Assessment of active pharmaceutical ingredients in drug registration procedures in Pakistan: implications for the future

Introduction: There are concerns over the quality of generic medicines in Pakistan. This is due to perceived non-compliance with good manufacturing practice (GMP), whereby the quality of the raw materials is not being assessed. If not addressed, this will impact on the potential for generics exports from Pakistan, as well as on patient care. Consequently, there is a need to assess the current assessment and regulatory situation in Pakistan and to recommend a way forward that ensures the future quality of products. Objective: To assess the quality of the raw materials that are either imported to, or manufactured in Pakistan, that are then used to produce a leading analgesic (ibuprofen). As part of the assessment, the presence and levels of impurities will be determined. Subsequently, the findings will be used to recommend potential regulatory changes to improve patient care. Methods: The quality of 27 sourced raw materials and the reference product were assessed using a variety of quality assessment methodologies, including assay tests, and infrared spectroscopy and UV-spectrophotometry. The calculated values were then compared to values documented in the Certificate of Analysis (CoA), and high performance liquid chromatography (HPLC). Results: All but one sample passed the spectroscopy identification tests. However, 81.5% of samples failed to comply with pharmacopoeia assay limits. There were also concerns with the use of HPLC methods used to assess the quality of raw materials, and over the fact that assay values obtained were not the same as those listed in the CoA. In addition, where manufacturers had concerns over the amount of ibuprofen in the raw material, rather than rejecting the product, they typically used higher quantities to make up any shortfall. Conclusions: The results of this study demonstrate that there is an urgent need to improve the registration process for generic products in Pakistan. This should include implementing Common Technical Documents (CTDs) based on international standards. In this way, we will see generics being produced that result in improved patient care and that have potential for export from Pakistan.