Production of Antiretroviral Drugs in Middle- and Low-Income Countries

Abstract

This review outlines the main issues concerning the production of antiretroviral (ARV) drugs in middle- and low-income countries and the relevant political, legal and technical requirements for supporting such production. The requirements for efficient local production, including the manufacture of generic and branded products and public demand, have been considered from economic, market and socio-political perspectives. A steady and consistent government policy is crucial to success. Additional crucial factors in establishing local production are adequate infrastructure, qualified human resources in technical and managerial areas, and production-distribution logistics systems. The creation or strengthening of a national drug regulatory agency is a basic requirement. Production of ARVs relies on the structure of the international market for active pharmaceutical ingredients (APIs), which are highly monopolized for inclusion in branded or patented drugs, or are concentrated in a few Asian generic companies. Countries seeking to begin local production must develop strategies to overcome the various barriers. For instance, sub-Saharan African countries may benefit from developing multilateral health agreements with neighbouring countries. Such agreements are recommended and should be complemented by technology transfers, especially for the manufacture of APIs. Achieving a production level that is sustainable in the long term is crucial to maintaining patients' access to ARVs.

Essential medicines for universal health coverage

“…176 Weak regulatory authorities and a dearth of human resources are among the economic and institutional barriers that have impeded domestic production in many settings. 176,177 The problem of aff ordability of single-source medicines under patent protection might well be most acute for MICs excluded from voluntary licensing agreements. These countries are obliged to grant patent protection for pharmaceuticals and are vulnerable to political pressures when they attempt to apply TRIPS fl exibilities.…”

Aid conditionalities, international Good Manufacturing Practice standards and local production rights: a case study of local production in Nepal

“…Our PubMed search identified only three studies on the issues of GMP in relation to local pharmaceutical production in low- and middle-income countries; these concerned the production of vaccines [26], antiretrovirals [27], and anti-malarials [28]. All three studies emphasize the need for local producers to invest in their production facilities and comply with GMP.…”

Simulating Intestinal Transporter and Enzyme Activity in a Physiologically Based Pharmacokinetic Model for Tenofovir Disoproxil Fumarate

“…The AUC 0 -24 and C 24 for the 75-mg dose could not be determined from the clinical data, as TFV was undetectable at the 0-and 24-h time points on the plasma concentration curve. Therefore, clinical AUC [1][2][3][4][5][6][7][8][9][10][11][12] (480 ng · h ml Ϫ1 ) and C 12 (34 ng ml Ϫ1 ) were compared to simulated AUC [1][2][3][4][5][6][7][8][9][10][11][12] (488 ng · h ml Ϫ1 ; 0.02-fold lower) and C 12 (28 ng ml Ϫ1 ; 0.21-fold higher) (Fig. 2B).…”

“…However, the cost and dosing schedule of treatments are a significant concern in low-and middle-income countries (L&MICs). Several effective antiretroviral drugs are now manufactured as generics and are marketed with significant cost savings to payers (1,2).…”