With a COVID-19 vaccine expected to be made available within the next few weeks, many are already questioning the logistics of shipping. As the vaccines will be needed to be kept at a specific temperature throughout the supply chain, last-mile delivery will be the most significant challenge posed to get them around the world. Truckloads of shipments will be broken down into small units to be distributed to hospitals, clinics, pharmacies, and many more. It becomes increasingly challenging to ensure temperature stability over time.
Temperature indicators which are designed for last-mile delivery and point of administration use can help to ensure a smooth distribution. They help to assure that healthcare professionals receive vaccines that have been maintained at the proper temperature during the final stage of delivery before injecting it into a patient. Alternatively, time-temperature indicators such as the WarmMark®, which will take into account temperature excursions that occurred and duration. These time-temperature indicators aids in protecting human health and ensure the effectiveness of the vaccine, as well as providing a useful tool for healthcare professionals to manage inventory and avoid wasting vaccines.
So, how do the indicators help in facilitating the delivery process of the vaccines? The cases of vaccines are separated into many boxes where they will be individually shipped and placed in a freezer upon arrival. This method could lead to the possibility of freezer failure, which will cause a tremendous amount of waste. By placing these temperature indicators with the inventory, it will help indicate which vaccines have experienced temperature excursions and which can still be used. As temperature indicators do not cost a lot – less than 50 cents when bought in bulk compared to $5 or more for other loggers – using these indicators is a viable solution. SpotSee®’s WarmMark® time-temperature indicator can detect a range of temperatures from -18°C (deep freeze), 8°C (refrigeration), 25°C (room temperature), and excursion times from 30 minutes to 168 hours. Besides, they are customisable to fit vaccine specifications.
Temperature labels will visibly change colours to indicate temperature excursions. For example, the WarmMark temperature labels will change from white to red to show the temperature excursions and duration. Being able to track this information can be the deciding factor of administering or destroying the vaccine. In an ideal situation, a time-temperature indicator would be placed every time a bulk shipment is broken down and shipped. To develop such a vaccine involves many companies and research labs. According to ClinicalTrials.gov, approximately 260 vaccines are in development, and nearly 60 vaccines are in Phase III trials which is the final step before approval for distribution to the public. Some are expected to be approved before the end of 2020 whereas, others are highly likely to be authorised throughout 2021. Being able to monitor vaccine storage and shipping temperatures is a global challenge that worsens by different handling temperatures due to the various vaccines.
The vaccine comes in many forms such as mRNA and DNA-based vaccines, protein subunit vaccines, live attenuated virus vaccines, and many more. Some are unique where storage and temperature requirements are different from previous vaccines. For example, some mRNA vaccines require deep frozen temperatures. Vaccines developed by Pfizer and BioNTech must be store at -70°C. When it is refrigerated at 2°- 8°C, it lasts only ten days. Pfizer has a $1.95 billion contract with the U.S. government to supply up to 100 million doses of its vaccine.
Preparation of vaccines for administration is also time-temperature sensitive. Vaccines will be supplied in multi-dose vials. Before the vaccine is administered to a patient, they have to be thawed and prepared; this leaves a window of opportunity where it will be susceptible to temperature changes. Before a vial is thawed, it must be just that enough patients will arrive in a given time frame to be able to open the vial. Protecting vials with time-temperature indicators gives additional assurance that the vaccine will remain safe and effective. The WarmMark three-window temperature indicator gives additional assurance, accurately provides time-temperature data, and is cost-effective. For vaccine manufacturers and carriers, there are many factors to consider outside of arranging extra flights. As most of the vaccines require special handling, they must ensure that the cold chain remains intact during its peak shipping season.
In response, companies such as UPS and Deutsche Lufthansa have plans to expand their freezer farms at airport hubs. FedEx and DHL are adding temperature monitoring systems to ensure that vaccines are being handled properly throughout the cold chain. McKesson, who has agreed to deliver the vaccine as part of a contract signed in 2016, provided the H1N1 vaccine during the H1N1 pandemic and is currently supplying the majority of flu shots. They plan on bringing in new facilities online and adding employees to assemble the vaccine kits of needles, syringes, protective equipment. Ensuring the cold chain remains intact can be challenging with such a monumental task. It is estimated that between 5% to 20% of vaccines will spoil during transportation due to improper temperature control. With good packaging spoilage rate could be reduced between 1 billion to 4 billion doses of COVID-19 vaccine due to cold chain failures.
As temperature requirements differ drastically depending on the vaccine, each of them will require evidence that safe temperatures were maintained throughout the storage and shipping process as anything can go wrong even with the best procedures, and distribution getting further from reliable power and refrigeration, the evident risk that vaccines will experience temperatures that degrades their potency. Even though many transportation hubs have the capabilities of ensuring temperature stability; however, as vaccines move out of the United States, packages start to become smaller, leading to a decrease in thermal mass. This decrease will lead to vaccines being warm at a faster rate in small containers as compared to a larger one. Also, refrigeration facilities may be at more risk as the vaccine moves from distribution centres to pharmacies or physician’s offices.
From 2014 to 2019, Australia lost nearly AUS $26 million worth of vaccines from 12,000 cold chain breaches. As a result, an estimated 747,000 vaccines were destroyed – 1.65% of all vaccines distributed in Australia. Refrigeration failures are the most common reason cited; however, some were caused as the vaccines were stored on the lowest shelf, which is the coldest part of the refrigerator. A study of German physicians indicated that 16% had experienced cold chain breaches, and a review of 21 refrigerators showed they were out of their set temperature ranges more than 10% of the time.
The cost extends beyond unvaccinated people, and the cost of the vaccine itself as companies have to destroy wasted vaccines as medical waste regardless of whether they spoil in transit or at the point of administration. For Manufacturers and healthcare providers, this leads to a loss in revenue. It also means additional costs for manufacturing, packaging, storing, and shipping. Therefore, it is easier and safer to monitor the vaccine to reduce the risk of these temperature excursions. Through monitoring, it acts as an early warning system, even though it will not prevent the temperature excursion. However, it will alert the users in time to minimize the impact. When choosing vaccine packaging, it should be done with the possibility of delays in mind, as packages may be lined up and awaiting clearance. Other possible factors are changes in weather between the northern and southern hemispheres which may place additional stress on the cold chain when the distribution point is as large as this where it is every health care facility and pharmacy around the world, the cost-benefit ratio changes.
For such situations, using a data logger for the shipment is the safest, most reliable, and cost-effective solution, with time-temperature indicators strategically placed within the cargo. With strategic placement, it allows those receiving the vaccine to decide whether products in the middle have been maintained at an acceptable temperature, even if those on the outside have failed. When the bulk package has been broken down into smaller quantities for individual clinics and pharmacies, time-temperature indicators are the most cost-effective option. By knowing the length of an excursion, it allows the manufacturer to determine the safety and potency of the vaccine. Even deep-frozen vaccines which are thawed before administration, a temperature excursion could mean that the shipment is not impaired, but it has to be used within a time frame, typically within hours.
These vaccines are too necessary not to safeguard. As there is no information available regarding whether the vaccines are susceptible to cold, but vaccines using inactivated viruses can be damaged by freezing. Adding on, some vaccines will lose all potency when frozen. Brief heat excursions may also reduce potency but still allow these vaccines to be used. Temperature indicators provide an indication when the vaccine has been too hot or cold. Carriers are going to great lengths to protect the cold chain for what seems to be the largest-scale inoculation to be done. However, plans may go awry, where refrigerated units may not be plugged in between off-loading and hands-offs, compressors failing, transportation delays, and even when built-in thermometers and alarms fail. All vaccines are valuable, but the COVID-19 vaccines are too precious to risk just by relying on packaging alone. Additional temperature monitors provide extra security to assure that the correct temperature was maintained or give a warning where excursions occurred so only safe and effective vaccines are administered.