SAVING LIVES THROUGH RELIABLE AND INNOVATIVE TECHNOLOGY

01 | 03 B Medical Systems

Blood Management Solutions

B Medical Systems Contact Shock Freezers: Technological Innovations for Rapid Cooling of Plasma

Fresh frozen human plasma is an important transfusion component

and also functions as a raw material for the production of coagulation

factor concentrates used in patients with haemorrhagic disorders [1].

Freezing of plasma is a critical processing step that has an impact

on the quality of plasma, especially concerning Factor VIII. B Medical

Systems Contact Shock Freezers are designed for the quick freezing of blood

plasma to a core temperature of -30°C. This paper discusses the impact of various

technological innovations used in the Contact Shock Freezers by B Medical Systems to enable rapid cooling

of plasma bags. This includes inclination of the freezing plates and the linear actuators, which enable

homogenous and rapid cooling of plasma bags. It was found that inclining the freezing plates to an angle

of 5° helps increase the plasma bag contact area without air, by an average of 19%, with the highest

incremental difference of 31% identified in the case of 50ml air inside the bag.

BACKGROUND

Human plasma is an important raw material in the production of coagulation factor (FVIII) concentrates for patients with different coagulopathies [2]. To minimize loss of coagulation activity, the production process of factor concentrates has to be optimized and freezing of plasma plays a critical role in the same. Several papers in the past have discussed the effect of fast or slow freez-ing on plasma quality [3,4,5,6,7,8]. In an international forum pub-lished in 1983 [9], Freidli and co-workers demonstrated that slow freezing results in the formation of a cryoprecipitate, which has about twice the weight of cryoprecipitate that is obtained by fast freezing. Plasma containing a heavier cryoprecipitate contains factor VIII with lower specific activity and hence, plasma should be frozen rapidly.

Contact Shock Freezers are designed for the quick freezing of blood plasma to a core temperature of -30°C/-40°C. However, multiple issues can occur while using a traditional shock freezer that can also have an impact on the final freezing time.

Some of them are:

• The uneven filling of blood bags leading to creation of air pock-ets, which act as an insulation layer during shock freezing lead-ing to increased cooling time as measured against the standard operating time (Fig 1)

• Unevenly filled and different sized bags kept together during the freezing cycle resulting in irregular cooling (Fig 2)

CSFRANGE

Fig 1: Air pockets in plasma bag

due to uneven filling

Fig 2: Unevenly filled/different sized bags

between freezing plates

02 | 03 B Medical Systems

Blood Management Solutions

This paper discusses the impact of inclining the freezing plates of the contact shock freezer and the function of linear actuators. Inclining the freezing plates can lead to an increase in the contact area of plasma without air pockets and the use of linear actuators can result in anti-parallel movement of the plates, both having an impact on the cooling of the plasma bags.

Five test plasma bags of 350ml were filled with saline solution with a net volume of 250ml. Test equipment simulating the force exerted by the plates of the contact shock freezer and a force gauge were used to simulate and measure this force. The uneven filling of the bags produced the air pockets that develop during or after the preparation of plasma bags. These bags were then exposed to a force of 1KN, which generally is the force experienced by the bags during the contact shock freezing process. The test bags were then inclined at 0°, 5°, 10°, 15°, and 90° using a custom built inclination frame. The process was repeated for 10ml, 20ml, 30ml, 40ml and 50ml of air inside the bags. During each of these tests, the percentage of the contact area with and without air was noted. These tests were conducted at an ambient temperature of 25°C and at standard testing conditions at B Medical Systems Hosingen, Luxembourg.

fig.

B M

edic

al S

yste

ms

Cont

act

Shoc

k Fr

eeze

r (M

odel

CSF

10

1)

RESULTS

The presence of air pockets in plasma bags has been a topic of discussion in Blood Processing Centers. Even when handled with utmost care, it has been observed that there are chances of air bubbles entering the bags due to fill volume. Some centers tend to remove the air bubbles from the storage bags, but this is not a widespread practice across all processing centers. In theory, there is always an insignificant amount of air inside the bags, but in practice, depending on the process of creating the blood/plasma bags, there could be a significant amount of air present inside the bags. Due to the lower density of air as compared to the blood plasma, these air pockets act as an insulation layer that increases the freezing time when compared with freezing under standard conditions.

Fig 3 describes the changes in the position of air pockets at 0°, 5° and 90° inclination of the plates. The difference in the percentage contact area with and without air for different plate inclinations are shown in table 1 for 0° and 5° inclinations.

0° inclination of plates 5° inclination of platesContact area without air

Contact area with air

Contact area without air

Contact area with air

10 ml 84.38% 15.63% 86.46% 13.54%

20 ml 64.52% 35.48% 77.66% 22.34%

30 ml 46.15% 53.85% 63.74% 36.26%

40 ml 30.43% 69.57% 59.78% 40.22%

50 ml 21.51% 78.49% 52.69% 47.31%

AIR

Plate inclined at 5°

AIR

Plate horizontal

10 ml air 20 ml air 30 ml air 40 ml air 50 ml air

Incl

inat

ion

at 9

0°

Incl

inat

ion

at 5

°In

clin

atio

n at

0°

OBjECTivE

METHODOLOGY

Fig 3: Position of air pockets for various plate inclinations Table 1: Difference in the percentage contact area with

and without air bubbles for 0° and 5° plate inclinations

B Medical Systems S.à r.l.

17, op der Hei L - 9809 Hosingen, Luxembourg

Tel. : (+352) 92 07 31 - 1 Fax : (+352) 92 07 31 - 300 info@bmedicalsystems.com www.bmedicalsystems.com

SAVING LIVES THROUGH RELIABLE AND INNOVATIVE TECHNOLOGY

Luxembourg, in the heart of Europe

Blood Management Solutions

This paper is based on the standard testing conditions at the B Medical Systems manufacturing plant at Hosingen, Luxembourg. However these functionalities are subject to change without prior notice. This paper is for informational purposes only. All indications without guarantee and excluding all liability due to faulty, incomplete or outdated information. All technical data subject to change without prior notice. B Medical Systems and the B Medical Systems logo are trademarks or registered trademarks of B Medical Systems S.à r.l.

29% 31%

13% 18%

2%

10 ml 20 ml 30 ml 40 ml 50 ml

Amount of air inside the plasma bag

During the test, it was observed that the contact improves with more inclination (e.g. 10°, 15° etc.). However, it was also observed that the plasma bags start slipping off the freezer plates as the inclination of the freezer plates increases. Hence, an inclina-tion of 5° was found to be optimal, keeping in mind the safe handling of plasma bags and ergonomics. The absolute increase in the % contact area without air of the plasma bags for varying volume of air pockets (10ml, 20ml, 30ml, 40ml and 50ml) compared to horizontal (0° inclination of the plates) can be found in Fig 4.

Inclining the freezer plates at 5° showed an average absolute increase of contact area without air by 19% for various volumes of air pocket inside the bags. The highest impact was observed when the bags had 50ml air pockets, wherein inclining the plates by 5° re-sulted in an absolute increase of percentage contact area by 31% and an actual increase of surface area without air contact by 145%.

B Medical Systems Contact Shock Freezers also have silent acting linear actuators that self-adjust for proper force against plasma bags, and act anti-parallel up to 10mm thereby delivering homogeneous freezing of the bags even when the bags have slightly different fill volumes, when loaded as per the standard operating procedure described in the operations/user manual (Fig 5).

DiSCUSSiON

Human plasma is an important transfusion component and also functions as a raw ma-terial for the manufacturing of coagulation factor concentrates, but at the same time is expensive and supplies are limited. The freezing process is an important step that may result in loss of activity if it is not handled optimally [1]. Even when using the contact shock freezers, there could be a deviation in the freezing time and irregular freezing of plasma bags due to the presence of air pockets that can act as an insulation layer, or the irregular size of the plasma bags, which prevent optimised contact of the freezer plates. Inclining the freezing plates of the contact shock freezer to 5° can lead to an average absolute increase of percentage contact area without air by 19%. For bigger air pockets (like 50ml), inclining the plates at 5° can lead to an actual increase of surface area with-out air contact by 145% for a 350ml bag. This along with the silent acting linear actua-tors, which can move anti-parallel up to 10mm, can help in the rapid and homogenous freezing of plasma that can have a strong positive impact on the quality of the plasma.

Fig 5: Linear Actuators

Fig 4: Absolute Increase in the % contact area

without air for 5° inclination

Sources:

[1] Swärd-Nilsson AM, Persson PO, Johnson U, Lethagen S: Factors influencing factor VIII activity in frozen plasma. Vox Sang 2006 Jan; 90(1):33

[2] Farrugia A: Plasma for fractionation: safety and quality issues. Haemophilia 2004; 10:334–340

[3] Carlebjörk G, Blombäck M, Pihlstedt P: Freezing of plasma and recovery of factor VIII. Transfusion 1986; 26:159–162

[4] Åkerblom O, Bremme K, Dackland ÅL, Fatah K, Suontaka AM, Blombäck M: Freezing technique and quality of fresh-frozen plasma. Infusionstherapie 1992; 19:283–287

[5] Myllylä G: Factors determining quality of plasma. Vox Sang 1998; 74:507–511

[6] Rock GA, Tittley P: The effect of temperature variations on cryoprecipitate. Transfusion 1979; 19:86–89

[7] Gabra GS, Prowse CV, Boulton FE: Importance of quality assurance scheme for factor VIII assays in quality monitoring of human plasma destined for fractionation into factor VIII concentrate. Vox Sang 1989; 56:65–70

[8] Farrugia A, Prowse C: Studies on the procurement of blood coagulation factor VIII: effects of plasma freezing rate and storage conditions on cryoprecipitate quality. J Clin Pathol 1985; 38:433–437

[9] Allain JP, Friedli H, Morgenthaler JJ, Pflugshaupt R, Gunson HH, Lane RS, Myllylä G, Rock GA, Stryker MH, Woods KR: International Forum: What are the critical factors in the production and quality control of frozen plasma intended for direct transfusion or for fractionation to provide medically needed labile coagulation factors. Vox Sang 1983; 44:246–259