Why potentially millions of doses of mRNA Covid vaccines are lost in the vials

By and

The messenger RNA (mRNA) vaccines against Covid-19 infection are apparently highly effective, but they are also in too short supply to meet current demand. In France, doctors have found that vials of the mRNA vaccines from Pfizer and Moderna contain more than the indicated number of doses. By collecting the dregs of the bottles, there is the potential of producing millions more doses from existing supplies. But the French health authorities are refusing to authorise the practice. Joseph Confavreux and Caroline Coq-Chodorge report.

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Messenger RNA (mRNA) vaccines against Covid-19 infection increasingly appear as potentially the most effective way out of the worldwide crisis caused by the coronavirus. In Israel, the mRNA vaccines are demonstrating their efficacy, at least regarding the most severe forms of Covid-19; after a vast campaign of vaccinations of the elderly with the Pfizer-BioNTech mRNA vaccine, the numbers of their hospitalisations due to Covid-19 infection have fallen dramatically.

In France, three vaccines are currently in use, all of them requiring the administration of two doses. The most recently authorised is the adenovirus vector vaccine produced by AstraZeneca, while the remainder, one from Pfizer-BioNTech and the other from Moderna, are both mRNA vaccines

The side effects of the Pfizer-BioNTech vaccine have so far been reported as relatively minor in people with no underlying health problems. The French national agency for monitoring the safety of medicines, the ANSM, reported in an update published on February 11th, just one alert for the Pfizer-BioNTech vaccine; that concerned 73 incidents between January 30th and February 4th of an “increase in blood pressure immediately after vaccination”. It reported no side effects of concern for the Moderna vaccine. Meanwhile, the AstraZeneca vaccine, which was first rolled out for healthcare workers beginning on February 6th, was by February 10th reported to have caused strong flu-like symptoms among 149 out of around 10,000 of those vaccinated, causing some to take sick leave. The ANSM noted that no similar problems were reported among 21 other countries that were using the same batch of the AstraZeneca vaccine.

French health minister Olivier Véran, a neurologist by training, was administered a dose of the AstraZeneca vaccine on Monday, and has apparently suffered no such side effects judging by his appearance at a press conference on Thursday to present a latest update on the coronavirus epidemic in France. He described the situation as being “under control”, but also “fragile” and “uncertain” because of the progress of new variants of the coronavirus. He warned that some local lockdowns may have to be introduced – the last national lockdown in the country was lifted in December – in particular in the north-east département (county) of Moselle, where there are clusters of the variants first discovered in South Africa and Brazil, and which are causing the health authorities the most concern.  

In Europe as a whole, the slowness of vaccination rollouts, caused in part by a shortfall in supplies, mean that it will be several months at least before their effects will be seen. On February 3rd, Véran gave a somewhat confusing message of both reassurance and warning when he announced that, “We will never have enough vaccines straight away, but we will always have enough vaccines at the right moment”. Martine Aubry, a former socialist health minister and now mayor of the northern city of Lille was more precise with her observation that France was up against “really a shortage of vaccines”.

France’s vaccination programme, which began on December 27th, is lagging behind other major European countries in terms of the number of doses already administered per 100 people. On Friday, that figure was 3.83 jabs per 100 people, representing a total of just more than 2.5 million doses.

In the context of the urgent response required by the current health crisis, pharmaceutical firms have obtained numerous guarantees from public authorities regarding their exoneration from the legal and financial consequences of unforeseen side effects from the vaccines. The contracts for supplies of vaccines signed by the European Commission, of which some heavily redacted versions have been made public, show that the EU member states have pledged to indemnify pharma firms and absolve them of all responsibility in the case of third-party action taken against them.

Syringes prepared with the mRNA Comirnaty (Pfizer-BioNTech) vaccine during the first phase of the vaccination programme at a teaching hospital in Starsbourg, north-east France, on January 8th. © Claude Truong-Ngoc / Wikimedia Commons / cc-by-sa-4.0 Syringes prepared with the mRNA Comirnaty (Pfizer-BioNTech) vaccine during the first phase of the vaccination programme at a teaching hospital in Starsbourg, north-east France, on January 8th. © Claude Truong-Ngoc / Wikimedia Commons / cc-by-sa-4.0

France is currently due to receive 30 million doses of the Pfizer-BioNTech vaccine, marketed under the brand name Comirnaty. These are delivered in the form of vials of concentrated vaccine which, after being diluted with a saline solution, theoretically produces six doses. That number is already one more than the five doses Pfizer had originally indicated the vials contained – which was amended to six in January after EU and US regulators recognised that this was easily attainable when using specific types of syringes.

It is usual to have an extra volume as a margin of security to ensure that the official number of doses can be obtained. But beyond the now officially recognised six doses that are contained in the Comirnaty vials, doctors in France have found it is often possible to extract even more – generally by using the dregs of several vials. Given the shortage of vaccine supplies, they are calling for authorisation to use the excess solution to create more doses.

“Technically it’s really not complicated, even if it requires a bit of deftness and habit,” explained to Mediapart the director of a vaccination centre in Paris, a general practitioner (GP) who asked for his name to be withheld – as did a number of other interviewees. Their coyness is because the French health authorities have firmly refused to authorise the practice.       

Another GP in charge of a vaccination centre in the French capital said he was also in favour of the idea, although he recognised its success was not automatic. “Technically it is sometimes possible but not all the time,” he said. “It depends on the preparation of each vial and the technical skill of the practitioner. As long as the method to do it is not [officially] validated we won’t do it. But if it can be, it could become interesting.”

A third doctor in charge of another vaccination centre suggested the refusal of France's Regional Health Agencies (ARS) – a national health ministry network that oversees the application of healthcare policies on a regional basis – to allow the extractions of further doses may be a commercial issue. “The response of the ARS, when they were asked if we could do it, was a categoric refusal, no doubt for a reason as commercial as it is technical,” he said. “It’s true that our nurses don’t always succeed in reconstituting a seventh dose, except by dipping into two vials, which is theoretically not what we’re supposed to do for reasons of traceability.”

Each Pfizer-BioNTech vaccine vial contains 0.45 millilitres of concentrated vaccine, which is diluted with 1.8 millilitres of saline solution (sodium chloride), producing 2.25 millilitres of vaccine. Because each administered dose of vaccine measures 0.3 millilitres, it is theoretically possible to produce seven and a half doses from each vial (although the greasy aspect of the product makes it difficult to avoid some wastage). But the calculation is above all theoretical because some of the vaccine solution is lost with each injection – this is what is called a “dead volume” that remains in the syringe and the needle which are both thrown away after the injection.

Laurent Fignon is a doctor specialised in geriatric care at a hospital in Cannes, south-east France. During the vaccinations of the elderly at his hospital, he and the nurses in his service attempted to extract extra doses. “We retrieved the [solution from] the bottom of the vials to reconstitute a dose,” he explained. “It is possible, but we threw out the doses because by manipulating the vaccine in this way you run the risk of bacterial contamination.”

“We, the vaccinators, need to have clear rules, which are defined under the authorisation [given] for the marketing of medicines,” he added. “These rules protect us; if we follow them and something happens, we’re not responsible. In the context of mass vaccinations, these rules must be simple, [and] easily applied by nurses and doctors who are not necessarily specialists in vaccination […] It’s always about finding a balance between the foreseen benefits and the possible risks.”

At a vaccine centre in Strasbourg, north-east France, anti-Covid-19 jabs are administered to people aged above 75, January 18th 2021. © Claude Truong-Ngoc / Wikimedia Commons / cc-by-sa-4.0 At a vaccine centre in Strasbourg, north-east France, anti-Covid-19 jabs are administered to people aged above 75, January 18th 2021. © Claude Truong-Ngoc / Wikimedia Commons / cc-by-sa-4.0

It was after the Pfizer-BioNTech vaccine received authorisations through December for use in more than 20 countries, beginning with the UK and later in the month by the US and EU, that doctors began realising they could, on condition of careful handling and using appropriate syringes, extract six doses of the vaccine from each vial – one more than the five doses which Pfizer originally labelled them for.

It was a significant development at a time when the vaccines were already suffering from supply shortages, allowing a potential 20% increase in the numbers of people who could be vaccinated. In early January, the EU’s European Medicines Agency and the US Food and Drug Administration recommended that the vials should be considered as containing six doses. Soon after, Pfizer officially marketed the vials as containing six doses, and because its contracts are for payments per dose, it upped the price of each vial while also reorganising supply quotas. Michael Ganio, senior director for pharmacy practice and quality at the American Society of Health-System Pharmacists, told The New York Times: “Now there’s more pressure to make sure that you get that sixth dose out.”

Obtaining the sixth dose requires specific equipment. “With traditional syringes, the ‘dead volume’ lost in the syringe was too much to be able to easily extract this sixth dose of the vaccine,” explained Laurent Fignon, who was among medics in France who campaigned early on for official authorisation to extract the potential sixth dose from Pfizer’s vials. “Since two weeks, Santé Publique France [Editor’s note, responsible for epidemiological monitoring of the population and notably introducing urgent policies in response to exceptional health crises] has therefore supplied syringes which limit this ‘dead volume’, in order to easily and routinely extract this sixth dose. One can fear in fact a shortage of this type of syringe if the whole world needs it.”

Frédéric Lagarce, a professor of pharmaceutical technology at the health faculty of the University of Angers in north-west France, and who is also a hospital pharmacist, suggests it was in fact a mistake to officially decide that the Pfizer vials contain six doses instead of five. “The contracts stipulate that payment is by the dose, so the labs make us pay for this sixth dose,” he said. “At first, this supplementary volume in the vial was a margin of security, as foreseen by European pharmacopoeia, and destined to be thrown away. By deciding to extract it, one has complicated the manipulation procedure and we’ve become dependent upon one single syringe model and upon a single supplier.”     

The demand in France for doses of the mRNA vaccine is such that hospital pharmacists have begun consultations with the authorities on the issue of extracting every possible drop left in the vial, and Lagarce is the co-author of a recommendation drawn up by a French hospital pharmaceutics study group, Gerpac, issued on January 27th. “This manipulation of the dregs of the vials is possible, but only in a hospital pharmacy under a flow of sterile air,” he said. “That would mean that the vaccine doses are made in a centralised manner, in the hospital pharmacies. It would require a lot of time, equipment and personnel that we don’t have. I am not sure that would be a good idea, and the laboratory [Pfizer] would bill us for the supplementary doses, which are very difficult to extract.”

Lagarce insists that outside of a sterile environment, “to transfer vaccine with a needle from one vial to another is not right, it doesn’t correspond with best practices. The risk of contaminating the vaccine is certainly limited, but it exists”.

Currently, Pfizer is to supply France with 30 million doses of its Comirnaty vaccine. That number of doses is contained in 5 million vials, each producing six doses as authorised at present. But. if one allows that the dregs from, for example, three vials can provide one extra dose – i.e.19 doses per three vials – that would represent obtaining a total of 31,666,667 doses from the same number of vials (an extra 1.6 million doses).

According to the first-cited GP in charge of a Paris vaccination centre, the refusal of the health authorities to allow extracting a seventh dose is medically groundless. “The risk in making a seventh dose is zero, he said. “And at stake is avoiding the loss of opportunity [to be vaccinated] of very numerous patients. It is always a question of finding a balance between the envisaged benefits and the possible risks. And in this case there’s no doubt.”

A number of the doctors overseeing the vaccinations have lobbied the health authorities for permission to practice the extra extraction. Mediapart has seen the email reply sent to one of them by a member of France’s High Authority of Health (HAS), an independent but public scientific body that advises, among other things, on best practices in the healthcare system. “I well understand your motivation, completely laudable, to economise doses in order to vaccinate the maximum number of people,” wrote the HAS member, whose name is withheld here. “Certainly, 7x03 ml do equal 2.1 ml. I nevertheless have doubts about the possibility of guaranteeing that one can extract 7 doses without losing 0.1ml. Furthermore, with the intention of opening a maximum number of [vaccination] centres, we run the risk of using personnel who are not very used to the practice. The risk is that some people do not receive the complete dose, or that some perform manipulations not very orthodox to fill their 7 syringes. I doubt, in any case, that the health authorities take that path.”

The issue is far from closed; the French vaccination centres are now also being supplied with the mRNA vaccine produced by Moderna, which is contained in vials marketed as containing ten doses but from which some medical staff believe 11 doses can be extracted. According to one of the heads of a Paris vaccination centre, cited above, this can even be raised to 12 doses “and there is still liquid in the vial”.



  • The original French version of this report can be found here.


English version by Graham Tearse




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