The biopharmaceutical industry is experiencing an unprecedented increase in demand, which is expected to continue for the foreseeable future. In response, companies are scaling up their operations as quickly as possible. However, since it is heavily regulated, rapid scale-up in biopharma is more complicated than other industries. Being able to scale up quickly and safely requires a detailed knowledge and adherence to GxP (good practices), and a healthy amount of planning.
In this article, we’re going to focus on temperature mapping, which is a GxP process that’s used when qualifying new storage areas or process units designed for thermal control. It is commonly done on:
While temperature is the most commonly mapped environmental parameter, humidity is often mapped simultaneously.
In this article, we’ll cover some of the reasons that mapping is important, and provide a step-by-step guide for how to run a successful mapping project. Like most GxP processes, it is highly detail oriented and heavy on documentation, but with a well-designed plan, it can be straightforward and highly informative.
One of the cornerstones of GxP is validation. In the context of pharmaceutical manufacturing, validation is the process of confirming and documenting that a piece of equipment or a process satisfies its intended purpose, through the use of objective data. For a temperature-controlled storage area, the intended purpose is to safely store materials, and the objective data is what you’ll generate in a mapping exercise.
Going one level deeper, validation of equipment is broken down into IQ, OQ, and PQ steps (installation, operational, and performance qualification). Mapping with the storage area empty and as-installed can be considered part of OQ, and mapping it with the storage area full, while simulating normal operations, can be considered part of PQ.
As the name suggests, mapping is the measurement of environmental conditions in three dimensions. This is done by systematically placing many temperature and/or humidity sensors throughout the area you are mapping, then monitoring them over a representative period of time. The results of a mapping project will help you understand environmental variations in critical spaces, as well as how the space is affected by stress conditions like loading, door opening, power outages, or anything else that might be expected during normal operations.
The sensors used for mapping are usually part of an integrated data logger that can store the recorded data internally, or continuously transmit it to a central location. A wide variety of logger configurations are available- we’ll talk more about where data logger and sensor selection should fit into your plan in the strategy section below.
It’s important to note that mapping is different from routine monitoring, when a smaller number of sensors are used during normal operations. (However, they are related, since mapping can guide your placement of sensors for monitoring.)
The primary goal of temperature mapping is quality control. Thoroughly mapping a storage space or process unit will confirm that the space is appropriate for its purpose, which is the central element of the qualification process.
Mapping can also indicate whether you need to rearrange your storage spaces- for example, by telling you how far from a warehouse door you should store materials, or whether boxes in a fully loaded freezer should be kept away from coils or fans. It’s also an indication of how well your environmental control equipment is working, and whether it is sized and tuned correctly.
Mapping is also a requirement for regulatory compliance. In the US, the FDA enforces safe handling of pharmaceuticals under various parts of 21 CFR, and you’ll see problems with temperature control come up frequently in observations and citations from audits. Compliance requires a justified, documented process for mapping, including how to follow up on mapping results.
Finally, the results of a mapping process are used to optimize the placement of monitoring sensors. For example, locations of temperature extremes can be used as monitoring points, to make sure that the sensors are capturing the full range of conditions in the space.
The most important part of a mapping project is to have a detailed plan that is justified through a risk-based thought process. This is a general requirement for many GxP processes, but beyond that, a detailed plan will make the later execution steps much easier.
One part of the plan should be focused on higher level strategy, and include:
A second part of the plan should provide logistical details such as:
The length of the mapping exercise and the placement of sensors should be determined in order to get a complete record of normal operations across the entire space. More specific guidelines are available from the WHO, ISPE, USP, and PDA. From a regulatory point of view, it’s important that any logistical choice you make is documented and justified.
Depending on the size of your organization, you may consider engaging with a third-party consultant for help with mapping. There are two main reasons for this: first, a large number of data loggers are needed for mapping, many more that you’re likely to use for routine monitoring. Second, the experience of a consultant can save time and effort on the part of your in-house staff.
Once you have a plan in place, here are the typical steps for executing a mapping project:
A final consideration for your report should be any events that would trigger re-mapping, like installing a new HVAC system or storing a different product mix, and whether re-mapping should be conducted on a regular basis.
Temperature mapping is a time consuming, meticulous process, but it is a necessary part of bringing new storage areas on line and expanding your operations. Having a detailed, well-documented plan is the most important element to making sure you’ll have a successful mapping project that generates actionable data and ensures regulatory compliance.
Questions about temperature mapping, validation, or environmental monitoring? Contact the experts at Dickson.