Vaccines are distributed through a refrigerated supply chain, known as a “cold chain”. For a vaccine to maintain its potency, this cold chain must be unbroken from manufacturing to administration at the healthcare provider. Vaccines generally fall into two classes, based on whether they should be refrigerated (held between 2 and 8 °C) or frozen (-15 to -50 °C) during storage. Exposure to temperatures outside of these ranges can cause damage that varies in severity from accelerated degradation to instantaneous deactivation. More specific guidance on storage temperature and the effects of temperature excursions for individual vaccines are given on package inserts.
An integral part of the cold chain is the system used to monitor temperature. Having a robust vaccine temperature monitoring system is important for a number of reasons beyond the fact that complete, accurate data is a critical part of GxP (good practices). For many vaccines, the effects of thermal degradation are not readily visible, so a complete and accurate temperature history is the only way to confirm that a vaccine has been kept at a safe temperature. This is particularly important for vaccines that are shipped via long, complex or intermodal supply routes with unpredictable environmental temperature variations.
The consequences of a failure in the vaccine cold chain can be financial, for example in the form of having to scrap or recall products, or to perform costly interventions on malfunctioning refrigeration equipment. If a harmful temperature excursion is not detected before administration, there’s also a risk to patient and community health, since patients will incorrectly believe they have been immunized. This, along with the need to re-administer potentially damaged vaccines, can damage public confidence in individual healthcare providers, or in vaccination in general.
It should be noted that, in the US, the safe distribution of vaccines is federally regulated, so problems in the cold chain can also result in citations and corrective actions being issued by the FDA. Vaccines that are subsidized through public funds, for example by the Vaccines for Children program (VFC) are also subject to additional state level regulation. The CDC and WHO also provide extensive, detailed guidance on vaccine storage and handling directed at healthcare providers.
Strategies for cold chain temperature monitoring have evolved significantly since this issue was first identified as a critical aspect of vaccine distribution. Today, digital data loggers (DDLs) connected and controlled by remote, cloud-based monitoring systems have emerged as the state of the art. This type of system has a number of advantages, including:
- Access to temperature data in real time, allowing fast and efficient response to issues through customized alerts
- The ability to summarize data collected across a complex network with many measurement points
- Automated storage and organization of temperature data, along with any associated corrective actions, calibration records, equipment operating parameters, and other information
- Easy integration into an existing quality management system (QMS), which includes being designed with regulatory compliance in mind
- Inherent ability to scale to larger, more complex networks, and to add features in response to changes in regulation or product profile
A system based on DDLs is recommended by the WHO and CDC as the primary tool for temperature monitoring, in combination with vaccine vial monitors, and the use of DDLs is a requirement for the VFC program.
Improving and scaling up vaccine handling capabilities is top of mind for many organizations currently, due to the unprecedented level of vaccine R&D activity in response to COVID-19. The rollout of a vaccine is likely to affect temperature monitoring needs in all parts of the supply chain, including manufacturing, transportation/distribution, and storage/handling at healthcare providers. In this article, we’ll talk about some of the key considerations for setting up and maintaining a vaccine temperature monitoring system, including the things you’ll want to think about when expanding the scale of your capabilities.
5 Best Practices for Vaccine Temperature Monitoring
1. Understand your organizational needs
When planning to implement a vaccine temperature monitoring system, a few broad areas should be considered.
The first is an assessment of your measurement needs. For example, how many DDLs should be used, where should they be placed, and how frequently should temperature data be recorded? Is it necessary to place temperature monitors on individual packages? This is also a good time to think about setting up additional monitoring, for things like humidity, light exposure, or vibration. Equipment diagnostics, to monitor whether refrigerators and other hardware is operating normally, can also be helpful in tracking overall system health.
Many, if not all of these questions can be answered through a thorough risk assessment process. This process, which should be part of the implementation of any type of quality management system, can identify the areas of highest risk to product and consumer safety, so that resources and processes can be focused on those areas. A risk-based approach is also recommended by the FDA specifically for electronic records systems.
Risk assessment can also be helpful in the next area of planning, which is to anticipate problems that could arise, and how the temperature monitoring system can be used to effectively respond to these problems. One of the most powerful uses of a real-time temperature monitoring system is to quickly identify trends that flag an issue for intervention before a temperature excursion takes place. To take advantage of this, it is helpful to dig into historical data, look for the most common types of equipment and process failures that lead to excursions, and determine what warning signs are present before these failures happen.
If worse comes to worse, and a temperature excursion takes place, a good temperature monitoring strategy can reduce the costs of the excursion by ensuring a fast response by the right personnel, and by simplifying the process of identifying and quarantining possibly damaged product.
Finally, an organization should consider how their temperature monitoring needs will grow and evolve in the future. For example, the expected wide-scale rollout of a COVID-19 vaccine will require significant infrastructure improvement in all elements of the manufacturing and distribution chain, including vaccine temperature monitoring systems.
2. Have a clear installation plan
Having a well thought out, simple to execute plan for installing your vaccine temperature monitoring system will help to avoid costly issues to correct installation mistakes later on. Here are a few areas to make sure to cover in your plan.
Based on risk assessment and temperature mapping, determine the number of sensors needed, and where they should be placed to optimize product safety and identify possible equipment problems as early as possible. Note that the CDC recommends that temperature probes in storage areas are “buffered”, by placing them in glycol, sand, or some other representative material. This is done so that temperature monitor readings are more representative of the actual temperature of the vaccine, rather than the surrounding air.
In this stage, the frequency of data collection should also be set. This can be determined by a risk assessment or, in some cases, by regulators. For example, the VFC program requires temperature readings to be collected at least once every 30 minutes.
Standard operating procedures (SOPs) should be written that cover routine operation of the vaccine temperature monitoring system, as well as response procedures for emergency situations. Again, the results of the risk assessment can be used to identify likely emergency situations that could arise.
In addition to step-by-step, clear and complete procedures, the SOP should also identify specific responsibilities of individual personnel and their contact information.
In a quality management system, the physical process of installation should be performed according to an IQ (installation qualification) process. This process involves thorough checks to ensure that equipment and software is configured correctly, that the manufacturer’s instructions are followed, and that any relevant documentation is preserved.
Sensor calibration is a critical aspect of the IQ process for vaccine temperature monitoring. The CDC recommends that calibration is performed to confirm accuracy to within ± 0.5 °C, using a NIST-traceable standard, by a lab accredited to perform calibrations (through ISO/IEC 17025, for example).
A system is also required to preserve and track calibration records and schedules for individual data loggers. This can be done through the temperature monitoring software, or by a separate system.
Note that these are areas where in-house experience may not be available, so companies often call in third-party consultants for assistance.
3. Establish Thorough Training Protocols
Any staff members involved in vaccine handling should have a “thorough understanding” of their job functions, according to 21 CFR Part 600.
Here are a few points to make sure to include in staff training for a temperature monitoring system:
- An overview of the monitoring strategy, its purpose, and how it is related to product and patient safety
- Basic functions of individual data loggers
- How to determine whether a data logger is operating correctly, and basic troubleshooting and maintenance
- Training on the software to be able to read individual data loggers and confirm overall system health remotely
- How to respond to common alarms and errors
- For staff members responsible for regularly reviewing data, how to generate reports and use them to quickly identify trends
- Tie back all training to procedures that are written in detail in the SOPs mentioned in the previous section
In addition to being required by regulators, the importance of a good training program has been proven in field studies. For example, a 2017 UNICEF review found that one of the main causes of low temperature excursions in vaccine handling is insufficient training.
4. Optimize Alarm Capabilities
Modern remote temperature monitoring systems have the ability to set up custom alerts. Customizable options can include the ability to send different types of notifications (SMS, automated phone call, or email), or to send alerts to different people or groups based on the type of problem detected.
Here are a few tips for setting up custom alerts in your temperature monitoring system:
- Set up alerts to ensure the fastest resolution to the problem. For example, alerts about malfunctioning pieces of refrigeration equipment can be sent to local support staff. Wider scale issues that require organization-level reallocation of resources can be escalated to the management level.
- Include a description of the problem in the alert. This will help the responding personnel to be prepared upon arrival.
- Use historical data to determine the conditions where an alert should be triggered. For example, look back at past temperature excursions to see what warning signs were present before the excursion took place, and set up alerts to warn staff when those conditions are present.
- Be mindful of “alarm fatigue”. This is a situation where excessive false alarms lead to staff ignoring or disabling alarm systems. This can be addressed by fine-tuning the alert system to minimize false alarms, and by acknowledging and addressing alarm fatigue in staff training.
5. Test, Track, and Reevaluate
Continuous improvement should be an integral part of any quality management system. In the context of vaccine temperature monitoring, this means regularly reviewing system-wide data, to identify trends and look for ways that the data stream generated by the temperature monitoring system could be used even more effectively, or ways that the system itself could be improved.
The CDC and WHO recommend these types of data reviews, combined with regularly summarizing the consequences and corrective actions related to temperature excursions. Without a centralized data collection system, these reviews could be labor intensive, but automating regular reports using a cloud-based application can take a significant amount of burden off in-house staff.
The ability to quickly summarize temperature monitoring data, highlighting excursions and corrective actions taken, can also be valuable during customer or regulator audits. This can demonstrate that a full record of data is collected and reviewed, and that problems are systematically and quickly addressed.
The vaccine temperature monitoring system is a critical component of maintaining a robust cold chain. The gold standard in the industry is a system of digital data loggers, remotely controlled and monitored using a cloud-based system. The system includes not just the measurement hardware and software, but the procedures and staff training associated with it.
In addition to proper hardware, training, and SOPs, organizations involved in the manufacturing, distribution, and administration of vaccines should regularly re-evaluate their needs in terms of improvement or expansion. This is especially true now, due to the anticipated need for enhanced distribution capabilities for an upcoming COVID-19 vaccine, as well as the increasing globalization of vaccine cold chains.