Cell Tissue Bank DOI 10.1007/s10561-015-9502-0
Validation of cold chain shipping environment for transport of allografts as part of a human tissue bank returns policy P. Rooney • M. J. Eagle • J. N. Kearney
Received: 11 December 2014 / Accepted: 16 February 2015 Springer Science+Business Media Dordrecht 2015
Abstract Human tissue is shipped to surgeons in the UK in either a freeze-dried or frozen state. To ensure quality and safety of the tissue, frozen tissue must be shipped in insulated containers such that tissue is maintained at an appropriate temperature. UK Blood Transfusion Service regulations state ‘‘Transportation systems must be validated to show maintenance of the required storage temperature’’ and also state that frozen, non-cryopreserved tissue ‘‘must be transported… at -20 C or lower’’ (Guidelines for the Blood Transfusion Services in the United Kingdom, 8th Edn. 2013). To maintain an expiry date for frozen tissue longer than 6 months, the tissue must be maintained at a temperature of -40 C or below. The objective of this study was to evaluate and validate the capability of a commercially available insulated polystyrene carton (XPL10), packed with dry ice, to maintain tissue temperature below -40 C. Tissue temperature of a single frozen femoral head or a single frozen Achilles tendon, was recorded over a 4-day period at 37 C, inside a XPL10 carton with dry ice as refrigerant. The data demonstrate that at 37 C, the XPL10 carton with 9.5 kg of dry ice P. Rooney (&) M. J. Eagle J. N. Kearney NHSBT, Tissue Services R&D, 14 Estuary Banks, Speke, Liverpool L24 8RB, UK e-mail: [email protected] M. J. Eagle e-mail: [email protected] J. N. Kearney e-mail: [email protected]
maintained femoral head and tendon tissue temperature below -55 C for at least 48 h; tissue temperature did not rise above -40 C until at least 70 h. Data also indicated that at a storage temperature lower than 37 C, tissue temperature was maintained for longer periods. Keywords Low temperature Container Transport Achilles tendon Femoral head Allograft
Introduction Temperature sensitive products such as biological materials, e.g. tissues or blood, should be shipped in temperature-controlled containers (Choi and Burgess 2007). For tissues, the Guidelines for the Blood Transfusion Services in the UK state that frozen, noncryopreserved tissue should be stored below -40 C for long-term storage, i.e. more than 6-months (Guidelines for the Blood Transfusion Services in the UK, 8th Edn. updated 2013). When frozen tissue is shipped, it must be shipped below -20 C or lower. To retain its expiry date; it must be shipped below -40 C. If the temperature rises to between -40 and -20 the expiry is reduced to 6 months maximum. Several studies have been performed on temperature controlled containers and cold chain management but the vast majority of these studies have concentrated on maintaining a temperature of 2–8 C or occasionally 1–10 C (Rentas et al. 2004; Elliott and Halbert 2005, Ohkawara et al. 2012; Miller et al.
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2013). Few studies have been performed on cold chain and temperature management of substances below -30 C and even commercial companies who manufacture complex cold transport boxes only state that for shipping substances below -20 C, dry ice should be used and the container should be a one piece moulded container (www.coldchaintech.com). NHS Blood and Transplant Tissue Services, ships up to 10,000 human allograft tissues to UK surgeons and hospitals each year in either a freeze-dried, frozen or cryopreserved state—at least 50 % of the tissue is supplied frozen or cryopreserved. Freeze dried tissue is sent at ambient temperature whereas frozen and cryopreserved tissue is sent on dry ice. Currently, frozen and cryopreserved tissue is shipped in flat-packed insulated containers which have been validated to maintain tissue temperature below -40 C for at least 24 h, (26 9 40 9 25.5 cm external dimensions—Cat. no. ED32048 and 60 9 60 9 30 cm external dimensions—Cat. no. ED32001; Eric Ditchfield, St. Albans). Most clinical procedures are planned to be performed within 24 h of the tissue being shipped, however, there are occasions where a longer storage time would be advantageous if a procedure is delayed and some hospitals have requested that if tissue, particularly frozen femoral head bone, is not used, it can be returned to the tissue bank for continued further storage. Preliminary studies have indicated that the flat pack boxes cannot reliably maintain tissue temperatures below -40 C for longer than 24 h, and that a moulded insulated container would be required. To enable Tissue Services to introduce a returns policy, a validation study has been performed on a commercially available moulded polystyrene container using femoral head bone and Achilles tendons as model tissues. A packing plan has been developed for bags of dry ice and tissue temperature was recorded for up to 4 days (96 h) at 37 C. The returns policy will involve sending and receiving a single tissue at a time, therefore only one femoral head bone or one Achilles tendon was used per box.
cut in half with a De Souter saw to allow insertion of a thermocouple probe inside the tissue. After inserting the thermocouple probe, each bone half was tied together to give two reconstructed bones with a probe in the centre and each was placed inside a 300 ml polypropylene container (Femoral Head Storage Kit, S401-K, MedFor) with a hole made in its lid, the thermocouple probe wires extended through the hole. This polypropylene container was then placed inside a larger, 500 ml polypropylene container (S401-K kit, MedFor); again with a hole in its lid and the probe wire was directed through the hole (Fig. 1). After insertion of the probes, the containers plus femoral head bones were re-frozen to -80 C until required. Two K-class thermocouple probes were used in this study linked to a Pico TC-08 datalogger (Pico Technologies Ltd). Two Achilles tendons (Male 50 years), with full consent for R&D work were also used. Each tendon package was thawed and cut open such that a thermocouple probe could be inserted into the package, touching the tissue. The package was then heat sealed closed and re-frozen to -80 C until required. The thermocouple probes were then attached to a digital temperature data logger. Moulded, insulated carton Three XPL10 moulded polystyrene cold box cartons (Excel Packaging & Insulation Co. Ltd) were used in
Methods and materials Human tissue and insertion of K-class thermocouple probes Two femoral heads, with full consent for R&D work were used in this experiment. Each femoral head was
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Fig. 1 Femoral head container with thermocouple probe wire extending from the lid
Cell Tissue Bank
this study and each carton was used three times (twice at 37 C and one at room temperature). External dimensions were 385 9 385 9 435 mm (64 l), internal dimensions were 250 9 250 9 305 mm (19 l), insulation thickness was 65 mm. Each carton came as one piece plus a lid and a unit consisted of the carton plus lid inside a cardboard box (Fig. 2). The cartons were made from expanded polystyrene (Grades E and F) and were manufactured without the use of either CFC or HCFC blowing agents, had an ozone depletion potential (OPD) of zero and were fully recyclable.
XPL10 carton tissue packing plan and temperature monitoring The XPL10 carton was found to hold 9.5 kg of dry ice when one femoral head container unit or one Achilles tendon was included. For this study, the definition of a ‘‘femoral head container unit’’ is a femoral head bone inside two polypropylene containers described previously and then placed inside a grip-seal bag (PolyBags, UK). 1.
Insulation potential of XPL10 carton To ascertain the efficacy of the XPL10 cartons, the cartons, without tissue, were filled with dry ice both as loose pellets and inside perforated plastic bags. The XPL carton could hold approximately 11 kg of dry ice without tissue containers. The lid was put onto the carton and cartons were sealed as they would be for shipment of tissue and weighed. The cartons were then incubated either at room temperature or 37 C for 72 h. They were weighed every 24 h and at the end of the 72-h period. The experiment was then repeated.
2. 3. 4.
5. 6.
7.
8.
9.
10.
11. Fig. 2 XPL10 carton with lid and cardboard outer packing
An XPL10 carton, minus lid, plus one femoral head container unit or tendon pack was weighed—a record was made of this weight plus what the final weight would be after adding 9.5 kg of dry ice. The femoral head container unit or tendon pack was removed. Four bags of dry ice were placed on the bottom of the carton. The femoral head container unit or tendon pack was placed on top of the dry ice, in the centre of the XPL10 carton and additional dry ice bags were placed down the sides and on top. The carton plus dry ice was weighed. Additional dry ice was added to one bag to bring the weight up to the required weight, recorded in step 1, if the weight was over, one bag was opened and some dry ice was removed. The lid was placed onto the XPL10 carton, ensuring that the cable for the thermocouple probe was placed at one corner of the carton. The outer cardboard box was closed and sealed with tape, again ensuring that the thermocouple probe cable was coming out of the box. The carton was placed either at room temperature* or at 37 C in a non-humidified incubator set to 37 C*. Only femoral head bone was measured at both room temperature and 37 C, cartons containing Achilles tendons were only measured at 37 C. The thermocouple probes were attached to a data logger set to record temperature at 5 min intervals. The datalogger was attached to a computer and recording began.
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12. 13.
Readings were taken either for 96 h or until tissue temperature rose above -40 C. All cartons were sealed with tape in the same manner as they would be for shipping to hospitals.
*The temperature of the laboratory and the incubator was continuously monitored with an environmental monitoring system (PharmaGraph). PharmaGraph records show that the mean laboratory temperature (room temperature) was 22.1 C (range 19.8–22.7 C). For room temperature measurements, the cartons plus cardboard outer’s were incubated on non-conducting Trespa surfaces and if more than one was used at a time, the cartons were at least 15 cm apart as recommended in ASTM Standard D3103. (Standard test method for thermal insulation performance of distribution packages, ASTM D3103-07, 2007). The experiment was performed with two cartons at one time and then with a single carton to provide three sets of data. For incubation at 37 C, incubator temperature, as assessed by PharmaGraph, ranged from 34.3 to 37.1 C with a mean of 36.6 C during the study period. The experiment was performed with two cartons at one time and then with a single carton to provide three sets of data.
sublimates into a gas and they allow operators filling and emptying the carton to hold the bag rather than touch loose dry ice pellets. Tissue temperature inside XPL10 cartons Femoral head bone—When stored at *22 C with 9.5 kg of dry ice, the XPL10 carton plus one femoral head container unit was capable of maintaining tissue temperature below -40 C for more than 100 h (Fig. 4). The data also indicated that tissue temperature was maintained below -75 C for approximately 72 h; below -70 C for approximately 82 h and below -55 C for 96 h (Fig. 4). When the XPL10 cartons were incubated at 37 C with 9.5 kg of dry ice (Fig. 5), the data indicate that tissue temperature was maintained below -75 C for approximately 55 h, below -70 C for approximately 66 h and below -40 C for approximately 90 h. Achilles tendons—When stored at 37 C with 9.5 kg of dry ice, the XPL10 carton plus one tendon unit was capable of maintaining tissue temperature below -40 C for more than 70 h (Fig. 6). The data also demonstrated that after 48 h of incubation, tissue temperature did not rise above -55 C.
Discussion Results Insulation potential of XPL10 carton Preliminary studies indicated that insulation in the XPL10 carton was good and that when 11 kg of dry ice was added; the mean rate of dry ice loss did not vary significantly whether the carton was stored at room temperature or at 37 C (Table 1). In addition, a similar rate of dry ice loss was observed using both loose-packed dry ice and dry ice placed inside perforated bags (Table 1). The pattern of dry ice loss over a 48-h period, using perforated bags, was similar no matter whether the cartons were stored at 22 or 37 C (Fig. 3). For health and safety reasons, all further work used dry ice inside perforated bags, each bag was filled with one scoop of dry ice and when weighed, one scoop was found to hold a mean of 0.92 kg of dry ice. Perforated bags allow evaporation of CO2 as the solid pellet
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Maintenance of human tissue temperature during shipping to hospitals for transplantation purposes is necessary for tissue safety and quality and is mandated as part of the regulations associated with tissue storage and transport (Guidelines for the Blood Transfusion Services in the United Kingdom, 8th Edn. updated 2013). Several studies have been performed on temperature maintenance in containers to maintain temperature within 2–8 C but few have been reported Table 1 Mean rate of dry ice loss over a 48 h period, XPL10 carton, 11 kg starting weight of dry ice (n = 2, error bars = 95 % CI) Dry ice packing
kg dry ice lost/h
Loose (room temperature)
0.091 (±0.007)
Loose (37 C)
0.091 (±0.004)
Bagged (room temperature)
0.099 (±0.002)
Bagged (37 C)
0.101 (±0.00)
Cell Tissue Bank
Fig. 6 Tissue temperature of three Achilles tendons during incubation at 37 C with 9.5 kg of dry ice in an XPL10 carton (n = 3, error bars 95 % CI) Fig. 3 Rate of dry ice loss in perforated bags in a XPL10 carton (n = 2, error bars 95 % CI)
Fig. 4 Mean tissue temperature of three femoral head bones during incubation with 9.5 kg dry ice at room temperature (n = 3, error bars 95 % CI)
Fig. 5 Mean tissue temperature of three femoral head bones during incubation with 9.5 kg dry ice at 37 C (n = 3, error bars 95 % CI)
for frozen tissue (Rentas et al. 2004; Elliott and Halbert 2005; Ohkawara et al. 2012; Miller et al. 2013). In this study we have investigated the potential of a commercially available moulded polystyrene carton, XPL10, containing 9.5 kg of dry ice, to maintain femoral head and Achilles tendon tissue temperature below -40 C when the carton was incubated at both 22 and 37 C for bone and at 37 C for Achilles tendon. The data indicate that at 37 C incubation, both tissues were maintained below -40 C for at least a 48-h period, therefore the acceptance criterion was met. In practice, when incubated at 37 C, femoral head bone remained below -40 C for at least 90 h and an Achilles tendon remained below -40 C for at least 70 h. Achilles tendons were only incubated at 37 C on the assumption that if tissue temperature could be maintained below -40 C for 48 h when incubated at 37 C, then at a lower storage temperature, the length of time tissue could be maintained below -40 C would be increased—this was shown to be true for bone; femoral head bone incubated at room temperature (20–22 C) remained at a temperature below -40 C for more than 110 h. Development of a returns policy for human tissues is required and return of un-used tissue would be within 48 h of the carton being packed. The data presented here indicate that the XPL10 moulded polystyrene carton with one femoral head tissue container or one Achilles tendon plus 9.5 kg of dry ice meets the acceptance criterion of maintaining tissue temperature below -40 C for at least 48 h. If a returns policy deadline of 48 h is set, these data
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provide leeway as a contingency in case of problems returning the tissue. Acknowledgments from the NHSBT.
We acknowledge support of this work
References ASTM Standard D3103 (2007) Standard test method for thermal insulation performance of distribution packages Choi SJ, Burgess G (2007) Practical mathematical model to predict the performance of insulating packages. Packag Technol Sci 20:369–380. www.coldchaintech.com/simple. php. Accessed 11/02/2013 Elliott MA, Halbert GW (2005) Maintaining the cold chain shipping environment for Phase 1 clinical trail distribution. Int J Pharm 299:49–54 Guidelines for the Blood Transfusion Services in the United Kingdom, Chapter 23, 8th Edn., updated 2013. The
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Stationary Office, London. www.transfusionguidelines. org.uk/Index.aspx?Publication=RB&Section=25&pageid= 700 accessed 08/02/2013 Miller TD, Maxwell AJ, Lindquirst TD, Requard J (2013) Validation of cooling effect of insulated containers for the shipment of corneal tissue and recommendation for transport. Cornea 32:63–69 Ohkawara H, Kitagawa T, Fukushima N, Ito T, Sawa Y, Yoshimine T (2012) A newly developed container for safe, easy and cost effective overnight transportation of tissues and organs by electrically keeping tissue of organ temperature at 3 to 6 C. Transplant Proc 44:855–858 Rentas FJ, MacDonald VW, Houchens DM, Hmel PJ, Reid TJ (2004) New insulation technology provides next-generation containers for ‘‘iceless’’ and lightweight transport of RBCs at 1 to 10 C in extreme temperatures for over 78 hours. Transfusion 44:210–216 Singh SP, Burgess G, Singh J (2008) Performance comparison of thermal insulated packaging boxes and refrigerants for single-parcel shipments. Packag Technol Sci 21:25–35
Validation of cold chain shipping environment for transport of allografts as part of a human tissue bank returns policy P. Rooney • M. J. Eagle • J. N. Kearney
Received: 11 December 2014 / Accepted: 16 February 2015 Springer Science+Business Media Dordrecht 2015
Abstract Human tissue is shipped to surgeons in the UK in either a freeze-dried or frozen state. To ensure quality and safety of the tissue, frozen tissue must be shipped in insulated containers such that tissue is maintained at an appropriate temperature. UK Blood Transfusion Service regulations state ‘‘Transportation systems must be validated to show maintenance of the required storage temperature’’ and also state that frozen, non-cryopreserved tissue ‘‘must be transported… at -20 C or lower’’ (Guidelines for the Blood Transfusion Services in the United Kingdom, 8th Edn. 2013). To maintain an expiry date for frozen tissue longer than 6 months, the tissue must be maintained at a temperature of -40 C or below. The objective of this study was to evaluate and validate the capability of a commercially available insulated polystyrene carton (XPL10), packed with dry ice, to maintain tissue temperature below -40 C. Tissue temperature of a single frozen femoral head or a single frozen Achilles tendon, was recorded over a 4-day period at 37 C, inside a XPL10 carton with dry ice as refrigerant. The data demonstrate that at 37 C, the XPL10 carton with 9.5 kg of dry ice P. Rooney (&) M. J. Eagle J. N. Kearney NHSBT, Tissue Services R&D, 14 Estuary Banks, Speke, Liverpool L24 8RB, UK e-mail: [email protected] M. J. Eagle e-mail: [email protected] J. N. Kearney e-mail: [email protected]
maintained femoral head and tendon tissue temperature below -55 C for at least 48 h; tissue temperature did not rise above -40 C until at least 70 h. Data also indicated that at a storage temperature lower than 37 C, tissue temperature was maintained for longer periods. Keywords Low temperature Container Transport Achilles tendon Femoral head Allograft
Introduction Temperature sensitive products such as biological materials, e.g. tissues or blood, should be shipped in temperature-controlled containers (Choi and Burgess 2007). For tissues, the Guidelines for the Blood Transfusion Services in the UK state that frozen, noncryopreserved tissue should be stored below -40 C for long-term storage, i.e. more than 6-months (Guidelines for the Blood Transfusion Services in the UK, 8th Edn. updated 2013). When frozen tissue is shipped, it must be shipped below -20 C or lower. To retain its expiry date; it must be shipped below -40 C. If the temperature rises to between -40 and -20 the expiry is reduced to 6 months maximum. Several studies have been performed on temperature controlled containers and cold chain management but the vast majority of these studies have concentrated on maintaining a temperature of 2–8 C or occasionally 1–10 C (Rentas et al. 2004; Elliott and Halbert 2005, Ohkawara et al. 2012; Miller et al.
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2013). Few studies have been performed on cold chain and temperature management of substances below -30 C and even commercial companies who manufacture complex cold transport boxes only state that for shipping substances below -20 C, dry ice should be used and the container should be a one piece moulded container (www.coldchaintech.com). NHS Blood and Transplant Tissue Services, ships up to 10,000 human allograft tissues to UK surgeons and hospitals each year in either a freeze-dried, frozen or cryopreserved state—at least 50 % of the tissue is supplied frozen or cryopreserved. Freeze dried tissue is sent at ambient temperature whereas frozen and cryopreserved tissue is sent on dry ice. Currently, frozen and cryopreserved tissue is shipped in flat-packed insulated containers which have been validated to maintain tissue temperature below -40 C for at least 24 h, (26 9 40 9 25.5 cm external dimensions—Cat. no. ED32048 and 60 9 60 9 30 cm external dimensions—Cat. no. ED32001; Eric Ditchfield, St. Albans). Most clinical procedures are planned to be performed within 24 h of the tissue being shipped, however, there are occasions where a longer storage time would be advantageous if a procedure is delayed and some hospitals have requested that if tissue, particularly frozen femoral head bone, is not used, it can be returned to the tissue bank for continued further storage. Preliminary studies have indicated that the flat pack boxes cannot reliably maintain tissue temperatures below -40 C for longer than 24 h, and that a moulded insulated container would be required. To enable Tissue Services to introduce a returns policy, a validation study has been performed on a commercially available moulded polystyrene container using femoral head bone and Achilles tendons as model tissues. A packing plan has been developed for bags of dry ice and tissue temperature was recorded for up to 4 days (96 h) at 37 C. The returns policy will involve sending and receiving a single tissue at a time, therefore only one femoral head bone or one Achilles tendon was used per box.
cut in half with a De Souter saw to allow insertion of a thermocouple probe inside the tissue. After inserting the thermocouple probe, each bone half was tied together to give two reconstructed bones with a probe in the centre and each was placed inside a 300 ml polypropylene container (Femoral Head Storage Kit, S401-K, MedFor) with a hole made in its lid, the thermocouple probe wires extended through the hole. This polypropylene container was then placed inside a larger, 500 ml polypropylene container (S401-K kit, MedFor); again with a hole in its lid and the probe wire was directed through the hole (Fig. 1). After insertion of the probes, the containers plus femoral head bones were re-frozen to -80 C until required. Two K-class thermocouple probes were used in this study linked to a Pico TC-08 datalogger (Pico Technologies Ltd). Two Achilles tendons (Male 50 years), with full consent for R&D work were also used. Each tendon package was thawed and cut open such that a thermocouple probe could be inserted into the package, touching the tissue. The package was then heat sealed closed and re-frozen to -80 C until required. The thermocouple probes were then attached to a digital temperature data logger. Moulded, insulated carton Three XPL10 moulded polystyrene cold box cartons (Excel Packaging & Insulation Co. Ltd) were used in
Methods and materials Human tissue and insertion of K-class thermocouple probes Two femoral heads, with full consent for R&D work were used in this experiment. Each femoral head was
123
Fig. 1 Femoral head container with thermocouple probe wire extending from the lid
Cell Tissue Bank
this study and each carton was used three times (twice at 37 C and one at room temperature). External dimensions were 385 9 385 9 435 mm (64 l), internal dimensions were 250 9 250 9 305 mm (19 l), insulation thickness was 65 mm. Each carton came as one piece plus a lid and a unit consisted of the carton plus lid inside a cardboard box (Fig. 2). The cartons were made from expanded polystyrene (Grades E and F) and were manufactured without the use of either CFC or HCFC blowing agents, had an ozone depletion potential (OPD) of zero and were fully recyclable.
XPL10 carton tissue packing plan and temperature monitoring The XPL10 carton was found to hold 9.5 kg of dry ice when one femoral head container unit or one Achilles tendon was included. For this study, the definition of a ‘‘femoral head container unit’’ is a femoral head bone inside two polypropylene containers described previously and then placed inside a grip-seal bag (PolyBags, UK). 1.
Insulation potential of XPL10 carton To ascertain the efficacy of the XPL10 cartons, the cartons, without tissue, were filled with dry ice both as loose pellets and inside perforated plastic bags. The XPL carton could hold approximately 11 kg of dry ice without tissue containers. The lid was put onto the carton and cartons were sealed as they would be for shipment of tissue and weighed. The cartons were then incubated either at room temperature or 37 C for 72 h. They were weighed every 24 h and at the end of the 72-h period. The experiment was then repeated.
2. 3. 4.
5. 6.
7.
8.
9.
10.
11. Fig. 2 XPL10 carton with lid and cardboard outer packing
An XPL10 carton, minus lid, plus one femoral head container unit or tendon pack was weighed—a record was made of this weight plus what the final weight would be after adding 9.5 kg of dry ice. The femoral head container unit or tendon pack was removed. Four bags of dry ice were placed on the bottom of the carton. The femoral head container unit or tendon pack was placed on top of the dry ice, in the centre of the XPL10 carton and additional dry ice bags were placed down the sides and on top. The carton plus dry ice was weighed. Additional dry ice was added to one bag to bring the weight up to the required weight, recorded in step 1, if the weight was over, one bag was opened and some dry ice was removed. The lid was placed onto the XPL10 carton, ensuring that the cable for the thermocouple probe was placed at one corner of the carton. The outer cardboard box was closed and sealed with tape, again ensuring that the thermocouple probe cable was coming out of the box. The carton was placed either at room temperature* or at 37 C in a non-humidified incubator set to 37 C*. Only femoral head bone was measured at both room temperature and 37 C, cartons containing Achilles tendons were only measured at 37 C. The thermocouple probes were attached to a data logger set to record temperature at 5 min intervals. The datalogger was attached to a computer and recording began.
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12. 13.
Readings were taken either for 96 h or until tissue temperature rose above -40 C. All cartons were sealed with tape in the same manner as they would be for shipping to hospitals.
*The temperature of the laboratory and the incubator was continuously monitored with an environmental monitoring system (PharmaGraph). PharmaGraph records show that the mean laboratory temperature (room temperature) was 22.1 C (range 19.8–22.7 C). For room temperature measurements, the cartons plus cardboard outer’s were incubated on non-conducting Trespa surfaces and if more than one was used at a time, the cartons were at least 15 cm apart as recommended in ASTM Standard D3103. (Standard test method for thermal insulation performance of distribution packages, ASTM D3103-07, 2007). The experiment was performed with two cartons at one time and then with a single carton to provide three sets of data. For incubation at 37 C, incubator temperature, as assessed by PharmaGraph, ranged from 34.3 to 37.1 C with a mean of 36.6 C during the study period. The experiment was performed with two cartons at one time and then with a single carton to provide three sets of data.
sublimates into a gas and they allow operators filling and emptying the carton to hold the bag rather than touch loose dry ice pellets. Tissue temperature inside XPL10 cartons Femoral head bone—When stored at *22 C with 9.5 kg of dry ice, the XPL10 carton plus one femoral head container unit was capable of maintaining tissue temperature below -40 C for more than 100 h (Fig. 4). The data also indicated that tissue temperature was maintained below -75 C for approximately 72 h; below -70 C for approximately 82 h and below -55 C for 96 h (Fig. 4). When the XPL10 cartons were incubated at 37 C with 9.5 kg of dry ice (Fig. 5), the data indicate that tissue temperature was maintained below -75 C for approximately 55 h, below -70 C for approximately 66 h and below -40 C for approximately 90 h. Achilles tendons—When stored at 37 C with 9.5 kg of dry ice, the XPL10 carton plus one tendon unit was capable of maintaining tissue temperature below -40 C for more than 70 h (Fig. 6). The data also demonstrated that after 48 h of incubation, tissue temperature did not rise above -55 C.
Discussion Results Insulation potential of XPL10 carton Preliminary studies indicated that insulation in the XPL10 carton was good and that when 11 kg of dry ice was added; the mean rate of dry ice loss did not vary significantly whether the carton was stored at room temperature or at 37 C (Table 1). In addition, a similar rate of dry ice loss was observed using both loose-packed dry ice and dry ice placed inside perforated bags (Table 1). The pattern of dry ice loss over a 48-h period, using perforated bags, was similar no matter whether the cartons were stored at 22 or 37 C (Fig. 3). For health and safety reasons, all further work used dry ice inside perforated bags, each bag was filled with one scoop of dry ice and when weighed, one scoop was found to hold a mean of 0.92 kg of dry ice. Perforated bags allow evaporation of CO2 as the solid pellet
123
Maintenance of human tissue temperature during shipping to hospitals for transplantation purposes is necessary for tissue safety and quality and is mandated as part of the regulations associated with tissue storage and transport (Guidelines for the Blood Transfusion Services in the United Kingdom, 8th Edn. updated 2013). Several studies have been performed on temperature maintenance in containers to maintain temperature within 2–8 C but few have been reported Table 1 Mean rate of dry ice loss over a 48 h period, XPL10 carton, 11 kg starting weight of dry ice (n = 2, error bars = 95 % CI) Dry ice packing
kg dry ice lost/h
Loose (room temperature)
0.091 (±0.007)
Loose (37 C)
0.091 (±0.004)
Bagged (room temperature)
0.099 (±0.002)
Bagged (37 C)
0.101 (±0.00)
Cell Tissue Bank
Fig. 6 Tissue temperature of three Achilles tendons during incubation at 37 C with 9.5 kg of dry ice in an XPL10 carton (n = 3, error bars 95 % CI) Fig. 3 Rate of dry ice loss in perforated bags in a XPL10 carton (n = 2, error bars 95 % CI)
Fig. 4 Mean tissue temperature of three femoral head bones during incubation with 9.5 kg dry ice at room temperature (n = 3, error bars 95 % CI)
Fig. 5 Mean tissue temperature of three femoral head bones during incubation with 9.5 kg dry ice at 37 C (n = 3, error bars 95 % CI)
for frozen tissue (Rentas et al. 2004; Elliott and Halbert 2005; Ohkawara et al. 2012; Miller et al. 2013). In this study we have investigated the potential of a commercially available moulded polystyrene carton, XPL10, containing 9.5 kg of dry ice, to maintain femoral head and Achilles tendon tissue temperature below -40 C when the carton was incubated at both 22 and 37 C for bone and at 37 C for Achilles tendon. The data indicate that at 37 C incubation, both tissues were maintained below -40 C for at least a 48-h period, therefore the acceptance criterion was met. In practice, when incubated at 37 C, femoral head bone remained below -40 C for at least 90 h and an Achilles tendon remained below -40 C for at least 70 h. Achilles tendons were only incubated at 37 C on the assumption that if tissue temperature could be maintained below -40 C for 48 h when incubated at 37 C, then at a lower storage temperature, the length of time tissue could be maintained below -40 C would be increased—this was shown to be true for bone; femoral head bone incubated at room temperature (20–22 C) remained at a temperature below -40 C for more than 110 h. Development of a returns policy for human tissues is required and return of un-used tissue would be within 48 h of the carton being packed. The data presented here indicate that the XPL10 moulded polystyrene carton with one femoral head tissue container or one Achilles tendon plus 9.5 kg of dry ice meets the acceptance criterion of maintaining tissue temperature below -40 C for at least 48 h. If a returns policy deadline of 48 h is set, these data
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provide leeway as a contingency in case of problems returning the tissue. Acknowledgments from the NHSBT.
We acknowledge support of this work
References ASTM Standard D3103 (2007) Standard test method for thermal insulation performance of distribution packages Choi SJ, Burgess G (2007) Practical mathematical model to predict the performance of insulating packages. Packag Technol Sci 20:369–380. www.coldchaintech.com/simple. php. Accessed 11/02/2013 Elliott MA, Halbert GW (2005) Maintaining the cold chain shipping environment for Phase 1 clinical trail distribution. Int J Pharm 299:49–54 Guidelines for the Blood Transfusion Services in the United Kingdom, Chapter 23, 8th Edn., updated 2013. The
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