The Dutch policy of limited testing for the coronavirus is largely caused by a shortage of laboratory supplies. Pharmaceutical company Roche dominates the market for lab materials and currently supplies a mere 30 per cent of the Dutch orders. Roche holds the key to the storage cabinet and has as of yet kept the recipe which could help overcome certain shortages under its hat.
This was revealed in a survey by Follow the Money of various insiders, the Dutch National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu – RIVM) and pharmaceutical company Roche. The majority of Dutch labs relies on the same manufacturer. These labs all use the machines of market leader Roche, which also makes them dependent on the test materials supplied by the pharmaceutical company. But Roche cannot meet the demand for these materials. These shortages are not readily resolved, because of the concept known as vendor lock-in; labs using the Roche machines also have to use Roche’s materials.
Labs could easily manufacture one of the testing materials which is currently in short supply – a type of solution whose precise recipe is only known to Roche. Follow the Money asked Roche if it was willing to disclose the recipe. That would be a highly exceptional step for the pharmaceutical company. Then again, these are exceptional times. Roche declined to answer this question.
The scarcity is an important reason why the RIVM has been closefisted with coronavirus tests. Last week, this issue sparked a public debate on testing for healthcare professionals, which due to these shortages cannot be done on a large scale.
‘We do not have a capability problem,’ Alex Friedrich, a medical microbiologist at University Medical Center Groningen (UMCG), said last week in De Groene Amsterdammer about the testing policy. His statement caused an uproar. Friedrich explained that – contrary to national RIVM guidelines – his laboratory widely tests healthcare workers for the coronavirus and is not hindered by shortages of testing materials.
This angered Hugo de Jonge, the Dutch Minister of Health, Welfare and Sport, who accused the Groningen lab of adopting an ‘every man for himself’ mindset: ‘This is not how you handle a crisis.’ De Jonge repeated that there is, in fact, a ‘serious shortage’ of testing materials.
Shortage, no shortage – where does this controversy stem from? Follow the Money contacted the RIVM and the UMCG with more questions and found the answer: Groningen is not dependent on one major supplier, but has spread the risks over various manufacturers, unlike most other Dutch labs. These labs have to purchase their testing materials from the market leader in the in vitro diagnostics sector. That market leader is the Swiss pharmaceutical company Roche. Its subsidiary Roche Diagnostics supplies the machines to most laboratories in the Netherlands, which are also used for the coronavirus tests. These machines require the use of Roche testing materials, such as certain types of solutions and pipettes.
‘This manufacturer supplies testing materials throughout the world, so the Netherlands has entered a global market where there is a huge demand for tests,’ explains the RIVM. ‘The Netherlands currently receives about 30 per cent of its orders, which is why the current testing policy is to use the capability wisely, taking account of the fact that we have to be able to sustain this in the long term’
‘The testing policy in the Netherlands is based on the recommendations of the Outbreak Management Team (OMT). The OMT is a group of experts which, under the auspices of the RIVM, formulates recommendations for combating the novel coronavirus outbreak. See also ‘How does the RIVM inform the Cabinet about the coronavirus?’
The testing policy is not determined by the RIVM alone. A lot of people are being tested for the coronavirus in the Netherlands. We follow the advice of the World Health Organization (WHO) as much as we can, while making smart use of our testing capability and taking account of the fact that we also have to be able to sustain this in the long term.
We have to use the available testing capability wisely. There is simply insufficient capability to test everyone in the Netherlands. We focus on identifying people from vulnerable groups who are at higher risk for complications. We have to know if these people have COVID-19 in order to give them the right treatment. Some regions in the Netherlands still have sufficient capability to test healthcare workers, while in other regions a more comprehensive testing regime would mean that patients have to wait longer for their tests. It is more important to know if patients have the novel coronavirus, because it impacts quick decision-making, such as if they have to be moved to a ‘coronavirus ICU’ or a regular ICU. We test if necessary, meaning if the test results have consequences for certain actions.
The manufacturer supplies its testing materials throughout the world, so the Netherlands has entered a global market where there is a huge demand for tests. The demand greatly outstrips supply. The Netherlands currently receives about 30 per cent of its orders, which is why the current testing policy is to use the capability wisely, taking account of the fact that we have to be able to sustain this in the long term. If we test extensively now, there could be a shortage in the long run. Moreover, comprehensive testing is not paramount: we test if necessary, meaning if the test results lead to actions.
The testing capability differs in the various regions of the Netherlands. The OMT always follows the national policy in its recommendations. The Netherlands is composed of more than one region. The OMT also considers the long-term capability. Testing extensively now could cause shortages in the long run. This is an important factor in the OMT recommendations.’
In short, supplies by pharmaceutical company Roche determine to a great extent the number of coronavirus tests the Dutch labs can carry out. Only the senior management of Roche – and possibly the governments of the countries where its plants are located – have control over how the manufacturer currently distributes products among its clients in the various countries.
What is the situation with the shortage of materials? In De Groene Amsterdammer Friedrich provided more clarity: ‘It is possible that a particular lab has a shortage of certain types of materials, but that is business as usual, which can be solved. It is not a problem as long as you are not dependent on one commercial party.’
In the world of medical microbiological research it works as follows: if you buy a machine from a certain manufacturer, you also need the test kits of that manufacturer. These kits consist of several parts, such as so-named Eppi tubes, which can hold small volumes of liquids, and matching pipettes and racks specifically designed for the machine. All parts fit together. A contract is concluded with the purchase of the machine for the take-up of these required materials. The same goes for the solutions that are used in the process. The manufacturer’s revenue model is not only based on the machine, but also on the regular supply of parts and solutions.
It is comparable to purchasing a printer: the brand you buy automatically determines which cartridges you need. Such a construction, in which the client is basically made dependent on a single supplier, is known as vendor lock-in.
Vendor lock-in has a large part of the Dutch labs hog-tied now that their main supplier Roche is facing excessive demand from around the world. The Swiss pharmaceutical company has informed Follow the Money that it has tripled its production capacity. But even then, the demand exceeds supply – leaving Dutch laboratories on hold.
The laboratory of Amsterdam Municipal Health Service (Gemeentelijke Gezondheidsdienst – GGD), a ‘primary laboratory’, is one of the laboratories that is waiting in line. It performs tests for GPs, nursing homes and municipal health services, and currently also carries out coronavirus tests. Mariken van der Lubben, Director of GGD Amsterdam, confirms that the Amsterdam lab also uses Roche equipment for its coronavirus tests and will probably be affected by shortages very soon. ‘We call suppliers every day, but there is great uncertainty about our standing orders.’
One of the materials the lab are running out of, besides plastic tubes and parts, is a special buffer solution called lysis buffer. It is a crucial component in testing for viruses. The lysis buffer breaks down the cell membrane, releasing the cell’s genetic information. Machines can ‘read’ the genetic information and determine whether or not a virus is present. Chantal Reusken, a virologist at RIVM, said in de Volkskrant that lysis buffer for coronavirus tests is running low.
The interesting aspect is that laboratories can easily make lysis buffers. The production of a couple of litres of the solution could provide a much-needed respite, as labs only need several millilitres of buffer per coronavirus test.
How is it possible that a shortage can occur? This is where vendor lock-in comes into play again. Laboratories that work with Roche also purchase lysis buffers from Roche. They cannot switch to self-made lysis buffer just like that.
Mariken van der Lubben explains how it works at her Amsterdam laboratory: ‘We have one Roche machine and we are dependent on them for the solution. We can also work manually, but we would need lysis buffer for that, which will possibly be hard to come by. If necessary, we can make it ourselves.’ She explains that a lab first has to validate the newly-made solution, meaning that it has to go through an extensive testing process to show that the self-made buffer acts in the exact same way as Roche’s lysis buffer. This is to prevent, for example, self-made lysis buffers from not only breaking down the cell membrane, but also destroying the virus itself, rendering it ‘unreadable’.
It would be a boon to the labs using Roche machines if they had the precise recipe for Roche lysis buffer. But that information is only known to Roche. While the package insert of Roche lysis buffer openly lists the chemical constituents of the solution, it does not provide the precise proportion of the constituents.
In the above-mentioned Volkskrant article, Ann Vossen, a medical microbiologist at Leiden University Medical Center (Leids Universitair Medisch Centrum – LUMC) and member of the RIVM Outbreak Management Team (OMT), essentially called on Roche to publish its recipe for lysis buffer: ‘They won’t like it, but needs must.’
The fact that Vossen expects Roche to ‘not like it’ is not entirely without reason. If laboratories have the recipe for the solution, which up until now they have had to purchase from Roche, the pharmaceutical company’s revenue model will take a beating. It would be tantamount to Hewlett Packard giving customers with an HP printer instructions for making their own ink and refilling their cartridges.
Follow the Money presented the statements of Vossen to Roche and asked if the company would be willing to share its lysis buffer recipe with the Dutch labs. We did not receive a direct response. Roche spokesperson Jan Peter Jansen did state that self-made lysis buffer is ‘usable’ in Roche machines. Unfortunately, this is of no use to the labs, because they would have to complete a lengthy validation process first before they can start using their self-made lysis buffer.
Roche sent Follow the Money the following statement in response to the questions about Roche’s lysis buffer:
‘Although Roche Diagnostics produces a lysis buffer, the recipe of lysis buffer is typically not a secret. Some laboratories make their own lysis buffer based on a recipe that is freely available.
Roche Diagnostics always does its utmost, but particularly in times of a health crisis, to meet the demand for the right medical resources for each patient. For your information: we have tripled our production capacity since the beginning of the coronavirus outbreak. However, the huge spike in demand continues to exceed our production capacity.
We would also like to inform you that we have a lysis buffer available through our Custom Biotech organisation, regarding which we have also informed our clients.’
Following up on this response, Follow the Money asked again: is Roche willing to reveal the precise recipe of its lysis buffer? We did not receive a further response.
Ann Vossen’s appeal to Roche to publish its recipe is welcomed by the laboratory of GGD Amsterdam. ‘It would certainly help,’ Van der Lubben said. But she also points out that other materials are in short supply as well. This is confirmed by Gijs Ruijs, a medical microbiologist at Isala Hospital in Zwolle, and Mariet Feltkamp, a medical virologist at LUMC. ‘It is a good thing that this is being questioned,’ Ruijs said. Feltkamp warmly supports the appeal of her colleague Vossen. ‘I also think that Roche has stipulated in its fine print that they cannot guarantee the results obtained with self-made lysis buffer,’ she notes.
Does Roche hold the key to the solution for the shortages in the Dutch laboratories? It is unclear how the company distributes its products among its clients all over the world. Some governments, including that of the United States, have proven to be willing to impose export bans on medical and diagnostic products. This means that the production of a particular factory could be reserved for domestic use only, even against the will of a company. For example, the United States currently considers imposing an export ban on Philips ventilators assembled in American factories. What we are left with is the unprecedented global demand, which Roche is unable to meet.
But Roche does control one thing: its recipes. The company could allow labs that have purchased its machines to independently solve their shortages. Roche could publish its buffer recipe.
Follow the Money posed some questions to Minister Hugo de Jonge and his ministry’s coronavirus crisis team. Is De Jonge willing to exert pressure on Roche and to take action, if necessary, to have the company reveal its lysis buffer recipe or send more goods to the Dutch laboratories? We did not receive a response to these questions.
What, if anything, can the minister do? He could learn lessons from how the Dutch labs have inadvertently manoeuvred themselves into a vulnerable position by largely relying on a single supplier. The UMCG does not experience shortages because it uses equipment from different manufacturers.
Not only has the Groningen lab’s risk distribution in terms of equipment proven to be a sound preparation for an emergency situation. The spokesperson of UMCG reports that – unlike other labs – their laboratory is not experiencing a shortage of pipette tips. The reason? ‘Years ago during the Ebola outbreak our microbiologist Bert Niesters had the foresight to stockpile pipette tips to create – in his words – ‘pandemic reserves’. We have maintained the reserves over the past years, which we are benefiting from now.’ The UMCG is not the only lab that is reaping the rewards of the reserves. ‘We even had a batch of machines we no longer used at the lab. We sent them to another lab where they still use them,’ Niesters added.
There are other options, as recently shown by Italian hackers. They managed to create valves for ventilators – which were desperately needed – with a 3D printer. Perhaps a skilful chemist will be able to analyse Roche’s lysis buffer or a Dutch manufacturer can reproduce the necessary plastic parts. The minister may consider supporting such initiatives or even urge them through the use of a compulsory licence. The government would be able to protect a manufacturer of such reproduced testing materials from claims instituted by the original manufacturers.
As of yet, the ball is in the court of the RIVM’s OMT to ease the shortages. According to an RIVM spokesperson, the OMT is looking for solutions: ‘A Diagnostics Task Force whose members comprise Diagned, the umbrella trade organisation, but also the RIVM, the Ministry of Health, Welfare and Sport and buyers of academic hospitals, is identifying the bottlenecks and is making an inventory of the available stocks. It is also reviewing a redistribution of materials in addition to exploring alternatives.’
Trade organisation Diagned consists of suppliers of machines and other equipment used for testing by the laboratories. As the market leader, Roche has an important voice in the trade organisation and has for years supplied the chairperson, currently Barbara Kamp. Roche therefore also influences the Dutch testing policy through this position on the OMT.
Should the OMT fail to find alternatives, there is much at stake. Testing will become even more difficult. Mariken van der Lubben of GGD Amsterdam foresees problems in maximising the testing capability of her lab due to the shortages at Roche, while the demand for testing is accelerating. ‘We also have other ways of manually testing for the coronavirus, which are labour-intensive. It means we would be able to do 100 tests a day at most – provided that all other solutions continue to be available. We are currently preparing for that situation.’