Things We Should Know About EMA’s Article 58

A decade into the European Medicines Agency’s (EMA) regulatory experiment to attempt to enhance access to drugs in low- and middle-income countries (LMICs) and the regulatory authority is experiencing minimal success, though improvements defined in a new report could raise the utility of the program.

Article 58 of Regulation (EC) No 726/2004, launched initially in 2004, enables EMA’s Committee for Medicinal Products for Human Use (CHMP) to give opinions, in collaboration with the World Health Organization (WHO), on medicines to stop or treat conditions of major public health interest and designed specifically for markets outside the EU.

Suitable therapies include vaccines utilized in the WHO Broadened Programme on Immunization or for protection towards a public health priority condition, along with drugs for WHO focused diseases like HIV/AIDS, malaria or tuberculosis.

For all positive CHMP ideas implemented under Article 58, EMA prepares and presents a European public assessment report (EPAR) showing the scientific conclusions.

To date, 7 medical products have been approved through Article 58, which include:

The decadal report:

A report assessing the 1st decade of the use of Article 58 from the EMA, European Commission and Bill & Melinda Gates Foundation identified that even though only 7 products have been accepted, manufacturers have identified the scientific advice obtained from EMA professionals to be “very beneficial” in shaping clinical plans and LMIC drug authorities that have been experts/observers while in CHMP reviews have identified the experience to be useful.

Still, the report describes five core limitations to Article 58 that prevent it from reaching its full potential:

1. Manufacturers are not clear/not convinced of its advantages, and are unwilling to use it due to a lack of previous successes.
2. The fees are burdensome or too high (especially the annual maintenance fees) for companies.
3. Many national regulatory agencies outside the EU are not aware of Article 58 or think about it to be a “lower grade review,” as it does not provide EU marketing approval.
4. Even where opinions are received well, the speed of national evaluation is no quicker than with other approvals from strict drug regulatory agencies, like the US Food and Drug Administration.
5. Poor co-ordination among EMA and WHO, “both with regards to general logistics, and the management of variations and pharmacovigilance,” restricts the possible impact for both national regulatory agencies and manufacturers.

“These seven drugs have experienced mixed commercial outcomes in the LMICs’ post-opinion,” the review says. “While over 60 percent of these drugs have been affected by very poor national regulatory authority recognition of Article 58 opinions, the majority of the products with positive viewpoint from Article 58 have suffered from poor commercial stability, irrelevant to the regulatory pathway.”

“Evaluation of the development pipeline shows that there are approximately 30 possible Article 58 candidates presently in progression,” the report notes, including that extended term concerns for Article 58 should include expanding its scope; Enabling simultaneous review of a product via the EMA’s central and Article 58 pathways; and launching significant new benefits, which includes possibly priority review vouchers or reduced charges on future products, or access to major funding and strategic advice.