Biodistribution, half-life and known toxicity of SARS-CoV-2 spike protein produced cellularly after COVID vaccination

Dr Lee Proctor made this Freedom of Information request to Medicines and Healthcare Products Regulatory Agency

Automatic anti-spam measures are in place for this older request. Please let us know if a further response is expected or if you are having trouble responding.

Response to this request is long overdue. By law, under all circumstances, Medicines and Healthcare Products Regulatory Agency should have responded by now (details). You can complain by requesting an internal review.

Dear Medicines and Healthcare Products Regulatory Agency,

Can you please provide data showing :

1) The biodistribution including tissues, organs, cells and human body organ systems for the spike protein produced by vaccination.
2) Can you provide a spike protein concentration-time plot from the point an individual is vaccinated. I am specifically interested in how long it takes for the peak concentration of spike protein to be produced and the half-life of spike protein.
3) known toxicological data for the spike protein such as the LD50, LC50, TDLo

Yours faithfully,

Dr Lee Proctor

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Thank you for your email.  This auto-response is to inform you that your
email has been received and will be reviewed by our Customer Service Team.
We will respond to you as soon as possible. 

 

Please note that we may not respond if your query: 

 

• contains offensive language
• has already been answered in a previous reply to you
• is illegible
• is selling or promoting a product
• is for information only 

 

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, 
Canary Wharf, 
London 
E14 4PU
gov.uk/mhra
Stay connected 
 
For information on how the Agency uses your personal data and your data
protection rights, please see our three centres’ Privacy Notices: MHRA,
CPRD and NIBSC. 

 

The UK has left the EU, and the transition period ends on 31 December
2020. Our [1]guidance and information can be accessed here. 

References

Visible links
1. https://www.gov.uk/government/collection...

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Our Ref: FOI 21/821

Dear Dr Lee Proctor,

RE: REQUEST UNDER THE FREEDOM OF INFORMATION ACT 2000

Thank you for your enquiry which we received on 14 July 2021.

I confirm that your request is now being handled under the Freedom of Information Act and you should receive a reply within 20 working days from our date of receipt.

If you need to contact us again about this request, please quote the reference number above.

Please be aware that we publish FOIs replies and these are redacted and are located on our website at the following link below.
https://www.gov.uk/government/collection...


Kind Regards,

MHRA Customer Service Centre

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU Telephone 0203 080 6000

show quoted sections

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

FOI 21/821

Dear Dr Lee Proctor,

Thank you for your email.

Information (including information for physicians and recipients of the vaccine, and Public Assessment Reports [PARs] for each vaccine) are available on the MHRA website. Links to these are provided below:

https://www.gov.uk/government/publicatio...
 
https://www.gov.uk/government/publicatio...

https://www.gov.uk/government/publicatio...
 
Please note that a marketing authorisation was granted for the Pfizer/BioNTech vaccine (Comirnaty) following a European Commission (EC) decision on 21 December 2020 (PLGB 53632/0002). Further information is available on the European Medicines Agency (EMA) website, a link to this is provided below:
https://www.ema.europa.eu/en/medicines/h...

Please also note that a marketing authorisation was granted for the Moderna vaccine on 31 March 2021 following an EC Reliance Procedure (PLGB 53720/0002). Further information is available on the MHRA website and the EMA website, links to these are provided below:
https://www.gov.uk/government/publicatio...
https://www.ema.europa.eu/en/medicines/h...

A marketing authorisation has been granted for the Janssen Covid-19 vaccine on 28 May 2021. Further information is available via the below link:
https://www.gov.uk/government/publicatio...

In addition, a marketing authorisation was granted for the Oxford/AstraZeneca vaccine on 24 June 2021 following an EC Reliance Procedure (PLGB 17901/0355). Further information is available on the MHRA website and the EMA website, links to these are provided below:
https://www.gov.uk/government/publicatio...

https://www.ema.europa.eu/en/medicines/h...

If you have a query about the information provided, please reply to this email

If you are dissatisfied with the handling of your request, you have the right to ask for an internal review. Internal review requests should be submitted within two months of the date you receive this response and addressed to: [MHRA request email]

Due to the ongoing Covid-19 situation, we are not able to accept delivery of any documents or correspondence by post or courier to any of our offices

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
Wilmslow
Cheshire
SK9 5AF

Yours sincerely

MHRA Customer Service Centre

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU

show quoted sections

Dear MHRA Customer Services,

Thankyou for your response and the multiple links to documents. I have read through all of the documents provided and none address any of the specific items from my original FOI request - copied below:

Can you please provide data showing :

1) The biodistribution including tissues, organs, cells and human body organ systems for the spike protein produced by vaccination.
2) Can you provide a spike protein concentration-time plot from the point an individual is vaccinated. I am specifically interested in how long it takes for the peak concentration of spike protein to be produced and the half-life of spike protein.
3) known toxicological data for the spike protein such as the LD50, LC50, TDLo

I politely request the MHRA disclose information they have for the specific points raised above

Yours sincerely,

Dr Lee Proctor

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Thank you for your email.  This auto-response is to inform you that your
email has been received and will be reviewed by our Customer Service Team.
We will respond to you as soon as possible. 

 

Please note that we may not respond if your query: 

 

• contains offensive language
• has already been answered in a previous reply to you
• is illegible
• is selling or promoting a product
• is for information only 

 

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, 
Canary Wharf, 
London 
E14 4PU
gov.uk/mhra
Stay connected 
 
For information on how the Agency uses your personal data and your data
protection rights, please see our three centres’ Privacy Notices: MHRA,
CPRD and NIBSC. 

 

The UK has left the EU, and the transition period ends on 31 December
2020. Our [1]guidance and information can be accessed here. 

References

Visible links
1. https://www.gov.uk/government/collection...

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Dear Dr Lee Proctor,

Thank you for your email.

If you are dissatisfied with the response provided to your FOI request, you can request an internal review. During this, the response you received will be analysed to determine whether the request was answered and whether we could provide any additional information.

Please let us know if you would like an internal review to be conducted.

Kind regards,

MHRA Customer Service Centre

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU

show quoted sections

Dear Medicines and Healthcare Products Regulatory Agency,

Please pass this on to the person who conducts Freedom of Information reviews.

I am writing to request an internal review of Medicines and Healthcare Products Regulatory Agency's handling of my FOI request 'Biodistribution, half-life and known toxicity of SARS-CoV-2 spike protein produced cellularly after COVID vaccination'.

I was sent multiple links to documents all of which I
have read and assessed and none of the information requested in my original FOI was mentioned, described, discussed or evaluated in any of them. I once again politely ask for the information I originally requested to be disclosed or a reason given as to why this information is not available or being withheld from disclosure.

My original request is copied below:

Can you please provide data showing :

1) The biodistribution including tissues, organs, cells and human body organ systems for the spike protein produced by vaccination.
2) Can you provide a spike protein concentration-time plot from the point an individual is vaccinated. I am specifically interested in how long it takes for the peak concentration of spike protein to be produced and the half-life of spike protein.
3) known toxicological data for the spike protein such as the LD50, LC50, TDLo

A full history of my FOI request and all correspondence is available on the Internet at this address: https://www.whatdotheyknow.com/request/b...

Yours faithfully,

Dr Lee Proctor

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Thank you for your email.  This auto-response is to inform you that your
email has been received and will be reviewed by our Customer Service Team.
We will respond to you as soon as possible. 

 

Please note that we may not respond if your query: 

 

• contains offensive language
• has already been answered in a previous reply to you
• is illegible
• is selling or promoting a product
• is for information only 

 

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, 
Canary Wharf, 
London 
E14 4PU
gov.uk/mhra
Stay connected 
 
For information on how the Agency uses your personal data and your data
protection rights, please see our three centres’ Privacy Notices: MHRA,
CPRD and NIBSC. 

 

The UK has left the EU, and the transition period ends on 31 December
2020. Our [1]guidance and information can be accessed here. 

References

Visible links
1. https://www.gov.uk/government/collection...

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Internal Review of FOI 21/821
 
Dear Dr Proctor,
 
Thank you for your email.
 
We confirm that an internal review will be carried out on FOI 21/821. We normally aim to respond to requests for internal review within 20 working days of receipt. However, due to high volumes of queries we are currently receiving related to COVID-19 please be aware that responses may take longer than usual.
 
Kind Regards
 
 
MHRA Customer Service Centre
 
Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU

show quoted sections

Dear MHRA Customer Services,

The internal review I requested regarding my FOI request is long overdue. By law, under all circumstances, the authority should of responded by now.

By law, public authorities must respond “promptly” to requests, the law states that they must respond within 20 working days.

Yours faithfully,

Dr Lee Proctor

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Thank you for your email.  This auto-response is to inform you that your
email has been received and will be reviewed by our Customer Service Team.
We will respond to you as soon as possible. 
 
Please note that we may not respond if your query: 
 
• contains offensive language
• has already been answered in a previous reply to you
• is illegible
• is selling or promoting a product
• is for information only 
 
Medicines and Healthcare products Regulatory Agency
10 South Colonnade, 
Canary Wharf, 
London 
E14 4PU
gov.uk/mhra
Stay connected 
 
For information on how the Agency uses your personal data and your data
protection rights, please see our three centres’ Privacy Notices: MHRA,
CPRD and NIBSC. 
 
The UK has left the EU, and the transition period ends on 31 December
2020. Ourguidance and information can be accessed here.

________________________________________ From: Dr Lee Proctor
<[FOI #773996 email]> Sent: Saturday, September 11,
2021 5:52:13 AM To: MHRA Customer Services Subject: Re: FOI 21/821 CSC
62870 Internal review of Freedom of Information request - Biodistribution,
half-life and known toxicity of SARS-CoV-2 spike protein produced
cellularly after COVID vaccination Dear MHRA Customer Services, The
internal review I requested regarding my FOI request is long overdue. By
law, under all circumstances, the authority should of responded by now. By
law, public authorities must respond “promptly” to requests, the law
states that they must respond within 20 working days. Yours faithfully, Dr
Lee Proctor -----Original Message----- Internal Review of FOI 21/821 Dear
Dr Proctor, Thank you for your email. We confirm that an internal review
will be carried out on FOI 21/821. We normally aim to respond to requests
for internal review within 20 working days of receipt. However, due to
high volumes of queries we are currently receiving related to COVID-19
please be aware that responses may take longer than usual. Kind Regards
MHRA Customer Service Centre Medicines and Healthcare products Regulatory
Agency 10 South Colonnade, Canary Wharf, London E14 4PU
------------------------------------------------------------------- Please
use this email address for all replies to this request:
[FOI #773996 email] Disclaimer: This message and
any reply that you make will be published on the internet. Our privacy and
copyright policies:
https://urldefense.proofpoint.com/v2/url...
For more detailed guidance on safely disclosing information, read the
latest advice from the ICO:
https://urldefense.proofpoint.com/v2/url...
Please note that in some cases publication of requests and responses will
be delayed. If you find this service useful as an FOI officer, please ask
your web manager to link to us from your organisation's FOI page.

show quoted sections

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Dear Dr Lee Proctor,
 
Thank you for your email.
 
We have chased your enquiry with our Licensing experts and we can only apologise that you have not yet received a response. We have notified the team concerned and they will respond to you as soon as they can.
 
We are sorry for the length of time you have to wait for a response.
 
In the meantime should you require any further advice or assistance on this matter please feel free to call us on 020 3080 6000 or reply to this email.
 
Our opening hours are Mon – Fri 9am to 5pm (excluding UK Public Holidays)
 
With regards,

MHRA Customer Service Centre
Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU

show quoted sections

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

 
Dear Dr Proctor,
 
Thank you for your request for a review of your FOI request concerning
“Biodistribution, half-life and known toxicity of SARS-CoV-2 spike protein
produced cellularly after COVID vaccination'”. Thank you for your patience
while we completed the Internal Review. We have annotated your three
questions with our responses in italics.
 

 1. The biodistribution including tissues, organs, cells and human body
organ systems for the spike protein produced by vaccination.

 
We do not hold this information, however, the MHRA continues to monitor
real world data and information and data from RMP and PV activities with
respect to the safety of the COVID-19 vaccines.
 

 2. Can you provide a spike protein concentration-time plot from the point
an individual is vaccinated. I am specifically interested in how long
it takes for the peak concentration of spike protein to be produced
and the half-life of spike protein.

 
We do not hold this information, however, the MHRA continues to monitor
real world data and from RMP and PV activities with respect to the safety
of the COVID-19 vaccines.
 

 3. known toxicological data for the spike protein such as the LD50, LC50,
TDLo

 
The spike protein has not been administered to animals in toxicological
tests: therefore there are no figures available for values of LD50, LC50,
TDLo.  The vaccines were given to animals and for each of the approved UK
vaccines, the top dose used in animals was considered a tolerable dose
with the only notable changes seen explained by the immune system
responding to the vaccine.  Values for LD50 and LC50 were not sought in
this testing.
 
We would also like to mention that, we do not agree that the mRNA Covid-19
vaccines that result in the production of the spike protein are cytotoxic
products and we consider that the vaccines have acceptable safety and a
positive benefit-risk balance.  The public assessment reports (PARs)
provided by the MHRA and the EMA, and other competent authorities are
specifically written to give context, in terms of the overall assessment
of the COVID-19 vaccines. The PARs are comprehensive documents and the
premise of providing these was to highlight that the safety of each
vaccine has been studied in both animals and humans. We note that the
original response considered the questions asked and referred you to
information in the Public Assessment Reports.
 
The section of the PARs on primary pharmacodynamic studies may be of
direct interest to you with regard to the spike protein. However, please
also note that in vitro expression data were also submitted, and these
show the mRNA sequence is translated to the spike protein in cells without
resulting in cytotoxicity.  In addition, in toxicity studies in which
vaccinated animals were studied for cellular damage post mortem, there
were no indications of cytotoxic reactions to the spike protein. 
Furthermore, we would like to highlight the importance of the data
collected in humans, in particular, that from the clinical trials of the
COVID-19 vaccines which serve to show that the protein generated
post-immunisation did not give rise to any significant safety concerns.
Clinical trials are limited in terms of the diversity of the population
that can be included, and by the length of the trial period; however over
one billion doses of Covid-19 vaccines have now been administered
world-wide, with over 100 million administered in the UK, and
pharmacovigilance measures continue throughout the life-cycle of a
product.
 
Any cytotoxicity would have likely been identified in the assessment of
data from clinical trials which enrolled over 74,000 participants, half of
them having received an mRNA vaccine; however, if due to a remote chance
cytotoxicity was in fact an issue but did not happen to present in the
trial populations, we would expect harms from cytotoxicity, to instead, be
found within the vast amounts of pharmacovigilance (PV) data now
available. To date evidence of cytotoxicity due to spike (S) protein has
not been found in either the clinical trial data or PV data, and these
data continue to demonstrate that the benefits of mRNA COVID-19 vaccines
outweigh their risks.
 
Independent experts, in particular those members of the Vaccine
Benefit-Risk expert working group and Commission on Human Medicines review
pharmacovigilance data and other data on the COVID‑19 vaccines regularly,
and these groups of experts have not raised any particular concerns over
cytotoxicity of the Spike protein. They strongly echo the view that the
benefits of COVID-19 vaccination continue to outweigh the risks. On the
topic of risk management and pharmacovigilance, we would also like to
emphasize that the COVID-19 vaccines are also subject to a specific
monitoring process. The below strategy outlines the ‘Four main strands of
our proactive vigilance’.
 
[1]https://www.gov.uk/government/publicatio...
 
We hope you will be reassured by the above and the content in the public
assessment reports.
 
You may also be interested in the following fact checking reference
entitled ‘Fact Check - COVID-19 vaccines are not ‘cytotoxic’:
[2]https://www.reuters.com/article/factchec...
 
This concludes our Internal Review.
 
If you remain dissatisfied, you may ask the ICO to make a decision on
whether or not we have interpreted the FOIA correctly in dealing with the
request and subsequent internal review. The ICO’s address is:
The Information Commissioner’s Office
Wycliffe House
Water Lane
Wilmslow
Cheshire
SK9 5AF
 
Kind Regards
 
MHRA Customer Service Centre
 
Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU
 
 

show quoted sections

Dear MHRA Customer Services,

Thank you for replying to my FOI

I made this request base on the following reasoning.

The pharmacokinetics of injection are different from infection. A dose of 60ug-200ug of Spike mRNA equates to 26 Trillion to 80 Trillion mRNA molecules injected in a few seconds. The pharmacokinetics of this bolus
injection differs from that of viral replication that occurs over the course of several days. The human body is made up of 30-40 Trillion cells that means an individual is getting a dose of mRNA molecules greater than the total number of cells in the human body. It is estimated each mRNA molecule can produce 10-100 spike proteins. So taking the largest numbers; 80 Trillion mRNA molecules could produce 8000 Trillion spike proteins (that's eight sextillion!) which is 200 times more spike protein than you have cells in the human body.

Based on these numbers it is perfectly reasonable to ask the UK drugs regulator, MHRA, some basic elementary pharmacological questions; How long after injection does it take an individuals body to start producing spike protein? have there been or are there ongoing studies to monitor the build-up and peak concentration of spike protein in individuals? Where is the spike protein distributed, organs, tissues, cells? how long does the spike protein reside in the body, what is its half-life? How is spike protein excreted, does it remain intact or is it broken down what are the metabolites of the spike protein? what is the known toxicological data for the spike protein?

I am sure you would agree that for any new drug especially a drug authorised under emergency use orders for universal use within the population that such fundamental questions should warrant clear answers supported by solid scientific data and analysis.

In respect to the three specific questions I made in this FOI the answer from the MHRA was "we do not hold this information" which is the same as we do not know!

Yours sincerely,

Dr Lee Proctor

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Thank you for your email.  This auto-response is to inform you that your
email has been received and will be reviewed by our Customer Service Team.
We will respond to you as soon as possible. 
 
Please note that we may not respond if your query: 
 
• contains offensive language
• has already been answered in a previous reply to you
• is illegible
• is selling or promoting a product
• is for information only 
 
Medicines and Healthcare products Regulatory Agency
10 South Colonnade, 
Canary Wharf, 
London 
E14 4PU
gov.uk/mhra
Stay connected 
 
For information on how the Agency uses your personal data and your data
protection rights, please see our three centres’ Privacy Notices: MHRA,
CPRD and NIBSC. 
 
The UK has left the EU, and the transition period ends on 31 December
2020. Ourguidance and information can be accessed here.

________________________________________ From: Dr Lee Proctor
<[FOI #773996 email]> Sent: Monday, December 13,
2021 8:34:51 AM To: MHRA Customer Services Subject: Re: FOI 21/821 CSC
62870 Internal review of Freedom of Information request - Biodistribution,
half-life and known toxicity of SARS-CoV-2 spike protein produced
cellularly after COVID vaccination Dear MHRA Customer Services, Thank you
for replying to my FOI I made this request base on the following
reasoning. The pharmacokinetics of injection are different from infection.
A dose of 60ug-200ug of Spike mRNA equates to 26 Trillion to 80 Trillion
mRNA molecules injected in a few seconds. The pharmacokinetics of this
bolus injection differs from that of viral replication that occurs over
the course of several days. The human body is made up of 30-40 Trillion
cells that means an individual is getting a dose of mRNA molecules greater
than the total number of cells in the human body. It is estimated each
mRNA molecule can produce 10-100 spike proteins. So taking the largest
numbers; 80 Trillion mRNA molecules could produce 8000 Trillion spike
proteins (that's eight sextillion!) which is 200 times more spike protein
than you have cells in the human body. Based on these numbers it is
perfectly reasonable to ask the UK drugs regulator, MHRA, some basic
elementary pharmacological questions; How long after injection does it
take an individuals body to start producing spike protein? have there been
or are there ongoing studies to monitor the build-up and peak
concentration of spike protein in individuals? Where is the spike protein
distributed, organs, tissues, cells? how long does the spike protein
reside in the body, what is its half-life? How is spike protein excreted,
does it remain intact or is it broken down what are the metabolites of the
spike protein? what is the known toxicological data for the spike protein?
I am sure you would agree that for any new drug especially a drug
authorised under emergency use orders for universal use within the
population that such fundamental questions should warrant clear answers
supported by solid scientific data and analysis. In respect to the three
specific questions I made in this FOI the answer from the MHRA was "we do
not hold this information" which is the same as we do not know! Yours
sincerely, Dr Lee Proctor -----Original Message----- Dear Dr Proctor,
Thank you for your request for a review of your FOI request concerning
“Biodistribution, half-life and known toxicity of SARS-CoV-2 spike protein
produced cellularly after COVID vaccination'”. Thank you for your patience
while we completed the Internal Review. We have annotated your three
questions with our responses in italics. 1. The biodistribution including
tissues, organs, cells and human body organ systems for the spike protein
produced by vaccination. We do not hold this information, however, the
MHRA continues to monitor real world data and information and data from
RMP and PV activities with respect to the safety of the COVID-19 vaccines.
2. Can you provide a spike protein concentration-time plot from the point
an individual is vaccinated. I am specifically interested in how long it
takes for the peak concentration of spike protein to be produced and the
half-life of spike protein. We do not hold this information, however, the
MHRA continues to monitor real world data and from RMP and PV activities
with respect to the safety of the COVID-19 vaccines. 3. known
toxicological data for the spike protein such as the LD50, LC50, TDLo The
spike protein has not been administered to animals in toxicological tests:
therefore there are no figures available for values of LD50, LC50, TDLo.
The vaccines were given to animals and for each of the approved UK
vaccines, the top dose used in animals was considered a tolerable dose
with the only notable changes seen explained by the immune system
responding to the vaccine. Values for LD50 and LC50 were not sought in
this testing. We would also like to mention that, we do not agree that the
mRNA Covid-19 vaccines that result in the production of the spike protein
are cytotoxic products and we consider that the vaccines have acceptable
safety and a positive benefit-risk balance. The public assessment reports
(PARs) provided by the MHRA and the EMA, and other competent authorities
are specifically written to give context, in terms of the overall
assessment of the COVID-19 vaccines. The PARs are comprehensive documents
and the premise of providing these was to highlight that the safety of
each vaccine has been studied in both animals and humans. We note that the
original response considered the questions asked and referred you to
information in the Public Assessment Reports. The section of the PARs on
primary pharmacodynamic studies may be of direct interest to you with
regard to the spike protein. However, please also note that in vitro
expression data were also submitted, and these show the mRNA sequence is
translated to the spike protein in cells without resulting in
cytotoxicity. In addition, in toxicity studies in which vaccinated animals
were studied for cellular damage post mortem, there were no indications of
cytotoxic reactions to the spike protein. Furthermore, we would like to
highlight the importance of the data collected in humans, in particular,
that from the clinical trials of the COVID-19 vaccines which serve to show
that the protein generated post-immunisation did not give rise to any
significant safety concerns. Clinical trials are limited in terms of the
diversity of the population that can be included, and by the length of the
trial period; however over one billion doses of Covid-19 vaccines have now
been administered world-wide, with over 100 million administered in the
UK, and pharmacovigilance measures continue throughout the life-cycle of a
product. Any cytotoxicity would have likely been identified in the
assessment of data from clinical trials which enrolled over 74,000
participants, half of them having received an mRNA vaccine; however, if
due to a remote chance cytotoxicity was in fact an issue but did not
happen to present in the trial populations, we would expect harms from
cytotoxicity, to instead, be found within the vast amounts of
pharmacovigilance (PV) data now available. To date evidence of
cytotoxicity due to spike (S) protein has not been found in either the
clinical trial data or PV data, and these data continue to demonstrate
that the benefits of mRNA COVID-19 vaccines outweigh their risks.
Independent experts, in particular those members of the Vaccine
Benefit-Risk expert working group and Commission on Human Medicines review
pharmacovigilance data and other data on the COVID‑19 vaccines regularly,
and these groups of experts have not raised any particular concerns over
cytotoxicity of the Spike protein. They strongly echo the view that the
benefits of COVID-19 vaccination continue to outweigh the risks. On the
topic of risk management and pharmacovigilance, we would also like to
emphasize that the COVID-19 vaccines are also subject to a specific
monitoring process. The below strategy outlines the ‘Four main strands of
our proactive vigilance’.
[1]https://eur01.safelinks.protection.outlo...
We hope you will be reassured by the above and the content in the public
assessment reports. You may also be interested in the following fact
checking reference entitled ‘Fact Check - COVID-19 vaccines are not
‘cytotoxic’:
[2]https://eur01.safelinks.protection.outlo...
This concludes our Internal Review. If you remain dissatisfied, you may
ask the ICO to make a decision on whether or not we have interpreted the
FOIA correctly in dealing with the request and subsequent internal review.
The ICO’s address is: The Information Commissioner’s Office Wycliffe House
Water Lane Wilmslow Cheshire SK9 5AF Kind Regards MHRA Customer Service
Centre Medicines and Healthcare products Regulatory Agency 10 South
Colonnade, Canary Wharf, London E14 4PU
------------------------------------------------------------------- Please
use this email address for all replies to this request:
[FOI #773996 email] Disclaimer: This message and
any reply that you make will be published on the internet. Our privacy and
copyright policies:
https://eur01.safelinks.protection.outlo...
For more detailed guidance on safely disclosing information, read the
latest advice from the ICO:
https://eur01.safelinks.protection.outlo...
Please note that in some cases publication of requests and responses will
be delayed. If you find this service useful as an FOI officer, please ask
your web manager to link to us from your organisation's FOI page.

show quoted sections

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Dear Dr Proctor,

 

Thank you for your follow-up reply to the internal review, to which we
provide the following response.

 

We reiterate that the Public Assessment Report (PAR) for each of the
COVID-19 vaccines explains how each vaccine was assessed and its
authorisation recommended, as well as its conditions of use. We, along
with all the major international regulatory authorities, believe that the
benefit/risk profile of the COVID-19 vaccines is positive. In a similar
vein, we draw on the below from our previous response:

 

“Any cytotoxicity would have likely been identified in the assessment of
data from clinical trials which enrolled over 74,000 participants, half of
them having received an mRNA vaccine; however, if due to a remote chance
cytotoxicity was in fact an issue but did not happen to present in the
trial populations, we would expect harms from cytotoxicity, to instead, be
found within the vast amounts of pharmacovigilance (PV) data now
available. To date evidence of cytotoxicity due to spike (S) protein has
not been found in either the clinical trial data or PV data, and these
data continue to demonstrate that the benefits of mRNA COVID-19 vaccines
outweigh their risks.”

 

Please note on the basis of the regulation on vaccines, this type of
information i.e. the number of immunogens generated per dose or per part
dose, is not requested as this information is not necessary for the
evaluation of vaccine safety and efficacy. Rather the focus is on the
immune response to the vaccine (humoral and cellular), and the different
classifications of adverse events that are recorded from clinical trials
and post-authorisation surveillance / pharmacovigilance activities. In
addition, where there is a novel adjuvant component, its distribution
should be studied, with the exact details of such studies depending on the
relevant guidelines and characteristics of the adjuvant.

 

We apologise for the delay, and would like to mention that we are
currently drafting a reply to your other question which relates to the
Janssen vaccine nucleotide sequence.

 

If you remain dissatisfied, you may ask the Information Commissioner (ICO)
to make a decision on whether or not we have interpreted the FOIA
correctly in dealing with the request and subsequent internal review. The
ICO’s address is:

 

The Information Commissioner’s Office

Wycliffe House

Water Lane

Wilmslow

Cheshire

SK9 5AF

 

 

Yours sincerely  

 

 

 

MHRA Customer Experience Centre

Communications and engagement team

Medicines and Healthcare products Regulatory Agency

10 South Colonnade, Canary Wharf, London E14 4PU
Telephone 020 3080 6000

 

show quoted sections

Dear MHRA Customer Services,

Thank you for replying to my FOI.

My request was filled on 14th July 2021 and since that date more information has become available. I am highlighting this information below for your reference and for public record.

The Pfizer EMA assessment report for BNT162b2 was published on 19th February 2021

https://www.ema.europa.eu/en/documents/a...

As you highlight no data for exists for the biodistribution of the spike protein antigen but data is presented in the report for the biodistribution of a LNP-formulated luciferase surrogate reporter.

To determine the biodistribution of the LNP-formulated modRNA, Pfizer studied distribution of the modRNA in two different non-GLP studies, in mice and rats, determined the biodistribution of a surrogate luciferase modRNA formulated with a LNP with identical lipid composition used in BNT162b2 (mouse study) or the biodistribution of a [3H]-Labelled Lipid Nanoparticle-mRNA Formulation (rat study). Radioactivity was detected in most tissues from the first time point (0.25 h) and results support that injections site and the liver are the major sites of distribution. The greatest mean concentration was found remaining in the injection site at each time point in both sexes. Low levels of radioactivity were detected in most tissues, with the greatest levels in plasma observed 1-4 hours post-dose. Over 48 hours, distribution was mainly observed to liver, adrenal glands, spleen and ovaries, with maximum concentrations observed at 8-48 hours post-dose. Total recovery (% of injected dose) of radiolabeled LNP+modRNA outside the injection site was greatest in the liver (up to 21.5%) and was much less in spleen (≤1.1%), adrenal glands (≤0.1%) and ovaries (≤0.1%). Furthermore, no data on placental transfer of BNT162b2 is available from Pfizer EMA assessment report.

Given the huge uptake in the liver this maybe a concern!

On the 25th of February 2022 a full peer-reviewed paper was published by De Marinis et al in Curr. Issues Mol. Biol.2022, 44, 1115–1126 titled:

“Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line” https://doi.org/10.3390/cimb44030073

This paper specifically addressed the effects of BNT162b2 in vitro on human Huh7 liver cells, the study showed:

“BNT162b2 can be reverse transcribed to DNA in liver cell line Huh7, and this may give rise to the concern if BNT162b2-derived DNA may be integrated into the host genome and affect the integrity of genomic DNA, which may potentially mediate genotoxic side effects. At this stage, we do not know if DNA reverse transcribed from BNT162b2 is integrated into the cell genome. Further studies are needed to demonstrate the effect of BNT162b2 on genomic integrity, including whole genome sequencing of cells exposed to BNT162b2, as well as tissues from human subjects who received BNT162b2 vaccination.”

The results also showed:

“BNT162b2 mRNA readily enters Huh7 cells at a concentration (0.5 g/mL) corresponding to 0.5% of the local injection site concentration, induce changes in LINE-1 gene and protein expression, and within 6 h, reverse transcription of BNT162b2 can be detected. It is therefore important to investigate further the effect of BNT162b2 on other cell types and tissues both in vitro and in vivo”

I believe this paper should act as a catalyst for further research especially in vivo studies on vaccinated patients as well as thorough investigation regarding the potential of BNT162b2 mRNA to reverse transcribe into genomic DNA.

The elevated expression of LINE-1 is of particular concern because when LINE-1 retrotransposition is out of control it can lead to diseases particularly cancer. Reverse transcription of non-endogenous RNA by LINE-1 is a nascent field but the results in the De Marinis paper suggests this requires urgent investigation within the context of mRNA vaccines.

Finally, I would like to thank you for your efforts replying to my FOI requests and look forward to your reply on the Janssen vaccine nucleotide sequence.

Yours sincerely,

Dr Lee Proctor

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

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________________________________________ From: Dr Lee Proctor
<[FOI #773996 email]> Sent: Thursday, March 3, 2022
8:18:33 AM To: MHRA Customer Services Subject: Re: FOI 21/821 CSC 62870
Internal review of Freedom of Information request - Biodistribution,
half-life and known toxicity of SARS-CoV-2 spike protein produced
cellularly after COVID vaccination Dear MHRA Customer Services, Thank you
for replying to my FOI. My request was filled on 14th July 2021 and since
that date more information has become available. I am highlighting this
information below for your reference and for public record. The Pfizer EMA
assessment report for BNT162b2 was published on 19th February 2021
https://eur01.safelinks.protection.outlo...
As you highlight no data for exists for the biodistribution of the spike
protein antigen but data is presented in the report for the
biodistribution of a LNP-formulated luciferase surrogate reporter. To
determine the biodistribution of the LNP-formulated modRNA, Pfizer studied
distribution of the modRNA in two different non-GLP studies, in mice and
rats, determined the biodistribution of a surrogate luciferase modRNA
formulated with a LNP with identical lipid composition used in BNT162b2
(mouse study) or the biodistribution of a [3H]-Labelled Lipid
Nanoparticle-mRNA Formulation (rat study). Radioactivity was detected in
most tissues from the first time point (0.25 h) and results support that
injections site and the liver are the major sites of distribution. The
greatest mean concentration was found remaining in the injection site at
each time point in both sexes. Low levels of radioactivity were detected
in most tissues, with the greatest levels in plasma observed 1-4 hours
post-dose. Over 48 hours, distribution was mainly observed to liver,
adrenal glands, spleen and ovaries, with maximum concentrations observed
at 8-48 hours post-dose. Total recovery (% of injected dose) of
radiolabeled LNP+modRNA outside the injection site was greatest in the
liver (up to 21.5%) and was much less in spleen (≤1.1%), adrenal glands
(≤0.1%) and ovaries (≤0.1%). Furthermore, no data on placental transfer of
BNT162b2 is available from Pfizer EMA assessment report. Given the huge
uptake in the liver this maybe a concern! On the 25th of February 2022 a
full peer-reviewed paper was published by De Marinis et al in Curr. Issues
Mol. Biol.2022, 44, 1115–1126 titled: “Intracellular Reverse Transcription
of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver
Cell Line”
https://eur01.safelinks.protection.outlo...
This paper specifically addressed the effects of BNT162b2 in vitro on
human Huh7 liver cells, the study showed: “BNT162b2 can be reverse
transcribed to DNA in liver cell line Huh7, and this may give rise to the
concern if BNT162b2-derived DNA may be integrated into the host genome and
affect the integrity of genomic DNA, which may potentially mediate
genotoxic side effects. At this stage, we do not know if DNA reverse
transcribed from BNT162b2 is integrated into the cell genome. Further
studies are needed to demonstrate the effect of BNT162b2 on genomic
integrity, including whole genome sequencing of cells exposed to BNT162b2,
as well as tissues from human subjects who received BNT162b2 vaccination.”
The results also showed: “BNT162b2 mRNA readily enters Huh7 cells at a
concentration (0.5 g/mL) corresponding to 0.5% of the local injection site
concentration, induce changes in LINE-1 gene and protein expression, and
within 6 h, reverse transcription of BNT162b2 can be detected. It is
therefore important to investigate further the effect of BNT162b2 on other
cell types and tissues both in vitro and in vivo” I believe this paper
should act as a catalyst for further research especially in vivo studies
on vaccinated patients as well as thorough investigation regarding the
potential of BNT162b2 mRNA to reverse transcribe into genomic DNA. The
elevated expression of LINE-1 is of particular concern because when LINE-1
retrotransposition is out of control it can lead to diseases particularly
cancer. Reverse transcription of non-endogenous RNA by LINE-1 is a nascent
field but the results in the De Marinis paper suggests this requires
urgent investigation within the context of mRNA vaccines. Finally, I would
like to thank you for your efforts replying to my FOI requests and look
forward to your reply on the Janssen vaccine nucleotide sequence. Yours
sincerely, Dr Lee Proctor -----Original Message----- Dear Dr Proctor,
Thank you for your follow-up reply to the internal review, to which we
provide the following response. We reiterate that the Public Assessment
Report (PAR) for each of the COVID-19 vaccines explains how each vaccine
was assessed and its authorisation recommended, as well as its conditions
of use. We, along with all the major international regulatory authorities,
believe that the benefit/risk profile of the COVID-19 vaccines is
positive. In a similar vein, we draw on the below from our previous
response: “Any cytotoxicity would have likely been identified in the
assessment of data from clinical trials which enrolled over 74,000
participants, half of them having received an mRNA vaccine; however, if
due to a remote chance cytotoxicity was in fact an issue but did not
happen to present in the trial populations, we would expect harms from
cytotoxicity, to instead, be found within the vast amounts of
pharmacovigilance (PV) data now available. To date evidence of
cytotoxicity due to spike (S) protein has not been found in either the
clinical trial data or PV data, and these data continue to demonstrate
that the benefits of mRNA COVID-19 vaccines outweigh their risks.” Please
note on the basis of the regulation on vaccines, this type of information
i.e. the number of immunogens generated per dose or per part dose, is not
requested as this information is not necessary for the evaluation of
vaccine safety and efficacy. Rather the focus is on the immune response to
the vaccine (humoral and cellular), and the different classifications of
adverse events that are recorded from clinical trials and
post-authorisation surveillance / pharmacovigilance activities. In
addition, where there is a novel adjuvant component, its distribution
should be studied, with the exact details of such studies depending on the
relevant guidelines and characteristics of the adjuvant. We apologise for
the delay, and would like to mention that we are currently drafting a
reply to your other question which relates to the Janssen vaccine
nucleotide sequence. If you remain dissatisfied, you may ask the
Information Commissioner (ICO) to make a decision on whether or not we
have interpreted the FOIA correctly in dealing with the request and
subsequent internal review. The ICO’s address is: The Information
Commissioner’s Office Wycliffe House Water Lane Wilmslow Cheshire SK9 5AF
Yours sincerely   MHRA Customer Experience Centre Communications and
engagement team Medicines and Healthcare products Regulatory Agency 10
South Colonnade, Canary Wharf, London E14 4PU Telephone 020 3080 6000
------------------------------------------------------------------- Please
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show quoted sections

MHRA Customer Services, Medicines and Healthcare Products Regulatory Agency

Dear Dr Lee Proctor,

Thank you for your email.

This is has been passed on to the relevant team for their information.

Kind Regards

MHRA Customer Service Centre

Medicines and Healthcare products Regulatory Agency
10 South Colonnade, Canary Wharf, London E14 4PU Telephone 0203 080 6000

show quoted sections