Moji razgovori s Emom, sedmi dio: Polymerase and polymorphism

Greetings,

I have some additional questions regarding Covid-19 vaccines.

Questions to EMA related to the COVID-19 mRNA Vaccines Comirnaty and Spikevax
 
1. Which RNA polymerase is used for the in vitro transcription of Comirnaty vaccine mRNAs?
 
2. What is the error rate (mutation rate) of the RNA polymerase used in the synthesis of Corminaty mRNAs?

3. What is the mRNA polymorphism level within single dose of Comirnaty?

4. How mutations that contribute to polymorphisms are distributed along the Comirnaty mRNA sequence?

5. Which RNA polymerase is used for the in vitro transcription of Spikevax vaccine mRNAs?

 6. What is the error rate (mutation rate) of the RNA polymerase used in the synthesis of Spikevax mRNAs?

7. What is the mRNA polymorphism level within single dose of Spikevax?

8. How mutations that contribute to polymorphisms are distributed along the Comirnaty mRNA sequence?

Thank you.

Dec 23, 2021, 1:09 PM

Dear Mr Sinčić,

Thank you for contacting the European Medicines Agency again regarding the mRNA COVID-19 vaccines.

Due to the quite detailed and technical/scientific nature of your latest questions, which go beyond the general type of enquiries which are dealt with directly by us as Institutional Liaison, we have passed them to our dedicated team in EMA who handle all external requests for information.

As such, EMA’s requests-for-information team will reach out to the relevant scientific experts at the Agency and they will try to reply to you within a reasonable time limit, without delay, and in any case no later than two months from the date of receipt. You can consider this email as acknowledgement of receipt.

For future reference, in case of product-specific scientific/technical questions we would like to invite you to send them directly using the dedicated online form for request for information from the EMA, which can be found at the link below:

https://www.ema.europa.eu/en/about-us/contact/send-question-european-medicines-agency

For other, more general questions on EMA’s activities or on the procedures for authorising new medicines in the EU, of course feel free to continue contacting us directly.

We thank you for your interest and in the meantime we wish you a Happy New Year.

Best regards

Hilde

Jan 5, 2022, 6:12 PM

Dear Mr Ivan Vilibor SINČIĆ MEP,

Thank you for contacting the European Medicines Agency (EMA).

We have carefully considered your questions and would like to inform you that for most of them, except for questions 3 and 4 (answered further below as the information is already in the public domain), providing an answer would entail disclosing commercially confidential information on the pharmaceutical development and manufacturing process of the medicinal product, i.e. disclosing information which is not in the public domain or publicly available and where disclosure may undermine the economic interest or competitive position of the owner of the information (as further explained in the HMA/EMA guidance document on the identification of commercially confidential information and personal data within the structure of the marketing authorisation application – release of information after the granting of a marketing authorisation: https://www.ema.europa.eu/en/documents/other/heads-medicines-agencies/european-medicines-agency-guidance-document-identification-commercially-confidential-information_en.pdf).

We therefore cannot provide further details on these matters due to the Agency’s legal obligation to protect commercially confidential information.

Please find below our answers to questions 3 and 4:

3. What is the mRNA polymorphism level within single dose of Comirnaty?

4. How mutations that contribute to polymorphisms are distributed along the Comirnaty mRNA sequence?

In response to a request to complete characterisation of the active substance and finished product, which is a condition to the Marketing Authorisation (Special Obligation SO1), the Marketing Authorisation Holder (MAH) has provided additional characterisation data as requested, summarised here:

a) The potential for truncated transcripts to produce proteins/peptides was further investigated using a cell-free in vitro expression system. No truncated or other protein species were detected beyond the background bands observed in the negative control sample. The MAH will complement the characterization exercise using the cell-free in vitro translation system with additional tozinameran batches.

b) It is sufficiently demonstrated that the major proportion of fragmented species contains the 5’-cap but lacks the poly(A) tail.

c) Western Blot results obtained by three different antibodies, specific for the S1 domain, the receptor binding domain and the S2 domain, respectively, were presented and compared to theoretical masses of the S-protein and the subdomains in glycosylated and non-glycosylated forms. It is sufficiently justified that the major band monitored corresponds to the heavily glycosylated S-protein.

For more details see the entry II-0056-G in the table of procedural steps available at: https://www.ema.europa.eu/en/documents/procedural-steps-after/comirnaty-epar-procedural-steps-taken-scientific-information-after-authorisation_.pdf

Best regards,

Pharmaceutical Quality Office

European Medicines Agency

Wed 2/23, 3:27 PM