Tiered manufacturing of pharmaceuticals as a commercial determinant of health: Implications for medicine quality and equity

Tiered manufacturing, the practice of adapting different levels of pharmaceutical production standards to low- and middle-income countries (LMICs) versus high-income countries, has not been investigated as a commercial determinant of health (CDoH), defined by the World Health Organization as a private sector activity affecting public health. This paper examines this practice and its implications for medicine quality, universal health coverage, and global health equity. Guided by the CDoH framework, we conducted semi-structured interviews with 31 mostly India-based experts in pharmaceutical development, manufacturing, procurement, and regulation between May and July 2025. Purposive sampling ensured variation in geography, organizational type, and role. Transcripts were coded deductively using CDoH domains and inductively for emergent themes. Respondents consistently described "tiered manufacturing" - using different production standards by market. Medicines for countries regulated by Stringent Regulatory Authorities (SRA) (now called WHO Listed Authorities (WLA)) adhere to international good manufacturing practices (GMP) through rigorous documentation, stability testing, impurity profiling, and advanced infrastructure. In contrast, products supplied to LMICs are often produced with uncertain GMP compliance, cheaper raw materials, weaker documentation, and less stringent oversight, leading to variable quality and shortened shelf life. Commercial drivers were key determinants. Proposed solutions include improved mechanisms to verify versions of products being received, reliance on WHO prequalification or WLA approvals, procurement conditionality and strengthened local regulatory and manufacturing capacity. Tiered manufacturing was widely perceived as a common practice among respondents. Recognition of this practice as a CDoH is essential to strengthen regulatory reliance and enforcement, procurement leverage, and sustainable capacity-building, ensuring quality medicines for all globally.