A growing trend in the pharmaceutical industry is the development of more complex and fragile products, like biologicals, chemical mixtures, and large molecules (COVID-19 vaccines are an example of this trend).
These products generally require more stringent temperature controls to prevent them from degrading or deactivating during storage and shipment. Making the situation more complicated, different products require storage at different temperatures, from ‘ultra-cold’ (below -50 °C) to normal room temperature (20-25 °C).
An integral part of safely handling these materials is having a temperature mapping protocol in place. Temperature mapping is also important for maintaining regulatory compliance, earning accreditations, and reducing or eliminating the loss of valuable products due to temperature excursions.
In this article, we’ll cover the basics of temperature mapping, how it’s done, and some of the key elements to include in a temperature mapping protocol.
What is Temperature Mapping?
Temperature mapping (or thermal mapping) involves placing a large number of sensors throughout a temperature-controlled space, to thoroughly measure how the temperature of the space varies in three dimensions. Mapping also tests how temperature varies during “stress conditions” like power outages, door openings, shift changes, and variations in outdoor temperature. Several organizations, including the US Pharmacopeia and the World Health Organization, provide detailed guidance on mapping.
It’s important to distinguish between temperature mapping and routine temperature monitoring. Mapping is an exercise where a large number of sensors are placed for a temporary period, to fully characterize the behavior of a space. Monitoring, on the other hand, is conducted continuously, using a smaller number of strategically placed sensors.
The main objectives of a temperature mapping protocol typically include:
- Qualifying or validating a new or upgraded piece of equipment to ensure it is designed and working as intended
- Determining the optimal placement of sensors for ongoing QA monitoring
- Understanding the thermal behavior of a space as part of developing SOPs
The spaces that are mapped in this context include refrigerators, freezers, loading docks, holding rooms, or even entire warehouses. Essentially any part of the pharmaceutical cold chain- specifically, the temperature-controlled spaces used to maintain consistent refrigeration from the point of manufacture to the consumer- can be temperature mapped. Mapping is becoming even more critical as distribution chains become more complex, with many storage locations and the use of multimodal transportation.
How is Mapping Conducted?
A temperature mapping protocol, particularly for highly regulated industries, is thorough and detail-oriented. It can be broken down into three phases:
- Planning, including determining optimal sensor type and placement, and how the system will be stressed during mapping
- In execution, where sensors are placed temperature data is collected over a representative period of time
- Data review
Note that mapping, like most GxP processes, involves creating a full set of records at each step.
Mapping can be carried out in-house, or by an external partner. Using a consultant for mapping is often the most economical option, since a large number of sensors are used (much more than would be needed for routine monitoring), and often the expertise needed to properly design and
execute a mapping project aren’t available in-house. This is especially true for mapping conducted as part of a documented quality assurance program in highly regulated industries.
Part of a comprehensive temperature mapping protocol is to repeat mapping regularly (the WHO recommends every 3 years, for example). Re-mapping can also be triggered by specific events, like installing a new HVAC system or storing new or different types of products.
Best Practices for Temperature Monitoring
The pharmaceutical industry adheres to several requirements and best practices that should be used to correctly perform temperature monitoring and avoid breaking the cold chain during transportation and storage.
Several of these important requirements are set forth by the World Health Organization (WHO). First, medicines and biologics stored in pharmacies should be stored in areas where the temperature is in range of what the manufacturer indicates. Every product’s specific requirement should be noted so that it is not inadvertently placed into general storage if it needs special conditions. General storage, as defined by WHO, is a temperature between 15°C (59°F) and 25°C (77°F).
In spite of best intentions and good equipment, unforeseen complications do occur, such as power outages, heat waves, and other environmental factors. To make temperature mapping protocol and temperature monitoring as accurate and effective as possible, follow these best practices:
- Airflow: proper airflow in a space helps dissipate heat. This can mean open vents, windows, and fans as needed.
- Packaging: Proper external packaging, including the seals and covering that are suitable, help protect medicines from temperature changes.
- Air conditioning: In warm climates and seasons, this is a necessity for storage areas, but attention should be given to scheduling regular maintenance to ensure it remains operable when needed the most.
- Placement: Tightly packed storage conditions can trap heat and cause the gradual buildup of overheated conditions. Boxes should have airflow between them.
How Often Should Temperatures Be Recorded?
An important part of the temperature mapping protocol is setting the frequency of data collection, which is typically variable on modern digital data loggers. During mapping, this frequency should be set to be able to accurately capture the temperature variations that take place during normal operation, like door openings, or temperature control equipment cycling on and off.
For ongoing monitoring, data collection frequency is set based on a balance of operational conditions (like battery life or memory capacity, on loggers that don’t continuously upload to cloud storage), and how often data collection is needed to ensure the safety of the particular product in storage or to meet regulatory requirements. As an example, for vaccine storage areas, the CDC recommends collecting a temperature data point every 30 min using a digital data logger.
Temperature mapping can also be used to determine the required data collection frequency since it provides a quantification of how quickly temperatures can change in space.
Temperature Monitoring Protocols for Pharmacies and Warehouses
A temperature mapping protocol, as we’ve discussed here, is an important component of ensuring product safety and regulatory compliance in areas where pharmaceuticals are stored.
Beyond temperature mapping, some other protocols or SOPs that should be considered are:
- Initial qualification of temperature control equipment
- Regular temperature sensor calibration (note that advanced monitoring solutions can provide automated tracking of calibration status)
- Preventative maintenance of refrigeration equipment, including sensors and loggers
- Review of monitoring data to identify trends (here again, modern, cloud-based monitoring approaches greatly simplify aggregation and review of key monitoring data)
- Response procedures for equipment failures, near misses, and temperature excursions
Understanding the Types of Temperature Conditions
In addition, when it comes to temperature monitoring, there are four types of temperature conditions that industry professionals should be aware of:
- Cool Storage: Defined as conditions between 46 and 59 degrees Fahrenheit or between 8 and 15 degrees Celsius.
- Room Temperature: This is one of the most common storage requirements, and is defined as between 68 and 77 degrees Fahrenheit, or between 20 and 25 degrees Celsius.
- Fridge Storage: This temperature type is defined as between 25 and 36 degrees Fahrenheit or between -4 and 2 degrees Celsius. This is also a common range requirement for pharmaceuticals.
- Cold Storage: A standard defined as between 36 and 46 degrees Fahrenheit and between 2 and 8 degrees Celsius. Note that this temperature condition is the ideal range for inhibiting microbial growth and chemical reactions and is often used in pharmacies.
What Is Temperature Mapping Validation?
A temperature mapping protocol can also be part of a larger validation procedure. In the pharmaceutical industry, the term validation has a specific meaning, which is to demonstrate that a piece of equipment satisfies its intended purpose by collecting objective data.
This is broken down into installation, operational, and performance qualifications (IQ, OQ, and PQ). Temperature mapping fits into the OQ and PQ steps. Specifically, mapping a space empty, just after installation, could be part of an OQ plan, while mapping while the space is loaded, simulating operating conditions, can be part of PQ.
Technology’s Role in Temperature Mapping and Monitoring
With the importance of monitoring and maintaining ideal temperatures, most of the pharmaceutical industry now relies on technology rather than manual methods of data collection. The more automated and advanced the system, the less risk of dangerous and costly temperature excursions. Many facilities are trending towards cloud-based systems like those from Dickson. Cloud-based systems mean access from anywhere, anytime – monitoring the critical environmental factors that means safety and efficiency for biopharmaceuticals at any stage of the cold chain.
Another benefit of cloud-based systems like those by Dickson is the ability to track, trend, and store data off-site, safely. With important industry information secure in the cloud, there is very little risk of lost data, and key stakeholders can access it from anywhere. Continuous data monitoring with alarms, alerts, trending, and accessibility helps keep businesses thriving and patients safe while protecting the valuable supply of biopharmaceuticals.
Temperature mapping is an important part of commissioning and maintaining temperature-controlled spaces for pharmaceuticals. Mapping is a thorough, detail-oriented process that has significant hardware demands and requires thoughtful planning. For this reason, it is not uncommon to engage an external expert for mapping exercises.
Questions about temperature mapping, or temperature mapping for the pharmaceutical industry? Contact the experts at Dickson.