If we accept that ongoing dialogue about access to medical oxygen is a pre-requisite during a pandemic, if not a lesson learned from this oxygen crisis of the last 18 months, then might we also argue there is discussion to be had concerning its purity and accessibility itself?
There have proven to be many lessons to be learned from this pandemic, many of which have concerned the oxygen supply chain. A range of talking points have been raised through the course of this series of articles, not least the differences between medical-grade liquid oxygen produced and the oxygen produced onsite via purpose-built pressure swing adsorption (PSA) systems.
Yet another topic altogether is the subject of industrial versus medical-grade oxygen. With the experiences of the last six months in particular, when it appeared as though almost any grade of oxygen would do to meet insatiable demand in India for example, one might argue whether the ‘taboo’ topic of medical oxygen purity is now in question. Could barriers have been broken in our traditional understanding of what medical oxygen is or should be?
To better contextualise the discussion here, let’s begin with a recap on what medical oxygen is and how it’s produced.
Oxygen is one of the core air gases, and the bulk of it is produced via the air separation process in an ASU (air separation unit). Generally speaking, the air all around is comprised of 78% nitrogen, 21% oxygen (approx.) and 1% of argon and other constituents (rare gases like krypton, neon and xenon, for example). An ASU takes this abundant atmospheric air and, through several stages of separation and distillation, splits it out into those individual components (oxygen, nitrogen, argon).
Oxygen produced by the cryogenic process is typically produced at greater than 99% purity so that it can be used for essentially all applications, including for medical purposes. Medical oxygen, is, however considered as a drug or pharmaceutical product in the healthcare sector.
Oxygen produced by air separation is acceptable as medical oxygen without any additional purification steps. The air separation process itself removes contaminates to levels typically below those required to meet medical oxygen specifications. Although some air separation facilities may divert a portion of the oxygen they produce into dedicated medical oxygen tanks, this is not a universal practice, nor is it necessary; oxygen produced by air separation is, by nature of the process, acceptable as medical oxygen.
Many air separation facilities produce oxygen into a common tank, then use in-facility testing equipment to verify the product meets the specification for its intended use. In the case of medical oxygen, this in-facility testing equipment is also used to produce the test results that allow a qualified person to release the product as acceptable for use as medical oxygen. To be able to sell medical oxygen, plants must have the required licenses and ensure the stringent specifications to be met – but it isn’t just the plants that must go through these process steps. Regulation applies across the whole supply chain, from production through to supply to the patient and whether via liquid distribution or cylinder distribution, to ensure no contaminants are introduced into the final, qualified product. This may represent something of a red tape process, but it is nonetheless fundamental to oxygen’s safe use for the patient104.
There are always areas or risk that need to be managed, whether they are during transfer processes or when connected to the customer’s process, cases of backwards contamination for example. Even with PSA systems, precautions need to be taken to ensure unexpected contaminants are not introduced, whether from poor or deteriorating local air quality, poor maintenance, or even from a parked vehicle’s exhaust emissions too close to the air intake; the latter example is perhaps just one instance that those more removed from the subject would not previously have considered. gasworld also understands the industry, through its various associations and regulatory bodies, has had to do a lot of work in recent years to demonstrate to regulators that the cylinders used to supply medical oxygen do not add metallic contaminants to the gas.
The question of these practices or the required licences, was brought into focus in April 2020 at the height of the first wave of Covid-19 sweeping across the globe. And it was a development in India on 8th April – at that time having recorded just under 6,000 confirmed cases of Covid-19 and 178 fatalities, according to data from the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University – that many felt could be a breakthrough path for others to follow in the weeks ahead.
As reported by gasworld, the Government of India granted permission for manufacturers of industrial oxygen to temporarily manufacture and sell the gas for medical use, as the country continued to anticipate an escalation in its cases of coronavirus and resulting hospital admissions105. This was very much a balance of risks – the risk of supplying potentially impure or compromised product versus the risk of supplying no product at all. In all considerations, the risk was of course to the patient, rendering it an entirely complex decision to make – it appeared that the infection and fatality rates at that time, coupled with challenges in obtaining sufficient oxygen, ultimately forced the government’s hand.
The proposal was understood to have been put forward by the All India Industrial Gases Manufacturer’s Association (AIIGMA), to ensure the availability and supply of oxygen for medical use across the country. The grant was issued on 8th April by the Directorate General of Health Services (Government of India) and essentially enabled all manufacturers of industrial oxygen in the country to obtain a license to sell the product for medical use within 24 hours of their application being received.
Mere weeks later, in Europe, it also emerged that the European Directorate for the Quality of Medicine and Healthcare (EDQM) would be launching an extraordinary public consultation on how best to include oxygen at 98% purity obtained via two-stage concentrators in European Pharmacopoeia106.
The development was largely driven by the heightened need for medical oxygen during the current coronavirus pandemic, but also as a result of the advances in technology since the last monograph was published, particularly the rise of double-stage pressure swing adsorption (PSA) oxygen generators.
European Pharmacopoeia currently includes two monographs on oxygen, firstly Oxygen (0417) and secondly, Oxygen (93%) or Oxygen 93 (2455). Oxygen (0417) was drafted over 50 years ago and covers oxygen produced by cryogenic distillation, with an oxygen content specification of a minimum 99.5%. Oxygen 93 (2455) was first published in Europe in 2010 and covers oxygen produced by a concentrator that removes the nitrogen from ambient air using a PSA system.
At the time of the latter’s publication, the plants available on the market utilised a single-stage adsorption process which did not remove any argon from the air being processed. Advances have since been made in the design of PSA oxygen concentrators and companies like Novair and others are now producing double-stage PSA plants capable of producing oxygen with a nominal content of 98%. This has prompted the decision to elaborate a new monograph, Oxygen (98%) (3098), especially as the ongoing Covid-19 pandemic had at that time increased the demand for oxygen worldwide by as much as a factor of 10.
Twelve months later, and we would all go on to see desperate scenes across India as the country struggled to deal with a lethal second wave of Covid-19, the emergence of the Delta variant, and crippling medical oxygen shortages.
With daily confirmed Covid-19 cases of more than 250,000 and fast escalating, it was revealed on 19th April (2021) that new restrictions were to be implemented in India to manage the application of oxygen supply and prioritise its use for medical purposes107.
Several states across India were flagging oxygen shortages, and the government promptly announced that oxygen supply would be restricted to just nine industries. From 22nd April, industrial oxygen supply would be restricted to those entities involved in refilling cylinders, the pharma sector, steel plants, oil refineries, wastewater treatment, food and water treatment, nuclear energy facilities and continuous production sites that must keep processes running. In essence, the order of the day is essential industrial use only, with medical oxygen provision the priority.
The news came just over one year to the day since India had broken ground as the first country to temporarily allow industrial oxygen producers to manufacture and sell the gas for medical use. But the story would continue to rapidly evolve, and the following crises in securing and distributing oxygen supply would further question a paradigm shift in industrial versus medical oxygen.
Just four days later, on 23rd April, gasworld revealed that India was appealing to the international industrial gas community for urgent help in meeting its oxygen needs108. It was understood that the Indian High Commissions across the Middle East, Europe and Asia were all approaching gas companies and gas associations for help.
According to Saket Tiku – President of AIIGMA – the demand for medical oxygen in India had increased from its norm of around 800 tonnes per day (tpd) to unheard of highs of around 3,000+ tpd in the first pandemic spike – but during the second and still climbing wave that figure had doubled to 6,000 tpd. Tiku had spent the prior nine months being co-opted onto a special committee set up by Prime Minister Modi and, as conditions worsened and that oxygen demand had spiked, it was gasworld’s understanding that the Indian Government had issued a tender for 50,000 tonnes of medical liquid oxygen, open to the international community as well as those within India. Even the more unusual steps of using specially converted military transport aircraft that could fly liquid oxygen trailers within and into India were starting to take place and quickly became the subject of global media coverage.
In the weeks and months since, such scenes had prompted many to ask on the simplest of levels, if industrial-grade oxygen was justified for over a billion people across India, have we seen the barrier broken now in industrial oxygen for medical purposes?
A factor in the argument for medical oxygen?
There are no doubt many other factors to consider in this discussion, such is the many-splintered business of oxygen production, storage, delivery, monitoring and analysis. One of those has arisen from a left-field question concerning the proliferation of ‘black fungus’ in India.
Domestic publication The Indian Express reported on 27th May (2021) how black fungus had emerged as ‘a post-Covid complication that had startled the medical fraternity’ due to the way in which this rare disease had spiked during the lethal second wave of the pandemic in the country109. The report acknowledged that the dosage of steroids, uncontrolled sugar levels and low immunity were the chief factors behind the outbreak, but questioned whether the quality of oxygen being supplied in hospitals and the respective hygiene levels of industrial oxygen cylinders rather than medical cylinders had any impact.
Is there a possible correlation between the quality of oxygen and instances of black fungus, it questioned?
Black fungus, or mucormycosis as it is technically known, is a serious fungal infection, usually in people with reduced ability to fight infections. Symptoms depend on where in the body the infection occurs. It most commonly infects the nose, sinuses, eye and brain, resulting in a runny nose, one-sided facial swelling and pain, headache, fever, blurred vision, swollen and bulging eye, and tissue death. Other forms of disease may infect the lungs, stomach and intestines, and skin110.
According to the same definition by Wikipedia, black fungus is spread by spores of moulds of the order Mucorales, most often through inhalation, contaminated food, or the contamination of open wounds. These fungi are common in soils, decomposing organic matter (such as rotting fruit and vegetables), and animal manure, but usually do not affect people.
A fact sheet online from the US CDC (Centers for Disease Control and Prevention) affirms the seriousness and effects of black fungus. It explains, “Mucormycosis (previously called zygomycosis) is a serious but rare fungal infection caused by a group of moulds called mucormycetes. These moulds live throughout the environment. Mucormycosis mainly affects people who have health problems or take medicines that lower the body’s ability to fight germs and sickness. It most commonly affects the sinuses or the lungs after inhaling fungal spores from the air. It can also occur on the skin after a cut, burn, or other type of skin injury.”111
The Indian Express article described how black fungus cases started being reported among patients who were mostly in a post-Covid state and were on a combination of oxygen and steroids. An earlier BBC News article from 9th May (2021) had described the ‘black fungus maiming Covid patients in India’ and how, as a deadly second wave of Covid-19 ravaged India, doctors were reporting a rash of cases among recovering and recovered Covid-19 patients112. Likewise, an article from The Economist on 24th May (2021) explained that almost 9,000 people across India had been diagnosed with mucormycosis, many of whom had also been ill with Covid-19113.
By 21st July (2021), a further article from BBC News reported that more than 4,300 people had died from black fungus in India, in a ‘growing epidemic that mainly affects Covid-19 patients’. It continued to explain that at that time of writing, India had reported 45,374 cases of the infection, quoting Health Minister Mansukh Mandaviya114.
Large amounts of industrial oxygen were diverted for medical purposes in India, as we know, while industrial cylinders were also used to plug the shortfall in medical oxygen cylinders. In its May 2021 article, The Indian Express noted that some industrial cylinders were upgraded to medical-grade in states like Punjab – but this was not possible for all non-medical cylinders used by patients.
It proceeded to explain that this was relevant because, though ‘industrial oxygen is more pure than medical oxygen at 99.67%, the condition of industrial cylinders is not as good as medical oxygen cylinders. The former is treated roughly and without proper hygiene. Plus, they are prone to several micro leaks’.
The article proceeded to quote both a local gases company and a senior medical officer in Punjab, who appeared to affirm not only that industrial cylinders cannot be used for medical purposes without significant upgrading, but also that this protocol was often ignored due to sheer time and resource limitations in the face of such huge demand.
Ultimately, the fear of contamination was highlighted and the question raised, whether a link can be made between the quality of oxygen supplied through industrial cylinders and a spike in black fungus cases. It should be noted here that widespread reports of this growing black fungus epidemic, however, attribute the cause to the large deployment of steroids in the fight against Covid-19 which as described earlier, helps with treatment on the one hand but can lower the immune system on the other.