How important is temperature control?
Temperature is one of the most important parameters to control. Food and drug products must be stored and transported according to predetermined conditions (for example, 2°C – 8°C). Distribution of products must be transported, handled, and stored in a manner that mitigates the risk of exposure to temperature excursions. Current Good Manufacturing Practices (cGMP), according to the FDA requirements, are set in place to maintain the safety, quality, and efficacy of the products. Storage temperature is very important in maintaining these critical attributes, because drug products or samples stored are temperature dependent and must be well sustained and controlled.
Controlled Temperature Chambers (CTC) used to store drug products should be qualified.
We are all familiar with equipment such as freezers, refrigerators, incubators, and walk-in cold rooms, but perhaps we don’t all know what goes into keeping them maintained and in a state of compliance.
A manufacturing facility or a research laboratory operating in the Health and Life Science Industry must comply with regulatory requirements and that is no simple task. Doing so ensures that products are manufactured and delivered safely under meticulous regulation and standards. These regulations and standards are well-known to those in the industry, but the questions sometimes come from finding the best way to comply.
Everybody knows what needs to be done, but they’re not always sure how to get there. We definitely know how to get there because that’s what we do, over and over again. We do things in ways that have been proven to be effective
In the context of the Health and Life Science Industry, each firm is responsible for selecting suitable equipment that meets the stringent criteria for research, development, manufacturing, and storage. This ensures the production, distribution, and storage of quality products is in line with current regulatory requirements.
Their equipment should consist of the following, but limited to;
- be well-maintained
- equipped with alarms
- free from excess frost buildup
- allow for adequate air distribution and organized storage within the chamber
- equipped with sensors for continuous monitoring
- alarms located at the points representing the temperatures worst-case scenarios
- calibrated as required by a calibration program
- equipped with backup power or have alternate storage available in the event of a power failure
- equipment should be commercial grade and not be of any household type
Regulations also require that manufacturers in healthcare industries, pharmaceutical companies, and research laboratories use equipment, systems and processes that are up-to-date and fit for purpose.
For those of you that aim to comply with regulatory requirements there’s a continued emphasis by regulators on the need to perform temperature mapping on controlled temperature storage units
Validation: Proving the process ensures the end-product
Qualification of storage environments must be performed to ensure conditions match the stability requirements of the products. This is also a requirement as per international standards to ensure that the products are always stored and distributed within the specified temperature limits.
To ensure and demonstrate that proper environmental conditions and temperature and /or humidity controls are obtained, qualification and/or validation is expected to be carried out.
Temperature Mapping studies must be carried out regularly as part of the equipment installation and operational qualification (IOQ) to ensure that the controlled temperature chamber is capable of accurate and repeatable performance.
Temperature Mapping Studies: Equipment Qualification
A properly developed qualification protocol will help ensure that the equipment meets all documentation requirements and performs as expected, including the temperature mapping study is correctly carried out.
A trusted validation service provider can work with you to determine whether your qualification protocol is sufficient or help you generate a protocol to meet your requirements.
Generally, a protocol contains a documented approach to conduct the qualification process along with the procedure, scope, equipment description, responsibilities, test method, IQ/OQ/PQ test scripts, acceptance criteria, report, and approval.
Since these concepts are not entirely always clear, the ISPE Good Practice Guide: Controlled Temperature Chambers – Commissioning and Qualification, Mapping and Monitoring (Second Edition) provides guidance on commissioning and qualification, temperature mapping, periodic reviews and also provides examples and sample templates.
Quick Guide to Mapping Protocols
Here is a list of what a basic temperature mapping protocol should contain:
- Installation Qualification
The Installation Qualification (IQ) ensures that the equipment meets all specifications, is installed correctly, and all required components and documentation needed for continued operation are installed and in place.
IQ test sections are as follows:
- Standard Operating Procedures
- Equipment and Utility Installation Verification
- Documentation and Drawings Verification
- Calibration Status of Critical Instruments
- Test Instrument Calibration Information
- Operational Qualification
Operational Qualification follows the successful completion of Installation Qualification (IQ) test steps. The OQ testing provides documentation that the equipment performs as specified, when operated in accordance with Standard Operating Procedures and manufacturer’s recommendations; and confirms that the equipment is capable of meeting its intended use. Additionally, the OQ consists of temperature and /or humidity mapping of the empty chamber and it is performed to confirm that the empty chamber works within the specified limits throughout the chamber.
OQ test sections are as follows:
- Operational Controls and Setpoint Verification – Verify that the control system functions as specified by the equipment manufacturer, general system options, cycle length, temperature setpoints, etc.
- Alarm Verification – Verify the alarms associated with the equipment (High Alarm, Low Alarm)
- Empty Chamber Temperature Mapping Study – Perform an empty chamber temperature distribution mapping study. (Temperature Mapping & Humidity Mapping)
- We will place mapping sensors in pre-defined locations throughout the environment to ensure that critical data has been captured.
- Length of Temperature Mapping study – 24 hours.
- Additional qualification tests may include (as applicable – often for reference only):
- Open Door Verification test
- Power Loss Temperature test
- Performance Qualification
Following the completion of Operational Qualification (OQ), Performance Qualification (PQ) is conducted. The PQ testing provides evidence that the equipment consistently performs as intended under routine operating conditions. Loaded chamber testing will be conducted to provide documented verification that the system performs per its intended use when operated under routine challenged conditions and that the unit meets the pre-approved criteria.
PQ test sections are as follows:
- Loaded Chamber Temperature Mapping Study: A comprehensive temperature distribution mapping study is performed within a loaded chamber, which may also include Humidity Mapping.
- Simulation of Storage Conditions: The loaded condition should replicate a fully utilized storage space, or at least 60-70% capacity, to accurately reflect operational conditions.
- Strategic Sensor Placement: Mapping sensors are positioned in predetermined locations to capture essential data effectively.
- Study Duration: Length of Temperature Mapping study – 24 hours. Assesses the installation of the equipment to ensure it has been set up correctly and in accordance with the manufacturer’s and owners specifications.
Note: When determining mapping locations, the potential storage location should be considered. Probe locations; number of probes, distance between probes, usable space, direct path of air flow.
In Summary
The goals of qualification and mapping studies for controlled temperature units are crucial for ensuring that storage conditions meet the required standards and can be summarized as, aligned with the ISPE Good Practice Guide:
- To Demonstrate Environmental Uniformity for Temperature and Sometimes Humidity:
Qualification and mapping studies aim to confirm that the temperature (and sometimes humidity) across the controlled temperature unit is uniform and within the specified range. This ensures that all areas within the unit can maintain the required storage conditions.
- To Identify Unsuitable Storage Locations within an Area:
The studies help identify any locations within the unit that do not meet the required environmental conditions. These areas, which may exhibit temperature excursions or poor recovery times, are unsuitable for storing sensitive products and need to be addressed or excluded from use.
- To Determine Representative Monitoring Points:
Determining the most representative points for ongoing monitoring is essential. This ensures that the monitoring system can effectively track the conditions within the unit and alert operators to any deviations. The placement of sensors is based on the results of the mapping study to ensure comprehensive coverage.
The complete qualification and mapping study certifies that the equipment performs according to the required standards during the tests. It is important to note that while these studies verify performance at the time of testing, they do not guarantee continuous performance thereafter. Regular monitoring and periodic reassessment are necessary to maintain the qualified state.
Before performing qualification or requalification on any controlled temperature unit, it is essential to ensure all required documentation is available. This includes meeting both manufacturer and site requirements. Physically inspecting the unit before starting any documentation ensures that all necessary supplies and materials are accounted for, which is crucial for meeting the owner’s requirements.
The goals of qualification and mapping studies are foundational for maintaining the integrity of controlled temperature units. By demonstrating environmental uniformity, identifying unsuitable storage locations, and determining representative monitoring points, these studies ensure that storage conditions meet regulatory and operational standards. Proper preparation and documentation are vital for successful qualification and requalification processes.
By following the steps listed above, you will be on your way to successfully completing a temperature mapping study and well prepared for your next qualification.
Nathan Roman is a distinguished professional with over two decades of experience in Health & Life Sciences, specializing in commissioning, qualification, and validation. With a keen focus on temperature mapping, Nathan’s expertise ensures compliance solutions and product integrity. As a seasoned US Director of Marketing and Global Brand Ambassador at Ellab, he seamlessly blends traditional validation knowledge with contemporary marketing strategies. Nathan’s contributions extend to significant advancements in equipment qualification, temperature mapping, and co-authoring the ISPE Good Practice Guide for Controlled Temperature Chambers. His commitment to the industry is further showcased in his book ‘Six Steps to Effective Temperature Mapping’. Connect with Nathan to explore collaborative opportunities and discover innovative practices driving Health & Life Sciences excellence. (Connect on LinkedIn)
