Properly qualifying ultra-low temperature (ULT) freezers for pharmaceutical product storage is a complex but critical process. Any compromises can put drug safety and efficacy at risk. In a comprehensive Leading Minds Network webinar, experienced ELPRO qualification/validation engineers Melanie Krüger and Marisa Remsing provided detailed insights on avoiding common pitfalls that can invalidate mapping results.
Selecting Appropriate Data Loggers
A key first step is choosing data loggers that can accurately measure temperatures within the ULT range required. For example, data loggers rated down to -80 °C would be unsuitable for a -150 °C application. Matching the data logger specifications to the expected operating range is essential.
The calibration status of the data loggers is also crucial. Guidelines recommend that they be calibrated within the past year to ensure measurement accuracy. Having current calibration certificates available for each individual data logger is necessary for compliance. In addition, the logging interval can affect capturing temperature fluctuations during critical qualification tests. While 15-minute readings are generally acceptable, shorter 1-2 minute intervals are preferable to detect brief transients when doors are opened or power fails. This provides much more valuable qualification data.
Strategic Data Logger Placement
Simply using an adequate number of data loggers is not enough – their precise placement within the ULT unit is critical to identify potential hot and cold spots. Melanie Krüger advised following established mapping grids in current guidelines to ensure thorough coverage of the interior storage space. For example, a typical 3x3 layout on each shelf level alternates data loggers in the front, middle and back rows. Consistent documentation of exactly which data logger ID is located in each defined mapping location is also essential for analyzing results.
Using a Representative Thermal Load
Guidelines indicate that worst-case scenarios of both an empty unit and a fully loaded unit should be mapped. However, the materials used to simulate “product” in the loaded run must match the actual thermal mass of the real stored materials to provide meaningful data. Marisa Remsing cautioned against using empty cardboard boxes as placeholders during loaded mappings. The boxes interfere with airflow but do not replicate the heat absorption capabilities of actual product. Gel packs designed for pharmaceutical use better mimic drugs, vials and other materials typically stored. The fill level is also important – the unit should be loaded to approximately the same capacity expected during routine operation. Partially loading the unit changes air currents and heat distribution compared to completely full.
Maintaining Accurate Documentation
Meticulous record keeping is vital throughout the qualification process. Remsing noted that all references must be current, with acceptance criteria clearly defined upfront in documentation. This prevents issues arising during analysis of results. Engineers should document any deviations from protocols immediately at the time they occur on site. Trying to reconstruct details afterward to determine if a deviation invalidates any results is problematic.
Following testing protocols exactly as specified ensures consistent, controlled conditions between qualifications. Krüger pointed out some common execution lapses, like not fully opening unit doors for the defined duration of door opening tests. Only partially opening doors distorts airflow and temperature mapping results. Carefully replacing any loggers that must be temporarily moved to access units during loading avoids accidentally shifting logger positions. Even small location changes could mean missing a potential hot spot.
Avoiding Sole Reliance on Family Qualifications
While multiple identical units from the same manufacturer may seem interchangeable, Krüger advised qualifying each individually. Even units sitting side-by-side can experience slight differences in temperature gradients due to external factors like airflow. Assuming interior conditions are identical risks incorrect mapping data.
Several audience questions were also addressed during the Q&A session and presenters responded with the following:
- Calibration guidelines do not dictate specific intervals - annual recalibration is typically recommended as best practice.*
- Single-use data loggers for each mapping point are generally preferred over multi-channel units to simplify documentation.
- Acceptance criteria for calibration should be maximum ±0.5 °C from the reference value (according to WHO Guideline) at each calibration point.
- Complete remapping should be performed whenever physical changes are made to the storage unit configuration to capture new temperature profiles.
- Qualifying multiple identical units simultaneously is advantageous and compliant.
- Checking data logger function before and after use is determined by internal company procedures.
- While not required, open door and power failure tests provide useful supplemental qualification data in terms of commissioning (ISPE Guideline).
ULT storage demands stringent qualification protocols to ensure pharmaceuticals and valuable samples remain within specifications. This webinar provided valuable insights on avoiding shortcuts that could compromise critical temperature mapping data or validity. Investing the time upfront to perform comprehensive qualifications carefully helps ensure and maintain drug product safety and efficacy.