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’sregulatory oversight, the post-market reassessment of ARV quality is prohibitively resource intensive. The aim of thisstudy was to evaluate and compare the post-market quality of four fixed-dose combination (FDC) generics containingefavirenz (EFV) 600 mg, emtricitabine 200 mg, and tenofovir 300 mg against the innovator, Atripla® and accordingto the International Pharmacopoeia (IP). Generic tablet samples, sourced from a South African provincial depot, weresubjected to the identification, content assay, dissolution, uniformity of weight and disintegration tests. An in-housereversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated in lieuof the RP-HPLC IP method which proved to be unsuitable. All samples passed the identification, assay, uniformityof weight and disintegration tests and one generic FDC failed the dissolution test (at both stage 1 and 2), releasing62.23% (standard deviation 20.43) of EFV in 30 minutes. One generic first-line ARV combination that is currentlysupplied to the South African public health sector was found to be substandard and this reinforces the need for routineARV post-market surveillance, as well as reliable compendial methods to facilitate this undertaking