"Marcel de Graaff MEP
European Parliament
ASP 06E240
60, rue Wiertz / Wiertzstraat 60
B-1047 Brussels
Belgium
Email: marcel.degraaff@europarl.europa.eu
18 October 2023
EMA/451828/2023
European Medicines Agency
Please find below direct responses to the questions you raise in your letter.
(...)
5. Legal status of EU authorisations of Comirnaty and Spikevax
You have raised a number of concerns about EU Regulations and Directives. You question the initial
conditional marketing authorisations of Comirnaty and S pikevax, as you believe that Regulation (EU) 2019/57, Regulation (EU) No 2020/10438 and Regulation (EU) No 2021/7569 do not meet the
framework laid down:
− on environmental risk assessment and reporting in Regulation (EU) No 2001/1810 and Directive
2009/41/EC11;
− on safety for medicinal products laid down in Directive 2001/83/EC 12, Commission Directive
2003/63/EC13 and Regulation (EC) No 1394/200714;
− concerning the granting of a union licence laid down in Regulation (EC) No 2004/72615 and
Regulation (EC) No 2008/123416.
You also state that the changes in Regulation (EU) 2019/5 ‘should not be used to go outside the
framework of existing classification and categorisation, only clarification is allowed, no categories
can be added that conflict with the current system, full legislation is needed for that. ’
Further, you state that ‘the addition of codes/sequences’ in Regulation (EU) No 2021/756 ‘conflicts
with the classification and categorisation’ of Directive 2001/83/EC, Directive 2003/63/EC and
Regulation (EC) No 1394/2007.
You also assert that parts of Regulation (EU) No 2020/1043 (concerning trials of GMOs for COVID -
19) and Regulation (EU) No 2021/756 (concerning variations to marketing authorisations of coronavirus vaccines) are ‘contrary to Articles 141 and 168’ of the Treaty on the Functioning of the European Union. Furthermore, you say that Regulation (EU) 2019/5 was used in violation of Article 290(1) of the Treaty.
We read these concerns as being related to the Regulations and Directives themselves. While EMA is bound by them, we are not in a position to comment on the appropriateness of Regulations or Directives adopted by Parliament and the Council or on their compatibility with the Treaty.
With regard to extensions of marketing authorisations, you note that Regulation (EU) No 2021/756 (concerning variations to marketing authorisations of influenza and coronavirus vaccines) was adopted after the authorisations of Comirnaty and Spikevax. The implication is that the Regulation does not apply to adapted Comirnaty and Spikevax vaccines. Please note that the text of the regulation clearly recognises that ‘based on the scientific assessment by the European Medicines Agency, the Commission has thus far authorised several COVID -19 vaccines’, and the Regulation provides for variations to the authorisations of these and future vaccines.
You also highlight Article 19 of Regulation (EC) No 2008/1234 (concerning variations), which states that ‘an extension shall either be granted a marketing authorisation in accordance with the same procedure as for the granting of the initial marketing authorisation to which it relates or be included in that marketing authorisation’. Please note that this article does not preclude relying on relevant data from the initial marketing authorisation. Furthermore, and as noted above, the authorisation of the adapted vaccines for Comirnaty and Spikevax are covered by Regulation (EU) No 2021/756, which amends Regulation (EC) No 2008/1234.
With regard to Article 1 (4) of Directive 2001/83/EC, vaccines are listed as agents used to produce active immunity. You say that there is no evidence that these vaccines provide immunity (i.e. protection against infection or disease).
It is true that the protection wanes over time as the virus itself evolves, and this is one of the reasons why adapted vaccines have been authorised. It is important to note that with SARS-CoV-2, people may be exposed to the virus several times and repeated exposure may increase the chance of infection even in vaccinated people.
COVID-19 vaccines also provide protection against severe disease, including hospitalisation. This is particularly important for vulnerable people who are at increased risk.
You also state that ‘a vaccine must contain an antigen; this antigen requires its own registration in the Vaccine Antigen Master File (VAMF)’ as laid down in Directive 2003/63/EC. ‘The reason for this method’, you say, ‘is that homogeneity and quality and active dose can be determined per treatment. This is not the case with coding sequences.’
It is important to note that for mRNA vaccines, the antigen (the particle that triggers an immune response) is not the mRNA active substance itself but the spike protein formed after vaccination.That said, we would like to clarify what a VAMF is. EU legislation provides for the option of presenting all required information on a vaccine antigen as a VAMF (i.e. as a stand-alone part ofthe marketing authorisation application (MAA) dossier for a vaccine). A VAMF is particularly useful when a specific vaccine antigen is used in different vaccines. In such cases, with a single evaluation of a VAMF, authorities can assess the same antigen used in several vaccines at the same time. The VAMF system is therefore only aimed at simplifying the evaluation of vaccines, and the use of VAMFs is optional. When the option of a VAMF is not used, companies, like for any other medicine, have to include the relevant information on the vaccine antigen directly in the MAA dossier concerned.
6. EMA reflection papers
Citing EMA’s Reflection paper on the classification of advanced therapy medicinal products and EMA’s Reflection paper on criteria to be considered for the evaluation of new active substance (NAS) status of biological substances, you make the following case: that mRNA is considered an example of gene therapy and therefore any significant change in the sequence of mRNA require s a new application.
As you noted in your letter (1), Commission Directive 2009/120/EC does not consider vaccines against infectious diseases gene therapies, as the aim of vaccination is not to restore, correct or modify human genes. Furthermore, the extensions to marketing authorisations of COVID-19 vaccines are
covered by Regulation (EU) No 2021/756
You can find more information in the Guideline on Requirements for Vaccine Antigen Master File
(VAMF) Certification on EMA’s website.
Finally, we take note of your call for immediate action to suspend the marketing authorisations of
Comirnaty and Spikevax, including the authorisations of the adapted vaccines targeting the Omicron XBB.1.5 subvariant.
EMA’s CHMP can only recommend suspensions of the marketing authorisations if the evidence shows that the risks outweigh the benefits. The evidence continues to show that the vaccines provide protection, which is particularly important for vulnerable people. Removing these vaccines as an option for EU Member States and for health care professionals without due regard to available data would therefore be a great disservice to the EU and to public health."
Brief commentary on EMA's answers on the legal status of the EU authorisations:
1) (1) Statement in the letter to EMA:
"Regulation 2009/120/EC making change to Annex part IV namely art 2.1 "Gene therapy medicinal products shall not include vaccines against infectious diseases" offers no relief, the last rule should be
seen as mutually exclusive. After all, vaccine is already defined by the regulations that appeared before"
2) EMA -as any other european authority- is not only bound by the Authorisations and Regulations but by the Treaty and the Charter of Fundamental Rights of the Union
Compatibility of Authorisations and Regulations with those higher rules of the EU binds EMA and all european auhorities
Article 51 of the Charter, states:
1. The provisions of this Charter are addressed to the institutions and bodies of the Union with due regard for the principle of subsidiarity and to the Member States only when they are implementing Union law. They shall therefore respect the rights, observe the principles and promote the application thereof in accordance with their respective powers.
2. This Charter does not establish any new power or task for the Community or the Union, or modify powers and tasks defined by the Treaties.
3) The definition of "Gene therapy medicinal product" contained in Commission Directive 2009/120/EC
"Gene therapy medicinal product means a biological medicinal product which has the following characteristics:
(a) it contains an active substance which contains or consists of a recombinant nucleic acid used in or
administered to human beings with a view to regulating, repairing, replacing, adding or deleting a genetic sequence;
(b) its therapeutic, prophylactic or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence.
Gene therapy medicinal products shall not include vaccines against infectious diseases"
EMA's answer expressly recognizes mRNA "vaccines" are "gene therapy medicinal products" according to the EU Directive:
"It is important to note that for mRNA vaccines, the antigen (the particle that triggers an immune response) is not the mRNA active substance itself but the spike protein formed after vaccination"
The mRNA administered produces the genetic expression of its sequence: the spike protein formed after "vaccination"
The legal exclusion of vaccines as "gene therapy medicinal product" can only be interpreted as follows:
1) As exclusion of "vaccines" not consisting of a recombinant acid nuclei but containing an "antigen" that "contains" it
2) As exclusion of "vaccines" included in 1) aimed at "preventing transmission from one person to another" ("against infectuous diseases")
3) Any "vaccine" consisting of a recombinant acid nuclei with "therapeutic effect" must be considered a gene medicinal product not included in 1) and/or 2)
Otherwise, the legal definition of "gene medicinal product" would be self-contradictory: a "vaccine" can be a gene medicinal product (according to the legal definition of it) but not considered as such for legal purposes.
In fact, however, this is the legal "rationale" of EMA's legal interpretation of the Regulations: mRNA "vaccines" are excluded from Regulations of gene medicinal products.
But the 2009/120/EC Directive only states that Gene therapy medicinal products shall not include vaccines against infectious diseases: because they are not such products according to their legal definition or, if they were, because they have additional and different characteristics (effects) not listed in the legal definition of gene medicinal products. EMA does not claim anywhere in its letter that the last one is the case of any of the mRNA "vaccines".
At the same time, reiterating its previous self-contradiction, EMA considers that mRNA "vaccines" are not either vaccines subject to the Requirements for Vaccine Antigen Master File.
So mRNA "vaccines" are, according to EMA, neither gene medicinal products nor "vaccines" for legal purpsoses. They are, therefore, a tertium genus not included in any medicinal product regulation but applied through all of Europe.
Such conclusion is, in our opinion, not only astonishing but, as stated, devoid of any legal ground.
And in contradiction with the EU law.
No comments:
Post a Comment