Our webpage, Access to drugs for maternal health, stresses the fact that equitable access to vital maternal health drugs can make a substantial contribution to maternal health and reducing maternal mortality and morbidity. One of the critical areas that contributes to maternal mortality and morbidity in many countries is unsafe abortion and the lack of access to safe abortion services.

Medical abortion has an important role to play in the provision of safe abortion services, providing not only choice to women, but also creating the potential for provision of low cost abortion services if access to drugs of assured quality can be provided at an affordable price. However, until recently, existing manufacturers have shown either a lack of interest, willingness or ability to achieve the goal of making medicines for medical abortion of assured quality widely available at an affordable price in low-resource countries.

Increasing access to medical abortion is a central component of Concept Foundation’s access-to-medicines strategies, through its multi-country Medabon introduction programme, advocacy activities and ongoing research designed to further to improve and expand access to safe abortion services through medical abortion. For further information about Concept’s work on medical abortion, please contact helena.vonhertzen@conceptfoundation.org

 

Making product available

Concept Foundation assessed how an access-to-medicines programme for drugs for medical abortion might be achieved and how incentives could be developed that would allow a commercial partner to meet this goal. While Concept, through its license agreement with the World Health Organization, had access to data from clinical trials on the use of mifepristone followed by misoprostol for this indication, Concept was required to ensure that it could meet four critical requirements:

• Regulatory issues – since in most countries, misoprostol is used “off-label” for medical abortion, the product would be registered as containing both mifepristone and misoprostol for the termination of early pregnancy.
• Ease of use – the two drugs would be provided as a co-packaged product making it easier for both the provider and the woman.
• Price – the co-packaged product would be made available to the public sector and NGOs that do not add a margin to the product at a preferential price, making it affordable to many more women.
• Quality – the product would be manufactured in an USFDA/EMEA compliant facility, meeting international Current Good Manufacturing Practice (CGMP).

We undertook a global survey of manufacturers of mifepristone and misoprostol and found that very few had manufacturing facilities that complied with CGMP. Concept subsequently concluded an agreement, which addressed all four requirements, with Sun Pharmaceutical Industries Ltd. This resulted in the creation of a public-private partnership (PPP), in which Concept Foundation was able to provide all clinical and preclinical data required for an internationally compliant registration dossier. This, together with the proposed introductory activities by Concept, encouraged the company to make the investment necessary to manufacture the product under CGMP and establish a collaborative venture with Concept Foundation to make the product available.

Under this agreement, Concept is required to: complete clinical and preclinical components of dossier; develop support materials (service delivery guidelines, etc); support developing country activities (work with government, identify agents, organize introductory activities); while Sun Pharma manufactures the product under CGMP; provides it at a preferential price to the public sector of developing countries; and submits the regulatory dossiers through appointed distributors.

In order, to meet its obligations, Concept undertook supplementary analyses of data from WHO clinical trials; bioequivalence studies against innovator products; prepared an expert clinical review; additional genotoxicity studies; an expert toxicology review of mifepristone and misoprostol; and completed a dossier in an ICH-compliant format.

It has subsequently, registered the trademark, Medabon® in more than more than 50 countries; identified regulatory requirements and produced dossiers for submission by Sun Pharma in 14 developing countries; and identified candidate importer/distributors in these countries. The product is now registered in Cambodia, India and Nepal and this partnership between Concept Foundation and its pharmaceutical partner, Sun Pharma, is beginning to give women in several countries access to a high quality, affordable product for the termination of early pregnancy.

 

Regimens

Medabon® contains two medicines, mifepristone and misoprostol, that are widely used for medical abortion. Mifepristone is registered in more than 40 countries for medical abortion and is generally used in combination with misoprostol. Although misoprostol is only registered in a limited number of countries for this indication, it is commonly used in combination with mifepristone, at the discretion of a physician as off-label use. Medabon® is the first product to package the two medicines together, to be licensed as a combination product.

The current Medabon® regimen, 200mg of mifepristone followed 24-48 hours later by 800μg of misoprostol administered vaginally, is based on data from large multinational clinical trials undertaken by the World Health Organization (WHO,) and is consistent with guidance from WHO and the Royal College of Obstetricians and Gynecologists in the United Kingdom on safe and effective medical abortion. The recommended regimens are currently being updated to include the sublingual administration of misoprostol.

 

Getting product to those who require it

An access-to-medicines programme for medical abortion cannot be limited to enabling physical access to a drug, without ensuring the preparedness of a supportive health system to handle and utilize the medicine adequately, and to deliver it into an appropriately prepared environment. Drugs for medical abortion can be provided by trained mid-level providers but, in the few cases of incomplete abortion or excessive bleeding, there is need for access to referral services. A supportive health system must ensure that all women have access to a provider trained in the use of manual vacuum aspiration (MVA) and to blood transfusion services. It must be prepared to provide training to all levels of health care providers, and values clarification with providers. With medicines for medical abortion, there are sensitive policy, religious and societal issues, as well as potentially complex medical use of medicines, all of which require continuous advocacy with providers as well as the broader society.
  
Because of these issues, Concept believes that the optimal approach to making medical abortion available is through the development of appropriate national strategies for the introduction of medical abortion in the context of comprehensive abortion care. Concept has participated in the development of introductory strategies in three countries in collaboration with government, national and international NGOs. In Nepal, an exciting introductory study was recently undertaken in six districts, in  a collaboration between government, Ipas, PSI, Concept and other national NGOs. This has culminated in the development of a scaling-up strategy by the partners, together with WHO and Expandnet, for which implementation is being planned.

The Medabon introduction programme aims to introduce a dedicated combination pack of mifepristone and misoprostol into 26 low and middle income countries by 2011.

 

Partnership in action

In a partnership between Concept Foundation, PATH, and Ipas, a set of materials have been developed as a guide for health care providers and programme managers who are working to introduce Medabon®. The materials are also intended to serve a wide variety of audiences, including policy makers, the media, and women who choose to use Medabon®. The resource materials in this package are to be found on the “Information on Medabon®” and “Introducing Medabon® into national programmes” pages of the website, www.medabon.info.

In addition, the first meeting of the Medabon® Access Partnership (MAP) was held in Washington DC in April 2009, hosted by PSI, and attended by Concept, Ipas, WHO/RHR, PATH, PSI and MSI. It is intended to build on MAP over the coming year and add additional partners who are willing to work on making Medabon® widely available.