By Ilana Koegelenberg
Without reliable (and precise) refrigeration in the medical and pharmaceutical cold chain, the integrity of many temperature-sensitive items will be compromised – from vaccines to organs, and even bodies.
Refrigeration is everywhere in the medical field and maintaining the cold chain can be the difference between an effective life-saving vaccine and having to throw away millions of rands in spoilt product. Never mind the fact that people can (and have) died because of ineffective vaccines. The risk is often far greater than many realise…
So, where do we need refrigeration exactly? The short answer: anywhere perishable goods are involved – including certain drugs, vaccines, serums, blood, tissues, organs, and bodies – has to be kept at certain temperatures.
But why? It’s because particular bacteria are cultured and have to be maintained at very specific temperatures, explains Grant Ford of Matador Refrigeration. These bacteria must be kept under stringent control so that the product doesn’t get wasted.
Vaccines in particular are heavily reliant on proper refrigeration. At the turn of the millennium, a significant step was taken in resourcing programmes to bring medical capabilities to emerging markets through initiatives financed by NGOs such as the Bill and Melinda Gates Foundation (BMGF). The life expectancy of people in developed nations was continuing to climb, while in emerging markets it continued to stagnate.
The combined efforts of the United Nations International Children’s Emergency Fund (UNICEF), the World Health Organisation (WHO), NGOs and newly formed Global Alliance for Vaccines and Immunisation (GAVI), defined various projects to tackle the unacceptably high infant – and child – deaths due to diseases that could be prevented through vaccinations.
Billions of dollars were spent in producing and distributing these vaccines for a global campaign that continues today, explains Michael Werner of Minus 40, a company that manufactures medical fridges locally. In a WHO report released this year, it is estimated that in 2018, 20 million children globally (equivalent to 1 in 10) missed out on life-saving vaccines that included those for measles, diphtheria and tetanus.
“While these campaigns have significant success, there were still challenges that needed solutions, including the quality of the vaccine efficacy on inoculation,” explains Werner. All vaccines have a limited shelf life measured in months, up to 36 months from time of production under ideal storage conditions. This shelf life is adversely affected by exposure to prolonged higher temperatures or extensive light. Worse still is if vaccines are accidentally frozen at 0°C as this effectively ‘kills’ the vaccine.
In various studies, including in most of the African countries, there has been continued concern raised about the efficacy of vaccines where, in 2015, it was estimated that in many countries less than 50% of children inoculated were given sufficient vaccine booster requirements to protect them against specific diseases. “While much of the vaccine stock was still within its shelf life, root causes of reduced efficacy were due to storage and transport compromises undertaken in distributing the vaccines,” says Werner. “Unlike with perishable foods, there is no visual indicator on vaccines as to their level of efficacy, and hence process control assurances or laboratory tests are the only means to validate vaccine quality at the point of usage.”
But the refrigeration needs of the medical sector stretches beyond just vaccines. Think about blood… The blood bank of South Africa has an interesting job looking after platelets and blood supplies, as blood is stored at extremely low temperatures of -25°C and below (as low as-40°C) and the criticality of maintaining these low temperatures and cold chains thereof is crucial, explains says Kevin Walter of Lutz Refrigeration.
What about morgues? When a body is preserved through refrigeration, it is kept at a temperature below 4.5°C, which sufficiently delays decomposition. Refrigeration is also used if a body will be cremated, as some authorities require that a body be refrigerated for a given amount of time prior to cremation. If a body will be buried in a ‘green’ cemetery or natural burial ground, the body must be refrigerated as those locations generally do not allow for the burial of embalmed bodies.
When it comes to the refrigeration needs of the medical and pharmaceutical industry, it really is a matter of life and death.
If the cold chain is broken at any point, products can be spoilt or lose effectiveness. “When these products weaken because they weren’t properly stored at the correct temperatures, the financial loss is high because, generally, medical products are high in demand and high in cost,” explains Ford. “Also, their loss can lead to serious consequences for the health of those who need them.”
Vaccines critically need to be continually stored between 2°C and 8°C, otherwise, they become ineffective and if a vaccine has been frozen, it can even cause local reactions such as abscesses if administered, explains Ian Tansley, inventor of the Sure Chill vaccine storing technology and global expert on the use of renewable energy in cold chain logistics.
According to UNICEF, an estimated USD1.5-million worth of vaccines were lost within five months during 2011, often due to difficulties maintaining the cold chain and ineffective refrigeration. This is either due to power outages, which means they get too warm, or because they have become frozen because many medical refrigeration devices rely on ice to maintain the cool temperature.
It’s not always that easy to accurately monitor if a vaccine has stayed within the optimum temperature parameters before it’s administered, so you have to put your trust in the vaccine refrigerator you are using, explains Tansley. “The hidden danger here is that the practitioners can assume that everything is okay when they administer the vaccine. However, if the potency of a temperature-sensitive vaccine has been destroyed, the vaccine programme will need to be repeated not just in the effected region, but throughout the whole country.”
Regulations and standards
The medical/pharmaceutical field is heavily regulated and with good reason, considering the risks. What needs to be kept in mind before tackling such a project?
In February 2015, the Pharmacy Act was amended to require that anyone storing, distributing or administering vaccines, must use appropriate storage areas and temperature-monitoring instruments, along with conducting regular checks including annual temperature mapping. However, compliance to these regulations is poor, particularly in the private sector, including retailers.
“These regulations are explicit in terms of fridge performance requirements but there is a challenge in obtaining compliance with these guidelines which are seen as subservient to commercial decisions by particularly the private sector,” explains Werner, “whereas the public sector, through the various provincial and national department of health authorities, have been more accommodating to these pharmacy and vaccine fridge specifications over the last few years, so we see a transformation taking place.” The SA Pharmacy Guidelines also require every medical fridge to have temperature monitoring and recording to give assurance to all stakeholders that medicines are correctly temperature stored. “As per vaccine supply chains, medication follows similar monitoring and control methods, and IT capabilities is where the greatest development work is happening.”
The standards are all World Health Organisation (WHO) related as detailed in the main documents. These are grouped under four sections, namely:
- Oral Solid Dosage (OSD) – which are the normal tablets and powders.
- Sterile – these include injections, drips, and ointments, and are taken directly into the blood stream; hence, very critical in nature.
- Liquids – liquids that are taken by way of mouth (oral), as well as for wounds – external application.
- Biological – human tissue, as well as dangerous live organisms.
Good baseline guidelines are the WHO TRS 961 and 957, which lead to the other guidelines for sterile and so forth.
Then there are documents like ISO 14644 part 1 to part 4, which regulate the facility design and the requirements for this.
Look out for storage guidelines too; these normally come as supplementary guidelines.
ASHRAE has also published numerous standards, including a guideline specifically for HVAC&R in the medical field. This can be downloaded from their website upon registration.
With regard to refrigeration, some products are required to have 100% back up as well, explains Ford. This is available for energy failure where two separate refrigeration packs are run on rotation and equally maintained.
It’s important that maintenance plans are run in service level agreements to prevent racks or other refrigeration equipment from breaking or malfunctioning, resulting in vaccines or products reaching temperatures that render them ineffective. “Losing a vaccine because of an equipment failure is considered a preventable loss, which is generally related to the lack of equipment maintenance,” explains Ford.
How do you keep these products cold during transport?
Refrigerated trucks are extensively used to distribute the bulk vaccines which also deploy appropriate shipping boxes with temperature monitoring ‘tags’ in them, explains Werner. “This tends to be a better-managed, and lower-risk part of the supply chain.
Where there are still challenges is in the final stages of the inoculation process, where often health workers are required to visit remote villages using rudimentary road networks, and every form of transport that one can perceive in rural Africa.” The issue here is usually that the vaccines are transported in extreme heat conditions over extended time periods.
For these remote destinations, best practice has evolved with the deployment of vaccine cooler boxes that are polyurethane foam insulated with ice packs inside which ensure that the cooler boxes retain optimum temperature for the conveyance of the vaccines, explains Werner. Again, WHO has been instrumental in defining specifications and testing vaccine cooler boxes that are extensively deployed.
One has to be careful with the ice though. “There is a general assumption that ice is good, as it is powerful and cold, but it can be very dangerous near vaccines,” cautions Tansley.
Consistent, accurate cooling is imperative throughout the cold chain. “Ensuring that the vaccines are stored in a well-managed environment is essential,” says Tansley. “We have the potential to scale our technology at all points of the cold chain.”
How do you choose a refrigeration system then? “Based on capacity required and sensitivity of product to temperature change,” explains Ford. “You have to make sure the cold room stays at a consistent temperature, whether people enter of leave the room.” It’s also important to ensure that cleaning and maintenance prevents contamination of environments that need full protection against problematic bacteria. “It’s necessary to control the temperature environment and relative humidity very well,” he says. “That’s why temperature alarms and data registers are essential to monitor the environment.”
During storage, all trucks, airlocks and loading bays are refrigerated to the same temperature specifications as the long-term holding rooms, explains Walter. “In addition to this, very critical products are stored in insulated containers with temperature loggers to improve and verify cold chain integrity.”
“Lutz’s recommendation (and opinions do differ) is always to have numerous stand-alone systems with lots of extra capacity built into the units, so that if a system goes down, the remaining units can hold temperatures while repairs are being carried out,” explains Walter. Systems must be robust and over-engineered to ensure stress-free years of operation. “Proper early-warning alarms monitoring every inch of the systems possible are critical.”
“The most critical thing for the design process is to understand the customer’s requirements in terms of allowing for redundancy,” agrees Robert Hanssen of Cubicool. Sometimes this can mean installing two x 100% capacity systems per storage area, or else three x 50% capacity systems. When one considers the value of the products being stored (in monetary and general public safety/availability terms), in most cases this justifies the increased capital cost of the refrigeration systems. “In general, good airflow and maintaining very close control of temperatures are important,” adds Hanssen.
As mentioned, the ideal storage condition for most vaccines is stipulated as temperatures between 2°C and 8°C with no prolonged light exposure. Thus specific ‘vaccine’ fridge specifications have evolved to include precise temperature control, dark cooling chambers, and an ability to retain the cool temperature within the fridge chamber when electricity supply is interrupted, explains Werner.
The WHO has been at the forefront in defining these operating and testing standards for vaccine fridges, which has now become the industry standard. It is currently expected that a vaccine fridge must be able to retain cooling capability in the event of electricity supply failure, in excess of 48 hours before the chamber temperature breaches the 10°C high temperature limit, provided the door to the fridge is not opened during this power interruption, explains Werner. The low temperature limit is set at 2°C.
The technology to achieve these operating specifications continues to evolve and includes the development of alternative energy capabilities. “The fastest growing sector in the vaccine fridge category is now defined by Solar Direct Drive (SDD) power fridges, as reliable mains electricity has not reached many geographic locations,” says Werner. GAVI, in a report released in June 2019, indicated that their programmes alone would be purchasing approximately 24 000 vaccine fridges per year over the next five years, of which 60% would be SDD units, inclusive of the dedicated solar panel facility.
But the challenge does not end there. “We now have improved fridge technology, however this will not guarantee the efficacy of vaccines,” says Werner. “The human risk will continue to be monitored and significant awareness training applied.” Health worker training is focused on the treatment of patients and not on the technology or maintenance of the health assets. Hence technology capability has to further evolve with advanced IT capability being applied. “The advantage of applying information technology is that the health workers can now focus on what they do best – looking after their patients,” he says.
The bigger picture matters here, and one can’t simply look at this link in isolation. “The whole cold chain needs to have temperature control, and we advocate complete cold chain right to point of delivery,” says Tansley. “The cold chain is absolutely essential to the success of vaccination programmes and needs to be built on solid foundations: not using equipment that just isn’t fit for purpose.”
Back-up is essential. The big danger here is with power cuts or intermittent power. “It’s important to have a back-up because if the power goes down you only have a certain amount of time to get it sorted,” explains Tansley. “A conventional fridge gives you less than an hour, a more robust fridge will give you about an hour in a low ambient temperature, if it happens at the weekend, you’ll need several days to fix it.”
“Holdover is therefore very important, the longer the better. Most facilities need days (even weeks) to restore power in high ambient temperature region,” says Tansley. “And for areas where there is no power, then solar devices are the only way to obtain reliable power.”
A word of advice
What should and shouldn’t you do in terms of medical refrigeration?
Here are some expert tips from Tansley to keep in mind:
- Don’t use a chest-type freezer – chest refrigerators are very dangerous as cold pools in the bottom of the chest. Since cold air falls, there is a greater freezing risk to the vaccines stored in this part. Also, when you open the top, the hot air that enters stays at the top, which means the gradient of temperature throughout the device is not consistent.
- For chest refrigerators, you also need a variety of temperature probes throughout the device to measure its efficacy accurately plus a way of circulating the air to make the temperature even throughout. This makes it almost impossible to control and provide a consistent temperature.
- Ice is very dangerous to vaccines. If it’s anywhere in the air system thus cooling the air, then the air itself is a danger to the vaccine because of the ice particles present.
- You also need to be careful when you take the baskets out to retrieve the vaccines at the bottom, as they can be affected by the ambient temperatures in the room.
- Remote temperature monitoring is very helpful. It gives the visibility that we need to monitor the products, is consistent and isn’t reliant on human intervention.
It’s also important to look at refrigerants when putting up cold storage and choosing a refrigeration system. “A natural refrigerant should be considered as it’s a future-proof solution because synthetic refrigerants are being phased down currently,” advises Ford.
Redundancy matters in all areas. “We would strongly advise against multiplex units as this puts ‘all your eggs in one basket’, leaving you open to a major cooling loss should the system go down,” explains Walter. He prefers a minimum of two simplex units, both capable of doing at least 80% of the required peak cooling duty individually. This way, if a unit goes down, one will cope and carry the room for at least a few days while repairs are being carried out on the other.
“Don’t go cheap,” Hanssen advises. “Design and install reliable systems. Spend time on commissioning and ensure that a good monitoring or alarm system is installed for rapid response in case of any issues.”
If at all possible, don’t use domestic fridges, Werner cautions. The challenge is that the quality of pharmacy refrigerators deployed across the medical industry varies significantly. The key parameter to consider is that a pharmacy or hospital fridge tends to be opened regularly, requiring a high cooling capacity capability to ‘pull-down’ the fridge temperature rapidly after each door opening, while controlling air temperatures between the 2°C to 8°C range, explains Werner. “The majority of standard domestic fridges are not able to perform this rapid cooling function and tight
temperature tolerances, and these are often deployed in medical facilities.”
Energy savings matters
In the medical arena, safety and reliability is much more important than economy and saving energy. You’re saving lives here. However, due regard must be paid to energy.
“Energy saving is very important as it affects the cost of the product stored, but priority is the product integrity,” confirms Ford. “However, energy saving in any form is up for major consideration and depending on size or capacity required, depends on the system needed.”
Walter agrees. “Pharmaceutical storage, as with any industry, will always benefit from energy efficient designs as it brings down operational costs. However, the cost of losing product in the industry far outweighs the temptation to be pioneers in the energy game.” As such, a good balance between energy responsibility and system robustness must always be observed.
A few tips to maintain robust refrigeration plant designs without creating archaic energy guzzlers would be to oversize condensers, thus running at lower condensing temperatures, Walter advises. Also, oversizing of evaporators to bring up the suction pressure. “Both of these approaches increase compressor coefficient of performance (COP). Another tip is to include the installing of electronic expansion valves to allow for systems to run correctly under lower condensing temperatures while still delivering sufficient refrigerant to the evaporators. Unfortunately, fans have to run in the room irrespective of whether cooling is required or not, so this is not an avenue for energy savings. However, one could look into variable speed driven (VSD) fans that slow down when the room is on temperature to gently circulate air around the room, while adding less heat and using less energy.
What has changed and where are we going?
“Over the years we’ve seen a trend in temperature requirements changing from previous ‘drop temp’ levels of 10-15°C down to current 2-8°C temperature ranges,” says Walter. On top of this, the technology used to monitor rooms has increased in leaps and bounds. Current monitoring systems make use of various probes in every nook and cranny of the room, sending alarm emails or SMSes if temperatures begin to approach danger zones. In addition to this, portable temperature loggers are sent out with critical product during transport as well. “All of this highlights the precision and level of care taken in maintaining and monitoring of cold chains for every single item coming and going from manufacture to end user,” says Walter.
Due to the importance of medication in the well-being of both people and animals, and the relevant value of the medication, the supply chains are becoming more reliable and more robust, but not at the same standard across all segments, explains Werner.
“Generally, the highest quality of control and refrigeration peaks at the manufacturer and progressively becomes a higher risk the closer one gets to the point of consumption or application. Hence, more work and attention is needed in developing downstream solutions, he says. Due to this risk profile, supply chains are adapting to store medication in upstream locations for as long as possible where there are reliable refrigeration systems and more skilled management. This has seen an evolution of more regular supply in smaller quantities to clinics and health support facilities. “For refrigeration manufacturers like Minus 40, we are being challenged to evolve our fridges to smaller capacity and lower energy consumption, with better temperature ‘holdover’ capability and ever-improving proactive diagnostic monitoring and information enablers such as for stock management.”
As with the rest of our industry, refrigerants matter. Then there are the external challenges associated with our planet, where hydrocarbon refrigeration gases, predominantly R600a, but also R290a are the norm for developing a new generation of solar fridges and smaller vaccine fridges, explains Werner. Companies such as Minus 40 is now embracing ‘green’ technology, which includes alternative energy sources, specifically solar, technology, led by the global demands of NGOs. “Undoubtedly, the good news is that this technology will transfer to all our other specialist refrigeration offerings such as refrigerated trailers, that are solar powered, and also mortuary cabinets,” says Werner. “It is within reach that the cost of solar refrigeration will be such that this can become the mainstream source of power for the majority of fridges that we all use daily. The future is exciting for an industry that was once considered to be mature,” concludes Werner.