A post-market quality assessment of first-line, fixed-dose combination antiretrovirals in South Africa

Abstract

South Africa has the world’s largest antiretroviral (ARV) program and despite having stringent upstream medicine’s regulatory oversight, the post-market reassessment of ARV quality is prohibitively resource intensive. The aim of this study was to evaluate and compare the post-market quality of four fixed-dose combination (FDC) generics containing efavirenz (EFV) 600 mg, emtricitabine 200 mg, and tenofovir 300 mg against the innovator, Atripla® and according to the International Pharmacopoeia (IP). Generic tablet samples, sourced from a South African provincial depot, were subjected to the identification, content assay, dissolution, uniformity of weight and disintegration tests. An in-house reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated in lieu of the RP-HPLC IP method which proved to be unsuitable. All samples passed the identification, assay, uniformity of weight and disintegration tests and one generic FDC failed the dissolution test (at both stage 1 and 2), releasing 62.23% (standard deviation 20.43) of EFV in 30 minutes. One generic first-line ARV combination that is currently supplied to the South African public health sector was found to be substandard and this reinforces the need for routine ARV post-market surveillance, as well as reliable compendial methods to facilitate this undertaking.