Temperature Monitoring in Pharma: Think Big, Start Small

In this candid Q&A, Emanuel Schäpper, ELPRO’s head of the global business management group, shares insights on key challenges associated with safeguarding high-value, time- and temperature-sensitive pharma and biopharma products during storage and shipping. He also emphasizes importance of establishing a thoughtful, data-driven temperature monitoring strategy that can grow over time.

Q: The need to implement a reliable mix of hardware and software to monitor temperature accurately during storage and shipping of many pharma products is on the rise. What factors are driving demand for temperature monitoring today?

Several factors have been at play in recent years to help increase the need for temperature monitoring and control throughout the pharma/life sciences industries. These include the fast pace and unprecedented volume of the COVID-19 vaccines that have been distributed across the globe in 2021 and 2022. Is also includes ongoing approvals in the number of approved biologic therapies (and the number of patients taking them), growth in the number of high-value cell-and-gene therapies (CGT) and other forms of personalized medicines, along with the usual volume of pediatric and adult vaccines and seasonal flu vaccines. Against this backdrop, the global pharma supply chain has become increasingly complex, underscoring the importance of comprehensive digital monitoring solutions. Today’s high-value, temperature-sensitive pharma deliveries are often time critical, so monitoring solutions must deliver actionable insights that support accurate, reliable and timely decision-making.

Unfortunately, whenever there is a need for speed — in terms of delivering these high-value products before they have a chance to broach their specified temperature set points — the impact of potential points of failure will always become amplified. The industry has experienced many growing pains over the past few years, but fortunately — as is so often the case — some best practices have also begun to emerge.

Q: Can you describe some of these best practices?

When considering a protocol to support pharma shipments that must be maintained within a specific set point temperature range, the drug manufacturer and its third-party distribution partners must think about what type of temperature monitoring is required for the warehouse storage space and associated cold rooms. In addition, loading docks and planes, and the ships, trains and trucks that will move product require planning. The type of temperature monitoring that will be required for the product itself (in terms of monitoring strategies for individual packages, pallets and shipping containers) must also be carefully considered.

One useful best practice in this space is the concept of “think big but start small.” It is easy to get overwhelmed thinking about the totality of any cold chain monitoring infrastructure, in terms of the cost of installing hardware and software, and the complexity that will arise when a cumbersome new process is put in place. In reality, many cold chain efforts can be prioritized in such a way that the drug manufacturer can start with a relatively small-scale implementation and then scale the system so it grows over time, as needed.

Q: What are some of the pressing pain points that drug manufacturers and their third-party distribution partners face when it comes to safeguarding temperature-sensitive drugs and vaccines in transit?

Today, the distribution channels that are used to move pharma products often have both local and global elements. Rarely is the distribution of any given therapy handled by one single company from the point of manufacturing to the point of patient administration. Rather, distribution, storage and shipping activities are typically broken up into highly choreographed, tightly timed segments, with a variety of companies taking custody of the shipment along different parts of the journey.

This puts enormous responsibility on each player — to invest in state-of-the-art technology and staffing, to develop the appropriate capabilities and processes that are needed to adhere to the temperature-related rules and protocols that are defined by the pharma manufacturer (and dictated by the therapy or vaccine itself). Each of these companies must work in close coordination to ensure smooth, seamless handoffs along the way. In general, the temperature-monitoring devices and systems that are used to safeguard such pharma shipments must be reliable and easy to use, to ensure end-to-end continuity and reliability.

Q: Please tell us more about the different types of temperature-monitoring options that are used in this context.

Temperature-monitoring devices play an essential role in demonstrating that the temperature of any given pharma/life sciences therapy or vaccine has been maintained within the required setpoint range (whether it must be maintained at room temperature or at chilled, frozen or ultra-frozen temperatures). Several different types of monitoring devices and systems are available, allowing the solution to be matched appropriately with the application.

Considering that most companies would like to “right size” their initial investment and grow in a step-wise fashion over time — as opposed to entertaining a full-scale implementation right from the outset — it’s in their best interest to become familiar with the different technology options.

In terms of hardware, the options can be grouped into two broad categories:

• Temperature indicators — These are relatively inexpensive chemical indicators or electronic indicators that demonstrate whether the required temperature set point inside a shipped package has been breached. These relatively simple devices will only indicate whether any temperature deviations have occurred or not, without further details or time stamps

• Temperature monitors — These are electronic temperature-logging devices that continuously record the temperature inside a package or container and are able to save the data and display the temperature behavior over time, and compare the actual temperature data against the defined setpoint range to indicate whether and when the monitored space has deviated from the required temperature range

Meanwhile, when reviewing the different hardware and software options, it is useful to consider the different applications.

• Monitoring solutions for rooms and equipment:
  These solutions refer to the combination of localized stationary hardware (either hard-wired or wireless devices) and supporting software that is used to provide temperature monitoring for specific warehouses, rooms and equipment components. In these applications, the monitoring devices are installed as needed, and the associated software is often (but not always) operated on premises at the location. The local personnel who receive alerts or alarms can then take action quickly to intervene when an issue arises. The use of cloud-based solutions is also on the rise, which can also send alarms to onsite personnel

• Monitoring solutions for temperature-controlled logistics:
  These solutions refer to the data-monitoring schemes that are used to track the temperature of products while they are in transit. Typically, such installations cannot rely on a proprietary environment because, as noted above, many different companies must work in close collaboration to enable seamless handoffs of the temperature-controlled containers as they move from their point of origin to their point of destination.

Instead, data loggers are packed inside the product package or shipping container and rely on cloud-based or web-based data transfer that enables widespread access to the data and enables maximum interoperability among all players in the segmented distribution effort.

Wherever possible, the goal should be to keep such systems as straightforward and uncomplicated as possible — otherwise people won’t use them reliably — and to enable actionable alerts whenever something arises that could jeopardize the shipment by allowing the product to experience a potentially damaging or even devastating temperature excursion.

Q: What is the difference between passive temperature loggers and active temperature loggers?

Passive temperature loggers create just a recording of the shipment’s temperature experience but do not communicate the data in real time to any stakeholders. Instead, once the package has arrived, the data collected by the temperature logger during the journey is retrieved and uploaded to a computer in PDF format. With this relatively simple approach the manual temperature reports are available for assessment and analysis, and they must be stored in a central repository to meet regulatory compliance and audit requirements.

In simple terms, passive temperature loggers provide a “thumbs up or down” as to whether or not the temperature inside the package has remained within the set point range. Uploading the data is fast and straightforward. In the event of an excursion, a time- and labor-intensive process is undertaken to evaluate the situation, identify the cause of the excursion and verify the integrity of the package.

These uploaded temperature reports allow stakeholders to evaluate whether the shipment has remained within the temperature set point. The downside of this passive approach is that there is no way to react to an excursion during the actual shipment — only to recognize that it has occurred at the end of the shipment once the data from the data logger has been manually uploaded. However, this passive approach does provide visibility into the entire end-to-end shipping lane and provides comprehensive data-driven insights that would allow stakeholders to predict risks or inform operations or re-design safer logistics lanes.

By comparison, active temperature loggers, send regular updates to communicate the measured data through a cloud- or web-based application and thus allow for real time surveillance and intervention. Should a temperature deviation begin to occur, active loggers allow stakeholders to react in a timely fashion, and to execute other interventions that can prevent the situation from escalating. 

The decision to install passive versus active temperature loggers will be dictated by the product and its distribution channel. In many cases, different solutions may be needed at different points of the journey. And they can be operated in combination. In general, investment in increased capabilities enables greater end-to-end visibility into specific lanes or specific products, depending on the requirements.

Q: The process of investing in a temperature-monitoring and temperature-control strategy can be overwhelming. ELPRO likes to say, “Think big but start small.” What types of “limited scope” projects might provide a good starting point for companies?

Today, companies are understandably wary about making a huge investment in hardware and software. Fortunately, there are many options available that enable a step-wise approach, whereby companies can undertake a basic, cost-effective setup that can initially provide reliable temperature monitoring to track temperature without necessarily providing real time end-to-end visibility right from the outset. As stakeholders weigh their options and prioritize their investments in temperature monitoring and data-analytics capabilities, it’s always prudent to consider ‘whether the gain is worth the pain,’ as the saying goes.

Q: What is involved when a company wants to move to more automated approach?

Before you can start using real time monitoring devices, you will need to set up the right software to support the data that the logging devices are transmitting from in-transit shipments and stationary warehouses. When more sophisticated temperature monitors are used, the state-of-the-art software that supports them can provide actionable insights by analyzing not just the temperature data but other forms of environmental data associated with the shipment, too. Such software can then develop temperature curves over time, allowing stakeholders to identify not just immediate temperature excursions, but patterns that can be rectified with appropriate troubleshooting.

For example, does a repeat shipment always experience a temperature deviation two hours after being packaged? Or when the package is temporarily stored in a particular warehouse while en route? Does a repetitive temperature deviation tend to happen when one particular service provider has custody of the package while en route? Such data-driven insights help to focus the troubleshooting efforts that are needed to intervene effectively and rectify the issues to prevent further temperature excursions.

Q: Let’s focus on temperature-controlled warehouses for a moment. How are temperature monitors typically used in these settings to ensure that temperature-sensitive products are maintained within their setpoint range while they are in transit?

Warehouses that handle temperature-controlled pharma products often experience some variance in the controlled temperatures throughout the enclosed space. Temperature mapping is a useful and necessary process to demonstrate that all parts of the enclosed space are being effectively maintained within the setpoint range, and thus to prove that the room is fit for purpose. Temperature mapping is also part of the overall qualification process. The qualification plan for any temperature-controlled space spells out the specific processes and testing protocols that are required to both maintain the required temperatures and to verify that the temperature-monitoring system is meeting its specifications.

Ideally, temperature mapping is first carried out in an empty warehouse (to establish baseline values), and then again in a fully loaded warehouse, during summer and winter. The goal is to evaluate the factors that may influence the temperature zones that are maintained inside the warehouse space and use the information to install temperature monitors and other cooling systems more effectively. Factors that can cause temperature deviations inside an enclosed space may include the impact of doors being opened and closed, the addition of warmer inventory to the enclosed space, the impact of higher or lower staffing levels on the ambient temperature and more.

The temperature-mapping process uses data analytics and modeling to inform both how many data loggers must be used to monitor the temperature throughout the enclosed space, and where the temperature loggers and cooling systems should be installed to ensure continuity and reduce temperature excursions over time. Again, once such testing can demonstrate that the warehouse or enclosed space is able to remain at the setpoint temperature throughout these changes, then the space is deemed fit for purpose and the qualification process is satisfied.

Q: When it comes to concepts of qualification versus validation, why are the two concepts important, and how are they different?

In broad terms, the qualification process refers to efforts to validate the operation of any hardware components used. By comparison, the validation process refers to efforts to validate the overall operation (not just the hardware components themselves), in accordance with Good Manufacturing Practices (GMP) and Good Distribution Practices (GDP) requirements. As a handy rule-of-thumb, we like to say, “Anything that can be touched must be qualified, while anything you can’t touch must be validated.” More specifically:

• Qualification refers to the inspections and tests that are required to verify that the equipment — that is, the temperature loggers and temperature-monitoring systems and associated accessories — that are used in a warehouse, truck, shipping package or shipping container are deemed fit for purpose. The qualification process describes the specifications and operating procedures and testing protocols that must be carried out to validate that the hardware meets the specifications set forth in the qualification plan

• Validation is a documented and mandated process that guarantees the does two things: (1) Defines the required results and the acceptance criteria that is needed to verify that the entire process of temperature control for a given product meets the specification established by the company and required by the product, and (2) Verifies and documents that the process delivers the expected result by using the defined testing methodology. The more complex and integrated an overall solution is, the more complex the validation process will be

It is important to note that when we hear about comprehensive, global temperature-monitoring systems that are in place, it is likely that that the entire integrated system that has been set up to provide end-to-end visibility into the shipment is not actually validated — it is simply too costly and too cumbersome a process when many partners are involved in the segmented cold chain. So what is at stake for the pharma makers?

Some equipment vendors in the space are promoting centralized dashboard solutions, but customers must be careful because while these can certainly be useful, they are not necessarily validated. In order to release a medication upon delivery based on these dashboards alone, the company would need to add on another parallel step that can be validated.

Q: Alarms or triggers are essential to manage the pharma cold chain and enable rapid response when a temperature excursion occurs, but false alarms can lead to alarm fatigue. What are some best practices to help users of your equipment to minimize false alarms?

Appropriate alarming is essential to maintain the integrity of any time- and temperature-sensitive pharma product, but false alarms can occur as a result of temperature setpoint ranges that are too strict, and processing or handling errors. Today’s temperature loggers do a very good job of defining upper and lower limits that are acceptable for a given shipment and then recording an event or triggering an alarm when a temperature excursion has occurred. However, false alarms can arise when the device has been taken out of the box and is still recording temperature data in ambient conditions (thus creating an alert to suggest a temperature excursion).

Today, sophisticated temperature monitors can be programmed to create a temperature-excursion allowance model — also known as a temperature-stability budget — that establishes a certain amount of leeway in terms of the duration that a given shipment can be out of the set point range without risk of damage to the therapy. When the data logger is configured to include an excursion-allowance model — and thus a certain “grace period” — it can help to minimize the number of nuisance alarms without compromising the integrity of the temperature-sensitive product. Using such an approach, the data logger will not actually trigger an alarm until the total time the product has spent outside of the set point temperature range has been exceeded.

Q: How can today’s state-of-the-art software offerings help to improve the overall temperature-monitoring challenge?

With today’s advanced temperature-logging systems, the associated software provides a number of important functions. For instance, the software allows the data to be viewed according to individual data loggers or by shipment overview (when many data loggers are used for mixed products in the same shipping container). Similarly, today’s software capabilities can also provide deeper insights by analyzing temperature data and other types of shipping data (such as data related to humidity, vibration, the number and duration of open-door events and more) and integrate the data-driven findings into the drug manufacturer’s enterprise resource planning (ERP) system. Ultimately, the temperature data is most valuable when it can be used to support more informed decision making — such as the ability to enable more effective interventions, to develop more effective shipping lanes, to improve packaging design and more.

As long as a data logger or a real time temperature-monitoring system are used to collect temperature data during pharma shipments, it creates opportunities for many process advantages, ranging from live monitoring, to enhanced process automation, to improved end-to-end visibility and predictive analytics. At the end of the day, the goal is use such insights to enable the most effective interventions — those that keep costs low and reliability high — in order to safeguard the today’s high-value temperature-sensitive pharma therapies and vaccines.

Author

Suzanne Shelley, Contributing Editor
Suzanne is the principal/owner of Precision Prose Inc., and a contributing editor to Pharmaceutical Commerce, Pharmaceutical Technology, BioPharm International and Chemical Engineering magazines.