There is no part of the cold chain that can be overlooked when it comes to maintaining the integrity of temperature-sensitive products, yet it is all too easy to think first and foremost about the product security in transit rather than at the storage stage. The design of warehouses − and the technology installed to monitor and regulate temperature − are essential elements in the cold chain and of those, temperature mapping is one of the most important capabilities.
"It all starts with storage, which is why we have a big focus on monitoring storage temperatures to secure our products," confirms Marc-Oliver Rechsteiner, head of corporate supply chain operations at Octapharma. "Temperature mapping is a very important part of the process."
Octapharma is an independent company based in Switzerland that has specialised for more than 30 years in developing medicines derived from human proteins for use in haematology, immunotherapy and critical care.
The clinical trials that the company conducts for its products involve a large and geographically diverse network of state-of-the-art production plants in Austria, France, Germany, Mexico and Sweden, as well as 54 plasma donation centres in the US and Europe. For this reason, it puts the storage of its products high on its list of priorities when managing its cold chain, and has developed a clear strategy that involves keeping storage operations in-house as much as it can.
"For storage, we use our own warehouses whenever possible and we deploy technology that is suited to the temperature range at which specific products need to be stored," explains Rechsteiner. "We also have a big focus on qualifying warehouses, which includes modelling the different eventualities if there should be a failure in any of the systems. We also ensure that we have redundant systems in place.
"We spread temperature loggers throughout the warehouse facility, and monitoring is a manual process that we monitor very closely," he adds.
The science of compliance
Temperature mapping – the process of recording and mapping temperature variations within a three-dimensional (3D) space – is a vital part of any effort to make a warehouse fit for housing temperature-sensitive products. This is because temperatures vary, even in the smallest storage spaces, as anyone with a refrigerator in their kitchen will know.
Whether in a fridge, a cool room, a freezer or a warehouse, it is not uncommon to observe a temperature variation of as much as 10°C in different parts of the space, and since environmental variables will have an impact, these variations cannot be reliably predicted, hence the need for temperature loggers placed at key locations.
As well as the general principle that the centre of a 3D space will have a different ambient temperature to that measured in the corners, there are other factors to consider. Temperatures will be cooler, for instance, near cooling fans and warmer in the area nearest to the doors. Furthermore, factors that influence airflow, including whether the storage facility is full or empty, must be taken into account.
Although temperature mapping can be used to alter the cooling systems to change temperatures in specific parts of a storage facility, its aim is not to help produce a single consistent temperature reading throughout a warehouse. Instead, it is to understand what temperature variations exist in the facility and, therefore, what influences them. It enables the storage of specific products in parts of the warehouse that exhibit the appropriate temperature ranges in order to ensure that there are no temperature excursions that might put a product at risk and compromise compliance with the regulations governing the storage and transport of that item.
The regulatory angle is of the utmost importance in the pharmaceutical sector, as regulators are keen to emphasise compliance with good manufacturing practice (GMP) requirements for controlled-temperature storage requirements.
The GMP guidance provided by the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/S) states that: "Storage areas should be designed or adapted to ensure good storage conditions. In particular, they should be clean and dry, and maintained within acceptable temperature limits. Where special storage conditions are required (e.g. temperature, humidity) these should be provided, checked and monitored."
In the UK, guidance on wholesale distribution practice includes the following: "Large commercial refrigerators and walk-in cold rooms should be monitored with an electronic temperature-recording device that measures load temperature in one or more locations, depending on the size of the unit. Portable data-loggers that can be downloaded onto a computer may be used instead of a fixed device.
Records should be checked daily. Internal air temperature distribution should be mapped on installation in the empty and full state, and annually thereafter under conditions of normal use. Products should not be stored in areas shown by temperature mapping to present a risk (e.g. in the airflow from the refrigeration unit). Condensate from chillers should not be collected inside the unit."
For temperature mapping to work, careful consideration must be given to many variables that can influence temperature gradients (see ‘Temperature mapping sensor placement’, right), which include changes in the internal layout as warehouses are filled with product, the impact of internal systems for regulating temperature, and external environmental factors. Not only should warehouses be temperature mapped under different conditions, but also mapping should be repeated at frequent intervals, especially if any modifications are made to their layout or to the heating and cooling systems.
Above all, the constant temperature monitoring and calibration that occurs in most GMP facilities, even if the monitoring devices are regularly calibrated, should not substitute temperature mapping. For one thing, the temperature mapping process usually involves the measurement of many more points within the 3D space, and gives a clearer picture of the impact of interventions such as the opening of doors.
Keeping pace with technology
The technology used to monitor, control and map temperatures within storage facilities is constantly evolving and Rechsteiner believes that it offers a greater set of options for optimising warehouse conditions to ensure cold chain integrity.
"There are already more modern technologies emerging that use Bluetooth or radio-frequency identification (RFID) capability, and they offer a more automated way of tracking temperatures in storage areas," he says. "There is a lot of potential for improvement in processes, including active temperature monitoring and dashboards that allow remote monitoring.
"We are using that kind of technology in our new warehouses, which we try to make as energy-efficient as possible. Other ways in which we achieve that include the use of passive airflow and groundwater to cool the warehouses.
Active temperature monitoring is high on Rechsteiner’s list of priorities.
"More active temperature monitoring gives us a more accurate picture of the temperature flows and airflow movement in a warehouse," he says. "The more active and flexible the system is the more efficiently a warehouse operates. The data from such a system also gives us a better idea of how to manage the placement of products within the warehouse.
"There is growing demand for that kind of technology across the industry, not least because of the new GDP guidelines, which apply to transport and storage. They stipulate that you must have clear temperature controls."
One reason Rechsteiner is keeping an eye on technological advances is their potential impact on energy costs.
"The main goal is to keep our products safe and secure at the required temperature," he observes. "But some of our products go to temperatures as low as -70° and that requires a lot of energy. That is why energy efficiency is also a very important consideration.
"Energy efficiency means not only looking at ways to cool a warehouse in ways that use less energy, but also keeping products at the most efficient temperature without compromising their safety and quality. That requires a lot of integrity testing to assess the impact on a product of an increase in temperature of one or two degrees."
Implementing new technology comes, of course, with a price. Any investment decision made to improve energy efficiency must, therefore, be backed up with hard data.
"When you invest in new technology, for energy efficiency, you must have a clear business case, but there is certainly a long-term payback, especially because cold chain regulations will only get stricter and the price of energy is likely to keep rising," says Rechsteiner. "Above all, you have to ensure that your products remain 100% usable.
"We always look at new technology when we build a new warehouse, and the efficiency of temperature mapping is always a top priority, along with temperature control, monitoring and management. If there is a problem with any of these things, the big risk is that products will not be usable and cannot be distributed, which would have a financial impact. That is why we have double or even triple redundancy systems to ensure that our products remain safe. It is always worth investing a little more to protect valuable products."
Temperature mapping sensor placement
There are many factors to consider when choosing the placement of temperature sensors in a storage facility, including the:
- placement of control sensors
- location of doors and windows, and the response of external walls to changes in temperature outside the warehouse, all of these could result in significant variations in temperature
- variance in temperature gradients between cooler areas at floor level and warmer areas at ceiling level
- capacity of heating, ventilation and air-conditioning systems to move air, including the size of fans; systems must be able to adequately circulate air even when the warehouse is full to capacity
- layout of racks, shelves, pallets and any other surfaces on which product might be stored; the effect of all potential obstructions to airflow must be taken into account
- need to map areas that may not have racks or shelving, but which might be used for short-term storage before products are placed on shelves
- potential effect of unanticipated circumstances such as power failures.
