Nathalie Strub-Wourgaft, Medical Director, DNDi
The need for regulatory harmonization (i.e. either allowing for centralized drug registration in multiple countries as one single approval, or mutual recognition which entails expediting registration in additional countries once a drug has been registered in a primary country with sufficient regulatory capacities) in order to reduce the duplication of research efforts, use resources more efficiently, and especially to speed up the process to reach patients, was identified decades ago in Europe.
The process took nearly 40 years to come to fruition (EMEA created in 1995 and EEC in 1957).
This context is important to bear in mind when we analyse regulatory harmonization processes in neglected-disease endemic countries. For example, the African Medicines Regulatory Harmonization (AMRH) programme, in collaboration with the African Union Commission (AUC), Pan African Parliament (PAP), World Health Organization (WHO), World Bank (WB), Bill and Melinda Gates Foundation (BMGF), UK Department for International Development (DFID), and Clinton Health Access Initiative (CHAI), aims to support the African regional economic communities (notably the East African Community, the Southern African Development Community, and the Economic Community of West African States) in harmonizing drug regulations, strengthening regulatory capacities, and expediting registration of priority essential medicines. This need for harmonization was highlighted in a report published by DNDi in 2010, “Registering New Drugs: The African Context”, following the observation of an imbalance in regulatory capacities amongst the different African countries on the one hand, and the increasing requirement for new drug, vaccine, and diagnostic approvals, on the other. The findings were supported by the growing global research and development portfolio for communicable diseases. As part of the AMRH, The East African Community regulatory platform was launched in March 2012 in Arusha.
A current case study can be useful to examine regulatory harmonization in Africa: SSG&PM combination therapy is a new treatment option, which is a shorter 17 day course compared to a 30 day treatment that has been used in East Africa in the past for the treatment of visceral leishmaniasis (VL) – a disease that is fatal if left untreated. It was developed by DNDi in a large Phase III study, with its partners from Kenya, Sudan, Ethiopia, and Uganda of the LEAP platform (Leishmaniasis East African Platform). Following favourable study results, SSG&PM was recommended in 2010 by the WHO Expert Committee on the Control of Leishmaniases as first-line therapy for VL patients in East Africa. It was added to the treatment guidelines in Sudan in 2010 and more recently, on 26 September 2012, the Ministry of Health of Kenya officially released its new national guidelines for the diagnosis and treatment of visceral leishmaniasis, recommending SSG&PM as first-line treatment for VL.
However, both individual drugs have a different regulatory status in each of the countries of East Africa. Sodium stibogluconate (SSG) has been used for decades in East Africa but the registration process has to be renewed regularly, which is standard procedure. Paromomycin was approved in India only, in 2006, and thus has to undergo a completely new registration process for each East African country in order to be used in combination with SSG.
In 2011, Uganda registered paromomycin for the treatment of VL, and the renewal of registration of SSG is underway. The registration file for PM was submitted in 2012 to the Kenya Pharmacy and Poisons Board and approval is pending, whilst the status is not finalized yet in Ethiopia and Sudan even if the treatment has been added to their guidelines. The difference in approval processes and lack of an existing mechanism to facilitate a harmonized review for such an important treatment could potentially jeopardize sustainable access to it.
Despite new regulatory pathways such as EMA’s Article 58 and indirectly the WHO drug prequalification that were created to facilitate and speed up drug registration in developing countries, progress still needs to be made and the implementation of harmonized and high regulatory standards in many developing countries is urgent.
In the case of the anti-malarial ASMQ FDC, developed by DNDi and its partners in 2008, the situation is different. ASMQ was first registered in Brazil in 2008. Following a successful technology transfer from Farmanguinhos/Fiocruz in Brazil to the Indian manufacturer Cipla, it was registered in India in 2011, in Malaysia in 2012 and launched in Asia in Kuala Lumpur, Malaysia, early October 2012, following WHO prequalification. In 2010, there had been a common commitment on harmonized technical requirements among the Association of Southeast Asian Nations (ASEAN) countries. ASMQ FDC is now under review in the other ASEAN countries.
DNDi supports this type of harmonization initiative, which can indeed optimize drug – and more specifically neglected disease drug – registration in regions where the drugs are desperately needed. It is one of the key elements necessary to ensure that neglected patients gain rapid access to safe, efficacious, and affordable drugs. While realizing that regulatory harmonization was a long process in Europe, all actors involved in regulatory issues in developing countries should be encouraged in their efforts to work towards facilitating relevant evaluation of risks/benefits for patients affected in their countries, reducing the duplication of their efforts, and reducing the time between drug development and patient access.
Dr Nathalie Strub-Wourgaft
DNDi Medical Director