Warehouses Qualification / Thermal Mapping

The environmental parameters of rooms in a pharmaceutical facility are critical from the perspective of GMP/GDP (GxP) requirements. This is especially true for areas where medicinal products are stored for extended periods. The environmental parameters include:

Temperature
Relative humidity

In some cases, static differential pressure in the room may also be considered an environmental parameter, which refers to the air pressure inside the room relative to a reference area. This reference area could be other rooms, technical zones, the space above the ceiling, or outdoor atmospheric pressure. For rooms where no open product handling takes place, and which are not classified as cleanrooms according to the definitions in Annex 1 of the EU GMP Guidelines, differential pressure is generally not a critical parameter.

Depending on the size and geometry of the room, air temperature and humidity parameters may vary at different points within the room, resulting in a temperature and/or humidity gradient. The magnitude of such a gradient increases under the influence of the following factors:

Large room size
Elongated room shape
Presence of stagnant zones or insufficient air mixing within the room
Presence of heat or moisture sources inside the room
Proximity or presence of a door or gateway leading to areas with different temperature/humidity conditions, including outdoors

Typical rooms with the most significant temperature/humidity gradients, considering the factors listed above, are storage areas. Moreover, medicinal products spend the longest time in storage areas, making the impact of environmental factors potentially critical.

There are two types of activities to confirm that the environmental parameters in a room meet the requirements:

Measurement of environmental parameters as part of Operational Qualification (OQ) of the room
Monitoring of environmental parameters within the room

For small rooms, during the Operational Qualification (OQ), it is usually sufficient to measure environmental parameters in 1-2 points. For monitoring purposes, 1-2 sensors are also enough for such rooms.

In storage areas, where significant temperature/humidity gradients may occur, Operational Qualification (OQ) must cover a larger number of points. To gain a proper understanding, an investigation of the distribution of environmental parameters within the room is conducted. Since relative humidity requirements in storage areas are usually set within fairly broad limits, and moderate humidity gradients are unlikely to cause values to exceed permissible limits in certain zones, the investigation typically focuses on temperature.

Such an investigation may consist of the following steps:

Conducting a risk assessment and theoretical identification of potential "worst-case" zones where the temperature reaches its maximum or minimum values.
Measuring temperature with a handheld device at various points inside the storage room to confirm the previous theoretical assessment and more accurately determine the "worst-case" points.
Performing thermal mapping of the storage area using autonomous devices placed at various points inside the room, recording temperature values over an extended period – data loggers.

During thermal mapping, the required number of data loggers is placed in the previously determined "worst-case" points, while the rest are evenly distributed within the storage space at key points in a three-dimensional grid with a fixed spacing step. Since the warehouse gates are periodically opened for loading/unloading, and the frequency of these operations may vary depending on the day of the week, thermal mapping should cover all days of the week, meaning it should last at least one week. The typical duration of thermal mapping is two weeks.

Depending on the climate conditions in the area where the storage facility is located, seasonal repetition of thermal mapping may be required during the hottest and coldest periods. For most locations in the Northern Hemisphere, warehouse thermal mapping is performed twice a year: in winter and summer.

In cases where gradients and humidity fluctuations could be critical, humidity mapping is also conducted in addition to thermal mapping.

The results of the mapping are considered when determining the placement of monitoring system sensors for environmental parameters. These sensors should primarily be placed in the "worst-case" points confirmed by the study, accounting for both the cold and hot seasons. Similar to the loggers used during thermal mapping, some sensors are distributed within the storage space at key points in a three-dimensional grid with a fixed spacing step.

The specialists at Tarqvara Pharma Technologies have years of experience in conducting qualification, validation, and acceptance tests within the pharmaceutical industry, in full compliance with international, European, and national GMP/GxP regulations and standards.