By Ilana Koegelenberg
From the laboratory to the clinic, the pharmacy and even on the road — what is the importance of refrigeration in maintaining the medical cold chain?
Vaccines can become ineffective if stored at the wrong temperature for prolonged periods.
Image credit: getdoc.co
Refrigeration plays a major role in the medical field (I’m resisting the urge to call it ‘a matter of life and death’, even though it is). It is vital, particularly when it comes to storing vaccines, blood or organs — and even in the mortuary. Temperature-sensitive items rely on refrigeration that is reliable, consistent, and durable. What types of refrigeration are used in the medical field and what are the challenges we face in South Africa, in particular with regard to maintaining the medical cold chain?
|Disclaimer: As usual, this seemed like a pretty straightforward topic when I pinned it to my features list. However, when I started looking into it, I realised just how wide this topic actually stretched. Each sector could literally be its own feature. I’ve collected bits and pieces of information on the topic, but please note, once again, this is by no means a comprehensive guideline.|
Patient, product, operator
When it comes to all things pharmaceutical, my first call is always to Basil Mugwagwa, maintenance manager at Pharmacare Limited (trading as Aspen Pharmacare) and ad hoc RACA Journal contributor.
“The topic is quite wide as the medical side of refrigeration can be looked at from either the angle of patient safety (theatres, patient comfort, and so forth) or from medicinal product safety (looking at storage conditions, such as temperature and humidity control of medicines),” Mugwagwa explained.
“What you need to remember in the medical field is the golden rule of patient, product, and operator in all you do,” he said.
Patient: the medication must reach the patient in a safe manner and in the right state/form and dosage (temperature / humidity control is vital here).
“Vaccines are very temperature sensitive and must be stored within specifications.”
Product: must always be in its intended purest form (efficacy and purity) without any cross-contamination. (Think of the role of temperature and humidity when certain medicines change state, say from ointment to liquid.)
Operator: be it the nurse, doctor, pharmacist or any other medical personnel in the value chain, they should be protected from unintended intake of medication. (It’s all about the right temperature and humidity — think of liquids that can turn to vapour and inhaled unintentionally due to high temperature.)
At the centre of it all is the ventilation, air movement, and containment in the medical field. It’s not just about refrigeration, but HVAC as well. But for this particular feature, we’ll focus more on the refrigeration side of things, looking at how to keep product at its desired temperature.
So where does one start?
Why keep it cold?
Step one – why is refrigeration important when it comes to vaccines in particular? Not too long ago, there was an interesting article on health24.com about exactly this — and particular to South Africa. It highlighted that domestic fridges were often used in doctors’ rooms, which may not store temperature-sensitive vaccines properly, leaving them ineffective.
If vaccines are not kept strictly at the right temperature they will not work. There is growing concern internationally and in South Africa that many health care providers are unaware they are administering vaccines rendered useless through inadequate refrigeration in domestic or ‘bar’ fridges.
The problem can be addressed, however, through regular ‘temperature mapping’ of fridges, which is now a requirement of the Pharmacy Act.
Refrigeration is vital in mortuaries to keep bodies from decomposing too fast.
Image credit: rd.com
Vaccines are highly effective — if stored correctly. “Vaccines are very temperature sensitive and must be stored within specifications,” confirms Dr Melinda Suchard, head of the Centre for Vaccines and Immunology at the National Institute for Communicable Diseases.
Certain vaccines are particularly fragile. Live vaccines (such as for measles) may lose potency if stored at too high temperatures. Diluent (liquid mixed with some vaccines) may also be a problem if it is stored too cold and accidentally freezes. Vaccines for tetanus, human papilloma virus, pneumococcal disease, and rotavirus, for example, are destroyed by accidental freezing.
Health professionals may not realise they are administering an ineffective vaccine. The handling toolkit for the Centres for Disease Control and Prevention (CDC)’s vaccine storage states that when some vaccines accidentally freeze, there is no visual evidence this has occurred.
A recent review of research on temperature variations during refrigeration by the United States’ National Institute of Standards and Technology showed that 13.5% of vaccines get accidentally frozen. In South Africa, this number is probably even higher.
The CDC warns against using domestic or bar fridges to store vaccines, and recommends continuous temperature monitoring to avoid vaccine damage.
Dr James Southern, advisor to the Medicines Control Council (MCC), states that vaccines should be stored between 2°C and 8°C. “Many routine domestic refrigerators run at above this, some even at +15°C in hot weather. This shortens a vaccine’s overall shelf-life. Some vaccines are reasonably stable up to 25°C, but only for short excursions, up to an hour perhaps. Live vaccines are less stable, but they are freeze-dried for extra protection,” he says.
One dangerous practice is reconstituting freeze-dried vaccines, then returning them to the fridge, or leaving the vial on the bench for a while. They’ll usually be stable for a couple of hours, but then rapidly lose potency. Bright light can also damage their potency. Vaccines come with vial monitors that show if the cold chain has been broken and the product is no longer effective.
“Replacing multi-dose vials in the fridge after removing a few doses is also risky. Theoretically, they should be fine for a week or more, but any contamination or exposure to warmer temperatures can damage them,” says Dr Southern.
Douglas Siepman, CEO of 5nines, which conducts temperature compliance monitoring, reckons that around 90% of the domestic refrigerators they have analysed failed to meet vaccine storage standards.
Damaged vaccines are also a financial burden. For example, if a specific flu vaccine for infants costs about R500 a shot, a public health care facility can, at any given time, have half a million to a million rands worth of stock in a single fridge. If that refrigerator goes out of range (correct temperature) the vaccines would have to be discarded because they would have lost their efficacy.
Rules and regulations
Mugwagwa sent me a whole series of emails on standards and regulations that relate to the medical field which really is strictly regulated and precise (although, as usual, we struggle with non-compliance). There simply isn’t space (or time) to go into all of these in detail so here’s the ‘executive summary’.
You need very specific fridges when it comes to maintaining the medical cold chain — not just beverage coolers.
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.
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.
All about temperature control
The manufacturing of medical refrigeration must include effective and sturdy insulation. If there is a power cut and the refrigeration systems are left with no electricity source, the unit is expected to be able to hold its temperature for approximately one day — provided that the door remains sealed for the duration until power is restored.
Minus 40 has been manufacturing medical refrigeration and equipment for almost three decades at its modern plant situated next to Cape Town International Airport. From vaccine fridges and breast milk bank refrigerators to solar refrigeration and even mortuary equipment, they do it all, covering the entire spectrum from birth to death (for both humans and animals).
I chatted to Minus 40 managing director, Michael Werner, about the state of the local medical refrigeration industry and the challenges it faces.
Refrigeration is perceived as being a simple technology, and clients have their perception shaped by their contact with domestic appliances, explains Werner. “However, there is significant complexity with temperature control, inclusive of accommodating defrost cycles and temperature variability that occurs in daily operations when fridges are in use.”
There is a huge challenge to educate clients on how to specify their products correctly to the tolerances that their products require across the cold chain. This is solved by either receiving internationally set standards from customers, usually defined by manufacturers of medicines / vaccines or NGO organisations such as the WHO, or by interacting directly with the customers to help them define optimum operating specifications.
You need very specific fridges when it comes to maintaining the medical cold chain. For example, breast milk has to be kept at <-20°C for five continuous days to kill CMV viruses. Laboratories also have very specific requirements in terms of temperature and humidity control. The requirements have been set, but they are simply not always adhered to.
There actually is better compliance in the government sector than in the private sector, according to Werner. Various national companies are storing their products in domestic and commercial beverage fridges and not complying with regulations.
In 2013, the Gates Foundation did an assessment at the point of inoculation of vaccines in Africa and found the vaccine efficacy failure at a staggering 55% at the point of inoculation in rural areas. South Africa did not score much better either — but this study was not detailed enough. The bottom line is, we have a problem – a big one.
It’s not just about keeping product at the right temperature in the clinics and pharmacies. The correct transport of the sensitive product is also vital to maintain a proper cold chain. Otherwise, the product could be damaged or spoiled even before it reaches its destination.
The correct transport of the sensitive product is vital to maintain a proper cold chain.
Image credit: Twister
“The thermal stability of several pharmaceuticals places special demands on the refrigeration logistics,” explains Kenan Gröss, managing director at Twister Trans. Numerous statutory specifications and industry standards govern temperature-controlled transport operations and represent a great challenge for shipping and forwarding agents. “The effectiveness of medication and vaccines may become reduced considerably by unavoidable temperature fluctuations during transport,” explains Gröss.
To protect the patients dependent on the medication, the South African government has implemented the Good Distribution Practice (GDP) Directive.
In the morgue
When a body is preserved through refrigeration, it is kept at a temperature below 4.5°C, which sufficiently delays decomposition.
Refrigeration is often employed when there will be no viewing, wake, or visitation, or if the casket will remain closed during the service (as many funeral homes require that the body be embalmed if it is to be on display). Refrigeration is also used if the body will be cremated, as some authorities require that a body be refrigerated for a given amount of time prior to cremation.
If the 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.
It’s not just about installing the right equipment, but also looking after it properly. This is where regular maintenance comes in.
The level of maintenance required for medical refrigeration is quite strict. Regular checks must be made and logged to ensure that all equipment is safe, working at full capacity, and kept in accordance to relevant standards and guidelines.
The question is, is this being done?
Not doing maintenance doesn’t just put the product at risk but can also be costly in terms of having to replace faulty equipment later on. Medical budgets mean that savings must be made wherever possible, so efficient and reliable equipment is essential.
“Customers need to learn that modern refrigeration technology is reliable and durable, but not maintenance free,” explains Werner. “In medical environments such as in hospitals, we assume that the environment is ‘clean’, but the impact of lint, for example, in hospitals results in condensers being blocked, impeding cooling airflow, and ultimately results in fridge failures due to overheating.”
Having disciplined and regular cleaning of the refrigeration system will ensure reliable temperature control within set parameters as well as extending the life of the equipment to decades.
Measurement matters – BMS
Medicines and vaccines often contain active ingredients that are sensitive to light, heat, humidity, and other pollutants. If the environments in which they are manufactured, stored, and distributed are not controlled carefully, their efficacy may be impacted. That control is so important that it has been legislated in South Africa. Building management systems (BMS) and access control solutions are playing an increasingly important role in ensuring that legislation is met.
Proven and approved validation systems help pharmaceutical manufacturing and distribution organisations monitor and report on key processes employed in the manufacture of medicines, the environment in which they are stored, and the conditions under which they are handled and transported. “Validation is important for the management of dangerous pathogens — it’s important to control and be able to validate the laboratory conditions in which they are kept and handled, from origination to disposal,” explains Neil Cameron, Johnson Controls area general manager: building efficiency – Africa.
Intelligent BMSs with their capability to measure, monitor and control environments based on preconfigured requirements are important tools to help meet and enforce validation requirements. In South Africa, legislation requires that on receipt of goods the recording devices (temperature data loggers, refrigeration tags, freezer tags, log tags or cold chain monitoring cards) be checked and documented. Elsewhere in the world, more rigorous requirements are in place that require the use of validated technologies.
Vaccines come with vial monitors that show if the medicine has been out of the temperature range and is no longer effective.
In the US, for example, the Food and Drug Administration (FDA) sets out validation requirements for BMS. Today, pharmaceutical companies cannot export goods to the US that do not comply with FDA validation requirements. To achieve this validation, organisations must make use of processes and systems that measure, capture, and manage critical information related to the life cycle of the product (manufacture, distribution, and so on) in a secure way.
A BMS for validated environments will, for example, provide scalable configurations, system security, secure data management and reporting, electronic records and signatures, pre-selected and free-form annotations, time-stamped audit trails, extensive integration capabilities at all system levels, Web-based reporting (mean kinetic temperature, trend analysis and alarm analysis), and remote alarming (email, text messaging, and the like).
“Customers need to learn that modern refrigeration technology is reliable and durable but not maintenance free.”
In particular, technologies used for validation need to meet the FDA’s Electronic Records and Signature requirements. To comply, the computer systems used to collect and analyse data must be validated to meet the FDA requirements for electronic records and signatures — that is, these electronic signatures (authorisation) must be legally binding and the electronic records must be protected from point of creation to receipt, meaning any tampering with information must be detectable, explains Cameron.
Using an FDA certified BMS for validated environments the validation process can be integrated or configured within the organisation’s building automation system. Validation can be further implemented within access control systems — an important consideration in the control of disease and handling of dangerous pathogens.
FDA-certified BMSs for validated environments differ from standard BMS. Where a standard BMS will measure the temperature in an environment, a BMS for validated environments will measure and guarantee that temperature — it certifies that the temperature sensor is providing a true value, that the controller to which the sensor information is sent is responding as it should, that the information subsequently stored in the database is secure and cannot be tampered with, and that the output report containing the FDA-required information is protected.
“While implementation of validation systems require effort, once in place, they provide the assurance that validation processes are being followed and that the products the organisation is taking into the market are safe and effective and of the required quality,” says Cameron.
“It’s critical that South Africa begin to make use of the technologies now becoming available to manage, monitor, and validate processes related to manufacturing, storing, and distributing medicines in the country. It will protect us from human error and lower risks, but also help improve processes and raise standards in the industry,” Cameron explains.
Education is key
Werner says he sees a trend towards better education in the medical field. “People are aware that they need to do better; medical practitioners are getting a better understanding. But the finance people governing them do not necessarily understand — that’s the problem. They just want the cheapest model. This is more of a problem in the private sector, as government is more professional in its procurement practices.”
It all comes down to an education process. “Education and legislation go hand in hand. We’re getting there but it’s a slow process,” says Werner. Companies like Netcare for instance have started a drive to dispose of domestic fridges and are now procuring the correct medical fridges.
Government tenders are also becoming much better at specifying what they need.
We still have a long way to go.
So where are we going? “The medical industry is becoming more demanding in terms of specific specifications, including higher attention to quality and service standards due to poor experience from suppliers,” explains Werner. Also, the private sector is asking for increasingly eco-friendly products both in terms of energy efficiency and in materials (specifically refrigerant gases). The government sector is increasingly motivated to buy local to reduce import dependency.
Several exciting things are happening in the medical refrigeration field. For example, Minus 40 has engaged with clients and suppliers to innovate products on an ongoing basis. Recent work with a major South African health care company has resulted in a totally South African developed and manufactured Breast Milk Bank solution, inclusive of milk pasteuriser, fridge, and freezers specific to the milk bank duties, as well as a tracking and product control system to comply with proposed South African regulations coming into effect this year. The solution is a completely integrated Breast Milk Bank system, which is unique and costs less than half of the fragmented elements that were previously imported, with associated support back-up challenges that were prevalent with earlier practices.
Current projects include a unique South African designed and manufactured vaccine refrigeration solution that will comply with WHO PQS certification.
Watch this space. The medical refrigeration market may not be a huge one, but it is a critical one.