[0:05] Podcast Intro Welcome to Measuring Up, Thinking Out Loud, featuring news and information from Testo, your consultative resource for precision measurement technology and digital solutions, serving the pharmaceutical, industrial, and allied industries worldwide.

[0:23] Bill White: Hello again, this is Bill White for Testo. With us today is Nathan Roman. Nathan is a validation and compliance leader with more than 25 years of experience in the pharmaceutical and biotechnology industries and the author of a book we'll take a look at later in this interview. Nathan, welcome to the Testo Information Network.

[0:45] Nathan Roman: Hey Bill, thanks for having me on. I appreciate it.

[0:48] Bill White: Nathan, as an expert in temperature mapping, let's get started with your overview of temperature mapping, what it is and why it's important for us to understand it.

[0:59] Nathan Roman: That's a good question, Bill. A few years ago, I wrote a book called 6 Steps to Effective Temperature Mapping because I saw so many people responsible for these environments who knew mapping needed to happen but didn't always understand where it fit or how to approach it correctly.

So at its core, temperature mapping is the process for measuring and documenting temperatures throughout a controlled environment over time to prove that a space is suitable for its intended purpose. The easiest way to explain that is imagine there is invisible weather happening inside every controlled space, every controlled environment, and even if a refrigerator says 5 degrees Celsius on the display, the entire unit is not exactly 5 degrees inside everywhere. So we know that heat rises, cold air falls. We know that when you open a door that affects the temperature, and airflow, of course, creates hot and cold spots. So temperature mapping helps us scientifically understand what's actually happening throughout the space instead of just trusting the display.

[2:09] Bill White: Nathan, in general, where does temperature mapping apply in the life science, pharma, biotech industry?

[2:17] Nathan Roman: Temperature mapping applies almost anywhere that temperature sensitive materials are stored and handled. And for those listening, that if you're aiming to comply with regulatory requirements, there is a continued emphasis by regulators on the need to perform temperature mapping on these controlled temperature environments — and that would include ULT freezers, ultra low temperature freezers, refrigerators, incubators, walk-in cold rooms, stability chambers, warehouses, and of course the transportation systems.

I want to note that every environment behaves differently. A warehouse behaves very differently than a refrigerator because now you're dealing with airflow, HVAC systems, ceiling height, loading docks, and of course the seasonal conditions. So that's why temperature mapping strategy changes depending on the environment and the equipment, of course, and your risk applied.

[3:14] Bill White: Nathan, how do you actually perform temperature mapping?

[3:18] Nathan Roman: So temperature mapping is performed by placing calibrated sensors throughout the environment throughout the chamber in a structured grid pattern. So we're going to look at all four corners of the unit. We're going to look at the geometric center of the unit. So we're looking at top and bottom, middle. We're going to place near doors, and of course we place sensors near the control or the monitoring probe inside that unit or inside the space.

We are going to collect data over a defined period of time under operating conditions. So the goal is to understand how that temperature behaves throughout the entire usable space. Some of the tools that we use: we use calibrated data loggers for some environments, we are going to use thermocouple systems, of course we will use mapping software, we will have calibrated equipment that provides certificates, and of course we are going to build qualification protocols.

Before the study even begins, there is a lot of preparation before mapping. So we're going to put together the protocols, we're going to get approvals, we're going to need to have acceptance criteria. We're going to do a calibration review. Sometimes we will need a sensor placement rationale. We're going to go out and we're going to walk down the equipment, make sure everything is ready for execution. So good temperature mapping starts long before one data logger is placed inside that unit.

[4:43] Bill White: We're talking with Nathan Roman about temperature mapping in the pharma biotech industry. Nathan, what compliance criteria are driving temperature mapping projects nationwide?

[4:57] Nathan Roman: That's a good question, Bill. Actually, the regulations don't always tell us exactly how to perform mapping. So what they expect is proof of control — can you scientifically demonstrate that the environment consistently protects the product? That's what they are looking for.

So we are typically going to align testing our qualification with guidance from FDA, USP, WHO, ISPE (the International Society of Pharmaceutical Engineers), and we're going to follow good documentation practices and of course GLP or GMP expectations. The inspectors are going to want to see sound methodology. They are going to look for defensible data, proper calibration, and they are going to look for risk-based decision making and ongoing control of that environment. Documentation is your evidence for proving you have control over your temperature environment.

[6:02] Bill White: Temperature mapping requires proven methodology and documentation, of course. Nathan, what are some of the best practices that apply to temperature mapping?

[6:13] Nathan Roman: One of the biggest best practices is making sure the study reflects real operating conditions. Real facilities are dynamic — doors open, people come in and out, power potentially could fluctuate, HVAC systems cycle. So we often perform door opening tests, recovery studies, loaded studies, power failure assessments and alarm verifications.

Recovery testing is especially important because we want to know how long temperatures may have drifted, how severe that excursion was, and how quickly that unit can recover. Another major best practice is proper monitoring probe placement, so mapping data should help determine where your permanent monitoring probes belong, especially in worst case areas. We will take the data after a temperature mapping, analyze the results, and be able to recommend or suggest where those permanent monitoring locations should be placed.

[7:13] Bill White: Nathan, that process then involves many sensors and data points aggregated throughout the duration of the test. What happens to all of this information? How is it managed?

[7:27] Nathan Roman: Well, a mapping study, as you can imagine, generates large amounts of data, but the real value is understanding what that data means.

So we are evaluating hot spots, cold spots, min and max temperature readings, the uniformity, recovery behavior, excursions if there are any, and trends over time. We will take that information and look to improve the monitoring locations, improve our storage practices, maybe even alarm strategies. Sometimes we have alarm delays and we need justification on why we are setting the alarm delays at the value we are setting.

We use this information to help improve our SOPs, operational and use maintenance of refrigerated freezers. Sometimes the open door studies can help provide guidance as to how long you can actually hold that door open, and you proceduralize that and put that in your SOP. In a regulated environment, data integrity is crucial — everything must be calibrated, traceable, documented — because in validation there has been a saying for years and years: if it's not documented, it didn't happen.

[8:48] Bill White: Nathan, there are so many things that have to be done right insofar as temperature mapping obligations of any company or enterprise associated with managing biological, chemical specimens and materials. What are some of the mistakes to avoid through this process?

[9:06] Nathan Roman: One of the biggest mistakes is assuming that the temperature display represents the entire environment — we touched on this earlier, because we know that it usually doesn't. Another thing to avoid is poor sensor placement. Placement should always be intentional and risk-based. I also see organizations underestimate the airflow and operational impact. And honestly, another major mistake is treating mapping like just a paperwork exercise instead of a scientific investigation, because good mapping tells you how the system behaves, where the risks are, how quickly the environment can recover, and what monitoring should actually occur. These are where the real values exist and how temperature mapping can truly help us.

[9:57] Bill White: Great information, Nathan. Thank you so much for sharing. We mentioned at the onset of this podcast that Nathan Roman has written a booklet that offers insights and a broad look at temperature mapping in the industry, and the booklet is appropriately titled Six Steps to Effective Temperature Mapping. For a copy, it's available to download from Nathan's website at www.nateroman.com. The Testo U.S.-based service team offers expert temperature mapping services designed to meet GxP and regulatory requirements. To learn more reach out to us online at info@Testo.com. Until next time, this is Bill White for Testo.

[10:33] Podcast Close: You've been listening to Measuring Up, Thinking Out Loud — news and information from Testo, your resource for precision measurement technology and digital solutions for pharmaceutical, industrial, and allied industries worldwide.