在过去的20年中，人们对良好的分销实践有了新的监管，该法规规定了应如何运输监管产品。幸运的是，GDP的出现在及时及时创建了一个强大而有能力的冷链，以处理与Covid-19对抗的大量温度控制的疫苗发货。

Pfizer’s vaccine, for example, has storage specifications of -70°C, and is one of the highest profile instances of new challenges facing temperature-controlled distribution. The current distribution channels were not equipped to handle -70°C products. Most distribution centers do not have ultralow temperature freezers and our trucks and planes cannot be kept this cold. This presented a problem for distribution of a vaccine that requires ultra-low conditions.

Pandemic meets ultra-low temperature shipping solution

The answer was found in the thermal shipper.

热托运人基本上是运输箱和配有冷包装的冰箱的组合，可将内容物保持在正确的温度下。辉瑞的版本相当巧妙，具有高效的真空面板绝缘和干冰袋。托运人还包含一个启用GPS的温度数据记录仪，以跟踪温度和位置。这些物品都不便宜。但是，鉴于疫苗的关键性质，有效的低温运输容器是必要的创新。

完全包装的托运人可容纳近5000剂疫苗，每剂量约为20美元。每个盒子中价值100,000美元的产品，数据记录仪，绝缘和冷包的成本变成了名义。

但是，由于记录仪的技术问题或部署中的人为错误，数据记录仪可能会失败。这种不确定性创造了有必要使热托运人证明他们适合其预期用途。

Anatomy of a thermal shipper

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为了了解如何鉴定热托运人，看起来其基本解剖结构很有帮助。在最外层，它只是一个耐用的纸板箱。通常是三层和防水。因为托运人的价格最高为每块100美元，所以盒子必须坚固，以便可以重复使用。

The next layer is insulation. In our diagram, these are the white panels. For a normal frozen shipment, this would just be polystyrene foam. For an ultralow temperature shipment, Pfizer relied on vacuum insulated panels.

The next layer contains cold packs. In our diagram, these are the silver panels. For a normal frozen shipment, this would be a cold pack of some alcohol mixture engineered to have a phase change (to change from solid to liquid) at the product’s target temperature. The phase change temperature matters, because the cold pack will remain at the phase change temperature until the phase change is complete. For instance, regular old ice packs have a phase change at 0°C, and the temperature gets no warmer until all the ice has melted. For Pfizer's ultralow temperature shipper, the cold packs are made of dry ice, which changes phase from solid to gas at -78°C.

托运人的最内向层包含产品框。请注意，实际产品仅占可用空间的一小部分。根据经验，用于传统冷冻货物的精心设计的热托运人通常不到其可用于产品的容量的20％。

资格：证明它有效

Validation proves that a process achieves its intended result. Qualification is the term used when validating a piece of equipment. So, at the same time, when we are qualifying the thermal shipper, we are also validating the standard operating procedure for packing the shipper.

为了说明资格过程，想象一下托运人旨在在夏季进行为期四天的旅行中运输冷冻产品。产品的允许温度范围在-10°C至-30°C之间。

Begin by assembling the thermal shipper according to the SOP. The SOP will include specifications, such as the type of cold pack and the conditioning time and temperature required for the cold pack prior to assembly. Place the conditioned cold-packs and load the product containers with a conditioned placebo product. Next, because we are qualifying the shipper, we will add temperature sensors to the product area. Remember, space is at a premium in these boxes; so rather than placing entire data loggers in the box, remote probes on cables will be used. A thermistor probe is a good choice for this application as they are small and accurate, and are available in different operating ranges, and calibrated measurement ranges. A good example is the Vaisala VL-1416, rather than a data logger with internal sensors, like the Vaisala VL-1000.

The key to shipper qualification is to pack the box following the SOP as if it was an actual shipment. The only changes are that the product is a placebo, and that we included temperature sensors in the load.

Place the packed shipper in an environmental chamber that can simulate the temperatures that can be experienced during shipping. Since we are simulating a summer shipment in an unrefrigerated truck, we might set the chamber to 40°C for 12 hours to represent a sunny day, and ramp it down to 15°C for night. Repeat this cycle for four days to simulate a four-day shipment.

After this four-day challenge in the environmental chamber, review the temperature data from the data loggers. Note whether the sensors in the placebo product stayed within temperature specifications (-10°C to -30°C) for all four days. If that was the case, you can have confidence that the thermal shipper, when packed according to the packing SOP, can keep the product within specifications over a four-day trip during the summer with maximum daytime temperatures of 40°C. One study is not enough, so the process is repeated for two more four-day cycles. With three successful results, the thermal shipper is qualified.

The choice of test duration and challenge temperatures is made based on the intended shipping routes and analysis of expected weather patterns. You may need to qualify one thermal shipper and SOP for the summer, and another different shipper and SOP for the winter.

资格充满信心

The end result of a qualified shipper is confidence that the product will be at the right temperature during shipment. Even with an on-board temperature sensor, Pfizer still needed to have a qualified shipper. They had to prove that their single sensor accurately represented the conditions of the entire product area. They also needed confidence that the shipper could maintain the needed temperatures if the on-board sensor failed or the data was lost. In a more conventional scenario with a less critical product, qualifying a shipper can allow distribution with less monitoring. Instead of monitoring the temperature of the shipment with expensive loggers, we can check weather forecasts and make sure shipments arrive within their qualified time limits.

对良好分销实践的关注为更强大的冷链提供了支持，并且已经出现了新技术来支持它。现在，可以使用廉价和一次性数据记录仪直接监视许多货物，尽管准确性较低，但对于此应用程序仍然足够好。但是，运输时间和温度敏感产品的基本面没有改变。毫无疑问，随着辉瑞的热托运人的发展，我们看到了这一点。

非常低温的COVID-19疫苗是热托运人资格及其持续相关性的重要例子。就辉瑞而言，即使它们在托运人中包含了支持GPS的温度传感器，仍然需要资格。在温度传感器出现故障的情况下，他们需要证明托运人的有效性。资格确信热托运人的设计正确。他们需要确信自己的包装SOP适合预期用途，并且他们为干冰充电的程序有效。

In North America, SoftBox Systems created the thermal shipper for these vaccines. This article includes an interesting video detailing their efforts to develop their shipper. In the video, there is a thermal image of the boxes being challenged in an environmental chamber – the temperature sensor cables (possibly thermocouples) can be seen coming out of the boxes which are physically challenged by being stored upside down and on their sides.

“Softbox成功支持辉瑞在Covid-19疫苗的全球冷链分布中透明

In Europe, CSafe Global developed the thermal shipper used with the Pfizer/BioNtech vaccine. For more information about the CSafe design, here is a short article on their shipper.

“CSafe Global Providing Thermal Protection for COVID-19 Vaccine Shipments from BioNTech Facility透明

If you have any questions about validation or monitoring, pleasecontact us或在下面发表评论。