EMA offers parallel Article 58, centralized authorization reviews

Regulatory NewsRegulatory News | 14 January 2021 |  By 

The European Medicines Agency (EMA) on Thursday issued a draft guidance for consultation explaining how sponsors can pursue a parallel Article 58 (EU-M4all) opinion and centralized marketing authorization for medicines they intend to market in the EU and abroad.
The Article 58 procedure allows EMA’s Committee for Medicinal Products for Human Use (CHMP) to give opinions in cooperation with the World Health Organization (WHO) on medicines intended to be used in low- and middle-income countries outside the EU to address public health priorities. Examples of eligible products include vaccines and medicines to treat HIV/AIDS, malaria and tuberculosis.
So far, Article 58 has only been used to obtain opinions for 11 products, five of which have since been withdrawn for commercial reasons or due to changes to treatment guidelines. EMA says the procedure has led to 138 approvals in 90 non-EU countries as of July 2020. More than half of those approvals were for AbbVie’s HIV treatment Aluvia (lopinavir/ritonavir), which has been registered in more than 70 countries using the scientific opinion generated via the Article 58 procedure. The most recent product to receive an Article 58 opinion is the International Partnership for Microbicides’ Dapivirine Ring (dapivirine), which is intended to reduce the risk of HIV-1 infection via vaginal intercourse in women 18 and older.
While Article 58 is intended for products that will be used outside the EU, five of the 11 medicines that have gone through the procedure have also been centrally authorized in the EU, four before receiving an Article 58 opinion and one after.
Due to the interest in obtaining both a marketing authorization application (MAA) and Article 58 opinion, EMA says it will evaluate applications in parallel.
Parallel MAA/EU-M4all applications will be assigned the same CHMP and Pharmacovigilance Risk Assessment Committee (PRAC) rapporteurs and will be assessed in parallel, though EMA says that timetables for the two procedures may differ.
To be eligible, the active substance(s) in both applications “must be identical and the intended indication(s) must be comparable” and EMA says it, “Expects both procedures are submitted by the same applicant.”
However, the medicines may have different formulations, pharmaceutical forms, storage conditions or routes of administration. “This means that the intended medicines must be chemically/biologically and clinically identical but can be physically distinct,” EMA says.
EMA also explains that at filing, two separate electronic common technical document (eCTD) submissions are required and that the applications cannot cross-reference each other. And, while the dossier requirements for the centralized procedure and EU-M4all applications are mostly the same, EMA says applicants should reference its guideline on Article 58 procedural advice and identify any differences between the dossiers during the pre-submission phase. Pre-submission meetings are “strongly advised” at least 6-7 months before the intended submission date.
EMA notes that EU-M4all products are subject to good manufacturing practice (GMP), good laboratory practice (GLP), good clinical practice (GCP) and pharmacovigilance inspections and says that trials conducted to support such products must be conducted in accordance with GCP.
“Based on previous cases where EU-M4all clinical trials were performed in challenging conditions, Applicants are highly encouraged to share an overview of actual GCP compliance in early discussions such as Scientific Advice and/or pre-submission meetings,” EMA says.
Additionally, EMA says that EU-M4all opinion holders must keep the agency up to date on any changes related to their medicine by submitting variations, periodic safety update reports and other post-opinion applications and must meet the pharmacovigilance requirements for the product agreed with the agency.
EMA, draft guidance


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Tags: Article 58, EMA, EU

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