Recognition of tiered manufacturing as a common practice.

Respondents consistently acknowledged the existence of tiered or “dual-track” systems, although the terminology itself was not widely used. Respondents described companies as maintaining separate production streams: one aligned with SRA/WLA standards, and another for domestic or LMIC markets, which participants characterized as operating under less stringent regulatory oversight. Smaller firms (described as those that have no more than 150 employees) often framed this as part of a growth trajectory, beginning with less stringent production for local or “rest-of-world” (ROW) markets before upgrading to meet SRA/WLA standards. Larger multinationals were considered less likely to sustain differentiation, owing to reputational risks and the impracticality of parallel systems at scale.

One respondent informed, “Yes, we do have separate plants… they have a relatively next level down standards there” (KII10, Quality Assurance and Control, 30 + Yrs, India).

Disparities in APIs and excipients across markets.

Disparities in input quality were consistently reported between SRA/WLA-regulated and LMIC markets. According to respondents, APIs and excipients destined for the USA and EU typically required GMP certification and full pharmacopeial documentation, whereas those supplied to LMIC markets were reported to be sourced from lower-grade suppliers with minimal certification to reduce costs.

As one respondent explained, “For regulated market they always purchase pharma grade, USP [United States Pharmacopeia] grade API, Ph. Eur. [European Pharmacopoeia] excipients. While in non-regulated market, they are compromised with the grade of API and excipients so they can take some profit.” (KII11, Regulatory Affairs, 12 + yrs, India)

Disparities in manufacturing for LMICs versus SRA markets.

Respondents described marked differences between products destined for SRA/WLA-regulated markets and those for LMICs identified as non-SRA or not in the WLA list. Respondents reported that medicines for regulated markets underwent rigorous documentation, testing, and validation supported by advanced 21 CFR-compliant systems, whereas products for LMICs were perceived to be produced under weaker oversight, with equipment that participants said allowed greater scope for data manipulation.

As one respondent explained, “In regulated markets, 21 CFR systems prevent data manipulation because every step is recorded. In semi-regulated plants, machinery is often a step down, making manipulation easier” (KII15, Regulatory Affairs, 15 + yrs, India).

Larger firms with established innovator drug brands in SRA/WLA markets were said to maintain higher and more consistent standards, whereas smaller firms targeting less regulated markets prioritized sales over quality assurance.

One respondent elaborated, “Large companies have multiple facilities and strong brands, and they use higher-quality systems with substantial manufacturing capacity. Small companies, often with only 100–150 employees, produce mainly for small markets and focus on selling products rather than maintaining quality” (KII24, Regulatory Affairs, 14 + yrs, India).

Economic drivers.

Economic pressures were the most frequently cited driver of tiered manufacturing. Producing at lower cost for LMICs was described as a survival strategy in competitive generic markets, influencing testing intensity, input sourcing, and automation. Affordability dictated specifications, higher-grade inputs for wealthier markets and cheaper alternatives for others. Though tiered manufacturing was described as occurring in small and large size companies, it was said larger firms with strong reputations tended to uphold higher standards. Competition from low-cost suppliers, further encouraged less rigorous sourcing even when bioequivalence was uncertain.

One respondent noted, “[Large company x] maintains very high standards… they spend more on quality, so their product will be more costly… some companies do not” (KII5, Quality Assurance/Control, 17+ yrs, India).” Another explained, “[some] suppliers… make the API so cheap that you have no option than either discontinue selling in US… or follow the herd” (KII12, Procurement transformation, 15 + yrs, India).

Strategic drivers.

Beyond economics, strategic factors shaped how firms applied SRA/WLA standards. Respondents cited reputational risk, market growth, and logistical efficiency as key considerations. Some companies maintained higher standards in LMICs as a long-term investment in trust, while others pursued short-term gains where oversight was weak. Publicly listed firms were viewed as more risk-averse, whereas privately held ones often sustained differentiated systems. Contract manufacturing for LMICs was seen as particularly vulnerable to data manipulation due to limited oversight.

As one respondent noted, “For short term they can cheat… but for long term… they always prefer health first, then business” (KII11, Regulatory Affairs, 12 + yrs, India). Another added, “In regulated markets… always a tech transfer… for ROW markets… some data can be manipulated at the CMO [contract manufacturing organization] vendor end” (KII15, Regulatory Affairs, 15 + yrs, India).

Regulatory drivers.

Variation in regulatory environments was seen as central to sustaining tiered manufacturing. Strong, harmonized frameworks in regions such as the US, EU, and Japan compel adherence to high standards, whereas weaker or fragmented systems allow faster registration, minimal data, and higher impurity limits. Such gaps enable lower-quality products and, in some cases, document manipulation, reflecting what regulators are willing or able to enforce rather than outright illegality.

As one respondent elaborated, “Sometimes the same data submitted to the US can also be submitted to Kenya, which may not require as thorough a review” (KII6, Quality Assurance/Control, 15 + yrs, India). Another added, “Companies are not even performing those tests… they are doing manipulation in the document without performing” (KII19, Regulatory Affairs, 11 + yrs, India, US, Canada).

Stability, shelf life, and batch variability.

Respondents noted that medicines destined for SRA/WLA markets undergo rigorous stability testing, impurity profiling, and bioequivalence studies, ensuring potency and shelf life. By contrast, products supplied to LMICs were often described as skipping long-term stability studies or reducing batch-level testing and often undergo no bioequivalence testing against the established innovator product. Respondents perceived these practices as contributing to variable assay performance, greater impurity levels, and shorter shelf life, particularly in hot and humid climates where degradation is accelerated, though they acknowledged that systematic measurement of these outcomes was rarely conducted by manufacturers themselves.

As one respondent noted, “Improper training and weak CAPA [Corrective and Preventive Action] during audits often result in out-of-specification batches… automation is helping reduce these risks, but many sites still rely on manual integration which increases variability” (KII17, Regulatory Affairs, 15 + yrs, India). Another added, “In the US specifically, you have to manufacture based on attribute batch by batch, not commercial batches generally” (KII6, Quality Assurance/Control, 15 + yrs, India).

Excipient and input safety.

Beyond APIs, respondents highlighted excipients as a critical dimension of product safety and cost determinants. For regulated markets, excipient vendors were expected to provide detailed certification packages, including nitrosamine and elemental impurity studies. In LMIC markets, however, manufacturers frequently sourced from lower-tier suppliers, with documentation limited to basic certificates of analysis. One respondent characterized system of “A,” “B,” or “C” category excipients, where poorer markets often received the lowest-quality categories, though this framing reflects one participant's characterization rather than a formally recognized industry classification.

As one respondent explained, “In regulated markets, every step must meet strict GMP requirements. For smaller companies, maintaining those standards can be difficult, especially for excipients. I have seen the same product supplied to Europe and to African countries, but with different excipient grades—USP or CEP [Certificate of Suitability to the European Pharmacopoeia] grade for regulated markets and lower-grade materials for emerging markets where requirements are less strict.” (KII18, Regulatory Affairs, 14 + yrs, India). Another added, “In ROW markets, inspections often check GMP processes and SOPs, but not the product itself… unlike regulated markets where inspections cover formulation, stability, and product lifecycle” (KII15, Regulatory Affairs, 15 + yrs, India).

Patient safety implications.

We also inquired about concerns related to patient safety risks associated with tiered manufacturing. Respondents highlighted that cost-driven procurement decisions often led governments and buyers in LMICs to accept medicines of compromised quality, and that the absence of simple markers made it difficult to distinguish manufacturers serving regulated versus non-regulated markets.

As one respondent explained, “Albendazole for deworming children in Africa and Southeast Asia… is of such low quality that it doesn’t even dissolve properly. Yet governments procure and use it because it is the only drug available” (KII1, R&D, 20 + years, India, US). Another added, “There is no simple parameter to identify if a company produces for regulated or non-regulated markets… but CEP listings and the Orange Book in the US allow us to know who supplies higher-standard medicines” (KII11, Regulatory Affairs, 12 + yrs, India).

Regulatory harmonization, recognition, and reliance.

Respondents frequently emphasized that fragmented oversight across LMICs weakens quality assurance. Regional initiatives such as the African Medicines Agency (AMA) were described as essential to harmonize standards, reduce duplication, and pool scarce technical and enforcement expertise. Participants also highlighted reliance mechanisms, such as recognition of approvals or inspection outcomes from stringent regulatory authorities (SRAs/WLAs) or WHO prequalification as practical pathways for regulators with limited resources, provided they receive the same product version assessed and inspected by the SRA/WLA or WHO, which in many tiered manufacturing scenarios could be difficult for the regulators in LMICs to determine.

As one respondent explained, “If LMIC regulators can rely on WHO PQ [prequalification] or SRA approvals, they don’t need to repeat everything, recognition can save time and cost” (KII24, Regulatory Affairs, 14 + yrs, India).

Leveraging market power and transparency.

Market-shaping was considered a powerful tool to drive higher standards. Respondents recommended pooled procurement and conditional purchasing tied to WHO prequalification or SRA/WLA authorization, even when cheaper alternatives exist. Donors and major procurement agencies were seen as best positioned to enforce these requirements. Transparency measures, such as independent audits, public inspection reports, and patient reporting tools like hotlines or mobile apps, were also emphasized to enhance accountability and detect poor-quality medicines more quickly.

As one respondent noted, “If procurement agencies clearly state that only WHO-prequalified or SRA-approved products will be purchased, then manufacturers will comply. Market leverage works faster than regulation in many cases” (KII11, Regulatory Affairs, 12 + yrs, India). Another added, “Public disclosure of inspections and third-party audits can make a big difference, if a company knows their practices will be visible, they will think twice before cutting corners” (KII3, Quality Assurance/Control, 17 + yrs, India).

Building capacity, harnessing technology, and ensuring sustainability.

Respondents emphasized that capacity-building must extend beyond regulators to the wider manufacturing and health workforce. Training factory workers in GMP, continuous professional development for QA staff, and refresher courses for inspectors were viewed as essential for sustaining quality improvements. Technology, such as electronic batch records, track-and-trace systems, and automation, was seen as critical to prevent data manipulation, while sustainable financing beyond donor start-up support was deemed vital to maintain laboratory and digital infrastructure.

As one respondent summarized, “GMP training should not just be for regulators; factory workers also need to know why each step matters, otherwise the same mistakes repeat” (KII3, Quality Assurance/Control, 17 + yrs, India).

Across interviews, respondents described a clear contrast between products destined for SRA/WLA‑regulated high‑income markets and those supplied to LMICs. For high‑income countries, respondents perceived that companies emphasized stringent GMP compliance, higher‑grade APIs and excipients, extensive stability and bioequivalence testing, and 21 CFR‑compliant digital systems that limit data manipulation. In LMIC markets, by contrast, respondents reported greater use of lower‑grade inputs, reduced testing, and more manual or fragmented documentation, facilitated by weaker or less harmonized regulatory oversight. Several respondents noted that this tiered approach allows companies to offer lower‑priced products that support coverage in resource‑constrained settings, but often at the cost of shorter shelf life, greater batch variability, and higher risks of substandard quality.