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Thermal Analysis of Refrigeration 

Systems Used for Vaccine Storage:

Report on Pharmaceutical Grade Refrigerator 

and Household Refrigerator/Freezer

Michal Chojnacky

Wyatt Miller

Gregory Strouse

NISTIR 7753
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NISTIR 7753

Thermal Analysis of Refrigeration 

Systems Used for Vaccine Storage:

Report on Pharmaceutical Grade Refrigerator 

and Household Refrigerator/Freezer

Michal Chojnacky

Wyatt Miller

Gregory Strouse

PML

September 2010

U.S. Department of Commerce

Gary Locke, Secretary

National Institute of Standards and Technology

Patrick D. Gallagher, Director
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ABSTRACT

Each year, billions of dollars of vaccines are stored in refrigerators at the facilities of a 

variety of medical providers. Many vaccines must be maintained in the range 2 °C to 

8 °C to retain product potency. We have tested the performance of two types of 

refrigerators to determine if these refrigerators are suitable to this task, and to identify 

proper storage and temperature monitoring methods. Nineteen calibrated Type T 

thermocouples, distributed through the refrigerator interior, served as reference 

thermometers. Attachment of thermocouples directly to vaccine vials gave accurate 

measurements of the vaccine temperature, which often differed from the air or interior 

wall temperatures during door openings or defrost cycles. A household type dual-zone 

refrigerator/freezer [refrigerator compartment capacity = 0.400 m

3

(14.13 cu. ft.)] and a 

pharmaceutical grade refrigerator [capacity = 0.489 m3] proved fully adequate at 

maintaining vial temperatures within the desired 2 °C to 8 °C range, independent of how 

the refrigerator was loaded. Tests of intermittent and continuous door opening and of 

simulated power outages demonstrated the value of adding water bottles to the door as a 

thermal ballast in the dual-zone refrigerator model. We tested five electronic data loggers 

as a means of continuously logging refrigerator temperatures. Properly located, data 

loggers and temperature monitors accurately monitored vial temperatures for extended 

periods.

1. INTRODUCTION

Each year, millions of dollars worth of vaccines are lost in the United States due to 

improper storage conditions. In order to maintain potency, many common vaccines must 

be kept refrigerated between 2 °C to 8 °C. When vaccines are exposed to temperatures 

above or below this range, their potency is reduced until they eventually become 

completely ineffective. 

A number of factors influence whether vaccines stored in a refrigerator remain within the 

prescribed temperature range. Vaccine storage trays or boxes can obstruct refrigerator air 

flow, creating areas pockets of colder or warmer air. Vaccines stored in certain locations, 

such as near the refrigerator cooling unit, may be kept significantly colder than if placed 

in the main body of the refrigerator. Some factors may vary drastically between different 

refrigerator types (e.g. dorm style, freezerless, dual zone or pharmaceutical grade). 

Parameters such as temperature control stability, air circulation patterns, defrost cycles, 

and long-term drift of the temperature set point can play a major role in determining 

whether a refrigerator maintains suitable vaccine storage conditions. Because of this, 

simply setting a refrigerator to a temperature between 2 °C to 8 °C may not actually 

result in stored vaccines being kept within that temperature range.

Accurate monitoring of vaccine temperatures requires attention to the type of monitoring 

system used and its installation in the refrigerator. Different types of temperature 

monitoring systems can influence both the accuracy of the temperature measurement and 

the ease of use. Depending on the placement of a temperature monitoring device, as well 
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as the time or frequency that its readings are recorded, the resulting temperature readings 

may or may not correspond to actual vaccine temperatures.

In this study, we explored a number of these factors in an attempt to determine which 

have the greatest impact on vaccine temperature. From this, we can make experimentally 

verifiable recommendations regarding the best and worst vaccine storage configurations 

and temperature monitoring setups. We used an array of calibrated thermocouples, 

mounted in multiple locations, as reference thermometers. An automated data-acquisition 

system measured the thermocouple temperatures continuously, for a wide variety of 

operating conditions. Attaching thermocouples directly to vaccine vials gave temperature 

measurements highly indicative of the actual vaccine temperatures. 

We report measurements for two refrigerator styles: a) “dual-zone” household 

refrigerator/freezer unit [total capacity = 0.515 m

3

(18.2 cu. ft.)], and b) a pharmaceutical 

grade refrigerator [capacity = 0.489 m3]. The pharmaceutical refrigerator demonstrated 

excellent temperature stability. However, both models are fully adequate for refrigerated 

vaccine storage, and with a few simple precautions both can successfully maintain 

appropriate storage temperatures under varying conditions.

In this investigation, we repeated the procedures used in our earlier evaluation of a 

dormitory-style refrigerator and a freezerless household refrigerator used for vaccine 

storage, as reported in NIST-IR 7656 [1]. Another study exploring the suitability and 

performance of pharmaceutical grade refrigerators for vaccine storage was conducted by 

the Test Research Group for the Australian General Practice Network [2]. For further 

information on vaccine storage practices, including official storage guidelines from the 

Centers for Disease Control, consult references 3 - 6. 

2. EXPERIMENTAL METHOD

Prior to this study, members of the NIST Thermometry Group visited seven Vaccines for 

Children (VFC) clinics in order to observe their vaccine storage practices. In our 

experimental trials, we attempted to replicate the range of vaccine storage conditions 

witnessed at VFC clinics. 

This range included variations in loading density. For example, during influenza season, 

a large influx of patients could leave a clinic with dwindling vaccine supplies. At this 

time, their storage refrigerator would probably contain a low packing density. Other 

times, such as immediately following a large vaccine shipment, the same storage 

refrigerator might be filled to maximum storage capacity with boxes of vaccines. This 

would be considered a high density load. By testing a variety of low, medium, and high 

packing densities, we were able to quantify how this type of normal inventory fluctuation 

affects refrigerator performance.

We also experimented with different packaging styles. Many of the clinics surveyed used 

plastic trays or bins to organize and store their vaccine inventory. We also observed 
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vaccines stored inside cardboard shipping boxes, as well as in their original light 

cardboard packaging. The Centers for Disease Control and Prevention (CDC) guidelines 

advise storing vaccines in plastic trays rather than uncontained on shelves or inside 

shipping boxes. However, during very busy times, clinic workers might temporarily store 

vaccines in their shipping containers until they can be organized into appropriate bins. As 

a result, we investigated whether these different packaging methods would affect the 

refrigerator’s ability to maintain the proper vaccine storage temperatures. In this study, 

we performed trials using three different packing styles: 1) vaccines stored exclusively in 

plastic trays; 2) vaccines stored inside various boxes, such as cardboard shipping boxes or 

their original thin cardboard packaging; and 3) vaccines stored in a mixture of plastic 

trays and cardboard boxes.

In our survey of VFC clinics, we noted multiple locations storing water bottles in 

refrigerator doors or in the main space of the refrigerator, a practice recommended by the 

Centers for Disease Control. This is because the additional thermal mass of the water 

bottles should act as a temperature ballast, lessening the impact of potential temperature 

fluctuation sources. To test the effectiveness of this practice, we performed some trials 

with water bottles filling the refrigerator door, and some trials without. The volume of 

water bottles used was equal to 4% of the total refrigerator capacity.

We performed a cycle of measurements on two different refrigerators (a full-size, dualzone refrigerator/freezer unit and a full-size, pharmaceutical grade model) using 

permutations of the variables described above. Prior to the first cycle of measurements,

the refrigerators were adjusted to give a storage temperature between 4 °C and 5 °C. A 

complete listing of the different trials and order in which they were performed is 

contained in the measurement matrix (Table 1) shown below. In our testing of the dualzone refrigerator model, we performed trials both with and without water bottles in place. 

We did not use water bottles in any of our trials of the pharmaceutical refrigerator, 

because the model we tested featured a sliding glass door rather than a solid door with 

storage compartments. After completing the trials with varying load densities, packing 

styles, and with/without water bottles, we performed some additional trials designed to 

simulate some of the different conditions that a VFC clinic might experience. In this 

study, our focus was primarily limited to storage practices for refrigerated vaccines. 

Because of this, while completing the matrix measurements using the dual-zone model, 

we only considered the refrigerator chamber of the unit. The freezer control settings were 

left unchanged throughout the course of measurement collection, and the freezer cavity 

was left empty. In practice, provider offices may use both the freezer and refrigerator 

compartments of a single unit to store refrigerated and frozen vaccine simultaneously. 

Several VFC program coordinators and on-site assessors have expressed concerns that 

adjusting freezer temperature controls might impact storage temperature inside the 

refrigerator cavity, possibly damaging vaccines. To address this issue, we performed a 

short case study examining whether varying freezer temperature has a resulting impact on 

refrigerator compartment conditions. Our method and results from this study are 

described in Section 3.1.10.
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During the first cycle of trials, the refrigerator door was kept closed. However, in every 

day use, it is not possible to keep a refrigerator door closed at all times. The door must be 

opened briefly in order to add and remove vaccines for use. To mimic the opening and 

closing of the refrigerator door that occurs with normal use, we performed trials in which 

the door was opened at 15 minute intervals for 15 seconds at a time, over the course of at 

least 2 h. We carried out these measurement using at least two different packing schemes 

for each refrigerator. We also recorded data with the refrigerator door left ajar for 

approximately 1 h, in order to observe what occurs if a clinic employee forgets to 

completely close the door.

Another non-idealized but common experience at VFC clinics is fluctuation in the storage 

room temperature. Poor HVAC control, inclement or seasonal weather changes, and 

planned or unplanned outages can all cause unexpected room temperature fluctuations.

We wished to determine whether these types of changes affect a refrigerator’s ability to 

maintain the required 2 °C to 8 °C temperature range. To do this, we recorded refrigerator 

temperature data while increasing the ambient room temperature by several degrees. As 

before, these trials were repeated for each refrigerator using at least two different packing 

schemes.

In the final set of trials, we observed what occurs to refrigerated vaccine stores in the 

event of a power outage. In these trials, the refrigerator was set up to run normally. After 

starting the measurement collection system, the refrigerator was unplugged and data 

collection continued overnight.

Table 1. Matrix of measurements performed for each refrigerator.

To determine the temperature distribution throughout the entire refrigerator space, we 

arranged 19 Teflon-insulated, Type T thermocouples in various regions in the refrigerator 

body. The thermocouples were attached to refrigerator walls or storage trays, hung in air, 

mounted inside of glycol-filled bottles, or most importantly, taped to actual vaccine vials. 

The most important feature of a refrigerator used for vaccine storage is its ability to 

maintain a vial temperature between 2 °C to 8 °C. Therefore, monitoring actual vial 

Trial Water Bottles Measurement Parameters

Low Medium High Trays Boxes Mixed (dual-zone trials only)

1 x x normal

2 x x normal

3 x x x normal

4 x x x normal

5 x x x normal

6 x x x normal

7 x x x normal

8 x x x normal

9 x x x increase room temp

10 x x x periodic door opening

11 x x x power off

12 x x normal

13 x x increase room temp

14 x x periodic door opening

15 x x power off

Load Density Packing Style
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temperature in addition to other locations inside the refrigerator enabled us to effectively 

evaluate each refrigerator’s performance. The installation pattern also allowed us to 

determine how well thermometers placed in different areas match the actual vaccine 

temperatures. This helped us produce useful guidelines for the best placement of 

refrigerator temperature monitoring devices.

The thermocouple reference junctions were maintained at 23 °C ±0.002 °C in an 

auxiliary stirred water bath. Prior to use, we calibrated each thermocouple at the melting 

point of ice (0 °C) by placing the thermocouple measuring junction in a Dewar flask 

containing crushed ice and distilled water. The flask itself rested inside the refrigerator 

under study. An automated, 6 1⁄2 digit voltmeter monitored the voltage produced by each 

thermocouple.

In addition to the 19 thermocouples used to monitor temperature, we tested several 

different electronic temperature loggers throughout the course of this study. At present, 

VFC clinic workers are required to check a thermometer placed inside the refrigerator at 

certain intervals each day. Barring any inaccuracies inherent to the device or poor 

placement of the thermometer, this type of monitoring is still likely to be insufficient. 

Refrigerator temperature is not constant over time, so a simple thermometer check once 

or twice a day will not give an accurate indication of whether the vaccines have remained 

within the designated temperature range. 

Inexpensive electronic data loggers (e.g. self-contained temperature recording devices) 

may provide a useful alternative by giving 24-hour-a-day monitoring of refrigerator 

temperature. To investigate their utility, we positioned six different data loggers inside 

each refrigerator throughout the study in order to compare their performance to that of the 

thermocouples. Placement of the thermocouples and data loggers was kept consistent for 

the duration of trials in each refrigerator. The thermometer installation patterns for each 

refrigerator are shown in Figs. 1 and 2 below.

Table 2 summarizes the equipment used for this study. 
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Fig. 1. Thermocouple and data logger installation pattern—dual-zone refrigerator.
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Fig. 2. Thermocouple and data logger installation pattern—pharmaceutical refrigerator.

Table 2. Equipment used for the present study.

Equipment name: Specifications:

Dual-zone Refrigerator  Fully automatic cycle defrost refrigerator with top 

freezer (120 V)

 Height: 1.68 m [66.125 in.]

 Width: 0.762 m [30 in.] 

 Depth: 0.759 m [29.875 in.]

 Total capacity: 0.515 m

3

[18.2 cu. ft.]

 Refrigerator compartment capacity: 0.400 m

3

[14.13

cu. ft.]

 Forced convection of cooling air

Pharmaceutical Refrigerator  Fully automatic cycle defrost refrigerator (120 V)

 Height: 1.79 m

 Width: 0.9 m

 Depth: 0.6 m

 Capacity: 0.489 m

3

 Forced convection of cooling air

 Electronic control system and digital thermometer
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 Temperature, air circulation and door alarms

Plastic trays  Stacking plastic storage trays/ bins

19 thermocouples  Type T (copper-constantan)

 0.5 mm diameter, 1.83 m length

 Teflon insulation

 Calibrated at 0 °C

Data logger A  Rugged high-temperature logger

 Metal housing with integral 2.6 cm rigid probe

 Temperature range: –40 °C to +150 °C

 Temperature resolution: 0.05 °C

 Calibrated accuracy: ± 0.5 °C (from manufacturer)

 Memory: 32,767 readings

 Battery life: 1 year

 Body dimensions: 12.2 cm x 2.6 cm dia.

 Probe dimensions: 2.6 cm x 0.5 cm dia.

Data logger C  Plastic-housing temperature and humidity Logger

 Temperature range: –35 °C to 80 °C

 Temperature resolution: 0.5 °C

 Accuracy: ± 0.3 °C (manufacturer rating)

 Memory: 16,328 readings

 Battery life: 1 year

 Nominal body dimensions: 10.2 cm x 2.3 cm max dia.

Data logger D  Data logger with flexible temperature probe

 Temperature sensors in readout unit and in a flexible 

probe

 Temperature range (readout): –40 °C to 85 °C

 Temperature range (flexible probe): –15 °C to 105 °C

 Temperature resolution: 0.1 °C

 Accuracy: ± 0.5 °C (manufacturer rating)

 Memory: 2000 readings per channel

 Battery life: 2 years

 Nominal body dimensions: 7.6 cm x 7.5 cm x 2.3 cm

Data logger E1, E2  Data logger with two flexible temperature probes

 Temperature sensors in flexible probes

 Temperature range: –15 °C to 105 °C

 Temperature resolution: 0.1 °C

 Accuracy: ± 0.5 °C (manufacturer rating)

 Memory: 2000 readings per channel

 Battery life: 2 years

 Nominal body dimensions: 7.6 cm x 7.5 cm x 2.3 cm

Data logger F  Wireless data recorder with external data logger 

unit/temperature sensor

 Data logger features flexible temperature probe and 

readout unit

 Temperature range: –60 °C to 155 °C

 Temperature resolution: 0.1 °C
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 Accuracy: ± 0.3 °C from -20 °C to 80 °C (mfc rating)

 Memory: 16,000 readings

 Battery life: 6 months

 Nominal body dimensions: 6.2 cm x 4.7 cm x 1.9 cm

 Wireless data transmission distance: Up to 100 Meters 

(Line of Sight and No Obstructions)

Thermocouple measurement 

system 

 6.5 digit multimeter with scanner

Table 3 contains the uncertainties corresponding to the measurement devices and systems 

used. To calculate the uncertainty, 

Table 3. Measurement Device Uncertainties

Device name: U(k=2), °C

Thermocouple measurement system 0.12

Data logger A 0.58

Data logger B 1.41

Data logger C 0.67

Data logger D 0.59

Data logger E1, E2 0.59

Data logger F 0.37

In general, each trial was started during the afternoon, and measurements recorded 

overnight and into the next morning. On average, we recorded 16 to 24 h of data for each 

trial, although some trials were continued over the course of several days. The only 

exception to this was the door opening trials, which only lasted 4 to 5 h. The 

thermocouple measurement system records readings once every 10 s. The individual data 

loggers can be set to various reading rates. In general, the loggers were set to record once 

every minute, except for logger F, which recorded at 30 s intervals. During the door 

opening trials, we increased the reading rate to once every 10 s to 42 s (depending on the 

capabilities of the logger). 

3. INTERPRETATION OF RESULTS

3.1 Dual-Zone Refrigerator

3.1.1. Effect of loading density

In trials performed using the dual-zone refrigerator, vaccine storage density had a slight 

impact on the refrigerator’s ability to maintain the desired temperature range. The 

photographs below (Fig. 4) show the levels of packing density that were tested. 
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Fig. 4. Typical packing patterns.

In general, the dual-zone refrigerator maintained a stable temperature profile throughout 

the different packing density configurations. During trials with higher density loads, the 

degree of location-specific temperature variation appeared to increase slightly. This is 

reflected in figure 5 below, as the vertical spread of the data is slightly larger in some of 

the trials with a high density loading scheme than in the lower density trials.

0

1

2

3

4

5

6

7

8

9

empty

lowtrays

medtrays

medtrays bottles

medboxes bottles

highboxes bottles

lowmixed bottles

medmixed bottles

highmixed bottles

highmixed bottles opendoor

medmixed

medmixed opendoor

Average temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

LA (low, in tray)

LC (mid)

LD (glycol - top)

LE1 (glycol - mid)

LE2 (glycol - low)

LF (glycol - mid)
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Fig. 5. Average temperature of freezerless refrigerator for all sensors, as a function of 

loading pattern. Labels on the abscissa correspond to entries in the measurement matrix 

of Table 1.

Figure 5 shows the average reading for each thermometer across all of the closed-door 

dual-zone refrigerator trials, as well as for the periodic door-opening trials. The majority 

of the thermometers recorded average temperatures within the prescribed 2 °C to 8 °C

window across the range of testing, regardless of whether the refrigerator load was low, 

medium, or high density. The average temperatures of the sensors attached to vaccine 

vials did not vary by more than 1.7 °C between trials, remaining centered around 5 °C to 

6 °C throughout the study. 

However, during the high density, door-opening trial, two thermometers recorded 

average temperatures outside the prescribed range. Thermometer 1, attached to the top 

wall of the refrigerator, recorded an average temperature of 8.3 °C, while thermometer 

19, a thermocouple inside a glycol-filled bottle on the top refrigerator shelf, recorded an 

average temperature of 1.5 °C for the trial. Both of these thermometers displayed outlier 

behavior across the range of testing, and therefore are not good indicators actual vaccine 

vial of properly stored vial temperatures. The dual-zone refrigerator model tested featured 

a cold air vent centered at the top wall of the refrigerator space. The glycol-filled bottle 

containing thermocouple 19 was positioned directly on the glass shelf underneath this 

cold air vent. As a result, this thermometer consistently recorded temperatures 2 °C to 5 

°C colder than those in the rest of the refrigerator space. By contrast, thermometer 1 was 

taped to the top refrigerator wall, away from the cooling vent, causing it to record slightly 

warmer temperatures than thermometers in the main body of the refrigerator. In both 

cases, thermometers 1 and 19 showed the largest deviations during the high density 

loading schemes. Because the refrigerator’s air circulation patterns are inhibited by 

higher density loads, pockets of warmer and cooler air are formed. This effect is 

magnified for the less ideal locations, such as the top refrigerator walls (where warm air 

rises) and directly under the cooling vent. However, for the temperature sensors placed 

throughout the rest of the refrigerator space, including those attached to vials, the 

increase in location-specific temperature variation at high density loads was not 

pronounced enough to result in thermal excursions. 

Considering a refrigerator used for everyday vaccine storage, the arrival of a large 

vaccine shipment or the onset of influenza season is likely to result in a sudden increase 

or decrease in the amount of material stored in the refrigerator. Because these types of 

load density variations did not greatly affect overall temperature stability, the dual-zone 

refrigerator model appears to be suitable for normal vaccine storage. However, care 

should be taken to avoid storing vaccines directly under the cooling vent. An unpackaged 

vaccine placed in this location may be susceptible to thermal excursions below 2 °C, 

particularly during a time of high density refrigerator loading.
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3.1.2. Effect of packing style

Changing the vaccine packing style did not have a noticeable impact on the overall 

refrigerator and vial temperature stability, whether plastic trays, cardboard boxes, or a 

combination of both were used to store the vaccines. (See Fig. 6.) While official 

guidelines for vaccine storage mandate that vials be stored in permanent trays or 

containers and organized by type, we observed other storage conditions during our visits 

to the VFC clinics. For example, a busy clinic with a sudden influx of vaccines might 

temporarily store vaccines inside their shipping boxes. The measurement results indicate 

that the dual-zone refrigerator model would be able to withstand this practice, continuing 

to preserve the prescribed vaccine storage temperature range regardless of packaging 

style.

Fig. 6. Various vaccine storage methods.

3.1.3. Effect of door opening and closing—normal use simulation

During the trials in which the refrigerator door was periodically opened and closed to 

simulate a normal use pattern, the dual-zone refrigerator successfully kept monitored 

vaccine vials within the 2 °C to 8 °C range. The overall impact of the door opening on 

vaccine vial temperature was quite small. For the sensors attached to vials, the mean 

temperature difference between the closed door and door-opening trials was 0.6 °C or 

less. However, well over one-third of all the remaining thermometers recorded large 

thermal excursions both above and below the prescribed temperature bounds during the 

door-opening trials. Figure 7 below shows the temperature responses of each of the 

thermocouples during a door-opening trial.
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Fig. 7. Door opening trial for the dual-zone refrigerator using a high density mixed load 

with water bottles. 

During the dual-zone refrigerator tests, we found that the temperature behavior of 

different sensors during door opening and closing trials varied drastically depending on 

sensor location and installation method. The results in the figure above show some of the 

sensors recording a large temperature spike each time the door is opened, followed by a 

dip that in some cases falls below 2 °C. The thermometers that displayed this type of 

temperature behavior were attached to the upper refrigerator walls or hanging in the open 

airspace. Another group of sensors recorded temperatures clustered around 5 °C to 6 °C 

for the duration of each trial, showing comparatively little response to the door opening 

and closing. This group consisted of sensors attached to vaccine vials as well as those 

placed inside glycol-filled bottles stored in the center of the refrigerator. Figure 8a,

below left, shows the data collected by these sensors only.

Fig. 8a. (Left) Door opening trial for the dual-zone refrigerator. Only thermocouples 

monitoring vial temperatures or inside glycol-filled bottles are shown.

Fig. 8b. (Right) Temperature response of same selected thermocouples, recorded 24 h 

later and with refrigerator door kept closed.

0

2

4

6

8

10

12

14

16

11:00 11:15 11:30 11:45 12:00 12:15 12:30 12:45 13:00

Time, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (vial - mfr packaging)

11 (vial - mfr packaging)

12 (vial - mid, in box)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

Refrigerator door opened at 15 minute intervals

2

3

4

5

6

7

8

10:45 11:00 11:15 11:30 11:45 12:00 12:15 12:30 12:45 13:00 Time, h:min Temperature, °C

6 (vial - crisper drawer)

10 (vial - mfr packaging)

11 (vial - mfr packaging)

12 (vial - mid, in box)

13 (vial - top)

17 (glycol - low)

18 (glycol - mid)

20 (vial - low)

Refrigerator door left closed

2

3

4

5

6

7

8

10:45 11:00 11:15 11:30 11:45 12:00 12:15 12:30 12:45 13:00 Time, h:min Temperature, °C

6 (vial - crisper drawer)

10 (vial - mfr packaging)

11 (vial - mfr packaging)

12 (vial - mid, in box)

13 (vial - top)

17 (glycol - low)

18 (glycol - mid)

20 (vial - low)
Page 16 of 59

Note: Due its placement under the cooling vent, thermocouple #19 recorded temperatures 

up to 6 °C colder than monitored vials and other sensors in glycol-filled bottles. Because 

of this, TC #19 is excluded from these graphs.

Figure 8a shows the response of the selected thermometers during one of the periodic 

door-opening trials, while figure 8b shows the closed-door, equilibrium temperature 

behavior of the same thermometers, for comparison. It is apparent from the figures that 

while the normal use pattern of opening and closing the refrigerator door does have an 

effect on the temperatures experienced by stored vaccines, the effect is not likely to be 

large enough to threaten the potency of the vaccines via large thermal excursions. These 

findings support the use of the dual-zone refrigerator model as an effective storage 

system for refrigerated vaccines under normal operating conditions.

While the vaccine vial temperatures remained relatively stable throughout the dooropening trials, a large percentage of the temperature sensors arranged throughout the 

refrigerator recorded an entirely different picture. The large temperature fluctuations 

recorded by some of the thermocouples hanging in the air or attached to the refrigerator 

walls underscore the importance of choosing the proper temperature monitoring location 

and method.

Fig. 9. Door opening trial for the dual-zone refrigerator, showing only thermocouples 

which recorded out-of-range data.

Figure 9 above shows data taken concurrently with that in figure 8a, but only the sensors 

that recorded temperatures outside the 2 °C to 8 °C bounds are shown. Each of these 

sensors, with the exception of sensor 19, recorded a large temperature spike each time the

refrigerator door was opened. The sensors hanging in the open air (7, 8, 9) saw the most 

0

2

4

6

8

10

12

14

16

11:00 11:15 11:30 11:45 12:00 12:15 12:30 12:45 13:00

Time, h:min Temperature, °C

1 (top wall)

4 (top back wall)

5 (air - deli drawer)

7 (air)

8 (air)

9 (air - top)

15 (back of tray)

19 (glycol - top)
Page 17 of 59

dramatic spikes, with temperature increases of 5 °C to 10 °C higher than their previous 

readings. A provider using a similar setup to monitor their vaccine storage system, such 

as a thermometer set up to record refrigerator air temperature, would most likely obtain a 

similar result. Every time a worker briefly opened the refrigerator door, the thermometer 

would likely record a large temperature spike exceeding the 8 °C limit. Although this 

temperature data would suggest that the vaccines were subjected to improper storage 

conditions, we saw in the results of our study that the thermal state of the vaccine vials 

remained relatively stable despite fluctuations in the refrigerator air temperature brought 

on by repeated door opening.

It is clear that choosing the right thermometer and correctly positioning it inside the 

refrigerator is critical to obtaining meaningful temperature monitoring data. The obvious

purpose of a vaccine refrigeration system is to maintain vaccine vials and packages at a 

temperature that is within 2 °C to 8 °C, while the goal of a vaccine temperature 

monitoring system is to provide quantitative evidence that the vaccines have in fact been 

kept within this range. During the course of normal refrigerator use, such as when the 

door is briefly opened and closed to add or remove stock, the interior refrigerator air 

temperature will experience fluctuations that are much larger or do not correspond to the 

temperature effects experienced by vaccines. A vaccine usually consists of liquid inside a 

glass bottle or plastic syringe, which is often contained in some type of cardboard 

packaging. As a result, a packaged vaccine has a much larger thermal mass than the 

same volume of air. This means that it takes the vaccines much longer to thermally “see” 

the effects of conditions like opening the refrigerator door.

A thermometer with a thermal mass similar to a stored vaccine can be used as an 

effective tool for determining vaccine temperature. If the thermometer probe itself does 

not meet this criterion, placing the probe inside a bottle filled with a liquid, such as 

glycol, is a simple way to mimic the temperature behavior of a vaccine inside a bottle.

During these door opening trials, we found that the data from both the thermocouples and 

data loggers with probe placed inside glycol-filled bottles closely followed the results of 

the thermocouples attached to vaccine vials. The one exception to this was thermocouple 

19, shown in figure 9 above.

Thermocouple 19 was contained inside a glycol-filled bottle and placed on the 

refrigerator shelf, near to stored vaccines. The other thermocouples in glycol, 17 and 18, 

recorded temperature data that mirrored the results of the vial-attached thermocouples 

throughout the range of testing. However, thermocouple 19 consistently recorded 

temperatures 2 °C to 5 °C colder than any of the other sensors across all of the trials. The 

difference lies in the thermocouple’s location inside the refrigerator. The glycol-filled 

bottle containing thermocouple 19 was placed on its side, directly on the upper glass 

refrigerator shelf. Located directly above this spot was the refrigerator cooling vent. This 

means that every time the refrigerator compressor cycled on, cold air was blown directly 

onto both the glass shelf and the bottle containing thermocouple 19. This clearly explains 

why the temperatures recorded from this spot were so much colder than from other areas 

of the refrigerator. During the door-opening trials, the repeated influx of roomtemperature air likely caused the refrigerator to pump out additional cold air to 
Page 18 of 59

compensate. This would in turn drive the temperatures of the shelf and the sensors near 

the vent down even lower. Our data supports this explanation, as the lowest temperatures 

recorded at any point in the study were measured by thermocouple 19 during the door 

opening trials.

During trials using the freezerless and dorm-style refrigerator models, we found that 

storing water bottles in the door of the unit improved overall temperature stability by 

reducing the impact of normal use conditions like opening the refrigerator door [1]. 

However, in trials of the dual-zone model, the difference in performance between the 

refrigerator with water bottles vs. without water bottles was less pronounced. Table 4

below shows the different door opening temperature changes for the two trials, with and 

without water bottles. In this case, the temperature change is defined as the difference 

between average temperature recorded during the closed door trial, and the average 

temperature from the door-opening trial with the same loading configuration. The closed 

door trial temperature averages were taken from a 2 h representative sample of data. The 

temperature averages from door-opening trial were taken over the entire duration of the 

trial, which was 2 h.

Table 4. Temperature changes during door-opening tests (all values in degrees Celsius).

The negative temperature change of many of the sensors indicates that the average 

recorded temperature was lower during the door opening trial than in the closed door 

trial. Although room temperature air entering the refrigerator each time the door is 

opened causes the internal temperature of the refrigerator to rise, the cooling unit 

compensates by pumping in additional cold air. From our results, it appears that the dualSensor High Density Mixed Medium Density Mixed

Name/Location With Bottles No Bottles

1 (top wall) 0.6423 0.5537

2 (mid wall) 0.1467 0.2842

3 (lower wall) -0.4250 -0.0251

4 (top back wall) 0.3464 -0.6174

5 (air - deli drawer) 0.5182 0.4871

6 (vial - crisper drawer) -0.2926 0.0958

7 (air) 0.3457 0.4844

8 (air) -0.2525 -0.0609

9 (air - top) 0.3814 0.0494

10 (in box) 0.3294 0.6409

11 (in box) 0.1940 0.4255

12 (vial - mid) -0.0106 0.2154

13 (vial - top) -0.1090 0.3425

14 (inside tray) -0.3291 -0.0145

15 (back of tray) -0.6643 -0.3806

17 (glycol - low) -0.2242 -0.0264

18 (glycol - mid) 0.1346 0.1369

19 (glycol - top) -0.7202 -0.4313

20 (vial - low) -0.2985 -0.1190

LA (low, in tray) -0.1531 -0.1330

LC (mid) 0.2551 0.0868

LD (glycol - top) -0.1058 0.4173

LE1 (glycol - mid) -0.0676 0.0293

LE2 (glycol - low) -0.2455 -0.0867

LF (glycol - mid) 0.2230 0.3599
Page 19 of 59

zone cooling unit may over-compensate slightly, driving the temperature several tenths of 

a degree below the original set point.

Twenty-one out of the twenty six sensors recorded a smaller temperature change when 

water bottles were used in the door. However, this effect was very small, amounting to a 

difference of half a degree at most.

The effect of the water bottles was much more pronounced during tests in which the 

refrigerator door was left cracked open for 1 h, to simulate an employee forgetting to 

completely close the door. Table 5 below shows the amount of time elapsed once the 

door was opened until each of the vials exceeded the allowed maximum temperature of 

8 °C.

Table 5. Time after opening door until vial temperature exceeded 8 °C.

* door closed after 60 minutes

All of the vials resisted thermal excursions above 8 °C for a longer period of time when 

the water bottles were in place. For two of the monitored vaccine vials, the effect of the 

water bottle ballast was significant enough to prevent any exposure to out-of-range 

temperatures.

3.1.4. Effect of Increasing Room Temperature

Although vaccine storage refrigerators should be kept in a fairly well temperature 

controlled room, considerable ambient temperature fluctuations may result from planned 

HVAC outages at night or weekends, or from unplanned circumstances such as an AC 

outage or poor thermostat control. To determine whether these fluctuations impact the 

dual-zone refrigerator’s ability to maintain its set point temperature, we performed three 

trials in which the room temperature was varied between 18 °C and 24 °C.

Data logger LD has a thermometer included in the main readout unit as well as an 

additional probe attached via cable. This probe was inserted into a glycol-filled bottle 

kept inside the refrigerator throughout all of the trials, while the readout unit was kept 

outside of the refrigerator, in a tray taped to the refrigerator door. In this way, we were 

able to simultaneously measure both the internal refrigerator temperature and the external 

ambient temperature using the same data logger. By comparing the relationship between 

internal refrigerator and ambient temperature, we can determine the effect an increase in 

room temperature can have on vaccine storage conditions. Data loggers LE1 and LE2 

High Density Mixed Medium Density Mixed

Name and Location With Bottles No Bottles

(minutes) (minutes)

vial 10 (inside original packaging) 5 4

vial 11 (inside original packaging) 24 18

vial 13 (in tray, upper shelf) 27 3

vial 12 (inside cardboard box) 62* 58

vial 20 (in tray, lower shelf) did not exceed 32

vial 6 (inside box, in vegetable crisper) did not exceed 53
Page 20 of 59

have the same specifications as logger LD, and both of these loggers also had 

temperature probes kept in glycol-filled bottles inside the refrigerator. Because of this, we

have also included the readings from LE1 and LE2 in the comparison analysis to better 

establish the relationship between ambient temperature and its effects on interior 

refrigerator temperature control.

Table 6 shows the temperature change recorded by each of the three refrigerator data 

logger probes scaled to the change in ambient temperature recorded by the external 

probe. So, for example, during the High Density Mixed with Bottles I trial, logger LE1 

recorded a temperature decrease of 0.02 °C for every one degree increase in room 

temperature.

Table 6. Refrigerator probe temperature change divided by room temperature change (°C

/ °C)

During trials using the freezerless refrigerator, we saw that room temperature and internal 

refrigerator temperature were directly related. For every degree rise in room temperature, 

the temperature inside the refrigerator also increased by some fractional amount. 

However, in trials using the dual-zone refrigerator, the relationship between room 

temperature and internal refrigerator temperature proved to be much more complex. Most

of the data in table 6 above suggests that there is an inverse relationship between room 

temperature and internal refrigerator temperature. This may be a product of refrigerator’s 

internal temperature control, which increases cooling power in response to the warmer 

environmental conditions. However, not all of the data fits within this paradigm. During 

the Medium Density Mixed load trial, logger LD recorded a temperature increase of 0.04 

°C per degree rise in room temperature. These inconsistencies are evidence that the 

complex relationship between exterior and interior refrigerator cannot be sufficiently 

captured by our limited investigation. 

A number of extenuating factors, such as refrigerator load density, timing of a cooling or 

defrost cycle, initial refrigerator temperature, and the time rate of change of room 

temperature, impact the resulting temperature response of the refrigerator. Because we 

did not investigate the full scope of these factors, we will not attempt to delineate the 

exact relationship between room temperature change and its effect on refrigerator 

temperature control. However, we can make some generalizations about the overall 

impact of room temperature variation on the performance of a dual-zone refrigerator in 

terms of its role in a vaccine storage system.

First, and most importantly, the impact of changing room temperature on the dual-zone 

refrigerator is small. At the high end of the spectrum, we saw data logger LE2 record a 

temperature decrease of 0.1 °C per one degree increase in room temperature during one 

of the three trials. The remaining data sets showed an interior refrigerator temperature 

Logger Name High Density Mixed High Density Mixed Medium Density Mixed

With Bottles I With Bottles II No Bottles

LD 0.00 -0.03 0.04

LE1 -0.02 -0.03 -0.04

LE2 -0.05 -0.10 -0.05
Page 21 of 59

change of 0.05 °C or less per degree change in ambient temperature across all of the 

trials. By extrapolation, this means that environmental conditions must vary by > 20 °C 

for the items stored inside the refrigerator to experience just one degree of temperature 

change. By this analysis, if the initial refrigerator set point is set correctly, a 20 °C room

temperature change is not likely to impact the efficacy of stored vaccines. 

The dual-zone refrigerator performance during these varying room temperature tests 

demonstrates that the unit is able to withstand moderate fluctuations in ambient thermal 

conditions without sacrificing its ability to maintain proper vaccine storage temperatures.

Only severe environmental temperature fluctuations are likely to have a significant 

impact on this refrigerator model’s performance. For example, if a clinic in a northern 

climate experienced a heating outage during a snowstorm, the resulting room temperature 

drop might be enough to produce unacceptable thermal excursions inside the unit.

It is important to note that because these assertions are based on the observed effect of a 

6 °C room temperature change, there may be additional thermal effects that occur under 

larger temperature swings. Any given refrigerator model may be subject to certain 

threshold operating conditions. If these conditions are exceeded, the refrigerator 

performance could be altered in an unexpected way. One way to effectively mitigate this 

risk is through the use of a continuous temperature monitoring system. This type of 

system puts the provider in control of their vaccine stock, alerting them of the status of 

their refrigerator at all times, under any environmental conditions. The data from the 

temperature monitoring device could then be used to identify possible weaknesses of the 

refrigeration system, such as inferior performance during moderate or extreme ambient 

temperature changes. Once these individualized weaknesses are identified, clinic workers 

will have the necessary tools to develop improved contingency plans, thereby enhancing

the confidence of vaccine suppliers and providers, as well as the recipients, in the 

efficacy of delivered vaccines.

3.1.5. Effect of a Power Outage

To observe what occurs following a power outage, we performed two trials in which the 

closed refrigerator was unplugged and monitored overnight. During these trials, the room 

temperature was stable to within 1.5 °C. In both trials, all of the thermometers recorded a 

fairly steep increase in temperature that slowed down slightly over time. All of the 

thermometers, including those attached to vaccine vials, exceeded the allowed maximum 

temperature in less than 3 h for the medium density (no bottles) trial, and in 5 h in the 

high density with bottles trial. Figure 10 below shows the temperature readings of all of 

the thermometers during one of the power off trials. The sudden drop in temperature 

following the peak corresponds to the point at which the refrigerator was plugged back 

in.
Page 22 of 59

Fig. 10. Thermometer response during a power outage event. Medium density mixed 

load, no water bottles trial.

The next graph (Fig. 11) shows the data collected starting from the time that the 

refrigerator was unplugged. The dashed red line indicates the 8 °C upper limit, and the 

blue dashed line shows the 2 °C minimum.

Fig. 11. Expanded view of thermometer response during a power-outage event. High 

density mixed load with bottles trial.

-2

0

2

4

6

8

10

12

14

16

18

20

22

0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00

Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

LA (low, in tray)

LC (mid)

LD (glycol - top)

LE1 (glycol - mid)

LE2 (glycol - low)

LF (glycol - mid)

1

2

3

4

5

6

7

8

9

10

11

0:00 1:00 2:00 3:00 4:00 5:00

Time elapsed since power off, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)
Page 23 of 59

To determine the required response time to preserve vaccine viability during a power 

outage situation, we examined the amount of time elapsed from the point that the 

refrigerator was unplugged until the thermometers attached to vials exceeded 8 °C. This 

information is reported in Table 7 below. 

Table 7. Time after power-off until vial temperature exceeded 8 °C.

We can make several pertinent observations about this data. Of the two vials that were 

not contained in boxes or packaging material, the vial stored on a upper refrigerator shelf 

exceeded 8 °C faster than the vial on a lower shelf in both trials. This is expected 

response. With the power off, the fans do not circulate air throughout the cavity, so the 

warmer air rises to the top of the refrigerator. Hence, vials stored in the top portion of the 

refrigerator are exposed to warmer air than those stored in the bottom. This effect will be 

magnified for vials that are left exposed to air without the additional thermal mass 

provided by packaging material. Overall, the vials contained inside a thicker cardboard 

box resisted thermal excursions for a significantly longer time period than either the 

completely unpackaged vials or the vials kept only in their original thin cardboard 

packaging. This is because the thermal energy first must be conducted through layers of 

cardboard before it is able to heat up a vial inside a box.

Even so, these findings do not signify that all providers should package their vaccine 

vials in multiple layers of cardboard boxes to protect against thermal excursions during 

power outages. The flip-side of the coin is that as additional layers of packaging materials 

are used to store vaccine vials, the amount of time required to remove vaccines from the 

refrigerator is likely to increase. This could translate to workers spending additional time 

in front of the refrigerator with the door open, and as a result, a greater chance of thermal 

excursions caused by exposure to room temperature air. Because of this, it is critical to 

evaluate the best possible storage solutions depending on a provider’s particular needs. 

For example, large, modern hospitals are likely to have backup generator systems to keep 

medical refrigerators running through power outages. Providers operating in this type of 

setting are likely to see many patients per day and have a high vaccine turnover rate, in 

which nurses must open and close vaccine storage refrigerators many times per day. In 

this case, minimizing the amount of time that the refrigerator door is open may be a more 

critical concern than protecting against power outages. If, by contrast, a provider office 

does not have a reliable backup generator and sees a comparatively small number of 

vaccine-related appointments, it might be worthwhile for them to package their stock 

more carefully to provide an extra safety margin in the event of a power outage.

High Density Mixed Medium Density Mixed

Name and Location With Bottles No Bottles

(hrs:mins) (hrs:mins)

vial 13 (in tray, upper shelf) 2:51 1:16

vial 10 (inside original packaging, middle shelf) 2:34 1:18

vial 11 (inside original packaging, middle shelf) 3:16 1:44

vial 20 (in tray, lower shelf) 4:42 2:05

vial 6 (inside box, in vegetable crisper) 4:10 2:08

vial 12 (inside cardboard box, middle shelf) 4:11 2:43
Page 24 of 59

The results shown in table 7 clearly support the value of using water bottles as a

temperature ballast. During the trial with water bottles in place, each of the vials resisted 

temperature increase above 8 °C for an extra 32 min to 2 h 37 min as compared to the 

trial without water bottles.

In order to observe the time required for the refrigerator to return to equilibrium 

following a power outage, we continued recording data after the refrigerator was 

powered. Figure 12 shows the data collected while the refrigerator cooled down back to 

its pre-outage temperature state.

Fig. 12. Recovery after restoration of power for a dual-zone refrigerator.

The length of the power outage and the resulting maximum temperature attained will 

affect the length of time required to get the refrigerator back down to its original baseline.

During the high density mixed load (including water bottles) trial, the refrigerator was 

left unplugged for 3 days, 17 h 28 min. During the medium density mixed load trial, the 

total power off time was 16 h 16 min. Because of this, the refrigerator reached a different 

maximum temperature in each trial, so the effect of loading density and water bottles on 

power outage recovery time cannot be evaluated based on these trials. The main point to 

note from the above data is that vials open to main refrigerator air flow returned to the 

specified temperature range the most quickly, while those contained in a thermally 

insulated container, such as a cardboard box or inside the vegetable crisper drawer, took 

the longest to recover to an allowed temperature. The dual-zone refrigerator required 

approximately 12 h to completely re-equilibrate from ambient temperature following the 

simulated power outage in trial with water bottles in place, and 9 h in the trial without 

water bottles.

0

2

4

6

8

10

12

14

16

18

20

0:00 1:00 2:00 3:00 4:00 5:00 6:00 7:00 8:00 9:00

Time elapsed since power on, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

LA (low, in tray)

LC (mid)

LD (glycol - top)

LE1 (glycol - mid)

LE2 (glycol - low)

LF (glycol - mid)
Page 25 of 59

3.1.6. Defrost Cycle

Throughout the course of the dual-zone refrigerator measurements, we noted the 

occurrence of periodic temperature spikes due to the refrigerator’s defrost cycle. The

defrost cycle appears to run at 28 h to 34 h intervals. As evidenced by the graph below

(Fig. 13), which shows a dual-zone refrigerator model defrost cycle, vaccine vial 

temperatures were not greatly affected by the periodic temperature increases. 

During the cycle shown, one of the vial-attached thermometers (13) measured 

temperatures above the 8 °C temperature limit for a period of approximately 10 min.

However, in the majority of the defrost cycles we observed, all of the monitored vials 

remained within 2 °C to 8 °C. The dual-zone refrigerator’s defrost cycle is likely to have 

minimal effect on drug potency, but this will depend on the manufacturer specifications 

for the number of hours the vaccine can be held at certain temperatures greater than 8 °C 

before suffering a loss of viability. 

Fig. 13. Temperature response during a defrost cycle.

However, depending on the placement of thermometers used to monitor vaccine 

temperatures, the incidence of a defrost cycle could cause a VFC worker to incorrectly 

surmise that vaccine temperatures strayed outside of both the allowed maximum and 

minimum temperature bounds. Referring again to the graph, some of the thermometers 

attached to walls (e.g. 1, 4), in close proximity to a wall (15), or hanging in the air (e.g. 7, 

9) recorded large temperature spikes followed by a drop below the 2 °C limit. If one of 

1

2

3

4

5

6

7

8

9

10

0:00 0:30 1:00 1:30 2:00 2:30 3:00

Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

LA (low, in tray)

LC (mid)

LD (glycol - top)

LE1 (glycol - mid)

LE2 (glycol - low)

LF (glycol - mid)
Page 26 of 59

these thermometers were used as an indicator of vial temperature, then employees may 

erroneously adjust the refrigerator set-point temperature and dispose of vaccines 

needlessly. As a result, care must be taken in determining the best placement for 

temperature monitoring devices in order to most accurately determine vial temperature 

during events such as refrigerator defrost cycles. 

3.1.7. General Stability of Vial Temperature and Suitability of Dual-Zone 

Refrigerator Model for Maintenance of Vaccine Storage Conditions

The dual-zone refrigerator performance appears suitable for vaccine storage. Vaccine 

vial temperatures remained within the specified 2 °C to 8 °C range throughout all of the 

packing variation trials, as well as during the 15 second door opening trials. Drift of the 

refrigerator control thermometer appears to be negligible.

3.1.8. Best and Worst Locations for Vial Storage

Throughout the course of the closed-door dual-zone refrigerator trials, vaccine vials 

remained within the desired temperature range regardless of their location in the 

refrigerator. However, based on the results of the door opening and power-off trials, it 

appears that some storage methods and locations within the refrigerator provide better 

thermal stability than others.

In general, vials stored inside a thermally isolated container experienced less temperature 

disruption during normal, periodic door-opening operation than unpackaged vials kept in 

trays. Although existing vaccine storage and handling guidelines often advise against 

storing vaccines in the vegetable bins of a refrigerator, we found in our study that a vial 

stored in this area was subject to significantly less temperature variation than vials stored 

in the main body of the refrigerator. This is not surprising, because the crisper drawer 

acts as an additional barrier to reduce the rate and amount of heat transferred to the vials 

inside. While the unpackaged vials stored in trays experienced small temperature spikes 

each time the refrigerator door was opened, the temperature of the vial in the vegetable 

bin (TC #6) was largely unaffected. During both the door left ajar tests and power outage

trials, vial number 6 was one of the last monitored vials to exceed the 8 °C threshold. 

If a provider chooses to store vaccines in the thermally isolated vegetable drawer, they 

should be aware of two possible caveats. First, while our test refrigerator did not have 

this feature, some refrigerator models include vegetable drawers with adjustable 

temperature or humidity controls. In this case, the provider should monitor the 

temperature inside the drawers, adjusting the controls as necessary until the required 

equilibrium conditions are met. Secondly, during our testing of the dual-zone refrigerator, 

we saw that the average temperature of the vegetable bin vial was generally about 1 °C 

warmer than that of the vials stored in the main refrigerator space. In our tests, this 

temperature difference was not enough to push the vegetable bin vial out of range. 

However, because the bins create a thermally isolated environment, workers cannot just 

assume that the temperature is the same inside and outside of the drawer. Again, any 
Page 27 of 59

possible issues can easily be detected and remedied by simply monitoring the temperature 

inside the bin to insure that proper vaccine storage conditions are maintained.

Vials stored in cardboard boxes also experienced greater temperature stability than those 

that were left unpackaged. Like the vegetable drawers, the extra layer of cardboard 

reduced heat transfer to the vials inside.

During the simulated power outage trials, the vials placed in the bottom portion of the 

refrigerator were the last to exceed the allowed maximum temperature. During normal 

operation, fans inside the refrigerator distribute warmer and cooler air to maintain a fairly 

uniform temperature distribution throughout the interior space. Once a power outage 

begins, pockets of warmer and cooler air begin to separate, as the cooler air settles around 

the floor of the refrigerator and the warm air rises towards the top. As a result, vials kept 

on the upper shelves and not contained in boxes experienced the fastest temperature 

increases. 

Throughout the range of tests performed, one thermocouple inside a glycol-filled bottle 

was kept on the top refrigerator shelf, underneath the cooling vent (TC #19). This 

thermocouple consistently recorded temperatures below the 2 °C threshold, and did not 

show temperature behavior consistent with the other sensors in the refrigerator. Because 

the glass bottle filled with liquid glycol approximates the thermal mass and properties of 

a vaccine vial, a vial placed in the same location would likely experience similar results. 

The proximity of the cooling vent above this location means that every time the 

refrigerator compressor cycles on, the stream of cold air drives the temperature 

downward. The dual-zone refrigerator model we tested featured glass shelves, which 

have more surface area and a greater heat capacity than the wire shelves in some other 

models. It takes more heat to change the temperature of the glass a certain amount than it 

does to change the surrounding air by the same degree. The result is that the temperature

of the glass shelf located underneath the cooling vent stays colder than some other areas 

of the refrigerator. In our study, the glycol-filled bottle in direct contact with this shelf 

experienced temperatures an average of 3 °C to 5 °C colder than the rest of the 

refrigerator.

Another thermocouple inside a glycol-filled bottle (TC #18) was placed one level down, 

directly on the middle refrigerator shelf. This thermocouple consistently recorded 

temperatures at least 0.5 °C colder than any of the glycol bottle or vial-attached sensors 

stored in trays or boxes. A maintenance temperature difference of 0.5 °C is not likely to 

cause thermal excursions unless there are existing issues with the refrigerator temperature 

set point adjustment or control. However, a 5 °C temperature difference is very likely to 

result in an out of range condition. Most providers do not have the equipment, time, or 

incentive to study the complete temperature distribution of their vaccine refrigerators, and 

as a result, they are not likely to know which shelves and areas correspond to hazardous 

“cold spots.” Because the potential for damage is high, providers should not store 

vaccines in direct contact with the surface of any glass shelf, regardless of its position 

inside the refrigerator. In addition, trays or boxes containing vaccine vials should not be 

placed directly under the cooling vent.
Page 28 of 59

3.1.9. Best and Worst Methods of Monitoring Vial Temperature

In this study, we used several different temperature sensing devices in various locations 

throughout the refrigerator in order to determine the best way to monitor actual vial 

temperature. While attaching a thermocouple thermometer to a vial is a very accurate 

way to determine vaccine temperature, this is not a feasible strategy for clinics or storage 

facilities. To determine the suitability of different vial temperature monitoring schemes, 

that is, the best and worst locations and monitoring devices for this purpose, we can 

compare the temperature readings of the vial-attached thermocouples to the readings of 

the other thermometers.
Page 29 of 59

Fig. 14. Response of thermometers with different mounting methods.

Thermometers Attached to Vaccine Vials

0

1

2

3

4

5

6

7

8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 Duration of measurement, h:min Temperature, °C

6 (vial - crisper drawer)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

20 (vial - low)

Thermometers on or Near Refrigerator Walls

0

1

2

3

4

5

6

7

8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

15 (back of tray)

Thermometers Inside Glycol-filled Bottles

0

1

2

3

4

5

6

7

8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 Duration of measurement, h:min Temperature, °C

17 (glycol - low, tray)

18 (glycol - mid, shelf)

19 (glycol - top, shelf)

LD (glycol - top, tray)

LE1 (glycol - mid, shelf)

LE2 (glycol - low, tray)

LF (glycol - mid, tray)

Thermometers Hanging in Air

0

1

2

3

4

5

6

7

8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 Duration of measurement, h:min Temperature, °C

5 (air - deli drawer)

7 (air)

8 (air)

9 (air - top)

Thermometers in Trays, on Shelf

0

1

2

3

4

5

6

7

8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 Duration of measurement, h:min Temperature, °C

14 (inside tray)

LA (low, tray)

LC (mid, shelf)

Medium Density Mixed - All Thermometers

0

1

2

3

4

5

6

7

8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air - deli drawer)

6 (vial - crisper drawer)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (vial - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low, tray)

18 (glycol - mid, shelf)

19 (glycol - top, shelf)

20 (vial - low)

LA (low, tray)

LC (mid, shelf)

LD (glycol - top, tray)

LE1 (glycol - mid, shelf)

LE2 (glycol - low, tray)

LF (glycol - mid, tray)
Page 30 of 59

Best Locations for Temperature Sensors

 A thermocouple contained inside a glycol filled bottle placed in a plastic tray matched 

the vaccine temperatures very closely (TC #17). During the door-opening and poweroff trials, this thermometer displayed a temperature response similar to nearby the 

vial thermometers. 

 However, two other sensors in glycol filled bottles (TC #s 18, 19) gave very different 

results, as they were both placed directly on upper refrigerator shelves, in contact 

with the glass and in close proximity to the cooling vent.

 A thermocouple kept inside a glycol filled bottle provides a good approximation for 

the thermal mass of a glass vaccine vial. However, if the bottle is placed in an area 

that is not representative of the main body refrigerator temperature, the readings will 

not give a good indication of vial temperature. The glass shelves directly under the 

cooling vent stayed at a colder temperature than the rest of the refrigerator, skewing 

the readings of TC #18 and 19, which were in direct contact with these shelves. By 

keeping TC #17 in a tray on a lower shelf instead of directly on the glass, this effect 

was mitigated.

 Loggers C, D, E1, and E2 agreed closely with the temperatures recorded by the vialattached thermocouples. 

 Loggers D, E1, and E2 each had a probe inside a glycol-filled bottle and was placed 

in a tray, closely replicating the thermal conditions of stored vaccine vials. 

Throughout the range of testing, the temperature variation of vials stored in different 

locations stayed within 1.5 °C. The readings of each of the loggers with probes in 

glycol bottles (LD, LE1, LE2) consistently stayed within the same temperature span 

as the vials. As such, temperature probes kept inside glycol-filled bottles appear to 

give a very good representation of vaccine vial temperature, provided they are not 

placed in an area with “outlier” conditions, such as directly under the cooling vent.

 As a general rule, the closer the thermometer is placed to the actual location where 

vaccines are stored, the closer its readings will be to actual vaccine temperatures. 

Mediocre Locations for Temperature Sensors

 Thermometers placed on main refrigerator shelves or inside of a tray in the areas 

where vaccines were stored produced data reasonably similar to that of the vial 

thermometers most of the time (TC #s 14, 18; LA, LF).

 Thermocouple 14 provided reasonable thermal mapping of recorded vial 

temperatures, although tended to average about 0.5 °C colder than the majority of the 

vial attached thermocouples.

 On average, thermocouple 18 measured 0.5 °C to 1 °C colder than vial temperatures. 

Perhaps because TC #18 was in direct contact with the glass shelf, one level down 

from the cooling unit. Placing temperature monitors directly on glass shelves should 

be avoided. Instead, the monitors should be kept in the same types of trays in which 

vaccines are stored. 

 Logger A (LA) showed temperature behavior similar to vial 20, as both were stored 

in trays in the lower portion of the refrigerator. Even so, the average temperatures 

recorded by LA were ~ 0.5 °C colder than those measured on vial 20. By contrast, 

logger F consistently recorded temperatures 0.5 °C to 2 °C warmer than vials stored 

nearby. Both loggers were kept in a plastic tray. 
Page 31 of 59

 One thermocouple (TC #5) was hung from inside the refrigerator deli drawer. This 

somewhat thermally isolated environment prevented the thermometer from reading 

the dramatic temperature fluctuations recorded by thermometers hanging in the main 

airspace of the refrigerator. However, during the door opening trial, this thermometer 

recorded much larger temperature spikes than any of the thermometers attached to 

vaccine vials. As a result, the interior of the refrigerator deli drawer is not an ideal 

location to store temperature monitors.

Unacceptable Locations for Temperature Sensors

 Thermometers attached to refrigerator walls (TC #s 1, 2, 3, 4) registered temperatures 

that differed greatly from vial temperatures. These thermometers measured dramatic 

temperature fluctuations in response to normal refrigerator temperature control and 

defrost cycles as well as during our simulation trials. Thermometers 1 and 4 were 

closest to the cooling unit, so they recorded very large temperature changes (5 °C to 7 

°C) in response to the standard refrigerator cooling cycle. This also caused TC #1 to 

repeatedly drop below 2 °C.

 TC #15, attached to the back of a tray, showed large temperature fluctuations similar 

to the wall-attached thermocouples, most likely due to its proximity to the wall.

 A thermometer set up to record air temperature is also not a good indicator of vial 

temperature. Thermometers hanging in the air of the main refrigerator cavity (TC #s 

7, 8, 9) showed large temperature fluctuations in response to the refrigerator cooling 

cycle. Thermometer 8 repeatedly showed a dip below 2 °C during closed-door trials. 

During door opening trials, all three thermometers hanging in air showed large 

temperature spikes exceeding 8 °C. 

 The thermal mass of a glass vaccine vial reduces its temperature sensitivity, so that it 

takes the vial longer to heat up or cool down in response to air temperature changes. 

Relying on air temperature as an indicator of vaccine storage conditions is likely to 

give false alarms, leading workers to believe a thermal excursion has occurred when 

in fact vaccine temperatures remained within range. 

 Temperature monitors should never be placed directly under the cooling vent, as the 

temperature in this area will be much colder than vaccines stored elsewhere in the 

refrigerator. TC #19, on a shelf directly under the vent recorded temperatures an 

average of 3 °C to 5 °C colder than the rest of the refrigerator. 

3.1.10. Dual-Zone Refrigerator Case Study: Does freezer setting affect refrigerator 

performance?

While completing the standard measurement matrix using the dual-zone refrigerator, we 

considered only the refrigerator compartment of the unit. The freezer compartment was 

kept empty for the duration of the study, and its temperature control settings were left 

unchanged. The preceding results from the dual-zone model tests address the unit’s 

suitability as a refrigerated vaccine storage unit only. Although the dual-zone model we 

tested featured separate refrigerator and freezer temperature controls, it is possible that 

changing the freezer temperature settings or adding contents to the freezer compartment 

could impact the temperature of the unit’s refrigerator compartment. VFC providers and 
Page 32 of 59

program managers have given anecdotal reports of dual-zone refrigerator chambers 

becoming excessively cold and freezing refrigerated vaccine supplies when the freezer 

temperature controls are adjusted to properly maintain frozen vaccines. An in-depth 

evaluation of the performance of dual-zone units used to store refrigerated and frozen 

vaccine simultaneously was outside the scope of our study. However, we performed a 

brief case study aimed at addressing some of the questions about synchronized 

refrigerator and freezer operation.

In this case study, we performed three trials using a medium-density, mixed container 

loading pattern in both the refrigerator and freezer compartments. We used the same 19 

thermocouples and 6 data electronic loggers as in the refrigerator-only testing. The 

temperature sensors were arranged throughout the refrigerator and freezer chambers, 

attached to walls, inside trays, with probes inside glycol-filled bottles, hanging in the air, 

and attached to vaccine vials. Thermocouples 1 through 10 were installed in the freezer 

compartment along with data loggers LC and LE2. Thermocouples 11 through 20, and 

data loggers LA, LD, LE1 and LF were placed in the refrigerator chamber. The labeled 

installation pattern is shown in figure 15 below.

Fig. 15. Thermocouple and data logger installation pattern—dual-zone 

refrigerator/freezer test.

Using this installation pattern, we performed three trials, varying the freezer temperature 

control setting while leaving the refrigerator temperature control unchanged. For the first 

trial, the freezer temperature control dial was set at the midpoint, halfway between the 
Page 33 of 59

minimum and maximum dial settings, the same setting used throughout our standard 

refrigerator-only testing procedures. During the second trial, the freezer temperature 

control dial was adjusted to 75% of the maximum cold setting. For the third and final 

trial, the dial was turned 100% of the way to the “coldest” temperature setting. 

Measurements for each trial were conducted in the same fashion as discussed in the 

closed-door refrigerator tests, collecting data overnight. 

The average temperature readings for each of the thermometers across the three trials are 

shown in figure 16 below. Thermometer temperature averages were taken over a 2.5 h 

representative sample of data from each trial. Data from the freezer sensors and 

refrigerator sensors are displayed in two equally-scaled graphs, for ease of comparison.

Fig. 16. Average temperatures recorded with freezer temperature dial set to 50%, 75%, 

and 100% of maximum cold setting. Data from thermometers inside the freezer 

compartment is shown on the left; refrigerator thermometer data is on the right.

As expected, the majority of the freezer sensors recorded colder temperatures when the 

freezer set point was adjusted to lower temperature settings. Comparing the subsequent 

temperature changes of the refrigerator sensors, we can see that certain locations inside 

the refrigerator did record a temperature drop in response to the freezer set point 

adjustment. However, the magnitude of the drop was much smaller than inside the freezer 

compartment. The relationship between freezer temperature change and its impact on the 

refrigeration chamber is only about 10:1, meaning that in order for the refrigerator 

temperature to drop by 1 °C, the freezer must be adjusted a full 10 °C colder. In our brief 

testing, we “maxed-out” the freezer’s cooling capabilities by setting it to its absolute 

coldest temperature. In the graphs above, we can see that even at the maximum coldest 

setting, the interior refrigerator temperature was not significantly impacted, and none the 

sensor temperatures dropped much below 5 °C. 

While the results of this brief investigation should not be taken as a hard and fast rule to 

all dual-zone refrigeration systems, in the case of our unit, it appears that merely 

adjusting the freezer set point control is unlikely to result in major changes in the 

refrigerator compartment temperature, much less cause vaccines to drop below 0 °C. 

However, in the case of a dual-zone unit with only one temperature control dial for both 

refrigerator and freezer compartments, it is much more likely that attempts to lower 

freezer temperature could result in an undesirably low refrigerator temperature. For this 

Freezer sensor temperatures

-19

-18

-17

-16

-15

-14

-13

-12

-11

-10

-9

50% 75% 100%

Average temperature, °C

1F (top back wall)

2F (low back wall)

3F (vial - in tray)

4F (ceiling)

5F (floor)

6F (vial - in box)

7F (glycol - in tray)

8F (mid right wall)

9F (air - top)

10F (glycol - top shelf)

LC_F (top shelf)

LE2 _F (glycol - in tray) Freezer temperature dial setting (% of max cold)

Refrigerator sensor temperatures

0

1

2

3

4

5

6

7

8

9

10

50% 75% 100%

Average temperature, °C

11R (floor)

12R (vial - tray)

13R (air - mid)

14R (lower left wall)

15R (lower right wall)

17R (glycol - in tray, top)

18R (glycol - mid)

19R (glycol - in tray, low)

20R (inside syringe box)

LA_R (low, in tray)

LD_R (glycol - in tray, top)

LE1_R (glycol - low)

LF_R (vaccine box - in tray) Freezer temperature dial setting (% of max cold)
Page 34 of 59

reason, attempting to store both frozen and refrigerated vaccines in a unit with only one 

temperature set point control is not a recommended practice.

Although our results seem to indicate that the freezer temperature in a dual-control dualzone unit can be adjusted without negatively impacting refrigerated vaccine storage, 

perhaps a more important question is whether this type of refrigerator-freezer unit is 

suitable for storing frozen vaccines in the first place. The two graphs in figures 17a and 

17b below show samples of data collected during the first and third case study trials, in 

which the freezer temperature was set to 50% and 100% of the maximum cold output, 

respectively. 

Fig. 17a. (Left) Temperature data collected during midpoint freezer setting trial.

Fig. 17b. (Right) Temperature data collected during maximum cold freezer setting trial. 

Temperature spike due to defrost cycle is also shown. 

The required storage temperature for most frozen vaccines is < -15 °C. This temperature 

is indicated by a red line on each of the graphs. The two monitored vials kept in the 

freezer are shown in bold green and yellow (thermocouples 3 and 6). When the freezer 

was set to the midpoint temperature, vial temperatures stayed out of range for the 

duration of the trial, with average temperature readings of approximately -12 °C. Even in 

the second graph, which shows data taken at the maximum cold setting, the two 

monitored vials consistently show temperatures above -15 °C at the peak of each 

compressor cycle, fluctuating between -19 °C and -13 °C. Even with the control dial set 

to its coldest temperature, the freezer does not appear to maintain suitable frozen vaccine 

storage temperatures. Furthermore, the normal temperature fluctuations associated with 

freezer control (up to 5 °C) are much larger than the corresponding fluctuations in the 

refrigerator compartment. This means that there is very little room for temperature set 

point error. Perhaps even more troubling is the temperature spike associated with the 

defrost cycle, which can be seen in the second graph. During the defrost cycle, one of the 

vials recorded temperatures as high as -6 °C, a major excursion above the specified -15°C 

maximum. Depending on the vaccine manufacturer’s storage specifications, repeated 

exposures to these types of temperature spikes could cause frozen vaccines to suffer a 

loss of viability. Coupled with the fact that this refrigerator-freezer unit simply does not 

appear capable of maintaining -15 °C freezer temperatures, users might question whether 

Midpoint Freezer Setting

-25

-20

-15

-10

-5

0

5

10

0:00 0:28 0:57 1:26 1:55 2:24 Time, h:min

Temperature, °C

Coldest Freezer Setting

-30

-25

-20

-15

-10

-5

0

5

10

15

20

17:00 18:12 19:24 20:36 21:48 23:00 0:12 Time, h:min Temperature, °C

1F (top back wall)

2F (low back wall)

3F (vial - in tray)

4F (ceiling)

5F (floor)

6F (vial - in box)

7F (glycol - in tray)

8F (mid right wall)

9F (air - top)

10F (glycol - top shelf)

11R (floor)

12R (vial - tray)

13R (air - mid)

14R (lower left wall)

15R (lower right wall)

17R (glycol - in tray, top)

18R (glycol - mid)

19R (glycol - in tray, low)

20R (inside syringe box)

LA_R (low, in tray)

LC_F (top shelf)

LD_R (glycol - in tray, top)

LE1_R (glycol - low)

LE2 _F (glycol - in tray)

LF_R (vaccine box - in tray)
Page 35 of 59

the dual-zone units are suitable for any frozen vaccine storage. Because our investigation 

into this issue was limited, we do not intend to completely rule out all dual-zone units for 

frozen vaccine storage. However, users should take extreme caution when relying on 

these types of units for maintaining correct freezing temperatures. Before attempting to 

store vaccines in this type of freezer, users should continuously monitor freezer 

temperature for several days to determine whether the unit consistently maintains an 

acceptable set point temperature. The thermometer used should be placed in the same 

location where vaccines will be stored. During the preliminary freezer evaluation, users 

should also examine whether defrost cycle effects will put stored vaccines at risk. If the 

freezer compartment is deemed suitable for vaccine storage after careful analysis of the 

preliminary data, users may cautiously proceed with loading vaccines. However, they 

should keep their continuous temperature monitoring system in place and frequently reevaluate new data to verify that the proper storage conditions are maintained.

The overall performance of the dual-zone freezer compartment during our testing was not 

suitable for vaccine storage. While adjusting the freezer set point did not appear to 

negatively impact storage temperatures inside the refrigerator chamber, the unit did not 

maintain the desired freezer temperatures, even at its maximum coldest setting. If 

possible, frozen vaccines should be stored in a standalone, freezer-only unit in order to 

avoid the issues we encountered during this case study.

3.2. Pharmaceutical Refrigerator

3.2.1. Effect of loading density

In trials performed using this refrigerator model, vaccine storage density did not appear to 

have a major impact on the refrigerator’s capability to maintain the desired temperature 

range. The photographs below (Fig. 18) show the various levels of packing density that 

were tested.

Fig. 18. Typical packing patterns.
Page 36 of 59

Throughout the course of the study, average thermometer temperatures remained within 

approximately a 2 °C range regardless of whether the refrigerator load was low, medium, 

or high density, as seen in figure 19. All of the thermometers maintained average 

temperatures within the prescribed 2 °C to 8 °C range, with the exception of two

thermocouples (2 and 3), which were both taped to the interior left wall of the unit. Both 

of these thermometers were fairly close to the access port which was used to connect all

of the sensor leads to the data collection system outside the refrigerator. This may have 

been a factor if an appreciable amount of heat leaked through the port. It is also possible 

that the nature of the cooling system and vents in this particular refrigerator model simply 

do not cool the side refrigerator walls to same temperature as the back walls or the rest of 

the refrigerator interior. Thermocouple 4, taped to the top back wall, and thermocouple 9, 

hanging from the refrigerator ceiling, also both recorded thermal excursions not 

experienced by thermometers placed in other areas of the refrigerator. Thermocouples 4 

and 9 maintained average temperatures within the prescribed 2 °C to 8 °C range 

throughout the duration of testing. However, these thermocouples routinely recorded 

point measurements below 2 °C in response to the refrigerator’s cyclic temperature 

control pattern. 

In general, outlier temperature behavior in the pharmaceutical refrigerator seems to be 

correlated to placement of sensors in direct contact with the refrigerator walls or near the 

top cooling vent. Relying on a thermometer placed in one of these areas to adjust the 

refrigerator set point could cause users to mistakenly set the refrigerator temperature too 

warm or too cold. As a result, temperature monitors should be placed in the main body of 

the refrigerator, away from walls and top cooling vent. In addition, users should not place 

vaccines in direct contact with the walls, a practice that is excluded by both manufacturer 

recommendations as well as CDC vaccine storage and handling guidelines. If these 

conditions are met, out of range wall temperatures will not negatively affect stored 

vaccines.
Page 37 of 59

Fig. 19. Average temperature of pharmaceutical refrigerator for all sensors, as a function 

of loading pattern. Labels on the abscissa correspond to entries in the measurement 

matrix of Table 1.

Figure 19 shows the average reading for each thermometer across all of the closed-door 

pharmaceutical refrigerator trials, as well as the periodic door-opening trials. Other than 

the two wall-attached thermocouples discussed previously, it is readily apparent that the 

main body of the refrigerator as well the vaccine vials themselves stayed within the 

prescribed temperature range, regardless of packing density variations. The temperature 

distribution of the remaining thermocouples, including all of those attached to vaccine 

vials, also remained consistent regardless of load density. Over the entire range of testing, 

a total of 45 days, the vertical shift of this distribution was less than one degree. This 

demonstrates that the pharmaceutical refrigerator maintains stable set point control across 

variable packing densities and schemes that are likely to occur in a vaccine storage 

system. As a result, the pharmaceutical refrigerator model appears to be more than 

sufficient for normal vaccine storage.

3.2.2. Effect of packing style

As with the loading density variation, changing the vaccine packing style had little to no 

impact on the temperature stability of the refrigerator, whether plastic trays, cardboard 

boxes, or a combination of both were used to store the vaccines. (See Fig. 20.) The 

measurement results indicate that the pharmaceutical refrigerator model successfully 

maintains proper vaccine storage temperatures range regardless of packaging style.

0

1

2

3

4

5

6

7

8

9

empty

empty II

lowtrays

medtrays

medboxes

highboxes

highboxes II

lowmixed

medmixed

highmixed

highmixed opendoor

medmixed

medmixed opendoor

Average temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air)

6 (vial - floor)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

LA (low, in tray)

LC (mid)

LD (glycol - top)

LE1 (glycol - LH mid)

LE2 (glycol - RH low)

LF (glycol - RH mid)
Page 38 of 59

Fig. 20. Various vaccine storage methods.

3.2.3. Effect of door opening and closing—normal use simulation

The results of the periodic door-opening trials also support the efficacy of the 

pharmaceutical refrigerator model. The only thermocouples which were subjected to 

thermal excursions in response to the door opening were those that were hanging in the 

air (e.g. TC #s 7, 9) or attached to the interior refrigerator walls (e.g. TC #s 2, 3). We 

already saw that several of the wall-attached thermocouples consistently recorded out of 

range temperatures during the closed-door tests. The only significant impact of 

periodically opening the refrigerator door was to cause brief spikes in the refrigerator air 

temperature. All of the remaining thermocouples, whether attached to vials or syringes, 

kept inside glycol-filled bottles or in plastic trays, as well as each of the electronic data 

loggers continued to record temperatures within the specific 2 °C to 8 °C range 

throughout the door-opening trials.
Page 39 of 59

Fig. 21. Door opening trial for the pharmaceutical refrigerator, using a high density 

mixed load.

In figure 21 above, two thermocouples (7 and 9), both hanging in the air, show 

temperature spikes above 8 °C each time the refrigerator door is opened. Both 

thermocouples 9 and 4 also continually drop below 2 °C in response to the refrigerator’s 

cooling cycle. However, this effect is present regardless of whether the refrigerator door 

is opened or kept closed, and as we can see from the remaining thermocouple data, does 

not impact the refrigerator’s ability to keep stored items within the specified temperature 

range. All monitored vaccine vials and thermocouples inside glycol-filled bottles were 

maintained at temperatures around 5 °C in spite of repeated exposure to room 

temperature air. Figure 22 below shows the data recorded by these sensors only.

Fig. 22a. (Left) Door opening trial for the pharmaceutical refrigerator. Only 

thermocouples monitoring vial temperatures or inside glycol-filled bottles are shown.

Fig. 22b. (Right) Temperature response of same selected thermocouples, recorded 24 h 

later and with refrigerator door kept closed.

0

1

2

3

4

5

6

7

8

9

10

11

0:00 0:15 0:30 0:45 1:00 1:15 1:30 1:45 2:00

Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air)

6 (vial - floor)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

4.2

4.4

4.6

4.8

5

5.2

5.4

5.6

5.8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 1:45 2:00 Duration of measurement, h:min Temperature, °C

6 (vial - floor)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

4.2

4.4

4.6

4.8

5

5.2

5.4

5.6

5.8

0:00 0:15 0:30 0:45 1:00 1:15 1:30 1:45 2:00 Duration of measurement, h:min Temperature, °C

6 (vial - floor)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)
Page 40 of 59

Figure 22a shows the selected thermometer responses to repeated door opening. Figure 

22b shows the closed-door, equilibrium temperature behavior of the same thermometers. 

The vertical scale of each of the graphs is only 1.6 °C. From this, it is clear that the 

pharmaceutical refrigerator preserves excellent temperature stability during normal use 

patterns. The net effect of opening the refrigerator door on stored vaccine vial 

temperature is extremely small. Only vial number 20, which was kept in an open tray 

rather than contained in a box or its original packing, showed any noticeable temperature 

spike each time the door was opened. Even then, this temperature spike was less than 

0.5 °C. Several other vials show either a gradual temperature increase or decrease over 

the course of the door opening trial, depending on their location in the refrigerator. 

However, these changes are extremely small, on the order of 0.2 °C or less. As the 

pharmaceutical refrigerator has already proven to possess excellent temperature set point 

control, it is highly unlikely that such miniscule temperature changes cause damage to 

stored vaccine. 

The table below shows the different door opening temperature changes of all the 

thermometers in the high and medium density load trials. In this case, the temperature 

change is defined as the difference between the average temperature recorded during the 

closed door trial and the average temperature from the door-opening trial with the same 

loading configuration. No trials using water bottles as a temperature ballast were 

performed with the pharmaceutical refrigerator. In tests of the other refrigerator models, 

we filled the refrigerator doors with water bottles. Because the pharmaceutical model we 

tested had sliding glass doors which could not be used to store water bottles, we chose 

not to perform any trials using water bottles in order to keep our measurement methods 

consistent. It would be possible for users to place water bottles along the refrigerator 

walls or on the floor level to act as a thermal ballast. The purpose of a water bottle 

temperature ballast is to add extra thermal mass, thereby making the refrigerator less 

susceptible to temperature changes. However, throughout our tests of the pharmaceutical 

model, we saw that the unit was not significantly affected by varying load densities (Fig. 

19). In practice, adding water bottles would likely produce an effect similar to adding a 

higher density vaccine load. Because the pharmaceutical model performed equally well 

under both high and low density packing schemes, the addition of water bottles would 

probably not have a major impact on refrigerator performance. Furthermore, the 

pharmaceutical refrigerator we tested featured air vents along the entire inner back wall 

of the unit. In this case, if users attempted to improve the system by placing water bottles 

along this wall, they might reduce air circulation and negatively impact refrigerator 

performance.
Page 41 of 59

Table 8. Temperature changes during door-opening tests (all values in degrees Celsius).

Table 8 above provides further evidence that the pharmaceutical refrigerator model is 

largely unaffected by repeatedly opening and closing the refrigerator door. The majority 

of the sensors recorded a change of less than one tenth of a degree between the dooropening and closed door trials, and the largest change was still less than 0.5 °C. 

Compared to other refrigerator models we tested, the pharmaceutical refrigerator resisted 

temperature change surprisingly well during trials in which the refrigerator door was left 

cracked open several inches for 1 h, to simulate an employee failing to completely close 

the door. Table 9 below shows the amount of time elapsed once the door was opened 

until the monitored vials exceeded the allowed maximum temperature of 8 °C.

Table 9. Time after opening door until vial temperature exceeded 8 °C. 

*Although 8 °C limit crossed, maximum temperature was less than 8.1 °C

During high density load trial, all of the vials remained within the specified temperature 

range despite the door being left ajar for 60 min. In the medium density trial, nearly all 

the vials remained within range, except for vial 10 which exceeded 8 °C after 35 minutes. 

Sensor Name/Location High Density Mixed Medium Density Mixed

1 (top wall) -0.2842 -0.1718

2 (mid wall) -0.0179 0.0667

3 (lower wall) -0.0526 0.1423

4 (top back wall) -0.4274 -0.3139

5 (air) -0.1218 -0.0091

6 (vial - floor) -0.2561 -0.1656

7 (air) 0.0923 0.0957

8 (air) -0.0012 -0.0371

9 (air - top) -0.1839 -0.0462

10 (in box) 0.0282 0.0557

11 (in box) 0.0222 0.0356

12 (vial - mid) -0.2008 -0.1203

13 (syringe in box - top) 0.0537 0.0330

14 (inside tray) -0.1264 0.0206

15 (back of tray) 0.0034 0.0198

17 (glycol - low) -0.0185 0.0017

18 (glycol - mid) 0.0789 0.0440

19 (glycol - top) 0.0766 0.0598

20 (vial - low) 0.0649 -0.0401

LA (low, in tray) 0.0665 0.0930

LC (mid) -0.1563 0.1215

LD (glycol - top) -0.0018 -0.0407

LE1 (glycol - LH mid) -0.1207 -0.1000

LE2 (glycol - RH low) 0.0545 0.1438

LF (glycol - RH mid) 0.0517 0.1625

Name and Location High Density Mixed Medium Density Mixed

(minutes) (minutes)

vial 10 (inside original packaging) did not exceed 35

vial 20 (in tray, lower shelf) did not exceed 53*

vial 11 (inside original packaging) did not exceed 57*

vial 13 (syringe in box - top) did not exceed did not exceed

vial 12 (inside cardboard box) did not exceed did not exceed

vial 6 (inside box, floor level) did not exceed did not exceed
Page 42 of 59

However, even this vial only reached a maximum temperature of 8.7 °C at the end of the 

trial. Vials 20 and 11 both exceeded the upper limit towards the end of the hour long test, 

but by less than a tenth of a degree. In either case, these small excursions are not likely to 

impact the potency of the vaccines. The differences between the high density and 

medium density trials can probably be attributed to the additional thermal mass in the 

high density trial contributing to resist temperature change, much in the same way that 

the water bottle temperature ballast worked in our tests of the other refrigerators.

Overall, the pharmaceutical refrigerator model performed very well in both the dooropening and door left ajar trials. The refrigerator exhibited excellent temperature control, 

compensating for the less than ideal operating conditions by adjusting the cooling output 

to maintain proper vaccine storage temperatures.

3.2.4. Effect of Increasing Room Temperature

To determine whether room temperature fluctuations impact pharmaceutical 

refrigerator’s ability to maintain its set point temperature, we performed three trials in 

which the room temperature was varied between 24 °C and 29 °C. We can analyze the 

results in the same manner as in the dual-zone refrigerator trials, by comparing the room 

temperature probe readings from logger LD to the refrigerator probe readings from LD, 

LE1 and LE2. This analysis is summarized in table 10 below.

Table 10. Refrigerator probe temperature change relative to room temperature change 

(°C)

Table 10 shows the temperature change recorded by each of the three refrigerator data 

logger probes scaled to the change in ambient temperature recorded by external probe. 

So, for example, during the High Density Mixed with Bottles I trial, logger LE1 recorded 

a temperature decrease of 0.01 °C for every one degree increase in room temperature.

As with trials using the dual-zone refrigerator, the pharmaceutical refrigerator model does 

not show correlated interior vs. exterior temperature behavior. Again, the inherent 

complexity of this relationship prevents us from making definitive statements based on a 

brief study of the issue. However, we can note that the degree by which the internal 

refrigerator temperature is affected by external room temperature changes is even smaller 

in the pharmaceutical refrigerator than in the dual-zone model. All three data logger 

probes recorded a temperature change of less than ± 0.02 °C per degree rise in room 

temperature. This effect is so small that it may be a product of extraneous factors rather

the changing room temperature. If we assume these changes are in fact due to room 

temperature variation and that the relationship is linear, we would need to vary 

environmental conditions by 50 °C just to see a one degree change in internal refrigerator 

temperature.

Logger Name High Density Mixed I High Density Mixed II Medium Density Mixed

LD -0.02 -0.02 -0.02

LE1 -0.01 -0.02 0.02

LE2 0.00 0.01 -0.01
Page 43 of 59

The pharmaceutical refrigerator’s performance in these trials indicates that it should be 

able to withstand even larger ambient temperature changes than the dual-zone refrigerator 

while maintaining proper vaccine storage conditions in its interior. However, it must be 

emphasized that because our study only monitored the effects of a 5 °C room temperature 

change, we may not have captured additional thermal effects that could occur during

much larger room temperature changes. The use of a continuous temperature monitoring 

system will allow workers to immediately identify any problem temperature effects 

resulting from different environmental conditions. 

3.2.5. Effect of a Power Outage

To observe what occurs following a power outage, we performed two trials in which the 

closed refrigerator was unplugged and monitored overnight. In both trials, all of the 

thermometers recorded a fairly steep increase in temperature that slowed down slightly 

over time. All of the thermometers, including those attached to vaccine vials, exceeded 

the allowed maximum temperature within 1:46 h:min for the medium density trial, and 

within 2:19 h:min during the high density trial. Figure 23 below shows the temperature 

readings of all of the thermometers during the high density load power off trial. The 

sudden drop in temperature following the peak corresponds to the point at which the 

refrigerator was plugged back in.

Fig. 23. Thermometer response during a power-outage event. High density mixed load 

trial.

The next graph (Fig. 24) shows the data collected starting from the time that the 

refrigerator was unplugged. The dashed red line indicates the 8 °C upper limit, and the 

blue dashed line shows the 2 °C minimum.

0

2

4

6

8

10

12

14

16

18

20

22

0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00 26:00

Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air)

6 (vial - floor)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

LA

LC

LD

LE1

LE2

LF
Page 44 of 59

Fig. 24. Expanded view of thermometer response during a power-outage event. High

density mixed load trial.

To determine the required response time to preserve vaccine viability during a power 

outage situation, we examined the amount of time elapsed from the point that the 

refrigerator was unplugged until the thermometers attached to vials exceeded 8 °C. This 

information is reported in Table 11 below. 

Table 11. Time after power-off until vial temperature exceeded 8 °C.

From this data, we can immediately see that vials kept in the powered-off pharmaceutical 

refrigerator were subjected to out-of-range temperatures much more quickly than in trials 

of the other refrigerator models. All of the vials exceeded 8 °C in less than 2.5 h, and in 

some cases, less than 1 h, depending on vial storage method. This does not leave a very 

large window of time for clinic workers to recognize the occurrence of a power outage 

and implement a backup storage method before vaccines are impacted by the prolonged 

exposure to temperatures above the upper limit. While the pharmaceutical refrigerator we 

studied appeared to perform exceptionally well as a vaccine storage unit across the range 

of tested criteria, including different loading configurations, variable room temperature 

conditions, and operation with the refrigerator door left open, the results of the power 

outage tests identify a significant limitation of this refrigerator model. The doors of the 

0

2

4

6

8

10

12

0:00 0:30 1:00 1:30 2:00 2:30

Time elapsed since power off, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air)

6 (vial - floor)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)

Name and Location High Density Mixed Medium Density Mixed

(h:min) (h:min)

vial 20 (in tray, lower shelf) 1:14 0:45

vial 13 (syringe in box - top) 1:12 0:50

vial 11 (inside original packaging) 1:40 1:01

vial 10 (inside original packaging) 1:50 0:58

vial 6 (inside box, floor level) 2:10 1:15

vial 12 (inside cardboard box) 2:19 1:46
Page 45 of 59

pharmaceutical refrigerator model used in our tests were the sliding glass variety. Some 

users may prefer glass doors since they are able to easily inventory refrigerator contents 

without exposing vaccine vials to room temperature air. However, a major known 

drawback to the glass doors is that they lack the insulation provided by a standard opaque 

door. This clearly becomes an issue in the event of a power outage. Once the cooling unit 

inside the refrigerator cuts out, warm ambient air is slowly conducted into the refrigerator 

interior, eventually warming the contents until the temperature inside and outside the unit

is in equilibrium. If the refrigerator door consists of only thin glass panels and rubber 

gasket, heat is conducted to the interior much more quickly than if it had to travel through 

a heavily-insulated, solid refrigerator door.

Even so, the limitations of glass refrigerator doors during a power outage event should 

not discount pharmaceutical refrigerator models as viable vaccine storage units. First of 

all, many pharmaceutical grade models feature solid, insulated-type refrigerator doors. 

These units are likely to have robust temperature stability, similar to our tested unit, with 

the added benefit of increased resistance to heating during outage events. Regardless of 

the glass doors issue, it is perhaps most important for each individual provider office to 

evaluate their own circumstances and determine which of many possible risks are the

most critical to their situation. For example, the average pharmaceutical grade 

refrigerator user may have different office and environmental conditions than a provider 

office with a standard household refrigerator. Hospitals and higher budget clinics are 

more likely to have access to the pricier pharmaceutical refrigerators, while smaller 

budget operations are likely to choose less expensive household models. The differences 

between these two settings are likely to extend beyond just their vaccine storage 

refrigerator of choice. The high-budget, modern hospital may have an excellent backup 

generator system in place to keep equipment running through power outages. In addition, 

the hospital has workers on duty 24-7, so risk the of a brief power outage going 

undetected is low. By contrast, a private practice operating out of a leased building might 

not have as much control over their power supply. This type of practice is also less likely 

to have workers on-site at all times, so an overnight power outage poses a greater risk.

While the glass door pharmaceutical refrigerator model did not resist thermal excursions 

during our power outage trials as well as some of the household models, the needs of the 

end user should be carefully evaluated before making blanket statements about which 

refrigerator is better based on a single criteria. For some settings, the single greatest threat 

to drug potency may be the direct result of high vaccine demand, such that the storage 

refrigerator door is constantly opened to retrieve vaccines. In this case, choosing the 

pharmaceutical refrigerator for its ability to maintain stable temperatures despite these 

conditions makes sense, even if it is at the expense of a more insulating door designed for 

resistance to power outages. 

Consistent with the results from other trials, we observed that vials contained in boxes or 

other packaging materials resisted thermal excursions for a longer time than unpackaged 

vials. This occurs because additional time is required for heat to transfer through the 

exterior packaging material before the vial temperature is affected. 
Page 46 of 59

Fig. 25. Recovery after restoration of power for a pharmaceutical refrigerator.

In both trials, the pharmaceutical refrigerator reached its pre-outage equilibrium 

temperature state approximately 7 h after being powered. 

3.2.6. Defrost Cycle in the Pharmaceutical Refrigerator

The pharmaceutical refrigerator model we tested features a defrost heater which is 

activated each time the refrigerator compressor is cycled off. According to the 

manufacturer, the defrost cycle will not have any discernible effect on the chamber 

temperature. Throughout the range of testing, we did not detect any interior temperature 

effects associated with the defrost cycle, nor did we observe accumulated frost. In the 

event of frost accumulation on the evaporator, which may occur under high-humidity 

conditions, a forced defrost cycle may be initiated.

3.2.7. General Stability of Vial Temperature and Suitability of Pharmaceutical

Refrigerator Model for Maintenance of Vaccine Storage Conditions

Our results indicate that the pharmaceutical refrigerator model is suitable for vaccine 

storage. Vaccine vial temperatures remained within the specified 2 °C to 8 °C range 

throughout all of the packing variation trials, as well as during the 15 second door 

opening trials. Furthermore, average vial temperatures varied by less than 1.5 °C 

throughout this entire range of testing. The pharmaceutical refrigerator exhibits excellent 

long-term temperature stability, even under varying conditions. 

0

2

4

6

8

10

12

14

16

18

20

22

0:00 1:00 2:00 3:00 4:00 5:00 6:00

Time elapsed since power on h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air)

6 (vial - floor)

7 (air)

8 (air)

9 (air - top)

10 (in box)

11 (in box)

12 (vial - mid)

13 (syringe in box - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low)
Page 47 of 59

3.2.8. Best and Worst Locations for Vial Storage in the Pharmaceutical Refrigerator

Throughout the course of the closed-door pharmaceutical refrigerator trials, vaccine vials 

remained within the desired temperature range regardless of their location in the 

refrigerator. This refrigerator model is purpose-built for vaccine storage. As a result, it 

features enhanced temperature set point control and more a sophisticated ventilation 

system than is included in most household refrigerator models. Because of this, vials 

stored in different areas of the pharmaceutical refrigerator were kept within a narrow 

temperature range of 1.5 °C or less. 

However, based on the results of the door opening and power-off trials, it appears that 

some storage methods and locations within the refrigerator may provide slightly better 

thermal stability than others. Just as we saw in trials with other refrigerator types, vials

stored inside thermally isolated containers experienced less temperature disruption during 

normal, periodic door-opening operation than unpackaged vials kept in trays. In the 

pharmaceutical refrigerator trials, this translated to an unpackaged vial experiencing a 

temperature spike of 0.4 °C each time the refrigerator door was opened, whereas the vials 

in boxes showed no discernible temperature spike. Similarly, during the power outage 

trials, the first vial to exceed 8 °C was kept unpackaged and in an open tray, while the last

vial to exceed the limit was stored inside a corrugated cardboard box.

Overall, the pharmaceutical refrigerator proved to be less resistant to thermal excursions 

during a power outage than some of the household refrigerator models tested. This can 

mostly likely be attributed to the pharmaceutical model’s glass sliding doors. The glass 

doors transfer heat to the interior of the refrigerator more quickly than more insulated 

doors. As a result, vaccines stored in a glass-door pharmaceutical refrigerator may be 

more susceptible to damage during a power outage event than those stored in a household 

refrigerator with well insulated doors. On the other hand, we found that the 

pharmaceutical model is able to consistently maintain vaccine storage temperatures with 

the door left open for prolonged periods of time. Because of this, when using a glass-door 

pharmaceutical refrigerator, it might be advantageous to thoroughly package vaccines in 

boxes or insulating material. If workers spend extra time with the refrigerator door open 

while getting vials in and out of the packaging, it is not likely to impact vaccines 

negatively because of the refrigerator’s robust temperature control. At the same time, the 

extra packaging will provide an additional layer of protection against heat transfer from 

ambient air in the event of a power outage.

Throughout testing of the pharmaceutical refrigerator, we intentionally kept one vial on 

the floor level of the refrigerator, below the bottom wire shelf. The manufacturer 

instructions specifically state not to store items on this level. However, the vial placed on 

the floor remained within the specified temperature range across all trials, and its 

temperature behavior mapped that of vials stored in other areas for most of the trials. This 

vial did tend to record colder temperatures than the rest of the vials, but the difference 

was generally less than 1 °C. So while we do not explicitly recommend vaccine storage 

in this location, if workers inadvertently placed vials on the floor level, or were forced to, 

for lack of other space, the vaccines probably would not be negatively affected.
Page 48 of 59

The only thermocouples that showed significant deviations from the tightly-controlled, 

4 °C to 5 °C temperature distribution recorded by the majority of the thermometers were 

those attached to the refrigerator walls. In particular, two thermocouples on the upper 

refrigerator walls consistently recorded temperatures above 8 °C across all of the trials. 

Our testing did not include the temperature behavior of vials placed in direct contact with 

the refrigerator walls, but it is possible that such contact could cause the vials to 

experience thermal excursions as heat if conducted from the walls. By keeping stored 

vaccines several inches away from the walls, workers can avoid any such nonstandard 

temperature effects.

3.2.9. Best and Worst Methods of Monitoring Vial Temperature

As with the dual-zone refrigerator results, we can determine the suitability of various 

methods for monitoring vial temperature in the pharmaceutical refrigerator by comparing 

the readings of vial-attached thermocouples to readings of other thermometers placed 

throughout the refrigerator.
Page 49 of 59

Fig. 26. Response of thermometers with different mounting methods.

Thermometers Attached to Vaccine Vials

0

1

2

3

4

5

6

7

8

9

0:00 0:05 0:10 0:15 0:20 0:25 0:30

Duration of measurement, h:min Temperature, °C

6 (vial - floor, in box)

10 (vial - inside packaging)

11 (vial - inside packaging)

12 (vial - mid, in box)

13 (syringe in box - top)

20 (vial - low, in tray)

Thermometers Attached to Refrigerator Walls

0

1

2

3

4

5

6

7

8

9

0:00 0:05 0:10 0:15 0:20 0:25 0:30 Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

Thermometers Inside Glycol-filled Bottles

0

1

2

3

4

5

6

7

8

9

0:00 0:05 0:10 0:15 0:20 0:25 0:30 Duration of measurement, h:min Temperature, °C

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

LD (glycol - top, tray)

LE1 (glycol - mid, shelf)

LE2 (glycol - low, tray)

LF (glycol - mid, tray)

Thermometers Hanging in Air

0

1

2

3

4

5

6

7

8

9

0:00 0:05 0:10 0:15 0:20 0:25 0:30

Duration of measurement, h:min Temperature, °C

5 (air)

7 (air)

8 (air)

9 (air - top)

Thermometers in Trays or on Shelves

0

1

2

3

4

5

6

7

8

9

0:00 0:05 0:10 0:15 0:20 0:25 0:30 Duration of measurement, h:min Temperature, °C

14 (inside tray)

15 (back of tray)

LA (low, tray)

LC (mid, shelf)

Medium Density Mixed - All Thermometers

0

1

2

3

4

5

6

7

8

9

0:00 0:05 0:10 0:15 0:20 0:25 0:30 Duration of measurement, h:min Temperature, °C

1 (top wall)

2 (mid wall)

3 (lower wall)

4 (top back wall)

5 (air)

6 (vial - floor, in box)

7 (air)

8 (air)

9 (air - top)

10 (vial - inside packaging)

11 (vial - inside packaging)

12 (vial - mid, in box)

13 (syringe in box - top)

14 (inside tray)

15 (back of tray)

17 (glycol - low)

18 (glycol - mid)

19 (glycol - top)

20 (vial - low, in tray)

LA (low, tray)

LC (mid, shelf)

LD (glycol - top, tray)

LE1 (glycol - mid, shelf)

LE2 (glycol - low, tray)

LF (glycol - mid, tray)
Page 50 of 59

The pharmaceutical refrigerator maintained vaccine vials within a very narrow 

temperature window throughout the course of our study. During normal, closed-door 

operation, as shown in figure 26 above, vial temperature variation due to both refrigerator 

compressor cycling and varying storage location was less than 1 °C. Even during door

opening trials, vial temperatures did not fluctuate by more than 1 °C, regardless of how 

the vials were packaged or where they were stored. Examining the above graphs, we can 

essentially divide the remaining thermocouples and data loggers into two groups: 

thermometers that closely followed the thermal behavior of the vial-attached 

thermocouples, and thermometers that recorded very different temperature behavior than 

the monitored vials.

Good Locations for Temperature Sensors

Thermometers that closely matched vial temperatures were stored in trays or on 

refrigerator shelves (TC #s 14, 15, 17, 18, 19; data loggers LA, LC, LD, LE1, LE2, LF). 

Like the monitored vaccine vials, the temperature distribution of these thermometers 

stayed centered about 4.5 °C to 5.5 °C throughout the range of testing. Whether or not the 

thermometer had a probe inside a glycol-filled bottle did not impact its ability to predict 

vial temperature to within a desirable range, which we define as ±1 °C. The thermometers 

with probes in glycol-filled bottles showed nearly constant temperature profiles over 

time, similar to the data collected by the vials stored inside thermally-isolating boxes or 

packaging. By contrast, the standalone data loggers with built-in probes as well as the

thermocouples attached directly to trays both showed small temperature fluctuations 

comparable to the variations recorded by the unpackaged vial stored in a tray. Because 

the pharmaceutical refrigerator appears to maintain its contents within a very small, 

consistent temperature window (±1 °C), placing temperature monitors anywhere inside 

the refrigerator where vaccines are normally stored produces readings that are 

representative of actual vial temperatures, regardless of whether the monitors are kept on 

a shelf or in a tray, and with or without a probe in a glycol-filled bottle.

Unacceptable Locations for Temperature Sensors

Thermometers attached to refrigerator walls or hanging in the air (TC #s 1, 2, 3, 4, 5, 7, 8, 

9) were poor indicators of actual vaccine vial temperature. While the pharmaceutical 

refrigerator we tested excelled at keeping its contents within a small, stable temperature 

band, the refrigerator walls and air experienced large temperature fluctuations 

(amplitudes of 1.5 °C to 6 °C or greater) corresponding to the refrigerator cooling cycle.

In addition, two thermocouples taped to the interior left wall of the unit, (2, 3),

consistently recorded mean temperatures between 7 ° and 9 °C, while vial temperatures 

remained around 5 °C. Relying on a thermometer attached anywhere to the 

pharmaceutical refrigerator’s interior walls or hanging in the airspace is clearly a poor 

choice for vaccine temperature monitoring. Many of these thermometers repeatedly 

experienced thermal excursions outside the required 2 °C to 8 °C storage temperature 

range, while vaccine temperatures remained nearly constant between 4.5 °C and 5.5 °C. 

Based on these results, thermometers used for vaccine temperature monitoring should not 

be kept in contact with refrigerator walls or hung in the air. This practice can result in 
Page 51 of 59

false out-of-range temperature alarms, leading to unnecessary disposal of still-viable 

vaccine or adjustment to an improper set point temperature.

4. DATA LOGGER EVALUATION 

Throughout the course of trials performed on both refrigerators, we tested the 

performance of several electronic temperature loggers along with the thermocouples. 

The data loggers tested, labeled LA, LC, LD, LE1, LE2, and LF are described in Table 3. 

We wished to evaluate the data loggers’ effectiveness at monitoring vial temperature. 

At present, many VFC clinics use digital display, analog, or liquid in glass thermometers 

to monitor the temperature of their vaccine storage refrigerators. They are only required 

to check and record the temperature readings of these thermometers twice each working 

day. Based on the results of our study, a number of factors, including the frequency of 

refrigerator door opening, refrigerator defrost cycles, room temperature increases, and 

power outages, could cause an employee to obtain a false representation of the actual 

refrigerator and/or vial temperature based on this methodology. For example, an 

overnight power or AC outage could cause the refrigerator and corresponding vaccine 

temperatures to rise outside of the viable range. If the outage is corrected before the next 

morning, the refrigerator may return to its cooled equilibrium state by the time employees 

come to work and check their temperature monitoring devices. In this case, they would 

fail to detect that the vaccine vials exceeded the allowed temperature range overnight, 

rendering them potentially unusable. This type of situation could pose a serious danger to 

clinic patients, since they could be unknowingly administered an ineffective vaccine. 

In the same light, other conditions could cause employees to record a “false positive” 

temperature, and discard vaccines unnecessarily. Depending on a thermometer’s 

accuracy, its placement inside the refrigerator, and the time that it is checked, its reading 

may or may not correspond to actual vaccine vial temperature. Some thermometers are 

more sensitive to temperature fluctuations than the fluid-filled vaccine vials, which have 

a larger thermal mass. If an employee happened to read one of these thermometers during 

the refrigerator’s standard defrost cycle, which produces a brief air-temperature spike, he 

or she might determine that the vaccines had exceeded the allowed temperature limit. In 

our experiments, we found that the actual vial temperatures were not greatly affected by 

the defrost cycle, but that some of the other thermometers indicated significant 

temperature increases. Because of these issues, we believe it is necessary for vaccine 

storage refrigerators to have in place continuous data loggers to obtain truly 

representative, reliable readings of actual vaccine temperatures.

In addition to providing continuous temperature data, the widespread use of data loggers 

in VFC clinics would reduce the overall workload involved in refrigerator temperature 

monitoring. At present, VFC workers must manually record refrigerator temperature two 

times a day. The VFC coordinator is then responsible for reviewing hand-written 

temperature logs to determine if any lapses occurred. Electronic data loggers connect to a 

computer via USB and can quickly download data through easy-to-use software 
Page 52 of 59

interfaces. Logger data for multiple days are automatically summarized into spreadsheets 

and graphs in a matter of minutes, relieving the VFC coordinator of all data entry and 

analysis work. As a result, we believe that the use of data loggers for vaccine temperature

monitoring would not only improve the reliability this process, but also make it 

significantly more efficient.

All of the data loggers we tested produced temperature data close to that of the vialattached thermocouples. Throughout our study, we saw that refrigerators do not maintain 

a completely uniform temperature profile throughout their interiors, but that the 

temperature varies according to location. As such, it would be impossible for a single 

data logger to capture the temperatures of all of the vials stored throughout the 

refrigerator at any given time. Instead, a logger used to monitor stored vaccines should 

produce data that is representative of vial temperature behavior, modeling temperature 

trends over time and within 0.5 °C to 1 °C of the range of vial temperatures.

During our study of the pharmaceutical and dual-zone refrigerator models, we saw that 

certain data loggers modeled vaccine vial temperature more closely than others. 

However, all of the data loggers consistently recorded temperatures to within 1 °C of 

nearby vaccine vial temperatures over the entire range of tests. 

Fig. 27. Sample of temperature data from a closed door dual-zone refrigerator trial, 

comparing vial temperatures and data logger measurements.

Figure 27 above shows a selection of data from a dual-zone refrigerator trial. 

Temperatures recorded by thermocouples attached to vaccine vials are shown as solid 

color lines, and electronic data logger readings are shown as triangular markers. Note that 

vertical span of data is less than 2 °C. From this, we can see that all of the loggers 

reported values closely matching actual vial temperatures. The differences between 

3.5

4

4.5

5

5.5

6

6.5

0:00 0:15 0:30 0:45 1:00 1:15 1:30

Duration of measurement, h:min Temperature, °C

6 (vial - crisper drawer)

10 (vial - mfr packaging)

11 (vial - mfr packaging)

12 (vial - mid, in box)

13 (vial - top)

14 (inside tray)

20 (vial - low)

LA (low, tray)

LC (mid, shelf)

LD (glycol - top, tray)

LE1 (glycol - mid, shelf)

LE2 (glycol - low, tray)

LF (glycol - mid, tray)
Page 53 of 59

individual vaccine vial and data logger temperatures are relatively small, and are most 

likely caused by location-specific temperature gradients or varying storage method inside 

the refrigerator. Our primary concern is maintaining the refrigerator and its contents 

between 2 °C and 8 °C, so these temperature differences (1 °C or less) are not likely to be 

a major issue. 

In order to effectively monitor vaccine stores, electronic data loggers must successfully 

capture any thermal excursions that occur under variable conditions such as repeatedly 

opening the refrigerator door, initiation of an automated defrost cycle, or a power outage 

event. Overall, we saw that the tested loggers replicated the temperature responses of the 

vial-attached thermocouples during these events, but to varying degrees of sensitivity. 

Logger sensitivity is affected by both its placement inside the refrigerator as well as the 

inherent design properties of the device. The various data logger models we tested can be 

divided into one of two main design types. The first type is a standalone unit with a builtin temperature sensor (data loggers LA, LC). In this case, the entire unit is placed inside 

the refrigerator for the duration of the measurement period, and then removed in order to 

connect and download the data to a computer. The second type of data logger we tested 

featured a main logger unit with an external temperature probe attached via cable (data 

loggers LD, LE1, LE2, LF). With this type of logger, we were able to keep the main unit 

outside of the refrigerator while the temperature probe was positioned inside the 

refrigerator. In order to download recorded measurements, the main unit could be 

detached from the probe and connected to a computer without opening the refrigerator 

door and removing the temperature sensor to ambient conditions. Throughout our study, 

the external probes of each of these devices were kept inside glycol-filled bottles. This 

provided additional thermal mass, similar to that of the liquid vaccine inside glass vials. 

As expected, the standalone data logger units responded to temperature changes under 

varying conditions more quickly than the external probes kept in glycol. This is because 

it takes longer for the entire mass of the glycol to change temperature than it does for the 

air surrounding a standalone data logger unit.

In terms of sensitivity to temperature change, we did not find one logger type to be 

especially advantageous over the other. For example, during the door opening trials, 

neither logger type registered much of a temperature spike each time the door was 

opened, most likely because the net internal temperature change of the refrigerator was 

both small and brief. During these trials, we found that the vaccine vials kept in boxes or 

their original packaging also did not record temperature spikes in response to the door 

opening. Only unpackaged vials kept directly on a shelf or in an open tray experienced 

noticeable temperature fluctuations in response to opening and closing the refrigerator 

door (e.g. TC #20).

In addition, the performance of loggers of each type varied between individual units. Of 

the loggers with external probes kept in glycol, logger LD tended to record temperature 

fluctuations consistent with the behavior recorded by packaged vaccine vials. By 

contrast, logger LF consistently measured an almost flat line temperature profile. 

Whether these types of variations are due to differences in device resolution, probe 

material, device placement within the refrigerator, or some other combination of factors 
Page 54 of 59

is unclear. Comparing the two standalone data logger units (LA, LC), we saw that LC 

was consistently more sensitive to temperature fluctuations than LA. In this case, the 

discrepancy can most likely be attributed to the materials that the loggers are constructed 

from. Logger LA features a heavy-duty metal sheath capable of enduring high 

temperatures and total submersion, while LC is mainly composed of plastic. As a result, 

the larger thermal mass of LA means that the logger takes a longer time to experience 

temperature changes. In this application, we found that the heavy-duty construction of 

LA may be a disadvantage. Each time we removed logger LA from the refrigerator to 

download data, we found that it required as much as 3 or 4 h cool down once it was 

placed back inside the refrigerator. During this time period, the logger is not very useful 

as a vial temperature monitoring device. By contrast, data logger LC, with its lighter 

plastic exterior, required approximately one hour of equilibration time once it was taken 

from room temperature and placed inside the refrigerator. 

During the simulated power outage trials, all of the data loggers recorded rates of 

temperature increase similar to that experienced by the vaccine vials. The length of time 

before the data loggers exceeded 8 °C generally fell within 15 min of the time that nearby 

vials also exceeded 8 °C. In general, if the data loggers are stored in the same fashion as 

the vaccine vials, whether in trays or inside cardboard boxes, and in the same part of the 

refrigerator, they will most likely give readings within their resolution (Table 3) of the 

actual vial temperatures. However, during a power outage, unless the problem can be 

remedied within an hour or two, the vaccines are likely to become unusable. In this case, 

having a continuous data logging system in place is critical to maintaining confidence in 

vaccine supply efficacy. Without a continuous temperature monitoring system, workers 

might have no way to tell if a temporary outage occurred outside of working hours, 

possibly damaging vaccines. All of the data loggers we tested clearly demonstrated the 

temperature effects of the power outage on a similar time scale to the monitored vaccine 

vials. As such, any of the data loggers we tested could be used to determine whether 

vaccine supplies have been subjected to inappropriate storage temperatures.

Although all of the data loggers we tested performed in a manner acceptable for vaccine 

temperature monitoring and management, we found that some loggers featured design 

characteristics that made them more efficient or user friendly than others. For example, 

the loggers featuring external temperature probes (LD, LE1, LE2, LF) eliminate the need 

to wait for thermal equilibrium after replacing a room temperature logger back into a 

refrigerator, since the external probes could be kept in a glycol filled bottle inside the 

refrigerator, while the main device unit was kept outside of the refrigerator. To download 

data, we simply detached the main unit from the cable, leaving the probe inside the 

refrigerator. The main unit was then connected to a USB data collection cradle, which 

allowed us to transfer the data to a computer. The main unit of each of these loggers also 

featured a readout display, enabling users to visually check current refrigerator conditions 

without having to open the door or download data. In addition to its external probe kept 

inside the refrigerator, logger LD also featured an internal sensor inside its main readout 

unit. If the main unit is kept outside the refrigerator, this device can simultaneously 

monitor room temperature and refrigerator temperature. Logger LF was enabled for 

wireless data transmission and download, a feature that could be especially useful in 
Page 55 of 59

circumstances like an overnight or weekend power outage. Users can configure the

device so that real-time refrigerator conditions can be checked from any computer with 

an internet connection. With a system like this in place, VFC providers could detect and 

deal with any potential refrigeration temperature problems immediately, rather than 

discovering ruined vaccines after the fact.

Overall, the tested data loggers’ performance seems to be sufficient for monitoring 

vaccine temperatures. The most important factor for temperature monitoring accuracy is 

the placement of the device inside the refrigerator. Regardless of the type of data logger 

chosen, it should be stored in the same manner as the vaccines in order obtain the most 

accurate readings. Simply placing a data logger directly on a refrigerator shelf is not 

likely to give the most accurate representation of vial temperatures. If the vaccine vials 

are stored inside trays or boxes, the data loggers should be stored in the same way.

In the next phase of our vaccine storage and handling study, we will perform a more 

detailed investigation of electronic thermometers used for cold-chain measurements. In 

this investigation, we will test a minimum of five data logger thermometers for out-ofbox performance, evaluating the manufacturer specified accuracy over the temperature 

range of 0 °C to 10 °C. In addition, we will quantify the stability of each logger over a six 

month period and determine the proper use within a vaccine storage system so that 

temperature measurements reflect vaccine vial temperatures. 
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5. SUMMARY

Table 9 below summarizes the results obtained in this study.

Table 9. Comparison of refrigerator performance in response to tested criteria.

COMPARISON OF REFRIGERATOR PERFORMANCE

IN RESPONSE TO TESTED CRITERIA

Criteria Dual-Zone Refrigerator Pharmaceutical

Refrigerator

Loading density

 Slight impact on performance

 High-density loading patterns 

increased location-specific 

temperature variation

 No impact on performance

Packing style 

(Trays, Boxes or Mixed)

 No noticeable impact on 

performance

 No noticeable impact on 

performance

Opening/ closing 

refrigerator door

 Vial temperatures showed small 

increases in response to door 

opening, but remained in 2 °C to 

8 °C range throughout trial

 Thermometers in air / attached 

to walls exceeded 8 °C

 Thermometers in close 

proximity to cooling fan 

recorded temperature decreases 

below 2 °C, as the refrigerator 

pumped out additional cold air 

to compensate for the door 

opening

 Keeping water bottles in door

did not have a major impact on 

temperature stability

 Excellent temperature 

stability preserved throughout 

door opening trial

 Most vials showed no 

significant temperature 

change in response to door 

opening

 Only one vial, which was 

kept in an open tray rather 

than contained in packaging, 

showed small temperature 

spikes (less than 0.5 °C)

Door left ajar

 Some vial temperatures quickly 

exceeded 8 °C (within 3 to 5 

minutes after opening door), 

while others resisted thermal 

excursions for up to one hour, 

dependent on vial storage 

method and location

 All vials resisted thermal 

excursions for a longer period of 

time with water bottle ballast in 

place

 Most vials remained within 

2 °C to 8 °C even with door 

left ajar for up to 1 h
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Increasing room 

temperature

 Complex relationship between 

room and refrigerator 

temperature, dependent on 

factors such as refrigerator load 

density, timing of a cooling or 

defrost cycle, initial refrigerator 

temperature, and the time rate of 

change of room temperature 

 To cause internal refrigerator 

temperature to change by 1 °C, 

ambient temperature must vary 

by >20 °C

 Overall effect of room 

temperature fluctuation is small 

and unlikely to impact 

refrigerator performance

 Continuous temperature 

monitoring system should be 

used to identify and mitigate any 

possible risks associated with 

large changes in ambient 

conditions

 Room temperature changes 

have very little impact on 

refrigerator’s ability to 

maintain internal temperature 

stability

 To cause internal refrigerator 

temperature to change by 

1 °C, ambient temperature

must vary by >50 °C

Power outage

 Depending on vial location and 

storage method, and it takes ~ 

1 h to 4 h for vials to exceed 

8 °C after power off

 Water bottle ballast provided an 

extra 32 min to 2 h 37 min

before vaccines exceeded limit

 Vials stored in boxes or original 

packaging, stored away from the 

upper region of refrigerator had 

slowest temperature increase

 Requires 9 h to 12 h to fully reequilibrate following an outage

 Depending on vial location 

and storage method, and it 

takes 45 min to 2 h 19 min 

for vials to exceed 8 °C after 

power off

 Glass sliding doors do not 

provide as much thermal 

insulation as traditional 

refrigerator doors

 Power outages pose a greater 

risk to vaccines stored in 

refrigerators with glass doors, 

as they may be exposed to 

out-of-range temperatures 

much sooner

Defrost cycle

 Defrost cycle runs every 28 h to 

34 h

 Most vials remained within 2 °C 

to 8 °C during defrost cycle, one 

vial exceeded 8 °C for ~ 10 min

 Thermometers placed in air / 

near walls recorded dramatic 

temperature spike followed by a 

drop below 2 °C

 Automated defrost cycle

 No discernible effect on 

refrigerator chamber 

temperature
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General stability of vial 

temperature

 Good

 Vaccine vials remained within 

specified temperature range 

during regular operation, 

regardless of packing density or 

type

 Excellent

 Vaccine vials remained 

within specified temperature 

range during regular 

operation, regardless of 

packing density or type, as 

well as during door opening 

trials

 Average vial temperatures 

varied by less than 1.5 °C 

throughout entire range of 

testing
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ACKNOWLEDGMENTS

We thank the Centers for Disease Control and Prevention for providing financial support 

for this project. Additional thanks to Dawn Cross, who assisted with the Vaccines for 

Children clinic tours.

REFERENCES

1. Chojnacky, M. J.; Miller, W. W.; Ripple, D. C.; and Strouse, G. F., “Thermal 

Analysis of Refrigeration Systems Used for Vaccine Storage”, NISTIR 7656, 2009.

2. Day, G., Rossetto, B., and Ho, J., Testing of Purpose-built Refrigerating Vaccine 

Storage Cabinets, Test Research Report E175VC-01, Marrickville, New South 

Wales, 2009.

3. Page, S. L., Earnest, A., Birden, H., Deaker, R., and Clark, C., “Improving 

vaccination cold chain in the general practice setting,” in Australian Family Physician

37, No. 10 (2008).

4. Proceedings of the National Vaccine Storage Workshop, edited by A. Langley, and S. 

Grant., Queensland Health, Brisbane, 2004.

5. “Performance characteristics of domestic fridges for vaccine storage,” E2E IT 

Solutions Pty. Ltd. Available from: http://www.temptrack.com.au/documents/Fridge 

Performance Report (Rev A).pdf

6. Vaccine Storage and Handling Toolkit, Centers for Disease Control. Available from: 

http://www2a.cdc.gov/vaccines/ed/shtoolkit/