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). The 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, are requirements to maintain the products’ safety, quality, and efficacy. Storage temperature is very important in maintaining these critical attributes because drug products or samples stored are temperaturedependent 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 regulations 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.
Each firm is responsible for selecting suitable equipment used in research and development, manufacturing, or storage to produce, distribute and store quality products in accordance with CGMP.
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 temperature’s 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
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 endproduct
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 correctly carrying out the temperature mapping study.
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:
1. 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
2. Operational Qualification
Operational Qualification (OQ) is performed after meeting each test step of the IQ. 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
3. Performance Qualification
The PQ testing provides evidence that the equipment consistently performs as intended under normal operating conditions. Loaded chamber testing will be conducted to provide documented verification that the system performs per its intended use when operated under routinely challenged conditions and that the unit meets the pre-approved criteria.
PQ test sections are as follows:
- Loaded Chamber Temperature Mapping Study- Perform a loaded 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.
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 airflow.
In Summary
The goals of the qualification and mapping studies can be summarized as:
- To demonstrate environmental uniformity for temperature and sometimes humidity
- To identify unsuitable storage locations within an area
- To determine representative monitoring points
The complete qualification and mapping study certifies that the equipment is performing as per the required standards during the tests and may be suitable for operation. However, it doesn’t mean that it will ensure the same performance continuously thereafter.
Prior to performing a qualification or requalification on any controlled temperature unit, ensure you have all documentation required to meet the manufacturer and site requirements. It’s recommended to physically see the unit before starting any documentation to ensure that all the supplies/materials are all accounted for in order to meet the owners’ requirements.
By following the steps listed above, you will be on your way to successfully complete a temperature mapping study and well prepared for your next qualification.
Expert at providing expertise
Nathan Roman is Director of Validation at Genesis AEC, responsible for Qualification and Validation consulting services. He has over 22 years of experience in commissioning, qualification, and regulatory compliance services and is an expert in CQV and CGMP, and GLP compliance.
Genesis AEC specializes in architecture, process engineering, construction management, as well as commissioning, qualification, and validation to the life science industry. For over 25 years, Genesis AEC has provided AE support and EPCMV (Engineering, Procurement, Construction Management, CQV) services. Services can include early preplanning during design through construction, execution and turnover, mechanical, electrical, and plumbing (MEP), and Fire Protection and Process Utility.
To learn more about Genesis’ Validation Services, please contact Nathan Roman directly at nroman@genesisaec.com or Follow Nathan Roman on LinkedIn.
