Cold Chain - Validation

Validation

A cold chain can be managed by a quality management system. It should be analyzed, measured, controlled, documented, and validated.

The food industry uses the process of Hazard Analysis and Critical Control Point, HACCP, as a useful tool. Its usage continues into other fields. PDA (Parenteral Drug Association) Technical Report # 39 gives a rough summary of how the cold chain can be validated.

The overall approach to validation of a distribution process is by building more and more qualifications on top of each other to get to a validated state. This is done by executing a Component Qualification on the packaging components. Next, an Operational Qualification that demonstrates the process performs at the operational extremes. The final piece is the Performance Qualification that demonstrates that what happens in the real world is within the limits of what was demonstrated in the Operational Qualification limits.

Think of the validation state in a simple manner like driving a car. One first wants to make sure there are four wheels, they are properly inflated and that the vehicle has gas. That would be like a Component Qualification. Next the car should be operated at its extreme conditions, as fast as possible in the worst weather and then as slow as possible. This is equivalent to the Operational Qualification, operating at the extreme conditions. The final step would be to take the car for a nice long drive like one would normally operate a car. 65 MPH on a nice little road trip, this would be equivalent to the Performance Qualification, the car functions as expected in nominal conditions. One may not operate their car at the extremes, but it sure is good to know that if you did have to operate in those conditions, one would have a high degree of confidence that it is achievable.

Currently there is a misnomer in the industry that three repetitive events equals a successful Validation. In reality, the process monitoring of the distribution process is the only assurance that a process has been successfully Validated. If at any point in time there is an anomaly in the distribution process, that process can no longer be considered Validated, as an anomaly would In-validate that process. Statistically speaking, a process would need at least 30 data points to demonstrate a process is in true control, but that's a separate topic that should be discus in detail.

The PDA's Technical Report states that a Component Qualification is required to demonstrate that a component can be manufactured to the design criteria of that individual component. This was put into the document because the industry did not understand the principles of Validation; all Validation processes were specific to equipment and not auxiliary processes such as shipping/distribution.

Performing thermal testing can also help with validating the cold chain. Certified test labs use environmental chambers to simulate ambient profiles that a package may encounter in the distribution cycle. Thermocouple probes and separate temperature dataloggers measure temperatures within the product load to determine the response of the package to the test conditions. Replicate testing based on a qualification protocols is used to create a final qualification report that can be used to defend the configuration when audited by regulators. It is normally best to have an individual that understands the principles of Validation, when defending such processes to a Federal Regulatory body of any nation.

Cold chains need to be evaluated and controlled:

• Carriers and logistics providers can assist shippers. These providers have the technical ability to link with airlines for real time status, generate web-based export documentation and provide electronic tracking.
• The use of refrigerator trucks, refrigerator cars, reefer ships, reefer containers, and refrigerated warehouses is common.
• Shipment in insulated shipping containers or other specialised packaging.
• Temperature data loggers and RFID tags help monitor the temperature history of the truck, warehouse, etc. and the temperature history of the product being shipped. They also can help determine the remaining shelf life.
• Documentation is critical. Each step of the custody chain needs to follow established protocols and to maintain proper records. Customs delays occur due to inaccurate or incomplete customs paperwork, so basic guidelines for creating a commercial invoice should be followed to ensure the proper verbiage, number of copies, and other details.

During the distribution process one should monitor that process until one builds a sufficient data set that clearly demonstrates the process is in compliance and in a state of control. Each time the process does not conform to the process, the event should be properly documented, investigated and corrected so that the temperature excursion do not occur on future shipments. Thus the process is continually evolving and correcting for anomalies that occur in the process. Eventually the process can evolve into periodic monitoring once sufficient data demonstrates that the process is in a state of control. Any anomaly that occurs once a process is in a state of control will result in the process being invalidated and not in control and result in product withdraw from the market to ensure patient safety.

It is necessary to develop an internal documentation system as well as multi-party communication standards and protocols to transfer or create a central repository or hub to track information across the supply chain. These systems would monitor equipment status, product temperature history, and custody chain, etc. These help ensure that a food, pharmaceutical, or vaccine is safe and effective when reaching its intended consumer.