Premise

Explain and contextualize is a must. Between July and August 2018, the Corvelva association sent the first analyzes of 7 vaccines to all the organs concerned. In our opinion, we have done what every citizen should do if he is aware of a possible non-compliance of some pharmaceutical products, in our case vaccines.
AIFA, together with the Ministry of Health, the Istituto Superiore di Sanità and EMA, have been continuously updated on all the analysis steps.
AIFA replied only on 18 January to the last questions asked, i.e. those on the chemical analyzes on the Priorix Tetra sample, but never on the metagenomics of the same vaccine and never on all the other vaccines which, according to our analyzes, present safety and non-compliance problems. .

Our answer, which you will find under the AIFA email, far exceeds their message, precisely because the questions asked have been rejected for 5 months. To date we still have no answer for most of the questions asked and even the few answers received are lacking in scientifically reliable data and elements.

Our response will be sent to the media and all politics for information.
For us, the AIFA controlling body has absolutely not fulfilled its mission. The silence of the Ministry of Health, however, is objectively embarrassing.

AIFA - Reply to our email of 22 November 2018

Dear Mr. Ferdinando Donolato,

in relation to your email dated 22/11, we represent the following:

• The Priorix Tetra vaccine is authorized with a mutual recognition procedure, a Community-type authorization procedure that allows the extension of a marketing authorization from a Member State that acts as a reference country (reference member state; in the case of the Priorix Tetra: Germany) to one or more countries of the European Union that act as concerned countries (concerned member state; in the case of the Priorix Tetra, 28 European countries including Italy);
• As part of this procedure, the country of reference is responsible for the administrative and technical-scientific evaluation of the documentation relating to the marketing authorization, variations, periodic safety assessments and renewals of the authorization, with the support from the countries concerned;
• The clinical and non-clinical aspects of the vaccines (including the quality aspects of the active substances and the finished product) are described in a series of guidelines publicly available on the website of the European Medicines Agency - EMA at the following address: https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-guidelines/multidisciplinary/multidisciplinary-vaccines and represent the guidelines for the development of vaccines by companies and for evaluation by regulatory agencies;
• The specifications of vaccines in terms of raw materials and finished products are reported in the European Pharmacopoeia (Eur. Pharm.), Available on the website of the European Directorate for the Quality of Medicines - EDQM, the body of the European Commission responsible for the development and monitoring of standards. of all medicinal products, including vaccines, to the following address: https://www.edqm.eu/en/european-pharmacopoeia-ph-eur-9th-edition, where the tests recognized as more suitable and specific for the determination of substances of various nature and relative concentration limits in the product are also defined (general monograph on vaccines and specific on individual vaccines);
• The European Pharmacopoeia is legally binding on the whole European territory and is continuously updated and compared with other pharmacopoeias, in relation to a global standardization and harmonization process.

It should also be noted that the verification of batch compliance with the standards required by the European Pharmacopoeia is the responsibility of an independent state laboratory, certified within the European network of official laboratories for the control of medicines (Official Medicines Control Laboratories - OMCL). These laboratories must be accredited by the EDQM (General European OMCL Network - GEON). The distribution of batches that obtain the release certificate is not necessarily national and may involve multiple Member States where the specific vaccine is authorized.  

With regard to the "preliminary results of the analyzes of the contaminants and chemical and protein impurities of the Priorix Tetra vaccine", sent by you to our attention, it is specified that they are not substantially assessable as presented, as they lack fundamental information, such as example the ISO or GLP accreditation characteristics of the laboratory responsible for the analyzes, the methodological details relating to the management of the samples, the controls used, the analytical procedure itself, the validation of the method, etc., information necessary for a correct scientific classification of the results summarized in summary in the document sent.

Best regards,

ARM

Corvelva - Reply to the AIFA email dated 18 January 2019

Dear d.ssa. ARM

in relation to your email dated 18 January 2019, we represent the following: the letter to which you, on behalf of the entity you represent, responds is only the last in order of time. The first email was sent to all the national and international bodies in charge, Ministry, Aifa, ISS, EMA, already in August 2018. In thanking you for your kind reply, we are also obliged to define it at least incomplete, if not inadequate to the problem.

Regardless of the fact that Priorix Tetra is recognized with the "mutual recognition procedure", as reported by you, this does not mean that your Agency does not act as a point of reference as regards the authorizations of medicines sold on the national territory, therefore we believe outside place to reply that the analyzes are carried out by another member country. Although it is envisaged that the analyzes carried out in a certain country can be made a reference for authorizations in other countries, this does not mean that the responsibility for the authorization lies with the regulatory agency of the individual country in which the medicine is marketed.
We ask you the following question: Aifa as a territorially competent body for the authorization of a specific product, must be aware of all the procedures that concern it and be able at any time to promptly evaluate and respond to any reports deriving from health workers or citizens?

We also believe that your response regarding the validity of our analyzes, "specifies that they are not substantially assessable as presented" does not give the right relevance to the seriousness of the evidence: we have notified you of the presence of possible contaminations that may constitute a risk for health, and signals of unidentifiable chemical compounds (to limit ourselves only to the last report, the one you are responding to, but in other vaccines you have been notified of the presence of Dna in important quantities and / or Dna that should not be present, lack of one or more antigens, and much more for which we are still waiting for answers).

If even one of the toxic elements that resulted as potential compounds associated with the identified brute formula were confirmed as a contaminant within the vaccine, this would be a safety and compliance problem.

Therefore, simply replying that the analyzes commissioned by us do not correspond to those identified as "suitable" by regulatory agencies for the authorization of the drug or vaccine, does not in our opinion make any sense: we are reporting a potential problem for a product in use in the Italian pediatric population, a product that, among other things, is used routinely to fulfill a legal obligation introduced in 2017; in light of all this, it is disconcerting for us that your agency limits itself to "downloading" the problem, dismissing our analyzes as "non-compliant"!

Corvelva is NOT checking the batch release and has NOT asked to use validated methods for batch analysis, as manufacturers, accredited laboratories and the ISS must do. What is being conducted is a simple investigation that is done early in the development of a vaccine, that is, screening. So how can AIFA request methods that are accredited for the release of the lot, for which it would take years for validation? Our purpose is not to become a certification body for batch release, and in fact the methods envisaged in the European pharmacopoeia for the analysis of vaccines are not used, but the latest generation methods, not yet acquired in the pharmacopoeia for this purpose. We believe that the very serious claim not to take into consideration the results presented because they have not been reviewed by the scientific community is completely evasive to our questions: the methods are already reported in the literature attached to the reports, and in any case we are talking about non-conformities that go beyond evaluation as research scientific because they have an impact on public health. Often medicines are withdrawn from the market because they are not compliant and we do not know that any publication is required, the samples are collected and analyzed.
In this regard, we take an example for all from the pages of your site, where we read that some batches of the Meningitec vaccine were withdrawn (http://www.aifa.gov.it/content/ritiro-vaccino-meningitec-13102014) ON SIGNALING FROM THE MANUFACTURER (as we have seen in almost 100% of cases of drug withdrawals in the last 3 years) due to "a reddish color". Now, you want to tell us that if a citizen had noticed the unusually reddish color of an injectable drug and reported it to you, your agency would not have followed up on the report because a human being's analysis with the naked eye does not “substantially evaluable as presented "?

Furthermore, following such serious and important reports, we would like to have an answer to a simple question: why don't you withdraw some samples and carry out checks using in-depth methods to determine the existence of a risk?

We, Citizens Association, given the "Activity Plan for the year 2018" approved by your agency with Resolution no. 22 of 18 June 2018, given the Decree of 27 February 2001 "Provisions to be applied in the event of the discovery of medicines with defects or containing foreign bodies", given the Legislative Decree 219/2006 "Implementation of Directive 2001/83 / EC" and having regard to " Compilation of Community Procedures on Inspections and Exchange of Information ”we ask ourselves: how does your agency consider intervening in case of reporting of a possibility of quality defect of a medicine?

Failure to intervene following reports of possible contamination or non-compliance exposes the Body which represents significant implications. You, understood as the Italian Medicines Agency, were made aware of the first results as early as August 2018, the date on which we submitted problems that in our opinion may compromise the quality of various vaccine samples. We also anticipated that all the analysis certificates had been attached to a complaint at the Public Prosecutor's Office in Rome on August 16, 2018 and the method of metagenomic analyzes, with the name of the laboratory in clear.

We are citizens who have submitted to all the competent authorities, including AIFA, an alleged discrepancy with respect to the technical data sheets of many drugs, and you have not considered it appropriate in 5 months to ask us for such data (which we are available to submit tomorrow with a confidentiality agreement) ?

Given the articles 443 and 445 of the penal code, was it not appropriate to consider the relevance of our results with reference also to the possible implications?

Finally, we believe that as an Italian Medicines Agency you have to dictate provisions, to protect public health, to be applied in the event of the discovery of medicines with defects or containing foreign bodies, but also to detect the seriousness of a report by citizenship which can assume, if correct, huge implications for public health. We remind you, with enormous kindness, that you answered us only on the Priorix Tetra vaccine and not on the other vaccines analyzed.

We hereby request to have, for legal reasons, all the references of the checks carried out by your agency before the placing on the market of all the vaccines analyzed by us so far and the documentation on the periodic safety assessments and the renewals of the previous authorization .

Corvelva Staff

Download: CORVELVA-response-AIFA-18gen2019.pdf