5 Frequently Asked Questions about Temperature and Humidity Validation/Mapping
This week's blog is based on Paul Daniel's recent Application Note (see below):"Five Frequently Asked Questions on Validation/Mapping."
Paul has over 15 years' validation experience in the pharmaceutical industry and is currently Vaisala's senior regulatory expert.
The FDA mandates validation of environmental conditions that can affect the strength, identity, safety, quality, and purity of pharmaceuticals, medical devices, or biologics. To meet these requirements for temperature or humidity, we perform a mapping validation, usually with an installation qualification and operational qualification of the area, incubator, fridge/freezer, stability chamber, cold room, or warehouse.
Most people who contemplate doing a mapping validation for the first time look for answers to these five questions:
- What limits should I use as an acceptable range for my study?
- What type of sensor(s) should I use?
- How many sensors do I need, and where should I place them?
- What kind of calibration do my sensors require?
- What is the appropriate duration for a mapping study?
What limits should I use as an acceptable range for my study?
This depends on what you are storing. You should be able to use the results of your stability studies, or the recommended storage conditions from the manufacturer of the product you are storing. You can use tighter limits if you wish, but it will be hard to justify using limits that are wider.
What kind of sensors should I use?
Your sensors should measure the attribute of concern—e.g., temperature and humidity. They should be accurate: An error of ±0.2°C is good for temperature, and ±3 percent is good for relative humidity. If you use devices that require software, you will need to show that the software has been validated and is compliant with 21 CFR Part 11.
How many sensors do I need?
The International Society for Pharmaceutical Engineering (ISPE) provided some guidance in its document, “ISPE Good Practice Guide: Cold Chain Management” published May 2011. For spaces less than 2 m3 in volume, nine sensors are recommended. For spaces between 2 m3 and 20 m3 in volume, 15 sensors are recommended. An additional sensor should be placed adjacent to the display, control, and monitoring probe(s), if applicable. If you are mapping spaces with volumes larger than 20 m3, there is no easy guideline. You must assess the space and determine likely sources of variation in temperature and humidity, such as HVAC systems, doors, and windows. An approach to larger spaces is to limit the sensor placement to the spaces where product is actually stored. However, if you map only the racks and shelves, the area will require procedural controls to ensure that product is stored only in the areas that were mapped.
What kind of calibration do my sensors require?
Sensors must be shown to be in calibration prior to the study, and the calibration must be verified following the study. NIST traceability is expected. If you have purchased or rented sensors, you can likely depend on the vendor to supply initial calibration services.
What is the appropriate duration for a mapping study?
Your study should be long enough to provide confidence that you have accurately captured the environmental dynamics of the space being mapped. Forty-eight hours is sufficient for most small spaces under 2 m3 and five to seven days is common for warehouses. However, the larger the space, and the more actively it is used during the study, the longer the expected duration of mapping. For a warehouse in use five days a week, a study duration of one week may be appropriate. Consider seasonal changes as well for large spaces, performing your mapping studies during the hottest and coldest times of the year.
For all of these questions, it’s important that you develop a clear rationale for your choices and document them in your validation protocol. Your rationale should be scientifically based, appropriate to your facility and product, and suitable for the intended use of the space being mapped.