To: MP’s email address
Cc: stephen.barclay.mp@parliament.uk;
Date xx/xx/xx
Dear MP
I am writing to you to raise my concerns about MHRA approval of covid bivalent boosters and what appears to be a dilution of approval processes for medicines in general.
MHRA appear to have diluted the approval requirements firstly for covid vaccines and even further for the bivalent boosters. Approvals have moved away from an efficacy-based approval to using the surrogate marker of antibody production. No level of antibody has been demonstrated to provide protection but it is easy for a pharmaceutical company to demonstrate a rise in levels.
- Moderna bivalent booster was approved based on antibody production. This happened despite lower efficacy in preventing covid than the original. The trial was on only 437 people!
- Pfizer BA4/5 bivalent booster was approved based on the data from testing the BA1 vaccine trial (a different vaccine). No human trial data on BA4/5 has been presented. Even the BA1 trial was only on 610 people.
- The original Astra Zeneca, Pfizer & Moderna original covid vaccines were approved based on efficacy at preventing symptomatic infections.
There is no transparency in the approval process:
- Public Assessment Reports are reports explaining the reasons a medicine has been approved. They were published within weeks of the original approvals. However they were only published 2-3 months after approval of the bivalent boosters and only after escalation to the ICO
- The Pfizer BA1 Public Assessment Report appears to be incomplete as it contains no research evidence at all.
- Questions via FOI about the approval process have been ignored even after the escalation to the ICO
The safety issues with Astra Zeneca vaccines appear to have been missed due to failure by MHRA. For example, the Danish government took the decision to stop AstraZeneca on 11th March 2021 having given a total of 724k doses of vaccine. By that point the UK had delivered 24 million doses without detecting an issue and continued to use AstraZeneca. (Telegraph article Why Britain’s regulator missed the link between the AstraZeneca jab and rare blood clots people were harmed, the vaccine was quietly withdrawn, but it still has temporary authorisation and there has been no public statement about these failures.
Given MHRA has publicly stated it has turned from a “Watchdog to enabler” I am concerned that approval may now be the priority over safety. A regulator’s role is to regulate not enable and there is a risk that patients’ lives could be put at risk if shortcuts are made.
MHRA is primarily funded by pharmaceutical manufacturers, various board members declarations of interests include pharmaceutical companies and articles in publications such as BMJ have raised concerns about their independence.
Is there a risk that either the desire for Britain to be 1st for covid vaccine approvals or external influence has resulted in the dilution of processes that could put patients at risk?
Please could you undertake an immediate independent inquiry into covid vaccine approvals by MHRA, especially given these new processes appear to have been made permanent.
This is in the public interest, I have signed a petition on the matter which has received over 9k signatures in its 1st 4 days.
I have provided the reasons for my concerns below and look forward to your response.
Kind regards
Your name
Your address
1) Moderna Bivalent booster
The Moderna Bivalent Booster was approved based anti-body production (“Summary of Product Characteristics“) rather than efficacy (the basis of the original vaccine approval), the trial was only on 437 people
- Efficacy data was available from Moderna’s Phase 2/3 trial interim results “A Bivalent Omicron-containing Booster Vaccine Against Covid-19” & showed lower efficacy than the original
- “In participants with no prior evidence of SARS-SoV-2 infection, starting 14 days after vaccination, SARS-CoV-2 infections, regardless of the presence of symptoms, occurred in 11 (3.2%) and 5 (1.9%) participants in the mRNA-1273.214 and mRNA-1273 groups, respectively”
- The antibody production data table MHRA published in the Summary of Product Characteristics appears to be taken from the above report, it would be difficult for MHRA to argue they haven’t seen the efficacy data
- Safety approval was based on the original vaccine, despite slightly higher levels of “systemic adverse reactions” than the original (source: A Bivalent Omicron-containing Booster Vaccine Against Covid-19)
- The approval was based on an EMA assessment despite the fact MHRA approved the vaccine 2 weeks earlier than EMA
2) Pfizer BA1 Bivalent booster
- Approval for the booster was based on anti-body production in a trial on 610 people (Summary of Product Characteristics), no trial data is available to the public.
- Safety data was evaluated, but details were only given for the original vaccine rather than the bivalent booster
- The Public Assessment Report is missing supporting information for “Quality aspects, non-clinical aspects and clinical aspects”
3) Pfizer BA4/5 booster
- Approval for the BA4/5 Bivalent booster was based on data from the BA1 booster (a different vaccine) (Summary of Product Characteristics)”
- “The efficacy of a booster dose of Comirnaty Original/Omicron BA.4-5 is inferred from the immunogenicity of an Omicron BA.1 adapted vaccine”
- The entire point of the boosters is to improve effectiveness against new variants, how can the effectiveness of a booster against one variant, be used to determine the effectiveness of a different vaccine against another variant?
- Safety data was evaluated from the BA1 booster & Original vaccine, not the BA4/5 booster
- “The safety of a booster dose of Comirnaty Original/Omicron BA.4-5 is inferred from safety data for a booster dose of an Omicron BA.1 adapted vaccine, as well as for a booster dose of Comirnaty Original”
- Data is not publicly available
4) AstraZeneca failure to identify warning signs
I do not wish to speak on behalf of the vaccine injured as they should have their own voice (I would recommend for you to speak directly to members of VIBUK and UK CV Family ), however it is a fact that people have been harmed and the following article from the Telegraph indicates the early signs of blood clots were missed link.
I recommend you read the article in full, but I will pull out a few key points:
“Prof Stephan Lewandowsky, a psychologist at the University of Bristol studying the rollout of Covid-19 vaccines, told the Financial Times on Friday: “The MHRA was slow in responding to the emergence of a specific constellation of symptoms associated with the AstraZeneca vaccine and slow to communicate what they were finding — and I am not the only one who thinks so.””
“This should be seen in the context of the “operational and logistical challenges” the regulator faced in the run-up to the UK formally leaving the EMA on December 31, and the MHRA formally becoming a sovereign regulator for the first time on January 1”
“It is not known exactly what parameters the MHRA set but it is clear they were not as sensitive as those used by some regulators in Europe.”
“Another reason for the MHRA’s slower reaction, suggest observers, could be that it lost access to Eudravigilance, the vast European database into which all adverse drug reactions are reported, when the UK left the orbit EMA regulation on 31 December last year.”
5) Transparency
- Public Assessment Reports were only published for bivalent boosters on 17th November, Moderna was approved in August 2022 and Pfizer in September 2022, reports were published 14 and 10 weeks later respectively.
- Public Assessment Reports were published 6 days after approval for the Astra Zeneca vaccine, 13 days later for the original Pfizer vaccine & 6 weeks later for the original Moderna
- An FOI was raised to request the Public Assessment Reports, to provide the trial reports used for approval, the approval process and the reasons for approval (Appendix 1)
- MHRA responded to the FOI stating a Section 22 Exemption (intent to publish at a later date) relating to the Public Assessment Reports, they completely ignored the remainder of the FOI
- ” As we plan to publish the Public Assessment reports in the next 8 weeks, we consider that your request is covered by section 22 of the Freedom of Information Act (information intended for future publication) and the information you have asked for is therefore exempt from disclosure.
- “Section 22 is a qualified exemption which means we have considered whether there is a greater public interest in releasing the information requested or withholding it. We recognise there is strong interest in seeing this data and accept it should not be withheld. We believe that the public interest will be best served by accompanying the publication of the data with an analysis to aid its interpretation which is currently under preparation”
- Why do the public need “an analysis to aid its interpretation”?
- This was not provided for any of the other vaccines
- Why do the public need “an analysis to aid its interpretation”?
- The FOI response was sent on 16th of September, the reports were not published within the 8 weeks stated in the response
- An internal review was requested on 16th September, Internal Reviews should be completed within 20 working days, it took over 40 days for a response
- The Public Assessment Reports were finally published after escalation to the ICO, however the remainder of my FOI remains unanswered
- Other FOIs have been raised to request the “Nucleotide base sequence” for the bivalent boosters
- You will note from the article in the Telegraph that they and other media have found it difficult to get information from MHRA “Despite requests from several newspapers including The Telegraph, the MHRA has not released the dates on which the deaths occurred or were reported into the Yellow Card system, citing the need to preserve patient confidentiality”
6) MHRA “From watchdog to enabler”
Given the UK is now “living with covid” rather than under an emergency, why have the requirements for covid vaccine approvals been further diluted post pandemic, than during the “pandemic”?
A presentation by June Raine during “Medics Day” on 5th March 2022 perhaps sheds some light on this “MHRA From Watchdog to enabler”, some key points are quoted below:
“The covid Pandemic has catalysed the transformation of the regulator from a watchdog to an enabler”
At a meeting about covid tests in the Cabinet Office June was asked “why a regulator was in the room”, Boris Johnson stated “The MHRA will stop us killing people”, she responded “No the MHRA will help us keep people alive, and that is the signal of the change from watchdog to the enabler”.
“What is the MHRA? The general view is that the rules are written on tablets of stone and there are a lot of policeman in these places that go around factories to find problems with trials and generally hold things up”
“We tore up the rulebook and allowed companies to immediately start juxtaposing, not sequential phases of clinical trials but overlapping, beginning the next one before the previous one had been finished and large scale manufacture being prepared at risk”
“We began in the middle of June 2020 to start to prepare what safety surveillance we would need”
“We only really learn about benefit risk in clinical use, and we knew there would be a vast influx of reports of side effects, no effective medicine or vaccine is without them”
“The so question then, will we be able to maintain this change in regulation permanently, and I believe in our own regulatory world we have changed our processes, there is no going back now, we can ensure that we are as speedy as possible with our approvals without cutting corners and that we don’t ever again keep our patients waiting”
7) Appendix 1: FOI request
Sent: 04 September 2022 07:54
Dear MHRA
Please could you
-Publish the Public Assessment Report for both the Moderna & Pfizer bivalent vaccines
-Give the reasons why these documents have not yet been published
-Confirm what evidence was used to establish safety & efficacy of each vaccine?
-What safety trials were run on these vaccines as opposed to the original?
-What efficacy trials were run on these vaccines as opposed to the original?
-Provide links to the trial reports for each vaccine
-Provide the reasons the Moderna vaccine was approved based on anti-body data, rather than efficacy?
-Is there any precedent of approving vaccines by antibody data only, if so please confirm which vaccines?
–What was the approval process MHRA went through to agree this methodology change?
-What consideration was made to this statement in the Moderna trial report “In participants with no prior evidence of SARS-SoV-2 infection, starting 14 days after vaccination, SARS-CoV-2 infections, regardless of the presence of symptoms, occurred in 11 (3.2%) and 5 (1.9%) participants in the mRNA-1273.214 and mRNA-1273 groups, respectively.”?
-Were human trials run for the Pfizer vaccine?
-If not is there any precedent of vaccines being approved with no human trials, please name the vaccines?
8) Appendix 2: FOI Initial response
FOI 22/953
Dear
Thank you for your email.
A marketing authorisation for the Spikevax bivalent Original/Omicron vaccine (PLGB 53720/0004) was granted on 12 August 2022. Further information is available via the following link:
A marketing authorisation for the Comirnaty Original/Omicron vaccine (PLGB 53632/0010) was granted on 02 September 2022. Further information is available via the following link:
As we plan to publish the Public Assessment reports in the next 8 weeks, we consider that your request is covered by section 22 of the Freedom of Information Act (information intended for future publication) and the information you have asked for is therefore exempt from disclosure.
Section 22 is a qualified exemption which means we have considered whether there is a greater public interest in releasing the information requested or withholding it. We recognise there is strong interest in seeing this data and accept it should not be withheld. We believe that the public interest will be best served by accompanying the publication of the data with an analysis to aid its interpretation which is currently under preparation
If you disagree with how we have interpreted the Freedom of Information Act 2000 with regards to your request, you can ask for the decision to be reviewed. The review will be carried out by a senior member of the Agency who was not involved with the original decision.
If you have a query about the information provided, please reply to this email.
Please remember to quote the reference number above in any future communications.
If you were to remain dissatisfied with the outcome of the internal review, you would have the right to apply directly to the Information Commissioner for a decision. Please bear in mind that the Information Commissioner will not normally review our handling of your request unless you have first contacted us to conduct an internal review. The Information Commissioner can be contacted at:
MHRA Customer Experience Centre
9) Appendix 3: FOI 2nd response
Dear
Following contact from the ICO regarding the above-mentioned case, we would like to provide you with attached response.
Kind Regards
MHRA Customer Experience Centre
Dear
ICO Case Reference: IC-197130-J2V1
MHRA Reference CEC 125746
Thank you for your correspondence.
We understand that an earlier release of the public assessment reports (PARs) would be desirable, however, we produce these documents as soon as is reasonably practicable.
MHRA regulates a vast number of products including many other important products that also require PARs, such as, cancer medicines, flu vaccines, heart and diabetes therapies and so on. We carefully balance these competing exigencies, and despite the challenges with regard to COVID-19, we have prioritised publication of the vaccine PARs, especially those of the first / Original mRNA vaccines. Please also note, the PARs are not the only source of information available to patients and the public; the SmPC includes the results of pivotal data which supports an application, while the package leaflet includes important information related to use of the product, side effects, interactions and so forth. Many of the vaccines are also authorised in Europe and so supportive data and the EMA’s assessments are often also available online.
Please find copies of the PARs below:
Spikevax bivalent Original/Omicron 01 mg/mL dispersion for injection
elasomeran/imelasomeran PLGB 53720/0004
MHRA Products | Search results
Comirnaty Original/Omicron BA.1 (15/15 micrograms) dose dispersion for injection (PLGB
53632/0010)
MHRA Products | Search results
As a general remark, we note that you have asked ten questions in your original request, and although some of the questions may appear simple by their phrasing, the answers we expect will take considerable resource to draft. In order, for us to maximise our resources which are not limitless, we would kindly ask that you peruse the PARs provided above and then if you still harbour questions about the assessment or data submitted, to then lodge these as a new request.
Please also note, when enquiries are made about more than one product this is often equivalent to doubling the list of questions.
Kind Regards
MHRA Customer Experience Centre
10) Appendix 4: MHRA followup
FOI 22/1127
Dear
Thank you for your email.
Regarding the authorisation of Comirnaty Original/Omicron BA.4-5 (15/15 micrograms)/dose dispersion for injection COVID-19 mRNA Vaccine (nucleoside modified – PLGB 53632/0012), the following information is on the European Medicines Agency (EMA) website (https://www.ema.europa.eu/en/medicines/human/EPAR/comirnaty):
“Apart from containing mRNA matching different, but closely related, Omicron subvariants, Comirnaty Original/BA.1 and Comirnaty Original/Omicron BA.4-5 have the same composition. Therefore, based on clinical studies showing that Comirnaty Original/Omicron BA.1 triggers an immune response to the original strain and Omicron BA.1, Comirnaty Original/Omicron BA.4-5 is expected to generate an immune response against both the original strain and the subvariants BA.4 and BA.5.
In particular, Comirnaty Original/Omicron BA.4-5 is expected to be more effective than Comirnaty at triggering an immune response against the BA.4 and BA.5 subvariants. These data are further supported by non-clinical laboratory data on the ability of Comirnaty Original/Omicron BA.4-5 to trigger an adequate immune response.”
The above medicinal product has not been granted temporary authorisation via Regulation 174, it has been granted a marketing authorisation. Further information, including the Public Assessment Report (PAR) published by the EMA is available via the link above. The UK Patient Information Leaflet (PIL) and Summary of Product Characteristics (SmPC) is available via the below link, a PAR will be published for this product in the next 60 calendar days.
If you have a query about the information provided, please reply to this email.
If you disagree with how we have interpreted the Freedom of Information Act 2000 in answering your request, you can ask for an internal review. Please reply to this email, within two months of this reply, specifying that you would like an Internal Review to be carried out.
Please remember to quote the reference number above in any future communications.
If you were to remain dissatisfied with the outcome of the internal review, you would have the right to apply directly to the Information Commissioner for a decision. Please bear in mind that the Information Commissioner will not normally review our handling of your request unless you have first contacted us to conduct an internal review. The Information Commissioner can be contacted at:
Information Commissioner’s Office
Wycliffe House
Water Lane
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Yours sincerely
MHRA Customer Experience Centre
