox (Figure 1B,C). An internal cold storage material (Thermostrageclear; SUGIYAMA‐GEN Co., Ltd.) was placed between the PRBC and ice packs to prevent direct contact, while maintaining a stable interior temperature.
2.2. Validation of cold storage function
Based on a previous study, 5 an ACD‐A‐filled blood bag with an inserted temperature probe was used as a simulated model to investigate temperature variations in PRBC. Anticoagulant acid citrate dextrose solution (280 mL; Karmipack ACD‐A, SB‐Kawasumi Laboratories, Inc., Kanagawa, Japan) was injected into a 400 mL blood separation bag (KBP‐400C, SB‐Kawasumi Laboratories, Inc.), which is the same type as that used for PRBC, and the bag was preconditioned at 2°C–6°C for at least 24 h prior to use. In a clinical setting, a digital thermometer with a temperature deviation alarm (12218–01; SUGIYAMA‐GEN Co., Ltd.) is used to monitor interior temperature fluctuations. In this study, a Testo 175 T3 (Testo K.K., Kanagawa, Japan) temperature data logger was used with a Waterproof Super‐Quick Needle Probe (Testo K.K.) and Flexible Oven Probe (Testo K.K.). A needle probe was used to measure the temperature inside the bag (Figure 1D), and a Flexible Oven Probe was positioned at the centre of the BioBox to monitor internal temperature. Frozen ice packs were added, and once the temperature recorded by the logger was ≤6°C, the bag of ACD‐A was placed inside the Biobox. Temperature was recorded every minute for 24 h with the BioBox placed in the transfusion laboratory at an ambient temperature of approximately 24°C, which is within the typical operating temperature range (20°C–28°C) at the institutional standard room. The experiment was triplicated.
2.3. Validation of stored PRBC quality
We aliquoted 3 mL of PRBCs that had exceeded the Japanese shelf life of 28 days into glass test tubes and stored them in the BioBox. According to the cooling performance experiments, the PRBC temperature remained stable and within the control range showing a plateau up to 10 h, and was maintained within the acceptable range of 2°C–6°C until approximately 19 h. Based on these observations, we divided the measurements and analyses into two groups: a short‐term group, with samples stored for 2, 4, 6, 8, and 10 h; and a long‐term group, with samples stored for 14 h (when a gradual temperature increase became detectable) and for 19 and 24 h. Control samples were stored in a temperature‐controlled refrigerator (2°C–6°C) for 10 h in the short‐term group and for 24 h in the long‐term group. All experiments were performed in triplicates.
The testing parameters used to evaluate PRBC quality were based on previous studies. 6 , 7 (1) The red blood cell count, haemoglobin concentration, and haematocrit were measured using an XN1000 (Sysmex Corporation, Hyogo, Japan). (2) The pH was determined using a glass electrode (RapidLab 1265; Siemens Healthcare Diagnostics, Inc., Tokyo, Japan). (3) The potassium concentration in the supernatant was measured with a LABOSPECT 008 (Hitachi High‐Tech Corporation, Tokyo, Japan) using the ion‐selective electrode method following centrifugation. (4) The ATP concentration was quantified using the firefly luciferase luminescence method with an ATP Assay Kit for Blood (TOYO B‐Net Co., Ltd., Tokyo, Japan) and a microplate reader (Mithras LB940; Berthold Japan K.K., Tokyo, Japan).
2.4. Statistical analysis
Statistical analyses were conducted using RStudio version 4.4.1 (Posit Software, PBC, Boston, MA, USA). All measurements are expressed as median and range, and comparisons were performed using the Wilcoxon signed‐rank test. The Bonferroni correction was applied to control for multiplicity errors, with the initial significance threshold set at 0.05.
3. RESULTS
3.1. Validation of cold storage function
The time required for the interior BioBox temperature to drop to ≤6°C following the addition of ice packs was 14.0 (13.0–15.0) min (data not shown). The simulated formulation exceeded 5°C at 14.6 (14.3–14.9) h, indicating the onset of warming toward the upper limit of the acceptable storage temperature range (2°C–6°C) and reached 6°C at 19.2 (19.0–19.8) h. After 24 h, the temperature of the simulated formulation was 9.9°C (9.3°C–10.5°C) (Figure 1E).
3.2. Validation of stored PRBC quality
The test results are summarised in Table 1. Because no temperature deviation occurred during the early storage period (up to 14 h), and no differences from control samples were observed at these time points, the table focuses on time points most relevant to potential temperature deviations. The ATP levels, as a measure of red blood cell survival following transfusion in the short‐term group were 5.0 (4.7–5.6) μmol/gHb for control samples and 4.8 (4.8–4.9) μmol/gHb for samples stored for 10 h. Conversely, in the long‐term group, the ATP levels were 4.7 (4.3–4.9) μmol/gHb in the control samples and 4.1 (3.4–4.2) μmol/gHb in the 24 h storage samples. No significant differences were observed in the ATP concentrations between measurement times, between the test and control samples, or in any of the other laboratory parameters.
TABLE 1.
Quality of stored PRBCs during BioBox storage.
| Storage time (h) | Control | 19 | 24 |
|---|---|---|---|
| pH | 6.34 (6.34–6.35) | 6.36 (6.35–6.36) | 6.35 (6.35–6.36) |
| RBC (106/μL) | 6.88 (6.87–6.92) | 6.80 (6.77–6.81) | 6.75 (6.70–6.78) |
| Hb (g/dL) | 20.6 (20.5–20.7) | 20.1 (20.0–20.2) | 20.2 (20.1–20.2) |
| Ht (%) | 61.6 (61.6–61.7) | 61.0 (60.8–61.1) | 60.0 (59.8–60.3) |
| K (mmol/L) | 72.9 (72.0–73.7) | 70.6 (70.4–71.3) | 70.9 (70.7–72.0) |
| ATP (mmol/gHb) | 4.7 (4.3–4.9) | 4.6 (4.5–5.5) | 4.1 (3.4–4.2) |
Note: N = 3. Median (Min–Max).
3.3. Comparison of the BioBox with the ATR700
Both the BioBox and ATR700 can accommodate five PRBC packs only. The BioBox (335 [W] × 235 [D] × 295 mm [H]) is more compact than the ATR700 (381 [W] × 231 [D] × 314 mm [H]). The BioBox is lighter (4 vs. 7 kg) and more cost‐effective (approximately USD 450 vs. USD 3205).
4. DISCUSSION
The interior temperature of the BioBox reached ≤6°C within 14 min of adding the ice packs, verifying that PRBC is stored in a temperature‐controlled environment. Additionally, the simulated formulation in the BioBox remained at ≤6°C for approximately 19 h. These features indicated that the BioBox can substantially contribute to reducing PRBC wastage during emergencies, particularly, when it is critical to reduce the risk of a PRBC unit exceeding the 60 min expiration limit 2 or recommended storage temperature range. Furthermore, studies on other transport containers have reported that increasing the packing density enhances the overall thermal capacity of the system, thereby extending the temperature retention time. 8 While this study evaluated a single pack, operations involving multiple packs are expected to achieve even longer temperature maintenance times than those obtained in this research, thereby enabling the simultaneous transport of multiple PRBC units and potentially reducing the frequency of single‐unit deliveries.
ATP levels in the BioBox samples did not differ significantly from the refrigerated control samples at above 2.3 μmol/gHb—threshold of red blood cell survival following transfusion. 9 No significant differences were detected in the other parameters in the BioBox samples and control samples, indicating no haemolysis or deterioration in quality. In addition, although this study used PRBC units that had exceeded the 28‐day shelf life, similar results are expected when using fresher blood units. 10
The ATR700 has been used for PRBC transportation to remote islands by ship and for vehicle‐based transport to in‐home transfusion scenarios. 11 In these cases, the primary weight burden occurs during loading and unloading, and its impact is considered to be minimal. However, for in‐hospital transport, where staff manually carry PRBC, lighter containers are preferred to reduce physical strain: the BioBox, which accommodates the same volume of PRBC units as the ATR700, is lighter, more compact, and, thus, better suited for in‐hospital transport. Although both are high‐quality transport containers, at approximately USD 450, the initial cost of the BioBox is lower than that of the ATR700, helping to reduce barriers to hospital adoption of this transportation box.
This study has limitations regarding the BioBox at room temperature, in terms of sample size, test parameters, and measurements. Additionally, the samples were aliquoted into test tubes; therefore, further studies are required to obtain more detailed data. Another concern is that aseptic testing was not performed. However, a previous study demonstrated that bacteria‐contaminated PRBC maintained at room temperature for 5 h or exposed five times at 30 min intervals did not reach clinical contamination threshold. 12
5. CONCLUSION
This study demonstrates that the BioBox is suitable for in‐hospital transport of PRBC owing to its strong cold‐retention, which helps prevent temperature deviation‐induced PRBC waste even in non‐refrigerated environments. As the BioBox is designed for transportation, its features are expected to support flexible blood transfusion practices, including temporary product storage.
AUTHOR CONTRIBUTIONS
Yohei Sakai, Takato Ozeki, Hideaki Matsuura, and Rie Nakagawa designed the study, analysed and interpreted the data, and drafted the manuscript. Yohei Sakai, Takato Ozeki, Rie Nakagawa, and Yuya Ishihara performed the experiments and collected data. Hideaki Matsuura, Rie Nakagawa, Yuya Ishihara, Hiroki Doi, and Yasuo Miura reviewed the manuscript and provided key insights. All the authors contributed to the writing of the manuscript and approved the final version.
FUNDING INFORMATION
This work was supported by the Ministry of Health, Labour and Welfare, Japan (Grant Number: 20KC1002).
CONFLICT OF INTEREST STATEMENT
The authors have no competing interests.
ACKNOWLEDGEMENTS
We express our gratitude to the staff of the Transfusion Department at Fujita Medical University Hospital for their cooperation in the data collection. Additionally, we thank Dr. Ryosuke Fujii, Mr. Hiroshi Okumiyama, and Mr. Kazuma Murakami (Departments of Preventive Medicine and Medical Laboratory Medicine, Fujita Medical University) for their guidance on RStudio.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.