WHO prequalification of medicines in low- and middle-income countries: Situational analysis of Nepali manufacturers and recommendations

Introduction The World Health Organization (WHO) prequalification (PQ) program is a critical gateway for generic medicine manufacturers in low- and middle-income countries (LMICs) to access the global market. Despite India contributing more than 66% of PQ products, LMIC’s share in manufacturing PQ medicine is less than 22%. Nepali manufacturers fulfilling 50% of domestic requirements of generic medicine are yet to achieve WHO PQ status. This study assesses compliance gaps among six Nepali manufacturers aiming to produce four priority generic medicines (amoxicillin tablets, azithromycin tablets, zinc sulfate dispersible tablets, and oxytocin injections) for WHO PQ and recommends corrections. Methods and findings The Department of Drug Administration (DDA) of Nepal, in collaboration with the Promoting the Quality of Medicines Plus program, invited domestic manufacturers for technical assistance towards the PQ of priority products. We shortlisted six manufacturers out of twelve applicants through document review and conducted an onsite inspection using WHO GMP criteria. Results We identified systemic deficiencies in pharmaceutical quality systems (>95% major nonconformities), documentation practices, and bioequivalence testing—a cornerstone requirement for generic drug approval. Key barriers included the use of non-prequalified active pharmaceutical ingredients (APIs), lack of Common Technical Document (CTD)-formatted dossiers, inadequate validation of analytical methods, and product development reports. Conclusion WHO PQ is a system-strengthening approach targeting overall quality compliance. Our findings mirror challenges faced by manufacturers in LMICs, highlighting the need for regulatory harmonization and targeted technical assistance. We recommend public-private partnerships to establish regional bioequivalence study centers and incentivize sourcing WHO PQ grade API. Success from India leading the manufacturing and exports of WHO PQ and generic medicines could be considered. Strengthening Nepal’s capacity to meet WHO PQ standards will position the country as a competitive player in the global generic market.