Regulatory systems ensure safety, quality, and effectiveness of pharmaceuticals [1]. In low-income countries (LICs), underdeveloped regulatory capabilities contribute to substandard, falsified, unregistered, or unlicensed medicines [2]. This could worsen if advances in AI outpace regulatory systems [3]. AI refers to computer systems that are devised to think or act rationally, like humans [4]. Similarly, mobile health regards the application of mobile or wearable devices in digital health services [5]. By using currently available simple and cheap technologies, like mobile phones, AI and mobile health enable process automation [6], pattern recognition [7], and decision-making with capacity to learn from large datasets [8].

AI is leveraged in drug discovery [9,10] and is increasingly applied in pharmaceutical regulation [11,12]. These applications include “pharmacovigilance,” which aims at “detection, assessment, comprehension and prevention of medicines-related problems” [13,14]. The World Health Organization (WHO), for instance, deployed AI during the COVID-19 pandemic to monitor adverse reactions to COVID-19 vaccines [15]. The WHO has also integrated it into version 2.0 of the Epidemic Intelligence from Open Sources system [16]. Process automation and predictive analytics enhance signal detection of adverse drug events (ADEs) or adverse drug reactions (ADRs), predict drug side effects, streamline safety reporting, map drug-drug interactions, delimit the population toxicity profile for a drug, and simulate clinical trials [17]. By early 2020, China harnessed AI in the pandemic response [18], and France used it for pharmacovigilance in 2021 [19]. Currently, the United States Food and Drug Administration is integrating AI into scientific reviews for pharmaceuticals [20]. Although these applications have positive externalities for LICs, including approval for drugs on the WHO’s Essential Medicines List [21], their potential impact in LICs is underexamined.

Pharmacovigilance in LICs is constrained by fiscal limitations, skills gaps, and poorly integrated regulations [22]. This limits access to high-quality medicines, which hampers health care effectiveness in LICs such as South Sudan [23,24]. Emerging evidence suggests AI could improve signal intelligence and, therefore, regulatory enforcement [17]. However, signal detection for ADEs is undermined by poor data integration and voluntary reporting, even in rich settings such as Australia, where compulsory reports by medicines sponsors outweigh the 16% voluntary reports by clinicians [25]. Automated reporting with AI could circumvent this constraint, as demonstrated in symmetry analyses of large health datasets [26-28]. Nonetheless, the evolving regulatory landscape—including whether AI should be regulated as a medical device [29,30]—risks neglecting LICs as the capabilities gap widens.

The current regulatory vacuum compounds underrepresentation in clinical trials [31,32], medicines production [33], and the dominance of influential global actors in determining the WHO’s Essential Medicines List [21,34]. Few older adults, Black people, children, women, and Indigenous people participate in clinical trials [35]. Barriers in LICs include limited financial capital, weak regulatory and ethical governance, and an underdeveloped research ecosystem [36]. However, AI’s impact on these inequities could be moderated by early interventions, including in digital twins [37,38] and diverse genetic databanks for training large language models (LLMs) [39]. These remain unexplored from a systems perspective.

Remedies for global inequity in pharmaceuticals include purchase agreements [40,41], which have varied effects [42,43], and in-kind foreign aid or humanitarian supplies [44], which are suboptimal [45,46]. However, pharmacovigilance is less mitigated by these measures: Africa and Asia struggle with controlling substandard or counterfeit medicines [47,48]. External regulatory support comes in 3 forms: direct agreements between LICs and regulators such as the European Medicines Agency, reliance on regulatory standards and methods of advanced economies, and research and capacity-building support from established regulators [49]. In the European Union, these outward measures are informed by its agenda on universal health coverage [50]. European Medicines Agency advises on medicines destined for third countries [51]; the European Council’s Directorate General for Research and Innovation finances development and testing of essential medicines [52]; and the EU requires compliance with WHO quality assurance standards [53]. The effects of these measures are mixed for Africa [52], and inequities may widen with divergent AI regulations [54,55]. Albeit peripheral to pharmacovigilance, a recently established 40-member UN scientific panel on AI [56] promises global coordination.

WHO’s “Medication Without Harm” agenda aims at stemming harm from medicines [57]. This builds on its commitment to pharmacovigilance, heralded by thalidomide in 1961 and later broadened to traditional and herbal medicines, complementary medicines, blood products, and medical devices [58]. The latest guidance emphasizes iatrogenic harm and commends national strategies for public and patient engagement, medicines monitoring, upskilling of health professionals, and establishment of systems for medicines management [57]. These are suitably adapted in rich settings, with the Australian Commission on Safety and Quality in Health Care, for instance, striving to mitigate “medication errors, ADEs and medication-related harm” [59]. Australia’s national strategy informs clinical governance for curbing polypharmacy, mitigating harm from high-risk medicines, and enhancing communication for safe medicines use [59]. Since 1978, the WHO has supported global pharmacovigilance through Sweden’s capabilities in registry and pharmacoepidemiologic methods at the Uppsala Monitoring Center [58]. By July 2023, the Uppsala Monitoring Center–managed global database—“VigiBase”—had received 35 million Individual Case Safety Reports under the WHO Programme for International Drug Monitoring (PIDM), which was established in 1968 [60]. Adding “VigiAccess” to this capability in April 2015 sought to leverage the digital revolution [61]. Underdeveloped capabilities in LICs constrain these efforts.

This viewpoint aims at informing global policy and regulatory practice on AI in pharmacovigilance. It uses clinical, policy, and regulatory practitioner insights to synthesize evidence on ethical, economic, and clinical contours of AI in pharmacovigilance and addresses 3 interrelated questions: what are the moral trade-offs in the introduction of AI in health care, what power dynamics impact the introduction of AI into health systems, and how could AI be used for pharmacovigilance in LICs? The analysis benchmarks Australia and South Sudan as respective examples of advanced and weak regulatory systems, using the WHO’s template for a national pharmacovigilance system. While not generalizable across LICs, this binary comparison of both extremes exposes the chasm that should be bridged in regulatory capabilities for equitable and effective global governance of AI in pharmacovigilance. It considers how AI is getting integrated in Australia’s advanced system, while delineating the constraints and opportunities for LICs through a case study on South Sudan. Moreover, a schema of AI-supported pharmacovigilance systems centers cybersecurity and risk management to underscore the critical role of humans in the loop. Governance challenges are further expounded through critical appraisal of ethical concerns and current applications of AI in pharmacovigilance, mapping these to major themes in the literature. Evaluative frameworks were then compared with a view to moderating these challenges, and conclusions subsequently drawn from a systems perspective. It argues that, although AI is potentially transformative, limited regulatory capacity in LICs constrains pharmacovigilance, contributes to poor health outcomes through substandard medicines, and could worsen global inequity with the adoption of AI. Equitable deployment of AI would benefit from integrated health systems evaluation and infrastructure and regulatory improvements in LICs.

The viewpoint progresses as follows: (1) it delimits WHO’s commendation for a pharmacovigilance system and contrasts its domestication in the rich context of Australia with the low-income context of South Sudan; (2) it examines implications of limited pharmacovigilance in LICs; (3) it considers how AI could redress these challenges; (4) digital health and health systems evaluation frameworks are interrogated in their capacity to mitigate harm from AI; and (5) a case study on South Sudan demonstrates opportunities and constraints in LICs.

WHO recommendations for a pharmacovigilance system stem from consultations among stakeholders, including WHO, Gavi Alliance, expert panels, and national governments [62]. These evolved, under the aegis of the WHO Advisory Committee on the Safety of Medicinal Products, into the minimum requirements encompassing 5 domains: a national pharmacovigilance center, a national spontaneous reporting system, a national database, an advisory committee, and a communication strategy (Figure 1). These integrate to achieve 8 primary goals: promoting pharmacovigilance, signal detection, risk assessment and management, quality control, risk communication, provision of public information, maintenance of drug use information, and identifying unregulated prescription [13,62].

A pharmacovigilance system establishes functionalities around what to report, when to report, how to report, and how to action reports on ADEs or ADRs [14,62]. These are embodied within medicines regulators, such as Australia’s Therapeutic Goods Administration, United States Food and Drug Administration, and South Sudan’s Drug and Food Control Authority (DFCA). Medicines regulators use reviews of Pharmaceutical Risk Assessment Committee reports to update safety warnings, inform evaluations for market authorization, and/or prompt recalls of regulated products [13]. AI promises transformation where tasks involve pattern recognition, but operationalization and validation within existing systems remain challenging [63,64]. Although digitalization may allow for risk assessment, resource gaps in LICs could compound existing challenges.

In rich countries, the WHO’s commendations are readily distilled into competencies. In Australia, for instance, these have evolved into practice-oriented guidelines (Figure 2). By contrast, small-sized and resource-constrained countries must prioritize and leverage scale through regionalization and digital technology [1]. Experience in South Sudan shows limited skills transfer with e-learning platforms for pharmaceutical management [65], suggesting challenges with complex capabilities.

Unlike Australia (Figure 2), weak institutions, poor infrastructure, and dominance of external actors constrain regulatory capacity in South Sudan [66]. Evidently, the majority of signals actioned by DFCA originated from outside its laboratories (Figure 3). This incapacitation is prevalent across LICs [67] and often assuaged with regional capabilities, such as East African Regulatory Affairs Professionals Association (Figure 3) or PIDM (Figure 1). However, amid divergent regulatory preferences [55,68], the likely impact of AI on this regulatory support system remains unexplored.

Poor-quality medicines contribute to the scourge of infectious diseases [69-72] and noncommunicable diseases [73,74]. These are estimated at 35% for falsified antimalarials in Africa [75], 70% for counterfeit drugs in Africa or Asia [48], and 88.4% for substandard antimalarials in Africa—relative to 53% for substandard antimalarials in Southeast Asia [47]. This explains 12,300 malaria-related annual deaths in Nigeria [76] and 8.1% annual excess deaths among Zambian children [72]. Globally, 1 million deaths result from counterfeit medicines, including 200,000 deaths due to fake antimalarials in Africa [48]. Besides health impacts, these impose economic and social costs [77,78], including US $150 million annually in Kinshasa and Katanga regions of the Democratic Republic of the Congo [79], US $193 million in Benin [80], US $31 million in Uganda [81], and US $893 million in Nigeria [76]. This pattern is driven by unaffordable costs of authorized medicines, weak medicines regulations and enforcement, and corruption [82]. They disproportionately impact the poorest wealth quintile [83], and culminate in ineffective treatment, distrust in therapeutics, and curtailed pharmaceutical investments amid competition with counterfeits [46,48].

The nomenclature that describes this scourge—substandard/spurious/falsified/falsely-labeled/counterfeit drugs [48]—doesn’t convey causes of poor quality [84]. However, concern about public harm is implied in “falsified medicine,” while “counterfeit medicine” highlights negation of intellectual property, and “fake medicine” suggests defectiveness [85]. Moreover, “substandard” drugs reflect deviation from specification, while “unregistered or unlicensed” denotes nonapproval by the regulator [67,85]. The significance of nomenclature gains as digitalization of pharmacies amplifies risks [48]. Although evidence is scarce, firmer intellectual property rights enable pharmaceutical monopolies, which may lessen medicines availability and affordability [86].

Brand competition and price adjustment improve affordability of patented drugs [87]. Between 2001 and 2016, the Trade-Related Aspects of Intellectual Property Rights agreement and Public Health improved drug availability in 176 instances in 89 countries, among which 84% covered 14 different conditions [88]. Fluidity in global preferences and definitions explains variations in estimates and regulation of counterfeit medicines [89]. The estimated 10% of ADRs in the WHO global surveillance system obscures 90% of instances of drug ineffectiveness, due to low dose or absence of active ingredient [48], or 94% median rate of underreporting in pharmacovigilance systems [90]. Nonetheless, harm from falsified medicines renders other categories suspect with public harm [47,48,72,75].

Regulations are crucial for good health outcomes, brand integrity, and health-enhancing innovations [47,48,91]. The estimated US $75 to US $200 billion market for counterfeit drugs [92] suggests profit motives that compound limited visibility and strong links to China, India, and Russia, and confound legitimate medicines exports [48,84,93]. Digital methods for curbing fake medicines include use of mobile, radio frequency identification, online verification, blockchain technology, and advanced computation methods [94]. However, 50% of drugs sold over the internet are falsified or counterfeit, which undermines digitalization [48]. Moreover, difficulty with visual distinction between drugs limits digital methods and underscores a role for field methods and advanced laboratory methods [89]. Bolstering these regulatory capabilities demands global cooperation and investments [95].

Current applications of AI are constrained by data quantity and quality [90], but well-trained LLMs could detect ADEs and ADRs potentially missed by a professional or predict occurrence of ADR and/or rank it on a severity scale [96-103]. Digital twinning also enables simulation of clinical trials [37] and could improve trial representativeness and lessen inequity in outcomes and pharmacogenomics [36,104]. These applications, although currently aspirational in use of mobile devices and requiring future research into generalizability, could leverage cheap technologies to complement human capabilities (Figure 4). These potential gains are discernible from a health economics perspective [105]. Wi-Fi and videoconferencing enable digital health care [106,107], which is increasingly feasible in South Sudan [23] and amenable to LLMs [108,109]. Gains could also proceed from data-driven needs assessment and demand-driven financing of pharmaceuticals (Figure 5), which is underdeveloped in South Sudan [24].

These could be further enhanced with policy and regulatory interventions: in Australia, for instance, literacy and technical know-how influence individuals’ access, utilization, and participation in agenda-setting for digital health care [110-112]. The poor, digitally illiterate, or less-educated populations were excluded from related debates, and access gaps emerged along rurality, age, and income categories [110,113]. In the UK, data sharing between Google’s DeepMind Technologies Limited and National Health Service stumbled on privacy and ethical concerns [103]. These could filter into AI, so gaps in current understanding impoverish full appraisal of AI’s value [114]. These could also be pronounced across cultural groups, due to nonrepresentative data (Table 1).

In medicine, knowledge vests doctors with greater power, relative to patients, and professional training in medical law and ethics redresses this imbalance [115]. However, using AI as a decision aid means some decisions are preloaded into software and, therefore, into the economics of health budgets [116], resulting in path dependence or AI determinism. Consequently, policymakers or administrators involved in purchase or health technology assessment, and programmers, become complicit in ethics that obtain [117,118]. The adoption and utilization are also impacted by stakeholder interests within a health system [119]. Moreover, AI could distort the doctor-patient relationship, including anchoring attention away from the patient [120,121]. The resultant physical or psychological barrier could discount empathic care [122]. Furthermore, technology companies are dominant actors in AI and could depersonalize ethics as “virtual sovereignty” obtains [123]. This invokes irony because AI promises advances in personalized medicine [124]. The potential inscrutability and limited traceability with AI introduces a permanency that could amplify on scale and across cultures and jurisdictions [125-132]. Similarly, cultural debasement with the unrepresentative evolution of AI [118,120] undermines the global vision of AI governance (Table 1).

Application of AI in pharmacovigilance encompasses data processing for detection of ADEs and ADRs (57.6%), classification of safety reports (21.2%), extraction of drug-drug reactions (7.6%) or population-based toxicity analysis (7.6%), side-effect projections (3.0%), clinical trial modeling (1.5%), and controlling for uncertainties in diagnostic classifications (1.5%) [17]. Moreover, social media is increasingly mined for ADRs and ADEs and currently limited by data quality [133-135]. Similarly, drug-drug interaction, which increases with polypharmacy, could be mitigated with AI predictions [136,137]. Premarket application could also build a database of side effects [138]. However, due to the complexity of medical text, natural language processing is currently inferior to manual review [139].

Pharmaceutical regulation in South Sudan lags in these capabilities. It is premised on the DFCA Act, 2012, which established the Pharmaceutical Quality Control Laboratory (Chapter X) for quality assurance and disposal of regulated products [140]. However, its legislated functions remain underdeveloped, resulting in DFCA largely enforcing signals from outside its designated laboratory (Figure 3). This impresses DFCA as incapacitated in requisite capabilities, except for communication system or strategy (Figure 1). The varied ways of harnessing AI in pharmacovigilance—including detection of ADEs and ADRs; processing safety reports; extraction of drug-drug interactions; drug toxicity modeling for personalized care; predicting side effects; simulating clinical trials; and diagnostics (Table 2)—could be improved with representative databases and digitalization in LICs. Current divergence in global capabilities and fractured regulatory regime [55,68] call for recalibration of “good AI society” [68].

Evaluation frameworks are currently limited in appraising all contours of AI [165]. Health economic models are outpaced [166], and this compounds limitations with digital health frameworks. “Benefits Management Framework,” for instance, is retrospective [167] and could overlook negative externalities and sociopolitical factors. “Digital Maturity Evaluation Framework” [168] ignores health financing and other levers. Moreover, “Nonadoption, Abandonment, Scale-up, Spread, and Sustainability Framework” [169] is service-oriented and neglects outcomes. Individually, each of the digital health evaluation frameworks is inadequate for capturing the full spectrum of technology investment evaluation, financing, adoption, and impact evaluation within health systems (Table 3).

Similarly, health systems frameworks are individually limited: “Flagship Framework” [170] applies ethical, political, and policy cycle analyses, aiming at system-level diagnostics and strategic solutions, but underappreciates operational functions—the sort that AI addresses. By contrast, “Building Blocks Framework” [171] informs strategic decisions by policymakers and analysts, and operational decisions by program managers. However, it overlooks the dynamics of reforms, as could occur with AI’s adoption. An integrated health system framework—developed by Hsiao and Sparkes [172] and reframed by Sparkes et al [173]—unifies and improves on “Building Blocks Framework” [171] and “Flagship Framework” [170] (Table 4).

As illustrated in Figure 6, the integrated health systems framework considers ethical and political factors, and leadership capacities—which filter into public sector decisions (“control knobs”)—and links these to implications for health systems. These are then evaluated for system-level impacts (eg, efficiency and cost) and individual outcomes (eg, quality, access, health status) (Table 4). Such systems analysis could interrogate assumptions in economic models of AI, enabling determination of where efficiency gains accrue within the health system and potentially mitigate harm (Figure 6). In LICs such as South Sudan, analysis would proceed from a priori ethical consideration and prioritization—such as using AI in advancing equitable, efficient, and effective health care. Hereafter, control knobs such as health financing considerations will be tempered by political decisions around health financing goals and the power of associated technology firms, as well as regulatory capabilities to operationalize acquired technology. These macro-organizational factors have direct influence on the structure of out-of-pocket costs and, therefore, demand for health services. These indirectly influence outcomes such as the quality and efficiency of care and cost management in the health system. An intermediate moderating consideration between macro-organizational factors and outcomes is building blocks. These encompass factors such as drug supplies (as illustrated in Figure 5), information systems, and service delivery, which could leverage AI for better targeting of services.

The foregoing operationalization suggests that the integrated health systems evaluation framework could anticipate system-level impacts of AI. Efficiency gains from AI, for instance, would be filtered through a priori considerations—encompassing ethics, regulatory and financing capabilities, and human resources within health systems. Consequently, potential resource shunting from foundational health systems investment could render procurement of AI unethical, inefficient, and ungovernable for South Sudan. Instead, a sequenced approach prioritizing digital infrastructure and essentials of pharmacovigilance would be determined appropriate course of action. The current limitations of digital evaluation frameworks and insufficiency of individual health system evaluation frameworks could undermine AI global governance, especially as aggressive marketing may confound institutional weakness and result in misaligned health system investments in poor settings.

Few countries in Africa are performing at maturity level 3 for medicines and vaccines regulation [174,175]. This implies regulatory stability and integration in less than 1% of African countries [176]. These include Ghana’s Food and Drug Authority, Tanzania’s Medical Devices Authority, Nigeria’s National Agency for Food and Drug Administration, the Egyptian Drug Authority, and Ethiopian Food and Drug Authority [175,177].

This incapacitation is worse for conflict-affected states like South Sudan, where the majority is impoverished [178] and tropical diseases such as onchocerciasis [179,180] and malaria [181] are prevalent. These conditions suggest it could benefit from innovations that circumvent geographical divides and infrastructure deficits [182]. Low regulatory capacity in South Sudan contributes to poor medicines regulation [183,184]. Nonetheless, it joined PIDM in 2024 [60], and its evolving technological landscape potentiates digitalization (Textbox 1). Digital health applications in South Sudan have aimed at efficiency in primary care [185] and distribution of mosquito nets [186]. However, these could extend to other services [23] and integrate AI. The improved access to internet that is afforded by Starlink for settings with limited infrastructure [187] improves the feasibility for South Sudan. Yet, an unguided procurement of AI in such settings risks “technological solutionism,” which could debase foundational health system investments.

South Sudan’s experience with Remote Access Community Hotspot for Education & Learning demonstrated the significance of relevant skills [188]. Similarly, efficiency gains from digitalization were demonstrated in its experience with Health Pooled Fund Quality-of-Care App, while underscoring the significance of suitable skills in technology adoption [189,190]. Allowing for suitable funding facility [191], programmed adoption [192], and network security constraints within the prevailing digital system [193-195], South Sudan’s experience also highlights the benefits of global integration through which cloud-based storage—which could be housed outside the sovereign jurisdiction and leveraged to support efficient and real-time analysis in regions with limited infrastructure [195-197]. Moreover, the disproportionate influence of global health funding agencies in settings such as South Sudan [198] presents the opportunity for humanitarian services to enhance AI-related health outcomes, while also underscoring that a poorly programmed adoption of AI could misallocate foundational health system investments. As identified in the first report of the UN’s Independent International Scientific Panel on Artificial Intelligence, limited capacity in LICs and skewed data used in LLMs would undermine effective global governance of AI [199]. Relegation of these low-income contexts within a “good AI society” [132] could impoverish global adoption of AI in pharmacovigilance.

This viewpoint sought to interrogate three related questions on moral trade-offs with the introduction of AI into health systems, the power dynamics that shape adoption, and how AI may be leveraged for pharmacovigilance in LICs. The viewpoint has established that AI is beneficially deployable in pharmacovigilance. However, low capacity in LICs constrains adoption of AI and undermines the evolving global regulatory regime. Moreover, an integrated health systems evaluation framework is necessary for anticipating and mitigating potential harms.

The viewpoint highlights emerging divergence in global capabilities in pharmacovigilance as AI gets integrated into advanced health systems while LICs struggle with building essential components of pharmacovigilance. This compounds the ethical concerns around AI, which encompass epistemic issues such as inscrutability and exclusivity of models behind AI; normative concerns such as cultural devaluation and unfair outcomes that segregate against minority groups; and metaethical issues such as the dominance of technology firms and a trust deficit, which render AI less governable. These could compound the current power imbalance in the global health system.

However, a synthesis of current applications of AI in pharmacovigilance uncovers potential gains for LICs, provided there is suitable investment in digital infrastructure in accompaniment of foundational health system investments. These applications range from detection of ADEs and ADRs, to processing of safety reports, to prediction of side effects and drug toxicity, which could guide personalized care. Even in well-resourced settings, these remain limited by data quality and also constrained by underrepresentation of certain population groups in clinical trials. Therefore, effective global governance of AI would demand that these applications are matched to necessary investments while not debasing foundational health system priorities in LICs.

Consequently, a suitable evaluation framework is important for health system planners, regulators, and global institutions of AI governance. The urgency gains with the need to anticipate downstream effects of AI adoption in health systems, especially because the inscrutability of the associated algorithms undermines the effectiveness of human-in-the-loop as a guardrail. Through interrogation of currently dominant digital and health system evaluation frameworks, the viewpoint identifies the suitability of using an integrated health systems evaluation framework to sequence risk identification and mitigation across the breadth of technology adoption. This approach is cognizant of the significant power vested by AI in a programmer or technology firm, which blunts physicians’ capacity to mitigate risk at the point of care. It suggests that, at the point of decision for acquisition, there must be a priori consideration of the ethics that would obtain, the macro-organizational dynamics, and the anticipated governance and managerial needs for the desired individual and system-level outcomes.

Finally, a vignette on South Sudan contrasted a low-capacity context against the advanced setting of Australia, underscoring the importance of primary health system investments, digitalization, and the benefits of global integration. As has been already highlighted in the preliminary report of the UN panel on AI, global imbalance in digital infrastructure and unrepresentative data would impair effective governance of AI. The juxtaposition of these varied contexts in this viewpoint systematically presents considerations for global governance of pharmacovigilance as it evolves with the adoption of AI.