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STIMULI TO THE REVISION PROCESS

Stimuli articles do not necessarily reflect the policies
of the USPC or the USP Council of Experts

The Use of Mean Kinetic Temperature to Aid Evaluation of Temperature Excursions: Proper and Improper
Application

Chris Anderson,a,b Robert Seevers,a,c Desmond Hunta,d

ABSTRACT This Stimuli article describes the use of mean kinetic temperature (MKT) to evaluate temperature excursions for
shipments of controlled room temperature (CRT) and controlled cold temperature (CCT) pharmaceutical products. Correct
and incorrect uses of MKT are described and supported by examples from actual events. The authors propose using 30 days
to calculate MKT for CRT products and 24 h for controlled cold temperature products, including excursion time. The
objectives of this Stimuli article are to initiate discussion and solicit public comments regarding the new USP position on how
to use MKT to evaluate temperature excursions for the shipment of pharmaceutical drugs.

INTRODUCTION

Temperature excursions happen, although organizations expend a lot of effort to avoid them. Describing the magnitude of
an excursion event as simply a high- or low-temperature event is meaningless without the factor of time. A typical
unplanned excursion has a fluctuation in temperature over a period of time as opposed to a static temperature change. If the
temperature at which the excursion occurred was static over time, it would be a lot easier to evaluate its impact on product
stability.

MEAN KINETIC TEMPERATURE

Mean kinetic temperature is a calculation that is considered an isothermal storage temperature that simulates the non-
isothermal effects of storage temperature variation (1). MKT expresses the cumulative thermal stress a drug product
experiences. The use of MKT is considered an acceptable practice for storage and can be considered for excursions during
transit (see Packaging and Storage Requirements 〈659〉) (2).

The greater the temperature variance of the excursion from the mean, the greater the difference between the calculated
mean and the MKT. The following examples illustrate this point. If a product experiences a low temperature of 29° and a high
temperature of 31°, then the calculated mean would be 30° with an MKT of 30.04°. However, if the low were 20° and the
high were 40°, the calculated mean would be 30° and the MKT would be 33.27°. If, instead, the high were 40° but the low
were 30°, the MKT would be 35.85°, 2.58° higher even with the same high temperature as the previous example. This
demonstrates how the variation in the observed temperatures during an excursion can impact the MKT for a given time
period.

Over the years, there have been misunderstandings and misuses of MKT, with the most significant being the use of 52-
week temperature data to calculate MKT during a temperature excursion. This is problematic because products typically do
not spend 52 weeks in a single location. Thus, the 52-week data used in the MKT calculation would not be a true reflection of
the storage time. This approach skews the results and could potentially lead a company to overlook the impact of the
excursion on the drug product. A closely related concern is the idea that a temperature excursion above a product's storage
temperature can be "fixed" just by lowering the temperature of a warehouse for an appropriate period of time so that the
resulting MKT calculation would provide an acceptable value. This ignores the fact that any degradation due to the higher
temperature is not reversible.

To illustrate this point, two examples of actual events involving CRT are shown here. [NЉЎϿ—CRT is defined as 20°–25°
(68°–77° F)]

CRT Example 1 (Acceptable 52-Week MKT, Unacceptable Temperatures)

In this example, 52 weeks (365 days) of temperature data were taken from warehouse 1, where temperatures were
recorded every 15 min (see Figure 1). The high temperature and low temperature for a given day were used to calculate the
MKT over the 24-h period. The 52-week MKT was 23.98° (75.16° F), which is within the 20°–25° (68°–77° F) storage range
for CRT products. However, if one looks at the actual temperature data points used (see Table A-1 in Appendix), there were
175 days with temperatures over 25° (77° F), with day 188 (7/7/2017) being the highest at 33.58° (92.44° F). The
temperature for this single day [with a low of 26.6° (79.88° F)] was outside the storage range for CRT products. Chapter
〈659〉 has an excursion allowance for CRT products of 15°–30° (59°–86° F) with short-term excursions up to 40°, as long as
they are less than 24 h in duration and the MKT is 25° (77° F) or less (2). The single day MKT of 30.7° (87.26° F) calculated
for day 188 does not meet the 〈659〉 MKT excursion criteria. As shown in this example, the daily data reveal a significant
problem that is not apparent in the 52-week MKT data (see Figure 1).

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Figure 1. Weekly mean kinetic temperature (MKT) for CRT Example 1.

If measuring a 52-week time period is unrealistic, would measuring one day demonstrate the realistic impact of an
excursion on the product? It should be noted that the maximum excursion temperature was within the excursion allowance
of less than 24 h.

A better approach would be to consider the average time that a product spends in a warehouse, which is 30.3 days in the
United States (3). In the following example (Table 1), if a 30-day MKT were calculated from the referenced temperature at
day 188 plus the previous 29 days, the result would be an MKT of 28.98° (84.16° F), which is over 25° (77° F) and is
unacceptable.

Table 1. 30-Day MKTa for CRT Example 1

Temperature (°C) Temperature (°C) Temperature (°C)
Dayb High Low Day High Low Day High Low
158 24.37 19.58 168 24.19 19.79 178 30.91 23.65
159 22.28 19.56 169 23.69 19.67 179 29.71 22.98
160 23 19.85 170 32.4 25.44 180 29.44 22.84
161 23.5 19.58 171 3210.72 26.01 181 28.49 22.84
162 23.43 18.93 172 31.04 24.61 182 28.64 21.83
163 22 19.34 173 30.52 23.58 183 30.17 22.06
164 22.43 19.54 174 29.6 23.92 184 29.99 23.58
165 22.92 19.56 175 30.98 24.19 185 31.44 24.21
166 23.94 19.34 176 32.27 25.91 186 32 24.83
167 24.92 19.83 177 32.2 27.23 187 33.58 26.6
a MKT calculated for 30 days was 28.98° (84.16° F), which was over 25° (77° F) and therefore unacceptable.
b Day within the 365-day study period.

CRT Example 2 (Acceptable 52-Week MKT, Acceptable Temperatures)

In this example, 52 weeks (365 days) of temperature data were taken from warehouse 2, where temperature was
recorded every 15 min (see Figure 2). The high temperature and low temperature from each day were used to calculate the

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MKT. The 52-week MKT was 22.75° (72.95° F), only 1.23° (2.22° F) lower than CRT Example 1. A review of the 52 weeks of
data (see Table 2) showed one single-day excursion temperature of 25.56° (78° F) on day 93 (4/3/2017). If one calculates a
30-day MKT from day 93 backwards, this provides a 30-day MKT of 23.14° (73.65° F), which falls within the 〈659〉 excursion
allowance. In this example, any day used to calculate a 30-day MKT provides acceptable results. This example shows that
using a 52-week MKT was not a significant problem because excursions occurred on only one day of the year and there was
an acceptable MKT in any 30-day period.

Figure 2. Weekly mean kinetic temperature (MKT) for CRT Example 2.

Table 2. 30-Daya MKT for CRT Example 2

Temperature (°C) Temperature (°C) Temperature (°C)
Dayb High Low Day High Low Day High Low
64 23.33 21.67 74 22.78 22.22 84 23.33 22.78
65 23.89 21.67 75 23 22.22 85 23.33 22.78
66 23.33 22.78 76 23.33 22.22 86 23.33 22.78
67 24.44 23.33 77 23.33 22.22 87 23.89 22.78
68 23.89 23.33 78 23.33 22.22 88 23.89 23.33
69 23.33 22.78 79 23.89 22.78 89 25 22.78
70 22.78 22.22 80 24.44 22.78 90 23.33 22.78
71 23.33 22.22 81 23.89 22.22 91 22.78 22.78
72 23.89 22.22 82 23.89 22.22 92 24.44 22.78
73 22.78 22.22 83 23.33 22.22 93 25.56 23.33
a MKT calculated for 30 days was 23.14° (73.65° F), which was under 25° (77° F) and therefore acceptable.
b Day within the 365-day study period.

Comparing the Same 30-Day Time Period for CRT Examples 1 and 2

If one compares the same time frame for both examples, the MKT is unacceptable for CRT Example 1 and acceptable for
CRT Example 2 (see Table 3, Table 4, Table 5, and Table 6). Although CRT Example 1 had a high-end temperature excursion
every day, it should be noted that both sites had an acceptable 52-week MKT.

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Table 3. Comparison of 30-Daya Temperature Data for CRT Examples 1 and 2

Example 1 Example 2
30-Day MKT 29.06° (84.31° F) 22.75° (72.95° F)
Highest temperature 33.58° (92.44° F) 23.9° (75° F)
Lowest temperature 21.17° (70.11° F) 21.67° (71° F)
a Days 183–212 within the 365-day study period.

Table 4. 30-Daya Temperature Data for CRT Example 1b

Temperature (°C) Temperature (°C) Temperature (°C)
Day High Low Day High Low Day High Low
183 28.64 21.83 193 32.54 26.34 203 31.47 25.46
184 30.17 22.06 194 32.38 25.84 204 31.64 25.46
185 30.54 23.58 195 32.61 25.86 205 29.12 25.21
186 31.44 24.21 196 31.84 26.18 206 30.69 24.94
187 32 24.83 197 31.69 26.84 207 31.33 24.39
188 33.58 26.6 198 23.89 25.84 208 31.76 24.83
189 33.36 21.62 199 31.84 25.67 209 31.36 24.83
190 33.72 27.02 200 32.45 26.45 210 30.6 23.96
191 28.64 21.83 201 32.54 26.34 211 31.47 25.46
192 30.17 20.06 202 32.38 25.84 212 31.64 25.46
a Days 183–212 within the 365-day study period.
b The data show daily high excursions and an unacceptable 30-day MKT of 29.06° (83.31° F).

Table 5. 30-Daya Temperature Data for CRT Example 2b

Temperature (°C) Temperature (°C) Temperature (°C)
Day High Low Day High Low Day High Low
183 23.33 22.22 193 23.33 22.78 203 22.78 22.78
184 23.33 22.22 194 22.78 22.22 204 23.33 22.22
185 23.33 22.22 195 22.78 22.22 205 22.78 22.22
186 23.33 22.22 196 22.78 22.22 206 22.78 21.67
187 23.33 22.22 197 23.33 22.22 207 23.33 22.22
188 22.78 22.22 198 23.33 22.22 208 22.78 22.22
189 23.33 21.67 199 23.89 22.78 209 23.33 22.22
190 22.78 22.22 200 23.89 22.78 210 22.78 21.67
191 23.33 22.22 201 23.89 22.78 211 22.78 21.67
192 23.33 22.78 202 23.89 22.78 212 23.33 21.67
a Days 183–212 within the 365-day study period.
b The data show no excursions and an acceptable 30-day MKT of 22.75° (72.95° F).

As these examples demonstrate, a 52-week MKT for a CRT product should never be used. These examples suggest that a
30-day period, or the average number of days that a product remains in a warehouse, provides a realistic MKT to use in
evaluating storage or shipping excursions, as long as an excursion is no longer than a 24-h period. The only exception to
these excursion limits would be a case where the product manufacturer states otherwise.

CONTROLLED COLD TEMPERATURE

Controlled Cold Excursions and the Use of MKT

The USP 31–NF 26 General Notices definition of controlled cold temperature (2°–8°), which was omitted in 2010, allowed
short-term excursions (less the 24 h) between 0° and 15° (32°–59° F) as long as the MKT did not exceed 8° (46° F) (4).
The issue with this definition was that it allowed an excursion down to 0° (32° F). Freezing can have a negative effect on the
efficacy and expiry of many refrigerated drugs, especially vaccines and proteins. It should be noted that the freezing point
depression in these drugs is not expected to be large enough to protect them at 0°. However, removing the short-term
excursion allowance is problematic, especially for delivery to caregivers.

Thus, refrigerated delivery or qualified passive thermal protection should be used for the shipment of CCT products (see
Good Storage and Distribution Practices for Drug Products 〈1079〉) (5). Delayed deliveries, delayed receipts, or short-term
storage failures can and do happen, and a reasonable allowance for documented excursions should be permitted. It is
proposed that acceptable excursions for CCT products are 2°–15° (36°–59° F) for less than 24 h with an MKT of 8° (46° F)
or below. This MKT should moderate any concerns about long periods of exposure to 15° (59° F).

The following examples are taken from actual events.

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CCT Example 1: Controlled Cold-Qualified Passive Shipper

A wholesaler had a cold shipper (i.e., passive thermal packaging system) qualified for 30 h, but chose to run the time in
the qualification thermal chambers out for an additional 24 h (a total of 54 h). When a company shipping a controlled
product works with a service provider to design a qualified shipper, they typically look at their maximum delivery times and
add extra time for a buffer. Although over-qualifying a thermal package costs a significant amount of money, transportation
space, and receiving space, a company may run a qualification test out further than the target time to obtain data to support
possible excursions. If a product in a 30-h shipper was delivered in 32 h and there were no data to support the additional 2
h, the product would be potentially nonsalable. A company needs temperature data to evaluate against excursion limits or to
provide to the product manufacturer for disposition.

In the shipper qualification case described below (see Figure 3), the additional time (24 h) beyond the 30-h qualification
time yielded a total of 54 h with a high temperature of 11° (51.8° F), a low temperature of 3.4° (38.12° F), and an MKT of
8° (46.4° F). These data meet the proposed criteria for controlled cold temperature excursions. However, if the data were
outside the proposed ranges, the supply chain member would have data within the tested time period to provide the
temperatures and MKT to the manufacturer for disposition. It is important to note that qualification testing should be
completed for the payloads shipped; this means that wholesalers shipping comingled controlled cold products should
complete qualification testing for minimum and maximum payloads as well as environmental seasons for the geography that
they ship to.

An alternative to using a qualified packaging system would be to use calibrated time–temperature monitors. To obtain
adequate data for calculating mean temperature and MKT, temperature monitors would need to collect data in 15-min
increments. Once downloaded, these data would provide access to time, temperature exposures, and MKT. Most time–
temperature monitors will calculate MKT. The calculated MKT should represent the duration of the trip.

Figure 3. Qualification summary for a controlled cold-qualified passive shipper (CCT Example 1). Worst case of the six tests
(three minimum and three maximum payloads) against a summer profile [high temperature of 11° (51.8° F) and an MKT of
8° (46.5° F)].

CCT Example 2: Controlled Cold Refrigerated Delivery

CCT EXAMPLE 2A

In this example (Figure 4), a refrigerated trailer making a 72-h delivery went out of controlled cold temperature range by
going above 8° (46° F) at hour 52 to 8.5° (47.3°). The temperature rose 0.27° every hour until delivery at hour 72. The
excursion lasted 22 h (within excursion limits), the maximum temperature was 13.9° (57.02° F) (within excursion limits),

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and the MKT was 10.77° (51.39° F) for the last 24 h (outside the excursion MKT limit). In this case, the product should be
quarantined and the manufacturer(s) should be contacted for disposition.

Figure 4 . Qualification summary for controlled cold refrigerated delivery (CCT Example 2A) with MKT outside the excursion
limit. Temperature went above 8° (46° F) at 52 h and continued to rise until delivery at 72 h with a high temperature of
13.9° (57.02° F). MKT for the last 24 h was 10.77° (51.39° F).

CCT EXAMPLE 2B

In this example (Figure 5), the excursion started at hour 63 and delivery occurred at hour 72. Temperature data revealed
that the excursion duration was 10 h (within excursion limits). The maximum temperature was 10.5° (50.9° F) and the MKT
was 7.45° (45.41° F)—both were within excursion limits.

Figure 5. Qualification summary for controlled cold refrigerated delivery (CCT Example 2B) with MKT within the excursion
limit. Temperature went above 8° (46° F) at hour 63 and the product was delivered at hour 72 with a high temperature of
10.5° (50.9° F). MKT for the last 24 h was 7.45° (45.41° F).

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Table 6. Comparison of 24-h Dataa from CCT Examples 2A and 2B

Example 2A Example 2B
2-h Temperature (°C) Temperature (°C)
Increment High Low High Low
1 6.5 5 5.2 5.1
2 8.5 7 5 5
3 9.04 8.77 5.3 4.9
4 9.58 9.31 5.8 5.6
5 10.12 9.85 6.3 6
6 10.66 10.39 7.1 6.6
7 11.2 10.93 8 7.4
8 11.74 11.47 8.5 8.5
9 12.28 12.01 8.9 8.7
10 12.82 12.55 9.2 9
11 13.36 13.09 9.7 9.4
12 13.09 13.63 10.5 10
MKT = 10.77° (51.39° F) MKT = 7.45° (45.41° F)
a The 24-h period includes excursion time.

CONCLUSIONS

This article highlights correct and incorrect applications of MKT to provide some perspective on the proper use of this tool.
Examples from actual cases are provided to alert readers to the consequences of applying MKT inappropriately. The
temperature data presented in this article support the conclusion that a 30-day period, or the average time that a product
spends in a warehouse, should be used to calculate MKT for CRT products. In contrast, for controlled cold temperature
products, a 24-h period should be used, and this time span should include the excursion time.

Factors that can lead to temperature excursions should be identified early in the process, and appropriate mitigation
strategies should be executed to eliminate or reduce the risks of excursions (see 〈1079〉) (5). In the event of short-term
storage or transportation/delivery excursions, MKT is a helpful tool that can aid in evaluating the impact on drug quality
when used in conjunction with USP excursion limits and product labeling (see 〈659〉) (2).

APPENDIX

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Table A-1. Original Temperature Data (°F) for CRT Example 1

Temperature (°F) Temperature (°F) Temperature (°F)
Date High Low Date High Low Date High Low
11/1/2016 71.33 64.7 3/2/2017 72.55 62.58 7/1/2017 83.29 73.11
11/2/2016 74.01 62.28 3/3/2017 73.48 63.25 7/2/2017 83.56 71.29
11/3/2016 77.57 68.58 3/4/2017 69.66 64.07 7/3/2017 86.3 71.7
11/4/2016 77.27 67.44 3/5/2017 67.18 64.51 7/4/2017 85.98 74.45
11/5/2016 75.35 66.66 3/6/2017 69.03 61.5 7/5/2017 88.6 75.58
11/6/2016 73.67 65.1 3/7/2017 72.67 61.95 7/6/2017 89.6 76.7
11/7/2016 75.76 64.4 3/8/2017 76.48 64.62 7/7/2017 92.45 79.88
11/8/2016 78.59 66.81 3/9/2017 77.49 66.36 7/8/2017 92.04 81.71
11/9/2016 80.03 69.44 3/10/2017 76.14 67.47 7/9/2017 90.45 80.64
11/10/2016 79.08 68.62 3/11/2017 76.25 67.33 7/10/2017 91.75 81.52
11/11/2016 78.78 68.51 3/12/2017 77.53 67.51 7/11/2017 91.34 80.53
11/12/2016 75.2 68.51 3/13/2017 78.78 67.62 7/12/2017 90.57 79.42
11/13/2016 76.1 67.81 3/14/2017 78.63 67.25 7/13/2017 90.28 78.51
11/14/2016 77.91 67.62 3/15/2017 79.19 68.18 7/14/2017 90.69 78.55
11/15/2016 76.06 67.18 3/16/2017 78.66 67.44 7/15/2017 89.32 79.12
11/16/2016 72.93 65.77 3/17/2017 78.66 67.25 7/16/2017 89.04 78.51
11/17/2016 71.22 62.8 3/18/2017 75.88 67.1 7/17/2017 89.8 78.51
11/18/2016 71.33 60.42 3/19/2017 76.1 67.33 7/18/2017 89.32 78.21
11/19/2016 67.92 60.01 3/20/2017 75.88 67.25 7/19/2017 90.41 79.61
11/20/2016 67.47 62.36 3/21/2017 72.11 67.21 7/20/2017 91.01 78.82
11/21/2016 68.4 62.62 3/22/2017 73.41 67.73 7/21/2017 89.8 77.3
11/22/2016 68.51 60.2 3/23/2017 74.34 67.25 7/22/2017 88.64 77.83
11/23/2016 69.07 60.42 3/24/2017 74.19 66.07 7/23/2017 88.96 77.83
11/24/2016 67.99 60.2 3/25/2017 71.62 66.81 7/24/2017 84.42 77.38
11/25/2016 69.21 60.05 3/26/2017 72.37 67.18 7/25/2017 87.24 76.89
11/26/2016 64.7 60.2 3/27/2017 73.26 67.21 7/26/2017 88.4 75.91
11/27/2016 62.88 61.17 3/28/2017 75.09 66.81 7/27/2017 89.16 76.7
11/28/2016 64.81 59.97 3/29/2017 76.85 67.7 7/28/2017 88.44 76.7
11/29/2016 65.85 60.79 3/30/2017 75.54 67.62 7/29/2017 87.08 75.13
11/30/2016 66.5 59.9 3/31/2017 74.64 67.4 7/30/2017 86.37 74.79
12/1/2016 66.22 60.46 4/1/2017 74.6 66.22 7/31/2017 88.4 75.28
12/2/2016 64.25 60.61 4/2/2017 75.54 67.36 8/1/2017 86.45 83.76
12/3/2016 64.73 60.23 4/3/2017 74.68 68.07 8/2/2017 88.64 81.25
12/4/2016 66.33 60.72 4/4/2017 77.42 67.77 8/3/2017 92.53 82.1
12/5/2016 66.84 60.5 4/5/2017 78.7 67.44 8/4/2017 91.79 80.45
12/6/2016 66.18 60.72 4/6/2017 78.06 67.36 8/5/2017 89.2 77.87
12/7/2016 66.36 60.16 4/7/2017 76.59 67.1 8/6/2017 87.88 76.36
12/8/2016 66.66 60.01 4/8/2017 73.75 67.4 8/7/2017 88.48 76.59
12/9/2016 66.1 60.08 4/9/2017 73.89 66.51 8/8/2017 89.92 77.12
12/10/2016 64.88 60.27 4/10/2017 76.4 66.73 8/9/2017 89.12 76.48
12/11/2016 65.36 61.43 4/11/2017 76.21 67.62 8/10/2017 89.28 76.82
12/12/2016 67.55 61.65 4/12/2017 76.48 67.33 8/11/2017 89.56 77.23
12/13/2016 67.96 61.32 4/13/2017 75.2 67.4 8/12/2017 88.12 76.78
12/14/2016 68.03 59.79 4/14/2017 75.24 67.18 8/13/2017 86.22 74.04
12/15/2016 66.18 59.75 4/15/2017 75.28 67.14 8/14/2017 85.82 74.83
12/16/2016 63.77 60.16 4/16/2017 76.18 67.7 8/15/2017 83.87 73.97
12/17/2016 62.84 59.07 4/17/2017 77.15 67.62 8/16/2017 84.18 73.15
12/18/2016 61.58 57.01 4/18/2017 77.12 69.07 8/17/2017 84.65 73
12/19/2016 64.66 57.72 4/19/2017 78.02 67.88 8/18/2017 85.31 74.01
12/20/2016 66.03 57.65 4/20/2017 78.7 67.18 8/19/2017 84.42 73.48
12/21/2016 64.33 61.39 4/21/2017 81.9 67.18 8/20/2017 83.52 72.81
12/22/2016 64.44 61.76 4/22/2017 82.02 70.21 8/21/2017 84.11 73.11
12/23/2016 65.29 62.25 4/23/2017 80.22 70.1 8/22/2017 85.47 72.44
12/24/2016 63.73 60.76 4/24/2017 75.5 68.21 8/23/2017 84.88 74.08

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Temperature (°F) Temperature (°F) Temperature (°F)

Date High Low Date High Low Date High Low

12/25/2016 61.32 57.23 4/25/2017 75.61 67.4 8/24/2017 84.61 74.01
12/26/2016 60.72 56.93 4/26/2017 77.76 67.4 8/25/2017 84.81 72.81
12/27/2016 64.77 56.74 4/27/2017 77.46 71.88 8/26/2017 85.47 73.48
12/28/2016 67.44 58.32 4/28/2017 80.37 67.7 8/27/2017 86.06 75.31
12/29/2016 68.18 59.56 4/29/2017 77.83 69.47 8/28/2017 89.56 85
12/30/2016 65.73 62.66 4/30/2017 79.57 66.92 8/29/2017 92.49 82.71
12/31/2016 63.55 61.21 5/1/2017 81.98 67.96 8/30/2017 93.52 82.64
1/1/2017 62.17 59.07 5/2/2017 83.02 70.14 8/31/2017 95.23 84.77
1/2/2017 62.17 59.97 5/3/2017 83.91 70.96 9/1/2017 95.23 84.92
1/3/2017 62.69 59.04 5/4/2017 84.18 71.4 9/2/2017 93.81 85.78
1/4/2017 63.81 58.32 5/5/2017 80.26 69.81 9/3/2017 94.02 84.34
1/5/2017 64.18 61.32 5/6/2017 71.88 67.07 9/4/2017 89.16 81.52
1/6/2017 66.51 61.35 5/7/2017 71.48 67.59 9/5/2017 89.56 78.63
1/7/2017 64.66 60.83 5/8/2017 75.95 66.59 9/6/2017 89.68 79.99
1/8/2017 66.59 60.94 5/9/2017 76.97 67.44 9/7/2017 89.24 77.68
1/9/2017 65.51 62.92 5/10/2017 73.19 67.66 9/8/2017 88.4 77.72
1/10/2017 64.73 62.28 5/11/2017 79.16 67.55 9/9/2017 85.31 75.5
1/11/2017 66.33 62.66 5/12/2017 78.59 67.03 9/10/2017 87.2 76.74
1/12/2017 64.4 62.43 5/13/2017 76.29 67.18 9/11/2017 89.48 79.27
1/13/2017 65.47 61.5 5/14/2017 76.51 66.99 9/12/2017 88.6 78.74
1/14/2017 65.77 60.46 5/15/2017 70.14 67.14 9/13/2017 85.51 75.69
1/15/2017 64.88 60.2 5/16/2017 72.07 67.77 9/14/2017 80.3 72.59
1/16/2017 66.29 61.24 5/17/2017 69.84 67.92 9/15/2017 80.56 73.15
1/17/2017 66.59 60.76 5/18/2017 76.59 66.7 9/16/2017 80.91 72
1/18/2017 64.66 60.2 5/19/2017 80.45 67.44 9/17/2017 79.99 72.07
1/19/2017 65.25 61.69 5/20/2017 81.25 68.81 9/18/2017 81.06 70.07
1/20/2017 63.81 61.65 5/21/2017 82.64 71.36 9/19/2017 80.95 72.52
1/21/2017 62.58 59.34 5/22/2017 84.61 72.03 9/20/2017 79.27 72.22
1/22/2017 61.43 59.79 5/23/2017 84.53 72.44 9/21/2017 77.49 70.14
1/23/2017 60.64 59.41 5/24/2017 82.44 71.4 9/22/2017 77.49 66.84
1/24/2017 62.73 57.31 5/25/2017 79.01 69.07 9/23/2017 76.1 65.96
1/25/2017 63.06 57.19 5/26/2017 79.23 68.21 9/24/2017 77.15 65.47
1/26/2017 63.25 56.89 5/27/2017 78.93 67.44 9/25/2017 79.54 68.07
1/27/2017 62.73 57.53 5/28/2017 80.03 67.07 9/26/2017 80.26 68.88
1/28/2017 65.1 59.07 5/29/2017 79.54 70.99 9/27/2017 81.25 73.71
1/29/2017 66.22 58.77 5/30/2017 79.19 68.62 9/28/2017 82.94 70.77
1/30/2017 69.58 60.12 5/31/2017 75.76 69.25 9/29/2017 83.33 71.92
1/31/2017 69.47 61.35 6/1/2017 78.36 68.58 9/30/2017 81.1 71.51
2/1/2017 69.07 61.43 6/2/2017 81.83 67.77 10/1/2017 79.19 70.81
2/2/2017 67.59 61.61 6/3/2017 81.41 70.1 10/2/2017 79.35 70.21
2/3/2017 65.88 63.21 6/4/2017 81.02 69.58 10/3/2017 78.13 69.58
2/4/2017 66.47 63.66 6/5/2017 81.71 69.7 10/4/2017 78.66 67.44
2/5/2017 64.7 62.66 6/6/2017 80.15 70.59 10/5/2017 79.8 67.14
2/6/2017 64.21 62.32 6/7/2017 80.49 70.47 10/6/2017 81.21 68.4
2/7/2017 65.73 63.06 6/8/2017 80.07 70.1 10/7/2017 80.91 70.07
2/8/2017 70.07 64.36 6/9/2017 80.03 67.81 10/8/2017 79.23 68.99
2/9/2017 72.89 64.62 6/10/2017 78.82 69.84 10/9/2017 78.51 69.81
2/10/2017 69.03 65.85 6/11/2017 76.93 68.1 10/10/2017 80.26 67.81
2/11/2017 68.81 65.77 6/12/2017 78.44 66.44 10/11/2017 79.16 68.77
2/12/2017 68.81 63.77 6/13/2017 80.49 67.29 10/12/2017 77.76 68.55
2/13/2017 71.4 63.92 6/14/2017 83.06 69.84 10/13/2017 77.72 67.18
2/14/2017 71.81 65.18 6/15/2017 85.04 71.85 10/14/2017 76.4 66.73
2/15/2017 72.89 64.51 6/16/2017 86.77 73.82 10/15/2017 82.33 73.52
2/16/2017 71.25 64.96 6/17/2017 86.14 74.87 10/16/2017 79.65 71.62

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Temperature (°F) Temperature (°F) Temperature (°F)

Date High Low Date High Low Date High Low

2/17/2017 68.84 66.33 6/18/2017 86.06 74.75 10/17/2017 76.78 70.29
2/18/2017 67.73 64.4 6/19/2017 88.52 76.4 10/18/2017 75.43 66.18
2/19/2017 66.44 64.36 6/20/2017 90.32 77.79 10/19/2017 76.97 66.73
2/20/2017 69.25 64.07 6/21/2017 90.89 78.82 10/20/2017 81.87 70.96
2/21/2017 70.21 65.7 6/22/2017 87.88 76.29 10/21/2017 86.06 79.65
2/22/2017 69.88 65.36 6/23/2017 86.93 74.45 10/22/2017 87.24 80.18
2/23/2017 68.99 63.47 6/24/2017 85.28 75.05 10/23/2017 84.34 74.87
2/24/2017 68.21 61.54 6/25/2017 87.76 75.54 10/24/2017 82.83 72.41
2/25/2017 66.59 61.35 6/26/2017 90.08 78.63 10/25/2017 79.95 70.59
2/26/2017 64.59 62.21 6/27/2017 89.96 81.02 10/26/2017 76.4 68.4
2/27/2017 63.7 61.65 6/28/2017 87.64 74.57 10/27/2017 74.87 69.1
2/28/2017 68.14 61.13 6/29/2017 85.47 73.37 10/28/2017 74.6 68.44
3/1/2017 68.99 60.98 6/30/2017 85 73.11 — — —

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Table A-2. Original Temperature Data for CRT Example 2

Temperature (°F) Temperature (°F) Temperature (°F)
Date High Low Date High Low Date High Low
11/1/2016 75 73 3/3/2017 74 71 7/3/2017 74 72
11/2/2016 77 74 3/4/2017 73 71 7/4/2017 74 72
11/3/2016 76 75 3/5/2017 74 71 7/5/2017 74 72
11/4/2016 76 73 3/6/2017 75 71 7/6/2017 74 72
11/5/2016 75 73 3/7/2017 74 73 7/7/2017 73 72
11/6/2016 74 74 3/8/2017 76 74 7/8/2017 74 71
11/7/2016 75 73 3/9/2017 75 74 7/9/2017 73 72
11/8/2016 76 73 3/10/2017 74 73 7/10/2017 74 72
11/9/2016 76 74 3/11/2017 73 72 7/11/2017 74 73
11/10/2016 76 73 3/12/2017 74 72 7/12/2017 74 73
11/11/2016 76 73 3/13/2017 75 72 7/13/2017 73 72
11/12/2016 75 73 3/14/2017 73 72 7/14/2017 73 72
11/13/2016 75 73 3/15/2017 73 72 7/15/2017 73 72
11/14/2016 76 73 3/16/2017 73 72 7/16/2017 74 72
11/15/2016 75 74 3/17/2017 74 72 7/17/2017 74 72
11/16/2016 75 74 3/18/2017 74 72 7/18/2017 75 73
11/17/2016 76 74 3/19/2017 74 72 7/19/2017 75 73
11/18/2016 76 74 3/20/2017 75 73 7/20/2017 75 73
11/19/2016 76 74 3/21/2017 76 73 7/21/2017 75 73
11/20/2016 74 73 3/22/2017 75 72 7/22/2017 73 73
11/21/2016 74 73 3/23/2017 75 72 7/23/2017 74 72
11/22/2016 74 73 3/24/2017 74 72 7/24/2017 73 72
11/23/2016 74 73 3/25/2017 74 73 7/25/2017 73 71
11/24/2016 74 73 3/26/2017 74 73 7/26/2017 74 72
11/25/2016 74 73 3/27/2017 74 73 7/27/2017 73 72
11/26/2016 74 73 3/28/2017 75 73 7/28/2017 74 72
11/27/2016 74 73 3/29/2017 75 74 7/29/2017 73 71
11/28/2016 74 73 3/30/2017 77 73 7/30/2017 73 71
11/29/2016 74 73 3/31/2017 74 73 7/31/2017 74 71
11/30/2016 75 74 4/1/2017 73 73 8/1/2017 73 72
12/1/2016 76 74 4/2/2017 76 73 8/2/2017 73 72
12/2/2016 75 73 4/3/2017 78 74 8/3/2017 73 72
12/3/2016 74 73 4/4/2017 74 71 8/4/2017 73 71
12/4/2016 74 73 4/5/2017 73 71 8/5/2017 72 71
12/5/2016 73 72 4/6/2017 72 71 8/6/2017 73 71
12/6/2016 74 73 4/7/2017 74 71 8/7/2017 73 71
12/7/2016 74 73 4/8/2017 74 71 8/8/2017 72 71
12/8/2016 74 73 4/9/2017 76 71 8/9/2017 73 71
12/9/2016 74 72 4/10/2017 74 73 8/10/2017 73 72
12/10/2016 73 72 4/11/2017 75 73 8/11/2017 73 71
12/11/2016 73 71 4/12/2017 75 73 8/12/2017 73 71
12/12/2016 74 72 4/13/2017 75 72 8/13/2017 73 71
12/13/2016 74 73 4/14/2017 76 71 8/14/2017 73 71
12/14/2016 74 72 4/15/2017 74 72 8/15/2017 74 71
12/15/2016 73 72 4/16/2017 74 72 8/16/2017 73 71
12/16/2016 72 71 4/17/2017 74 73 8/17/2017 73 72
12/17/2016 72 71 4/18/2017 75 72 8/18/2017 73 71
12/18/2016 74 72 4/19/2017 75 71 8/19/2017 73 71
12/19/2016 73 71 4/20/2017 75 72 8/20/2017 73 71
12/20/2016 73 71 4/21/2017 73 71 8/21/2017 73 71
12/21/2016 74 72 4/22/2017 71 70 8/22/2017 73 72
12/22/2016 74 72 4/23/2017 75 69 8/23/2017 73 72
12/23/2016 74 73 4/24/2017 75 71 8/24/2017 73 72
12/24/2016 73 73 4/25/2017 73 71 8/25/2017 74 71

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Temperature (°F) Temperature (°F) Temperature (°F)

Date High Low Date High Low Date High Low

12/25/2016 74 72 4/26/2017 72 71 8/26/2017 73 71
12/26/2016 73 71 4/27/2017 75 72 8/27/2017 73 71
12/27/2016 75 73 4/28/2017 75 73 8/28/2017 73 71
12/28/2016 74 73 4/29/2017 75 73 8/29/2017 73 71
12/29/2016 73 72 4/30/2017 75 72 8/30/2017 73 71
12/30/2016 73 72 5/1/2017 73 72 8/31/2017 73 71
12/31/2016 73 72 5/2/2017 73 72 9/1/2017 73 71
1/1/2017 74 72 5/3/2017 75 71 9/2/2017 73 71
1/2/2017 73 72 5/4/2017 77 72 9/3/2017 73 71
1/3/2017 73 73 5/5/2017 74 72 9/4/2017 72 71
1/4/2017 74 73 5/6/2017 74 72 9/5/2017 73 71
1/5/2017 73 72 5/7/2017 75 72 9/6/2017 73 71
1/6/2017 73 72 5/8/2017 74 72 9/7/2017 72 71
1/7/2017 72 71 5/9/2017 74 71 9/8/2017 73 71
1/8/2017 72 71 5/10/2017 76 72 9/9/2017 74 71
1/9/2017 72 71 5/11/2017 75 73 9/10/2017 73 72
1/10/2017 72 71 5/12/2017 75 72 9/11/2017 73 72
1/11/2017 75 72 5/13/2017 73 72 9/12/2017 74 71
1/12/2017 75 73 5/14/2017 72 71 9/13/2017 73 71
1/13/2017 75 73 5/15/2017 73 71 9/14/2017 73 71
1/14/2017 73 71 5/16/2017 74 72 9/15/2017 73 71
1/15/2017 73 72 5/17/2017 76 73 9/16/2017 73 71
1/16/2017 73 71 5/18/2017 76 73 9/17/2017 73 71
1/17/2017 74 72 5/19/2017 75 73 9/18/2017 73 71
1/18/2017 73 73 5/20/2017 76 72 9/19/2017 72 71
1/19/2017 74 72 5/21/2017 76 72 9/20/2017 72 71
1/20/2017 74 73 5/22/2017 74 71 9/21/2017 72 71
1/21/2017 75 73 5/23/2017 73 71 9/22/2017 72 71
1/22/2017 74 73 5/24/2017 74 71 9/23/2017 72 71
1/23/2017 73 72 5/25/2017 72 72 9/24/2017 73 71
1/24/2017 73 72 5/26/2017 73 71 9/25/2017 73 71
1/25/2017 74 72 5/27/2017 75 71 9/26/2017 74 71
1/26/2017 74 73 5/28/2017 74 71 9/27/2017 73 72
1/27/2017 74 73 5/29/2017 72 71 9/28/2017 74 72
1/28/2017 73 72 5/30/2017 74 71 9/29/2017 73 71
1/29/2017 73 72 5/31/2017 73 72 9/30/2017 73 71
1/30/2017 74 72 6/1/2017 74 71 10/1/2017 72 71
1/31/2017 74 71 6/2/2017 74 71 10/2/2017 72 70
2/1/2017 75 74 6/3/2017 73 71 10/3/2017 72 71
2/2/2017 76 74 6/4/2017 73 71 10/4/2017 73 71
2/3/2017 75 73 6/5/2017 72 72 10/5/2017 73 71
2/4/2017 75 74 6/6/2017 72 72 10/6/2017 74 71
2/5/2017 75 74 6/7/2017 74 72 10/7/2017 73 71
2/6/2017 76 74 6/8/2017 74 72 10/8/2017 73 71
2/7/2017 75 74 6/9/2017 74 71 10/9/2017 72 71
2/8/2017 76 74 6/10/2017 73 71 10/10/2017 72 71
2/9/2017 75 73 6/11/2017 74 72 10/11/2017 73 72
2/10/2017 74 73 6/12/2017 76 72 10/12/2017 72 71
2/11/2017 74 74 6/13/2017 77 72 10/13/2017 73 71
2/12/2017 74 73 6/14/2017 73 72 10/14/2017 73 71
2/13/2017 74 74 6/15/2017 73 71 10/15/2017 72 71
2/14/2017 75 74 6/16/2017 73 71 10/16/2017 72 71
2/15/2017 75 74 6/17/2017 73 71 10/17/2017 72 71
2/16/2017 75 74 6/18/2017 74 71 10/18/2017 73 70

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Temperature (°F) Temperature (°F) Temperature (°F)

Date High Low Date High Low Date High Low

2/17/2017 75 74 6/19/2017 73 72 10/19/2017 73 71
2/18/2017 75 74 6/20/2017 73 72 10/20/2017 73 71
2/19/2017 75 74 6/21/2017 73 72 10/21/2017 72 71
2/20/2017 75 72 6/22/2017 74 71 10/22/2017 73 71
2/21/2017 74 71 6/23/2017 74 72 10/23/2017 72 71
2/22/2017 75 72 6/24/2017 74 72 10/24/2017 72 71
2/23/2017 76 72 6/25/2017 73 72 10/25/2017 72 71
2/24/2017 77 74 6/26/2017 73 71 10/26/2017 72 71
2/25/2017 77 74 6/27/2017 73 71 10/27/2017 73 71
2/26/2017 74 72 6/28/2017 74 71 10/28/2017 73 71
2/27/2017 74 71 6/29/2017 73 72 10/29/2017 72 70
2/28/2017 75 72 6/30/2017 74 72 10/30/2017 71 71
3/1/2017 75 73 7/1/2017 74 72 10/31/2017 72 71
3/2/2017 75 72 7/2/2017 74 72 — — —
REFERENCES

1. Seevers RH, Hofer J, Harber P, Ulrich DA, Bishara R. The use of mean kinetic temperature (MKT) in the handling,
storage, and distribution of temperature sensitive pharmaceuticals. Pharmaceutical Outsourcing. 2009;10(3):30–39.
2. USP. Packaging and Storage Requirements 〈659〉. In: USP 41–NF 36. Rockville, MD: USP; 2017:529–534.
3. Center for Healthcare Supply Chain Research. Factbook: The Facts, Figures and Trends in Healthcare (2015–2016).
86th ed. Arlington, VA: Center for Healthcare Supply Chain Research; 2016:15.
4. USP. General Notices. In: USP 31–NF 26. Rockville, MD: USP; 2008:10.
5. USP. Good Storage and Distribution Practices for Drug Products 〈1079〉. In: USP 40–NF 35. Rockville, MD: USP;
2017:1242–1252. New title proposed in PF 44(4) [July–Aug. 2018]: Risks and Mitigation Strategies for the Storage
and Transportation of Finished Drug Products 〈1079〉.

a Packaging and Distribution Expert Committee. The authors did not declare any perceived or actual conflicts of interest related to the subject matter
of this Stimuli article. The views presented in this article do not necessarily reflect those of the organizations for which the authors work. No official
support or endorsement by these organizations is intended or should be inferred.
b Director, Quality Systems, Cardinal Health.

c Senior Advisor, Pearl Pathways.

d Correspondence should be addressed to: Desmond Hunt, PhD, Principal Scientific Liaison, US Pharmacopeial Convention, 12601 Twinbrook Parkway,
Rockville, MD, 20852-1790; tel +1.301.816.8341; email: dgh@usp.org.

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