Article 58: How EMA Helps Increase Access to Drugs in Low- and Middle-Income Countries

Regulatory NewsRegulatory News | 26 April 2016 |  By 

Ten years into the European Medicines Agency’s (EMA) regulatory experiment to try to increase access to medicines in low- and middle-income countries (LMICs) and the agency is seeing limited success, though enhancements outlined in a new report could increase the utility of the program.


Article 58 of Regulation (EC) No 726/2004, introduced first in 2004, allows EMA's Committee for Medicinal Products for Human Use (CHMP) to give opinions, in co-operation with the World Health Organization (WHO), on drugs to prevent or treat diseases of major public health interest and intended exclusively for markets outside the EU.

Eligible treatments include vaccines used in the WHO Expanded Programme on Immunization or for protection against a public health priority disease, as well as medicines for WHO target diseases such as HIV/AIDS, malaria or tuberculosis. 

For all positive CHMP opinions adopted under Article 58, EMA prepares and publishes a European public assessment report (EPAR) reflecting the scientific conclusions.

To date, seven medical products have been approved via Article 58, including:

  • Antiretrovirals from AbbVie (Aluvia) and ViiV (lamivudine and lamivudine/zidovudine);
  • Sanofi’s hexavalent vaccine Hexaxim to protect against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and Haemophilus influenzae type b;
  • GlaxoSmithKline’s Tritanrix, a quadrivalent vaccine to protect against diphtheria, tetanus, pertussis and hepatitis B;
  • Linepharma’s Hemoprostol, a treatment for postpartum hemorrhage;
  • Shin Poong’s anti-malarial medication Pyramax, which has won approval in four Southeast Asian and six African markets, following a positive CHMP opinion in 2014.

10-Year Report

A report evaluating the first decade of the use of Article 58 from the EMA, European Commission and Bill & Melinda Gates Foundation acknowledged that although only seven products have been approved, manufacturers have found the scientific advice received from EMA experts to be “extremely helpful” in shaping clinical plans and LMIC drug regulators that have been experts/observers during CHMP reviews have found the experience to be valuable.

Still, the report outlines five core barriers to Article 58 reaching its full potential:

1. Manufacturers are unclear/unconvinced of its benefits, and are reluctant to use it because a lack of prior successes.

2. The fees are burdensome or prohibitive (particularly the annual maintenance fees) for manufacturers.

3. Many national regulatory authorities (NRAs) outside the EU are unaware of Article 58 or consider it to be a “lower grade review,” as it does not confer EU marketing approval.

4. Even where opinions are well-accepted, the pace of national assessment is no quicker than with other approvals from stringent drug regulatory authorities, such as the US Food and Drug Administration.

5. Poor coordination between EMA and WHO, “both in terms of general logistics, and the management of variations and pharmacovigilance," limits the potential impact for both NRAs and manufacturers.

“These seven products have experienced mixed commercial success in the LMICs’ post-opinion,” the report says. “While over 60% of these products have been hampered by poor NRA recognition of Article 58 opinions, most of the products with positive opinion from Article 58 have suffered from poor commercial viability, unrelated to the regulatory pathway.”


In the short term, the report says the EC and EMA should:

  • Create additional incentives for manufacturers through clearer communication on fee waivers and potential access to the benefits of EMA’s orphan designation;
  • Enhance the Article 58 review process via clear procedures for the review of variations, renewals and label changes, as well as strengthened pharmacovigilance monitoring;
  • Allow more involvement of target NRAs and local/WHO experts during scientific advice to ensure clinical plans are better targeted towards end-users;
  • Ensure faster WHO prequalification of Article 58 medicines by removing barriers to simultaneous prequalification and Article 58 review for vaccines;
  • Accelerate post-opinion NRA assessments by ensuring access for all Article 58 treatments to WHO’s collaborative registration programs;  
  • Work with WHO to design back-to-back Article 58 and prequalification meetings with LMIC NRAs in London to allow for more efficient answering of questions and to walk NRAs through their assessments and save on the logistics of hosting separate meetings;
  • Renew the Article 58 brand and messaging for both manufacturers and NRAs with targeted conference presentations, journal articles and one-on-one meetings with NRAs for outreach, and possibly hold informal CHMP meetings in Africa, facilitating relationship building with key African NRAs.

“Analysis of the development pipeline confirms that there are up to 30 possible Article 58 candidates currently in development,” the report notes, adding that longer term considerations for Article 58 should include broadening its scope; Allowing simultaneous review of a product through the EMA’s central and Article 58 pathways; and introducing major new incentives, including possibly priority review vouchers or decreased fees on future products, or access to significant funding and strategic advice. 

Article 58 Strategic Review – Summary

Defining the strategic vision for the EMA ‘Article 58’ process

Article 58 applications: Regulatory and procedural guidance


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