Temperature-sensitive products (vaccines, for example) must be kept cold along the entire supply chain, from manufacturing to point of use. The equipment and procedures used to ensure this is referred to as a cold chain.
A key component of any cold chain is the system used to monitor the temperature of the products during storage and transit. In this article, we’ll identify and discuss six features that you should look for in an effective cold chain monitoring strategy.
What Is Cold Chain Monitoring and Why Is It Important?
One element of the cold chain is the physical equipment, like refrigerated intermodal shipping containers (“reefers”), insulated packaging, and refrigerated warehouses. A second element is the procedures and policies that are followed by personnel involved in maintaining the cold chain. SOPs for loading and unloading products, or tactics for responding to a power outage, for example.
Another element is the temperature monitoring system, which should be integrated with the other two elements.
Temperature monitoring is important in cold chains because:
- An accurate record of temperature from manufacturing to point of use is the only way to prove to customers and auditors that the product did not experience temperature fluctuations outside the acceptable window (temperature “excursions”).
- Real-time temperature monitoring can be used to identify temperature control problems and troubleshoot them before the product is harmed.
- In the worst-case scenario of a temperature excursion that damages product, monitoring data can be used to identify and intercept it before it reaches the consumer.
Cold chains are used extensively in pharmaceuticals, frozen foods, produce, beverages, and in certain specialty chemical and materials applications (photographic film, for example). Properly implementing the right storage and distribution practices for these products is an essential part of GxP, or good practices.
You’ll see vaccines used as an example throughout this article. That’s because the effects of temperature excursions in vaccines are potentially life-threatening and can be difficult or impossible to detect visually. Furthermore, vaccines are commonly distributed over long distances, through areas with less developed infrastructure, making vaccine cold chains particularly complex and challenging. For this reason, the CDC and WHO provide extensive guidance on the storage and handling of vaccines.
In highly regulated industries, maintaining the cold chain is an extension of good manufacturing practice (GMP). In these industries, the cold chain should be implemented and maintained as part of a quality management system, with a documented risk assessment and validation.
An unreliable, incomplete, or poorly maintained cold chain can have direct economic consequences (scrapped product, for example). A poorly conceived monitoring system can also result in the need for frequent intervention to save endangered material. In many cold chains, consumer safety is also at risk. In the case of vaccines that have lost their potency due to temperature excursions, there’s even a risk of outbreaks or loss of patient confidence.
Cold chain quality is regulated, in the US by the FDA through various parts of 21 CFR (Parts 203, 205, 211.150 subpart H) , for pharmaceuticals, and through the FSMA for foods. This means that cold chain monitoring equipment and procedures can be audited, with Form 483 citations issued if problems are found. The FDA also has the authority to initiate mandatory recalls. In other parts of the world, regulation is carried out through local ICH member bodies.
6 Qualities of an Effective Cold Chain Monitoring Strategy
Data collected from cold chain monitoring is much more useful if it is available constantly and in real time. This allows control systems and personnel to react immediately to resolve problems before an excursion takes place.
Even if a corrective action is not possible, real-time data can still be actionable. For example, real-time knowledge that a vaccine has lost its potency can allow the batch of vaccine to be intercepted before it is administered, avoiding the consumer safety issues we highlighted earlier.
In addition to temperature, other types of information, like location and condition (humidity, sensor or system failures, vibration, shock, light exposure, and others) can be valuable in identifying problems early, reducing their impact and helping to prevent them in the future. Depending on the material being shipped, these conditions are potentially just as important as temperature.
Precise Monitoring Capabilities
The reliability of a cold chain is only as good as the accuracy of its monitoring system. Any inaccuracy in the temperature measurement represents a potential gap in the cold chain.
Consider the process of unloading a shipment of frozen food from a refrigerated shipping container to a warehouse. If the only temperature sensors are on the truck and in the warehouse, all we know are the air temperatures in the two locations, not the true temperature of the product during this sensitive step in handling.
One way to address this risk is to monitor temperature at the package level, so that the actual temperature of the product is tracked through the entire distribution process, eliminating gaps in measurement and inaccuracy due to sensor placement. Package level monitoring can also identify temperature nonuniformity within a batch, like if products near a warehouse door are more likely to experience temperature fluctuations. (Note that temperature mapping can also be used to prevent this type of issue.)
Besides well-planned sensor placement, it is also important to confirm the accuracy of individual sensors. The best way to do this is through systematic calibration. For example, the CDC recommends calibrated probes with an uncertainty of less than ±0.5 °C, for monitoring of vaccines.
Reliable, Complete Analytics
In addition to having data in real time, enhanced data analysis capabilities also increase the power of a cold chain monitoring system.
One example of this is the ability to quickly analyze and summarize large data streams consisting of temperatures measured by many probes, across a complex distribution network. Automated analysis tools can identify trends in the data, identifying emerging problems and inefficiencies so they can be resolved before growing into larger issues.
Analytics are also a useful tool for regulatory compliance. A clear summary of a large data set can quickly show an auditor that a product is always within a safe temperature window during storage and distribution. Thorough data analysis can also be used to diagnose the root causes of excursions, and to develop plans for corrective actions.
One potential outcome of a GMP risk assessment is that damage to the product is not predicted simply by the minimum and maximum temperature it experiences, but a more complicated metric, such as the mean kinetic temperature (MKT). In a case like this, being able to calculate the MKT quickly on large data sets is critical.
Customizable Alarms and Alerts
A major advantage to using an automated monitoring system is the potential for customizable alerts. Some of the aspects that can be customized are:
- Who the alert is sent to, based on the type of problem
- Multiple alert recipients
- Auto-escalation for issues that are not addressed quickly
- What type of message is sent (phone call, text message, email)
- What triggers an alert- is it simply a single reading that is above or below a certain threshold, or a number of occurrences? Alerts can also be sent before readings exceed a limit that is dangerous for the product, or if they are displaying a trend that will lead to a problem if it is not addressed
- Including a description of the problem in the alert
Tailoring these aspects to your specific situation can ensure that the response is efficient and fast. For example, certain types of alerts, like one for malfunctioning equipment, can be sent to local facilities staff who can immediately troubleshoot issues. More wide scale issues can trigger an escalation if resources need to be reallocated to deal with a problem.
Customization also helps to reduce alarm fatigue. This is a situation where multiple false alarms lead to personnel ignoring or disabling alarms. Careful customization using historical data and experience can be used to ensure that only situations needing intervention generate an alert.
The ability to scale up is a major advantage for automated environmental monitoring. In this context, scaling up refers to adding new measurement locations, adding distribution routes, increasing the volume of products being shipped, adding new product lines, or new and different monitoring requirements. Beyond measuring and recording environmental conditions, in GMP-regulated industries, we also need to consider the need for tracking calibration status and logging corrective actions. A distributed, automated, and cloud-based monitoring system can seamlessly adapt to these situations.
Scalability is an important consideration for any operation that expects to grow in size. For cold chains specifically, we should expect the need for even more scalability in the future, driven in the short term by the development and rollout of a Covid-19 vaccine.
Longer term, trends toward globalization of distribution networks will also increase the value of scalability. For example, using an overseas manufacturing site requires more diligent monitoring, because of the long, complex, intermodal supply chains involved. Overcoming the challenges of a long cold chain also has the potential to open new markets and to allow the shipment of perishable goods to developing economies.
Ease of Use
Any personnel involved in the manufacture, handling, storage, or use of materials that are distributed via a cold chain should be trained in the use of the monitoring system (this is a key aspect to any GMP-related process). This means being able to recognize and respond to temperature excursions, equipment malfunctions, and situations that could lead to them. This makes it critical for the user interface of the monitoring system to be simple and intuitive.
The CDC recommends that temperature records be reviewed weekly to identify trends and possible problems. A simple user interface makes this a far less cumbersome task.
An added advantage to using an automated system is the easy logging of corrective actions, root causes, and other notes, so they can be stored along with the associated temperature data. This simplifies future troubleshooting and audits.
For temperature-sensitive products, maintaining a robust cold chain is essential for preserving value and regulatory compliance. A key piece of the cold chain is the temperature monitoring equipment and the monitoring strategy.
In this article, we’ve discussed six features of an effective cold chain monitoring strategy, all of which are found in the cloud-based DicksonOne system.
About the author: Before coming to Dickson, Director of Services Antoine Nguyen spent more than 18 years in quality and validation roles in the pharmaceutical and medical device industries.