Temperature and Humidity Validation: Mapping in Storage Area

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Pharmaceutical ingredients are placed or stored at various places for example raw material storage area, refrigerator, quarantine area, large cold rooms, packaging room, freezer, warehouse etc. Depending on given storing conditions (temperature and humidity) these are stored in different places.

  • Some are stored in refrigerators eg. Vaccines
  • Some are stored in ambered/dark coloured containers to prevent degradation from sunlight

So for maintaining proper storing conditions (temperature, humidity and light) mapping of areas is necessary. Mapping of these areas is important for maintaining stability as temperature and humidity plays crucial role in degradation.

Different materials have different temperature and humidity limits which can be tighten for better conditions and results. Temperature and humidity errors should not be more than ±0.2 ᵒC & ±3% respectively.

Need for temperature mapping:

  1. To check whether temperature in whole area is uniform or not and within given specified limits.
  2. To check temperature fluctuations at various locations within the specified area
  3. To record the temperatures at different areas of volume with sensors/probes or data loggers
  4. Preparation of mapping report and taking further actions for improvement in maintaining uniform temperature and air distribution

Mapping area may be any place where pharmaceutical ingredients can be stored or processed for any unit operation. It can be

  • Autoclaves
  • Large cold rooms
  • Incubators
  • Warehouses
  • Stability chambers

Warehouse is a place where pharmaceutical raw materials and finished products are stored and temperature and humidity should be controlled (within limits) in order to maintain their quality and efficacy because these are responsible for degradation. Mappings should be done hottest days of summer and coldest days of winter.

So, In order to protect materials from degradation due to temperature and humidity one should follow Clause 3.19 of PIC/S GMP guide which states that storage areas should be designed and adapted to ensure good storage conditions. They should be clean and dry and maintained within acceptable temperature limits.

validation data loggers in fridge

Large commercial refrigerators and walk-in cold rooms should be mapped with an electronic temperature recording devices which can measure temperature at different locations. Portable data loggers may be used in place of fixed ones. Internal air temperature distribution should be checked and recorded in empty and loaded state. Mapping should carried out every two to three years and can be repeated if needed, after changes in layout, placing of racks, and change in placing of data loggers.

Temperature mapping operation:

Each mapping operation should be carried out through selected/given protocol. A standard and detailed protocol should be used. Ideal mapping protocol should contain

  • Mapping dates and time
  • Approval page
  • Number of probes to be used
  • Change control history
  • Reviewed and mapped by
  • Acceptable limits and errors
  • Hot and cold spots
  • Methodology used
  • Reporting

 

Materials/Equipment:

Thermocouples/ data loggers or electronic data logging monitors (EDLMs) which should be

  1. Calibrated and have an accuracy of at least ±0.2 to ±5ᵒC.
  2. These equipments should have temperature range of -30ᵒC to +60ᵒC so that all ranges of temperature can be recorded.
  3. It should have data storage and analytical software that obeys regulatory requirements (21 CFR part11)

STEP 1: Survey of site of mapping

Following information should be collected from survey

  • Measurements of all three dimensional space length, width and height.
  • Number of racks in area, cooling and heating sources, fans for air distribution and mixing
  • Location of pre-installed sensors or probes.

 

STEP 2: Determination of critical mapping points

It is a cumbersome job to maintain uniform air temperature and distribution or temperature/humidity level in large open spaces, so it becomes mandatory to identify problem locations/spots. Problem locations/spots (hot or cold spots) may be defined as space where a temperature/humidity level fluctuates. It may include or occurs due to

  • Pellet racking stores with more heights are more vulnerable to temperature stratification and can create hot spots so it is very essential for mapping.
  • Variation in temperature due to slow/poor speed of fans or undersized fans
  • Areas near to ceiling and exterior walls may be warmer or colder in response to outside temperatures
  • In large storage areas chances of variation in temperature is more as size of area increases
  • Temperature will be higher or colder near to their sources as compare to distant area
  • Improper cooling or heating due to frequent door opening or doors that are left open

 

STEP 3: Placement of sensors/ data loggers

According to ISPE (International society of pharmaceutical engineering), for mapping of refrigerators, incubators, controlled chamber rooms, stability chambers

Area  2m³ in volume                   ————              use of 9 sensors

Area 2m³ to 20m³ in volume     ———–               use of 15 sensors

More than 20m³ volume           ————               more than 15 sensors

Placement of 9 sensors for area less than 2m³ should be adjusted in all corners and one in center.

If volume is between 2m³ to 20m³, 15 sensors should be used with additional placement on each wall, ceiling, and in center of floor.

For more than 20m³ volume, additional sensors can be placed equidistantly between walls and sensors.

For large open areas, previous studies have shown that spacing of every 100-300 feet between data loggers is suitable for correct reporting. Spacing shorter than 100 feet will add extra work and data which is not meaningful. Each sensors/data loggers should be labelled with a unique ID

STEP 4: Sample frequency

The correct way to determine sample frequency is not to take too large or too less samples. Large or extra samples will create statistical problem and will overload work. A gap of 15 minutes should be taken to evaluate readings.

STEP 5: Logged data download

After placement of loggers/ sensors and recording of data. Collect the data loggers and transfer it into computer

STEP 6: Documentation

Place all loggers back into their original spaces/spots as marked before mapping and document and consolidate the collected data for further analysis

STEP 7: Analysis and Interpretation

All collected readings of temperature and humidity should be analysed against accepted limits. Note and identify the variations in readings and in areas

  • Based on the collected data, fluctuations in readings should be shown in graph and table format with clearly mentioning of acceptance criteria so that easy interpretation can be done
  • Note down the factors that show collected temperature variations for example, variations near to and far away from cooling and heating sources.

 

Points to be remembered

  • All the data loggers/ sensors should be calibrated before mapping of area
  • Locations or spots should be marked before placing data loggers
  • All data loggers should be labelled with a unique ID
  • All operation should be done as according to the protocol
  • Given limits of temperature and humidity should be followed
  • Mapping operation should be carried out in normal working days instead of holidays
  • Areas should be mapped in empty and in loaded state in order to determine temperature in both conditions

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