European regulator raised concern over quality of early Pfizer vaccine batches, leaked emails show

High-ranking official flagged unexpectedly low levels of genetic molecule in November email

Senior figures at the European Union’s medicines regulator raised concern over the quality of early supplies of the Pfizer-BioNTech vaccine, leaked documents and emails show.

Official files that have been shared globally following a cyberattack on the European Medicines Agency (EMA) show that the regulator was concerned by the molecular integrity of vaccine batches made last autumn that had been initially earmarked for commercial markets.

It is thought these supplies were never delivered to one of the many governments that pre-ordered doses of the Pfizer vaccine, or used to inoculate members of the public.

Proven to be highly effective in providing protection against Covid-19, the Pfizer jab has been authorised for use in numerous countries across the globe, with millions of doses administered to date.

The British Medical Journal (BMJ), which has reviewed the leaked EMA documents, claims that a high-ranking official within the agency outlined a series of issues with early vaccine batches made by the pharmaceutical giant in an email sent on 23 November.

The EMA highlighted that commercial manufacturing was not producing vaccine supplies to the specifications expected, with experts said to be unsure of the implications, the BMJ reports.

Specifically, the European regulator reportedly had major concerns over unexpectedly low quantities of messenger RNA (mRNA) in batches of the vaccine intended to be delivered to buying nations.

In the context of the Covid-19 vaccines, mRNA is a genetic molecule that instructs the body’s own cells to display the “spike” protein coating the outside of the virus. This prompts the immune system to produce the necessary antibodies and T-cells that then provide protection.

For early clinical batches of the Pfizer vaccine, mRNA integrity was around 78 per cent - but this figure stood at 55 per cent for certain commercial supplies, the BMJ claims.

The root cause of this disparity was unknown and the impact of this loss of mRNA integrity on the safety and efficacy of the vaccine was not defined, the email reportedly said.

Ensuring RNA integrity is one of the biggest hurdles for manufacturers developing vaccines based on this type of technology. 

These genetic molecules degrade quickly and must be kept at very low temperatures to maintain their integrity, hence the stringent cold chain requirements that surround the Pfizer and Moderna vaccines - both of which are mRNA-based.

To protect against rapid degradation, the mRNA used in the Covid-19 jabs is encapsulated in lipid nanoparticles. 

But if molecular integrity is compromised in any way - such as during the production stage - this can affect the expression of the spike protein in the body’s cells, which means the correct immune response won’t be triggered and protection may not be complete. 

The BMJ reports that is is unclear how the EMA’s concerns were satisfied. However, according to another leaked email from 25 November, the agency noted: “The latest lots indicate that % intact RNA are back at around 70-75%, which leaves us cautiously optimistic that additional data could address the issue.”

The Pfizer-BioNTech vaccine was eventually authorised for use by the EMA on 21 December. “The quality of this medicinal product, submitted in the emergency context of the current (covid-19) pandemic, is considered to be sufficiently consistent and acceptable,” the agency noted at the time.

It later acknowledged that vaccine efficacy depends on the presence of suitable amounts of intact mRNA.

However, the BMJ’s findings raise questions of what percentage of molecular integrity is considered acceptable for these types of jabs.

The Medicines and Healthcare products Regulatory Agency, which was the first regulator in the world to approve the Pfizer-BioNTech vaccine for general use, did not comment on this when approached by The Independent, and nor did Pfizer.

However, the MHRA said there were no concerns surrounding the batches of Pfizer vaccine that had been delivered to the UK.

Siu Ping Lam, MHRA director of licensing, told The Independent: “The observations of lower levels of RNA integrity with certain early batches have been addressed, and are not an ongoing concern. 

“We are satisfied that the RNA integrity of all batches used in the UK to date have met the product requirements.”

Professor Adam Finn, a member of the Joint Committee on Vaccination and Immunisation, said the BMJ report demonstrated that regulatory authorities have been monitoring vaccine quality “carefully from the outset”.

“We can also be reassured by the emerging evidence of real world effectiveness of both vaccines currently in use reported from both Scotland and England,” he added. “This would indicate that the batches used during the early part of the UK programme have been doing their job well.”

Pfizer meanwhile said that all questions surrounding the efficacy, safety and quality of the vaccine were “addressed satisfactorily” and could by “demonstrated on the data submitted” to the EMA.

“It’s important to note that each batch of vaccines is tested by the official medicinal control laboratory (OMCL) – the Paul-Ehrlich Institute in Germany – before final product release,” a spokesperson added.

“As a result, the quality of all vaccine doses that are placed on the market in Europe has been double tested to ensure compliance with the specifications agreed upon with the regulatory authorities. 

“Should a batch not meet these required specifications, the product wouldn’t be released for use in Europe.”

EMA has said it is conducting a full investigation into the cyberattack on its systems.