SOP FOR TEMPERATURE MAPPING STUDY

Standard operating procedure of temperature mapping study in biological

incubators, refrigerator and freezer using calibrated probes and data logger in
pharmaceutical industries.

1.0 OBJECTIVE To lay down the procedure for temperature mapping.

2.0 SCOPE This SOP shall be applicable for walk-in coolers, biological incubators,
refrigerator and freezer.

3.0 RESPONSIBILITY Officer/ Executive/ Assistant Manager

4.0 ACCOUNTABILITY HOD of Engineering and QA

5.0 PROCEDURE 5.1 Temperature mapping is to be carried out by using the calibrated
temperature probes and data logger.
5.2 Identify positions & number of locations for temperature mapping such that, it covers
every corner & center of the chamber.
5.3 Prepare a protocol for temperature mapping indicating objective, scope,
responsibilities, methodology, acceptance criteria, calibration status, summary and
conclusion.
5.4 Protocol to be prepared by officer/ executive of concerned department, checked by
the head of concerned department and shall be approved by head QA/QC.
5.5 Place temperature probes at the identified locations without touching the tip to any
surface inside the chamber.
5.6 Select the number of channels and set the print interval of 30 minutes on the data
logger.
5.7 Start the mapping after stabilization of the displayed temperature.
5.8 Record the temperature readings of each probe in temperature mapping record.
5.9 If results do not fall within the specified limit, take necessary corrective actions to
rectify the failure & perform the mapping again.
5.10 Final report for temperature mapping to be prepared by officer/ executive of the
concerned department based on results obtained indicating the summary and
conclusion.
5.11 Report shall be checked by the head of concerned department and shall be
approved by head QA/QC.
5.12 After approval of the report daily monitoring shall be done at the identified hot spot.
5.13 For new equipment, the mapping is to be done for three consecutive days.
6.1 SOP: Standard Operating Procedure
6.2 QA: Quality Assurance
6.3 QC: Quality Control
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 TEMPERATURE AND HUMIDITY VALIDATION/ MAPPING IN
STORAGE AREA
Learn about the temperature mapping including the location and number of
sensors to be placed in the area. Temperature and humidity are important factors in the
stability of the pharmaceutical ingredients. Temperature sensitive materials can degrade
at a higher temperature, therefore, it important to validate the storage area for
temperature.
In pharmaceuticals refrigerators, incubators, stability chambers, controlled
sample rooms and raw material storage areas are need to be validated. These areas
are monitored for 24 hours for three consecutive days.
Limits of the temperature and humidity depend upon the material to be stored in
the area. These should be defined according to the recommendation of the
manufacturer. We can tighten the limits but it should be justified when we use the wider
limits.
Measurement of temperature and humidity should be accurate. Error in
temperature and humidity should not be more than ±0.2°C and ±3% respectively.
Thermocouples or data logger can be used for the monitoring of the area. If any
software is used for the collection of data then it must be validated and comply 21 CFR
Part 11 guidelines.
The number of sensors used in temperature and humidity mapping is a confusing
topic for the pharmaceutical professionals because most of the regulatory guidelines do
not say about the number of sensors to be used in mapping. According to USP a
suitable number of thermometers or other temperature recording instruments should be
used for temperature mapping.
But International Society for Pharmaceutical Engineering (ISPE) says to use 9
sensors for the area less than 2 m3 in volume. These sensors should be placed in all
corners and one in the center. If the volume of the area is between 2 m3 to 20 m3 , 15
sensors should be used for mapping. Placement of 9 sensors should be done as 9
sensor configuration and addition sensors should be placed at the center of the floor,
ceiling and four walls.
If the area is larger than 20 m3 , additional sensors should be used by
understanding the criticality of the area. Some distance should be maintained between
the wall and the sensors. All sensors must be calibrated before starting the mapping
and should be traceable to NIST.
Mapping should be done twice in a year in coldest and hottest days of the year in
any GMP storage facility. Hotspot should find the mapping and routine temperature
mapping should be done at this point.
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How many sensors should I use in a temperature mapping study?

Well, although there is no predicate rule establishing the amount of measuring sensors
to be used when mapping a volume, there is guidance to help you determine sensor
amount and placement. Guidance is available from The International Society for
Pharmaceutical Engineering (ISPE), the World Health Organization (WHO) and the
United States Pharmacopeia (USP), among others, as listed at the end of this article.
This article summarizes them for you.

Commercial-off-the-shelf freezers, refrigerators, incubators and environmental

chambers

Figure 1 - Recommended sensor placement for internal volumes up to 2 cubic

meters

Use 10 temperature sensors in chambers with internal volume of up to 2 cubic meters.

Place 9 sensors within the usable volume. Figure 1 suggests sensor placement. Place
an additional sensor near the probe of the device that monitors and/or controls the
system.

Why is this? You are mapping worst-case locations under the assumption that any other
location contained within the usable volume will not experience temperatures exceeding
these extremes. The corners represent the intersection of the most planes (3) that are
exposed to outside air temperature. Also, corners tend to have the least air circulation.
Therefore, each corner represents a potential worst-case location. Conversely, the
center of the usable volume is farthest from the outside air. It is also most likely to have
good air circulation. Likewise, it represents a potential worst-case location. Together,
these locations are most likely to experience temperature extremes. Include a rationale
in the temperature mapping protocol to explain all assumptions.

Figure 2 - Recommended sensor placement for internal volumes up to 20 cubic

meters

Use 16 temperature sensors in chambers with internal volume of up to 20 cubic

meters. Place 15 sensors within the usable volume as recommended in Figure 2. The
extended length of the sides in bigger chambers makes the center of each pane a point
of interest since its temperature might differ significantly from that of the corners. This is
due to its proximity to the center of the usable volume. Place an additional sensor near
the probe of the device that monitors and/or controls the system. This will be needed to
determine alarm and control offsets by correlating temperature differences between
these locations and the worst-case locations identified in the study.
Warehouses, cold rooms, walk-in freezers and walk-in refrigerators

Distribute sensors in a grid format every 5 to 10 meters along the width and
length of the area3. For very large facilities, sensors can be placed up to 20 or 30
meters apart. At each point on the grid, arrange additional sensors vertically forming
layers. Use three layers for rooms with ceiling up to 3.6 meters. Consider adding more
layers for rooms with ceiling above 3.6 meters. Place an additional sensor near the
probe of the device that monitors and/or controls the HVAC. Map product storage areas
only. Provide rationale if adding sensors in other areas of interest. Temperature
mapping should consider other factors that may contribute to temperature variability
such as the size of the space, location of HVAC equipment, sun-facing walls, low
ceilings or roofs, geographic location of the area being mapped, airflow inside the
storage location, temperature variability outside the storage location, workflow variation
and movement of equipment (weekday vs. weekend), loading or storage patterns of
product, equipment capabilities (e.g., defrost mode, cycle mode), and operating
procedures.