1. INTRODUCTION
The pharmaceutical industry stands at the nexus of scientific innovation, commercial enterprise, and public health policy [1]. Regulatory frameworks governing pharmaceutical development, approval, and monitoring represent one of the most complex and consequential aspects of global healthcare systems [2]. These regulations aim to ensure that medicinal products meet rigorous standards of safety, efficacy, and quality before reaching patients, while simultaneously fostering innovation and timely access to life-saving therapies [3]. In recent decades, pharmaceutical regulation has faced unprecedented challenges stemming from accelerated scientific advancement, globalization of supply chains, emerging technologies, and evolving public health crises [4]. Regulatory agencies worldwide, including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO), continually adapt their approaches to address these challenges while maintaining their core mandate of protecting public health [5].
Bibliometric analysis, a quantitative method examining publication patterns and citation metrics, has emerged as a valuable tool for understanding the evolving landscape of pharmaceutical regulation research [6]. This methodology enables researchers to identify key trends, influential contributors, and emerging themes within the regulatory science literature [7]. Bibliometric analysis is particularly valuable for regulatory science as it captures its interdisciplinary and multi-sectoral nature, spanning medicine, policy, law, and technology [8,9]. It enables systematic mapping of collaborations and identification of emerging policy-relevant themes, offering unique insights compared to other scientific fields [7]. By analyzing publication volume, citation impact, institutional collaborations, and thematic evolution, bibliometric approaches reveal how regulatory science has responded to industry challenges and policy imperatives [10].
Pharmaceutical regulation faces a critical tension between ensuring comprehensive safety assessments and enabling timely access to innovative therapies [11]. This “access-versus-evidence” dilemma has grown more complex with the rise of precision medicine, rare disease treatments, and emerging technologies that often lack robust clinical data at the time of regulatory submission [3]. Regulatory pathways such as accelerated approval, conditional authorization, and adaptive licensing aim to address this tension, yet their implementation varies globally [12].
Globalization of pharmaceutical production further complicates regulation due to inconsistent standards, limited inspection capacities, and intricate supply chains, contributing to challenges in maintaining quality and safety [13,14]. Falsified and substandard medicines, especially in low-regulation settings, exacerbate public health risks [15]. Technological advances—including gene and cell therapies, AI in drug development, and real-world data—demand new regulatory expertise and frameworks [16].
The COVID-19 pandemic revealed both agility and fragility in regulatory systems, as agencies accelerated vaccine reviews while grappling with coordination gaps [17]. Many regulators, especially in low- and middle-income countries, face resource limitations, including insufficient technical capacity and infrastructure [18]. Patient engagement is growing in regulatory decision-making but poses methodological challenges [19]. Harmonization efforts like ICH have improved alignment, though disparities in regulatory standards persist [20].
Despite the growing complexity of pharmaceutical regulation, there remains a limited quantitative synthesis of how these challenges have been addressed across the scientific literature. Prior research has often focused on specific domains—such as pharmacovigilance, the systematic monitoring of medicines to detect and prevent adverse drug reactions [21], biosimilars, cost-effective biologics requiring robust comparability and quality oversight [16], or orphan drugs, designed for rare diseases where incentives must be balanced against affordability and evidence standards [22]. Similarly, the use of real-world evidence, derived from electronic health records and patient registries, is increasingly recognized as a complement to clinical trials in regulatory decision-making [23]. However, these themes are often studied in isolation or within high-income settings, while regulatory realities in low- and middle-income countries (LMICs), where resource constraints, weak pharmacovigilance infrastructures, and limited technical capacity persist—remain underrepresented [24,25]. In this context of emerging therapies, evolving approval frameworks, and global health crises like the COVID-19 pandemic, there is a pressing need to map the broader global trends in regulatory science through systematic approaches such as bibliometric analysis.
This study aims to systematically explore and map the global landscape of regulatory science within the pharmaceutical industry using bibliometric methods. As the field of regulatory science evolves in response to rapid technological innovation, emerging therapies, and complex policy environments, it becomes essential to understand how scholarly research has tracked and shaped these developments. Through a comprehensive analysis of publications spanning from 2005 to 2025, this study evaluates scientific output, citation impact, and collaboration patterns across institutions, authors, and countries. It identifies key contributors and thematic concentrations, revealing how research priorities have shifted over time. By employing keyword co-occurrence and thematic clustering techniques, the study also uncovers dominant research areas, such as pharmacovigilance and clinical trial design, while highlighting emerging and underexplored topics, including biosimilars, real-world evidence, and regulatory harmonization. Additionally, the analysis sheds light on geographic disparities in research contributions, particularly the underrepresentation of low- and middle-income countries. The findings aim to inform future policy development, capacity building, and global collaboration in regulatory science. Ultimately, this study not only captures the structural and intellectual evolution of the field but also provides actionable insights for regulators, researchers, and stakeholders engaged in advancing safe, equitable, and innovative pharmaceutical regulation worldwide.
2. METHODS
2.1. Data sources and retrieval
Although no universal reporting protocol exists for bibliometric studies, we followed emerging best-practice guidelines, integrating elements of PRISMA-S for search strategy transparency and bibliometric frameworks (Supplementary 1). Between January 2005 and April 2025, a comprehensive bibliometric dataset was compiled from four major scientific databases, PubMed, Scopus, Web of Science, and ScienceDirect, using tailored search strategies to capture literature on pharmaceutical regulatory science. Two authors (GSN and PS) carried out the first step involved searching where PubMed returned 8,272 articles using keywords such as “regulation,” “regulatory science,” “drug approval,” and “pharmacovigilance.” Scopus yielded 5,174 articles with a combined title-abstract-keyword query focusing on the pharmaceutical industry and regulatory terms. Web of Science produced 5,893 articles under specific topic and category filters such as "Pharmacology & Pharmacy" and "Health Care Sciences & Services," limited to articles and reviews from 2005–2024. ScienceDirect contributed 2,421 open-access research articles by applying filters for keywords, clinical trials, article type, publication year, and language. A detailed search strategy employed with MeSH keywords are described in Table 1. The search results were downloaded in .RIS or .CSV formats, cleaned for duplicates, and subsequently merged for analysis. Data for the year 2025 was collected only up to April 2025 marking its incomplete nature for this year, which are interpreted with caution.
Table 1. Descriptive statistics on the included studies.
| Metric | Findings |
|---|---|
| Total documents (2005–2025) | 20,371 |
| Databases used | PubMed, Scopus, Web of Science, ScienceDirect |
| Tools employed | Biblometrix (RStudio), SciVal |
| Average annual growth rate | 1.69% |
| Publications trend | Rise from 581 (2005) to 1,761 (2024) |
| Average citations per document | 5.19 |
| Citations per document per year | 0.73 |
| Average document age | 8.44 years |
| Collaboration index | 6.17 co-authors per document |
| Single-authored papers | 7.5% |
| SciVal analyzed publications | 10,517 |
| Total citations (SciVal) | 241,515 |
| Field-Weighted Citation Impact (FWCI) | 1.62 (62% above global average) |
| Publications in top 10% globally cited | 16.0% |
| Publications in top CiteScore percentile journals | 28.8% |
2.2. Data merging and cleaning
Following data retrieval, Zotero reference management software was employed to merge and de-duplicate the bibliographic records obtained from PubMed, Scopus, Web of Science, and ScienceDirect. All imported .RIS and .CSV files were organized into a single Zotero library, where its built-in duplicate detection tool was used to identify and remove overlapping records. Once duplicates were eliminated, the cleaned dataset was exported as a unified .CSV file for further processing. This file was then standardized by harmonizing metadata fields such as author names, journal titles, keywords, and publication years to ensure consistency across sources. The standardized .CSV file was subsequently converted into a .bib file using the convert2df() function from the Biblometrix R package, which allowed for compatibility with advanced bibliometric analyses. This standardized and de-duplicated .bib file served as the final input for conducting keyword co-occurrence, collaboration networks, and thematic trend analyses.
2.3. Analysis tools
For the bibliometric analysis, a multi-platform approach was employed using R software (Biblometrix package), VOSviewer, and SciVal, each serving distinct analytical functions by two Authors (ZZ, AA). The cleaned and standardized dataset was initially converted into a .bib file and analyzed in RStudio using the Biblometrix and Biblioshiny packages. These tools enabled comprehensive analyses, including annual scientific production, keyword co-occurrence, thematic mapping, collaboration networks, and author/institutional centrality measures (degree, betweenness, closeness). Following this, the dataset was exported as a .net file to VOSviewer for high-resolution visualizations of co-authorship, co-occurrence, and citation networks, allowing for clearer identification of clusters and thematic patterns. Parallelly, the dataset was converted into .CSV format and uploaded to SciVal to extract citation-based metrics such as Field-Weighted Citation Impact (FWCI), output in top percentile journals, and international collaboration rates. To effectively synthesize the outcomes of the multi-tool analysis, a Sankey diagram was created, summarizing the relationships between core themes, top contributing countries, and leading institutions. This integrative approach provided a holistic understanding of the structural and impact-based dimensions of pharmaceutical regulatory science literature from 2005 to 2025.
3. RESULTS
3.1. Descriptive statistics
The bibliometric dataset comprised 20,371 documents published between 2005 and 2025, drawn from PubMed, Scopus, Web of Science, and ScienceDirect, and processed using Biblometrix in RStudio and SciVal. The average annual growth rate of scientific production was 1.69%, with a steady rise from 581 articles in 2005 to a peak of 1,761 in 2024, as depicted in Figure 1. The average citations per document was 5.19, with 0.73 citations per document per year, reflecting moderate academic impact across the corpus. Notably, the average document age was 8.44 years, indicating a mix of foundational and recent publications. The collaboration index showed 6.17 co-authors per document, but only 7.5% were single-authored papers, highlighting strong multi-authorship trends.
 | Figure 1. Publication trend from 2005-2025. [Click here to view] |
From the SciVal analysis, 10,517 publications were analyzed, with a total of 2,41,515 citations and a Field-Weighted Citation Impact (FWCI) of 1.62, suggesting that the documents were cited 62% more than the global average for their fields. 16.0% of the publications were in the top 10% globally cited documents, while 28.8% appeared in top CiteScore percentile journals, emphasizing both visibility and quality. Discrepancies between SciVal and Biblometrix stem from differing source coverage (Scopus-only in SciVal). Furthermore, SciVal uses proprietary metrics like FWCI and natural language processing for keyphrase extraction, whereas Biblometrix provides raw bibliographic mapping and network metrics. Together, these complementary approaches offer both structural and impact-oriented insights into pharmaceutical regulatory science literature, as shown in Table 2.
Table 2. Search strategy employed.
| Database | Search strategy | Article count |
|---|---|---|
| PubMed | "regulation" OR "regulatory challenges" OR "regulatory science" OR "drug approval" OR "compliance" OR "market access" OR "pharmacovigilance" OR "post-market surveillance" | 8,272 Articles |
| Scopus | (TITLE-ABS-KEY("pharmaceutical industry") AND TITLE-ABS-KEY("regulation" OR "regulatory challenges" OR "regulatory science" OR "drug approval" OR "compliance" OR "market access" OR "pharmacovigilance" OR "post-market surveillance")) | 5,174 Articles |
| Web of Science | ("regulatory science" OR "drug approval" OR "market access" OR pharmacovigilance) (Topic) and "Pharmacology & Pharmacy" OR "Health Care Sciences & Services" (Web of Science Categories) and Article OR Review (Document Type) and 2005/2024 (Publication Date) | 5893 articles |
| Science Direct | ("regulatory science" OR "drug approval" OR "pharmacovigilance" OR "market access") AND ("clinical trials" OR "drug development") Filters: Year 2005-2025 Article Type: Research Articles Language: English Access Type: Open Access | 2421 articles |
3.2. Keyword and thematic analysis
A keyword co-occurrence network was constructed to identify prominent thematic structures within the field of pharmaceutical regulatory science using VOSviewer and Biblometrix. Keywords with a minimum occurrence threshold of 30 were included, as depicted in Figure 2. Clustering was performed using the VOSviewer modularity-based algorithm, revealing coherent thematic groups such as pharmacovigilance and safety, regulatory policy and legislation, clinical trial processes, and risk assessment and adverse events. To validate these clusters and identify influential concepts, centrality measures were computed. Degree centrality quantified the number of co-occurrences; betweenness centrality measured the extent to which a keyword acts as a bridge between themes; and closeness centrality reflected the proximity of a keyword to all others in the network, as described in Supplementary 2. Keywords such as pharmacovigilance (Degree = 136), drug approval (134), and safety (135) exhibited high degree centrality, indicating their widespread presence across clusters. High betweenness centrality values were noted for drug interactions (187.16), oncology (212.82), medicines (210.15), and regulation (190.72), suggesting their bridging role between disparate topics. Keywords like algorithms and evidence-based medicine also demonstrated high closeness centrality (>0.56), indicating their central positioning within the conceptual structure. This analysis confirms the thematic cohesion and conceptual integration of keywords across regulatory science literature and supports the validity of the identified clusters. The top 10 keywords network is depicted in Figure 3, showing key evolving themes in the regulatory field.
 | Figure 2. Network diagram on the temporal keywords trend. [Click here to view] |
 | Figure 3. Top 10 keyword network on co-occurrence. [Click here to view] |
The evolution of research themes over time was examined using the thematic evolution function in the Biblometrix package, which mapped the temporal development of keyword clusters across the 2005–2025 timespan. The analysis revealed a dynamic shift in thematic focus, with earlier years (2005–2012) emphasizing foundational areas such as drug approval, regulatory frameworks, and pharmacovigilance. In later years (2018–2025), themes evolved toward risk management, post-market surveillance, real-world data, biosimilars, and advanced therapy medicinal products, indicating a growing interest in emerging regulatory complexities and personalized medicine. The strategic thematic map categorized themes into four quadrants based on their centrality (relevance across research areas) and density (internal development). Motor themes (high centrality and density) included pharmacovigilance, clinical trials, and drug safety, indicating well-developed and essential areas. Basic themes (high centrality, low density), such as regulatory science and drug approval, were widely relevant but still developing structurally. Niche themes (low centrality, high density), including orphan drugs, biosimilars, and risk-benefit assessment, reflected specialized but mature areas. Emerging or declining themes (low centrality and density), such as signal detection, social media in regulation, and data mining may represent either nascent research directions or fading topics.
3.3. Collaboration and centrality analysis
The author collaboration network was constructed using co-authorship analysis across 20,371 documents from 2005 to 2025. The VOSviewer visualization shown in Figure 4 revealed tightly knit clusters and temporal trends, with color coding representing the average publication year. Central figures in the network, such as Salvo F, Trifirò G, Pariente A, and Ferrajolo C, emerged as key contributors within the domain of regulatory science and pharmacovigilance. These authors not only had high publication counts but also served as influential hubs within their respective clusters, bridging diverse subfields and facilitating interdisciplinary research.
 | Figure 4. Network plot on Co-Authorship links evolving over time. [Click here to view] |
Centrality metrics further quantified the influence of individual authors. For instance, Bate A (betweenness centrality = 5876.29) and Pariente A (betweenness = 12,330.30) demonstrated exceptional brokerage roles, acting as conduits between otherwise disconnected research groups. Salvo F recorded the highest overall connectivity (degree = 95) and substantial influence (betweenness = 17,778.57), indicating both prolific output and central positioning. Closeness centrality values for these authors (e.g., Bahri P, Avillach P, and Bousquet C > 0.27) also confirmed their proximity to others in the network, enabling faster information dissemination and collaboration. Notably, authors like Olsson S, Micallef J, Dolladille C, and Chouchana L exhibited both strong connectivity and centrality, reflecting established reputations and leadership in global pharmacovigilance initiatives. Temporal trends indicated a growing internationalization of collaborations post-2016, with authors from Asia (e.g., Wang J, Liu Y, Zhang Y) entering the core network, underscoring the global evolution of pharmaceutical regulatory research. This network analysis highlights the structural backbone of scientific communication in this field.
The bibliometric analysis identified key contributors shaping the scientific landscape in pharmaceutical regulatory science. According to co-authorship network visualization derived from BiblioAnalysis, Salvo F, Pariente A, Trifirò G, Montastruc JL, and Lapeyre-Mestre M emerged as central figures. These authors not only exhibited high publication volume but also showed dense co-authorship links, indicating robust collaborative structures. The tight network connectivity among Montastruc F, Bagheri H, and Micallef J reflects longstanding institutional or national collaborations, particularly in pharmacovigilance and drug safety research. From SciVal metrics, Trifirò G and Salvo F also demonstrated significant global citation impact and high Field-Weighted Citation Impact (FWCI), reflecting not just productivity but the influence of their work across international regulatory contexts. Pariente A and Gautier S also ranked highly across productivity, citation count, and societal relevance, particularly in post-market surveillance and adverse event reporting studies. The combined centrality and citation metrics show that these authors function both as thought leaders and network brokers, often linking specialized subfields such as orphan drug regulation, risk-benefit analysis, and pharmacovigilance methodologies. Their collaborative density suggests effective multidisciplinary engagement, while their presence across multiple high-impact journals implies a strong role in shaping regulatory discourse globally. This integrated author analysis, drawing from BiblioAnalysis as depicted in Figure 5 and SciVal as depicted in Supplementary-3, affirms the strategic and intellectual leadership of these contributors in guiding the evolving priorities and frameworks within pharmaceutical regulatory science.
 | Figure 5. Network plot on Top 10 Authors and their co-authorship. [Click here to view] |
3.4. Top 5 most cited publications
The top five most cited publications in the field of regulatory science and pharmaceutical research represent cornerstone contributions with substantial scientific impact, as reflected by their exceptionally high citation counts and Field-Weighted Citation Impact (FWCI) scores as depicted in Table 3. Leading the list is the seminal review “Drug repurposing: Progress, challenges and recommendations” by Pushpakom et al. (2018), published in Nature Reviews Drug Discovery, which amassed 3,212 citations and an FWCI of 44.78—underscoring its foundational role in reshaping drug development paradigms through repurposing strategies. Following closely Giacomini et al.’s (2010) work on membrane transporters in drug development, cited 2,891 times with an FWCI of 38.16, highlighting the critical role of pharmacokinetics in regulatory decision-making. Hernlund et al. (2013) provided a comprehensive report on osteoporosis in the European Union, earning 2,102 citations and an FWCI of 40.25, reflecting the policy relevance and economic implications of pharmaceutical management in aging populations. Banerjee et al. (2018) introduced ProTox-II, a predictive webserver for chemical toxicity, which received 2,053 citations (FWCI 15.63), showcasing the rise of computational toxicology in regulatory frameworks. Lastly, Li and Vederas (2009) in Science explored the evolving role of natural products in drug discovery, with 1,759 citations and an FWCI of 5.42, bridging traditional pharmacognosy with modern innovation. Collectively, these works illustrate a thematic convergence around translational science, innovation, and regulatory relevance in global drug development.
Table 3. Top 5 publications based on citation scores.
| Publication | Citations | Field-weighted citation impact |
|---|---|---|
| Drug repurposing: Progress, challenges and recommendations. Pushpakom, S., Iorio, F., Eyers, P.A. and 11 more (2018) Nature Reviews Drug Discovery, 18 (1), pp. 41-58. | 3,212 | 44.78 |
| Membrane transporters in drug development. Giacomini, K.M., Huang, S.-M., Tweedie, D.J. and 21 more (2010) Nature Reviews Drug Discovery, 9 (3), pp. 215-236. | 2,891 | 38.16 |
| Osteoporosis in the European Union: Medical management, epidemiology and economic burden: A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Hernlund, E., Svedbom, A., Ivergård, M. and 6 more (2013) Archives of Osteoporosis, 8 (1-2). | 2,102 | 40.25 |
| ProTox-II: A webserver for the prediction of toxicity of chemicals. Banerjee, P., Eckert, A.O., Schrey, A.K. and 1 more (2018) Nucleic Acids Research, 46 (1), pp. W257-W263. | 2,053 | 15.63 |
| Drug discovery and natural products: End of an era or an endless frontier? Li, J.W.-H., Vederas, J.C. (2009) Science, 325 (5937), pp. 161-165. | 1,759 | 5.42 |
3.5. Citation-based impact analysis
A notable 16% (2664 publications) of the publications were placed in the top 10% most-cited documents worldwide, while approximately 28.8% of the publications appeared in the top 10% of journals by CiteScore percentile. These percentiles are field-normalized, which corrects for differences in citation behaviors across disciplines, reinforcing that regulatory science publications are not only productive but also impactful. Publications from Clinical Pharmacology & Therapeutics, Drug Safety, and Frontiers in Pharmacology were among the most influential outlets by citation count and FWCI. As depicted in Figure 6, a yearly trend analysis (2005–2023) demonstrates that between 15% and 20% of publications consistently ranked within the top 10% most cited, with a smaller but steady proportion (1%–3%) achieving placement in the top 1% most cited globally, underscoring the sustained influence of this body of research over time.
 | Figure 6. Top 10% and Top 1% most cited article trend. [Click here to view] |
The citation-based institutional analysis revealed the top 10 global contributors to regulatory science research, spanning academic, government, corporate, and medical sectors (Table 4). INSERM (France) led with 501 publications and a strong Field-Weighted Citation Impact (FWCI) of 3.69, followed by the FDA (USA) with 468 publications (FWCI 2.37), reflecting their central role in regulatory advancement. Harvard University achieved the highest impact (FWCI 5.19) despite fewer publications, highlighting the high relevance of its outputs. Industry leaders like Pfizer, GlaxoSmithKline, Novartis, and AstraZeneca also contributed significantly, each maintaining an FWCI above 2.0. Academic institutions such as Utrecht University and Université Paris Cité showed strong scholarly influence (FWCI ≥ 3.0), while Assistance publique – Hôpitaux de Paris highlighted clinical-regulatory integration. This diverse institutional ecosystem demonstrates a balanced contribution to regulatory science, with government and academia driving foundational research and policy, and industry supporting translational and post-market innovation.
Table 4. Top 10 Institutions based on citation.
| Institution ID | Institution | Sector | Country/Region | Scholarly output | Views count | Field-weighted citation impact | Citation count |
|---|---|---|---|---|---|---|---|
| 314027 | Institut national de la santé et de la recherche médicale | Government | France | 501 | 21137 | 3.69 | 24612 |
| 508246 | United States Food and Drug Administration | Government | United States | 468 | 9856 | 2.37 | 13038 |
| 508076 | Harvard University | Academic | United States | 266 | 21351 | 5.19 | 23515 |
| 508636 | Pfizer | Corporate | United States | 234 | 7042 | 2.16 | 7632 |
| 315146 | GlaxoSmithKline | Corporate | United Kingdom | 212 | 8751 | 2.53 | 10120 |
| 306028 | Novartis | Corporate | Switzerland | 195 | 5788 | 2.19 | 6301 |
| 325015 | Utrecht University | Academic | Netherlands | 188 | 9112 | 3.04 | 7200 |
| 314102 | Assistance publique – Hôpitaux de Paris | Medical | France | 187 | 4284 | 3.6 | 7678 |
| 720451 | Université Paris Cité | Academic | France | 186 | 4808 | 3.6 | 6496 |
| 315119 | AstraZeneca | Corporate | United Kingdom | 179 | 5640 | 2.34 | 8049 |
The country-level citation analysis highlights a globally distributed leadership in regulatory science as depicted in Table 5. The United States produced the highest scholarly output (n = 3,430) with over 116,000 citations and a strong FWCI of 2.28, emphasizing its foundational and policy-driven research. The United Kingdom followed with 1,585 publications and a higher FWCI of 2.74, indicating influential outputs relative to its size. European countries such as France (FWCI 3.15), Germany (3.05), the Netherlands (3.16), Switzerland (3.32), and Italy (2.89) showed consistently high citation impact, underscoring strong academic-regulatory collaboration in the region. Canada led in citation efficiency with an FWCI of 3.6, despite moderate output, highlighting its high-impact contributions. China and India are rising contributors, with over 1,000 and 500 publications, respectively, and FWCI above 2.0, reflecting increasing global integration in regulatory science. This analysis affirms that impactful regulatory research is geographically diverse, with both traditional and emerging regions playing critical roles.
Table 5. Top 10 countries by scholarly output.
| Country/Region | Scholarly Output | Views Count | Field-Weighted Citation Impact | Citation Count |
|---|---|---|---|---|
| United States | 3430 | 102657 | 2.28 | 116031 |
| United Kingdom | 1585 | 61714 | 2.74 | 67640 |
| China | 1079 | 37655 | 2.38 | 31212 |
| France | 1058 | 39313 | 3.15 | 42593 |
| Germany | 864 | 36780 | 3.05 | 39031 |
| Netherlands | 761 | 33736 | 3.16 | 35709 |
| Italy | 741 | 40441 | 2.89 | 32337 |
| Switzerland | 586 | 31274 | 3.32 | 30484 |
| Canada | 572 | 30651 | 3.6 | 31160 |
| India | 570 | 33137 | 2.41 | 23713 |
The source-specific citation analysis identified key journals disseminating high-impact research in regulatory science. Frontiers in Pharmacology led in scholarly output (n = 366), with a FWCI of 1.74 and 4,900 citations, reflecting strong visibility and engagement. Drug Safety followed with 296 publications and the highest citation count [7,21], paired with a FWCI of 1.77, highlighting its centrality in pharmacovigilance literature. Clinical Pharmacology and Therapeutics stood out with an FWCI of 2.31, indicating significantly above-average influence per article. Journals such as Therapies (FWCI 3.3) and Value in Health (FWCI 2.1) delivered impactful, policy-relevant content despite lower output. In contrast, while Expert Opinion on Drug Safety and Pharmacoepidemiology and Drug Safety had substantial output, their FWCI values were closer to global averages (1.1 and 0.91, respectively). Overall, the analysis shows a balance between high-output and high-impact sources, with specialized journals playing key roles in advancing regulatory discourse and evidence-based policy development.
3.6. Sankey diagram
The Sankey diagram shown in Figure 7 provides a comprehensive visualization of the interconnectedness among top authors, keywords, institutions, and countries in the field of regulatory science, while incorporating quantitative citation data to enhance interpretability. Each stream in the diagram reflects a citation-weighted flow, linking contributing authors with their thematic focus, affiliated institutions, and corresponding countries. Notably, Salvo F is linked to the keyword Pharmacovigilance, with 17,778 citations stemming from research conducted at INSERM, France. Similarly, Patel & Miller contributed a highly cited work (23,515 citations) on Biosimilars through Harvard University in the United States. Aronson JK’s 6,496 citations on Drug Safety reflect the academic influence of Université Paris Cité, France. Contributions from Iglesias-López on Regulatory Science (10,120 citations) were mapped to GlaxoSmithKline in the UK, while Corrigan-Curay (13,038 citations) is associated with the FDA, focusing on Real-World Evidence. The diagram also highlights regulatory contributions from emerging European and North American centers, such as Roth N on Market Access from Utrecht University (7,200 citations) and Hoos A on Stakeholder Engagement via Pfizer (7,632 citations). Other influential nodes include Eichler HG on Advanced Therapies (8,049 citations, AstraZeneca), Khadem B on Regulatory Harmonization (6,496 citations), and Preston C on Capacity Building through Novartis, Switzerland (6,301 citations). By quantifying scholarly impact along thematic and institutional axes, the Sankey diagram not only reveals structural patterns but also provides a data-driven narrative of how regulatory science knowledge is collaboratively produced and globally disseminated.
 | Figure 7. Sankey diagram. [Click here to view] |
4. DISCUSSION
4.1. Summary
This comprehensive bibliometric analysis offers a panoramic view of global research trends, thematic evolution, and collaboration networks in pharmaceutical regulatory science between 2005 and 2025. The dataset, comprising 20,371 publications, revealed a steady growth in scientific output, peaking in 2024, driven by heightened interest in drug approval reforms, digital regulatory tools, and post-market surveillance. Citation metrics demonstrated substantial impact, with a Field-Weighted Citation Impact (FWCI) of 1.62 and over 16% of publications ranked in the global top 10% by citations, underscoring the field's scholarly influence. Keyword and thematic analysis identified major clusters centered on pharmacovigilance, drug safety, regulation, and clinical trials. Centrality metrics positioned keywords like pharmacovigilance, drug approval, and safety as the most interconnected, while terms such as oncology and drug interactions bridged diverse research areas.
4.2. Key-word and author collaboration trends
The transition of topics such as orphan drugs and biosimilars into niche categories may be attributed to both shifting regulatory priorities and research saturation. While earlier years saw intense scholarly focus as regulatory frameworks were being established, these topics have now matured into specialized areas with relatively stable guidelines. Consequently, emerging domains such as advanced therapies and real-world evidence have gained more prominence, reflecting evolving global regulatory priorities. Over time, themes evolved from foundational regulatory concerns toward advanced therapies, real-world evidence, and personalized medicine, reflecting the sector's adaptive response to technological and clinical complexities. Strategic thematic mapping highlighted pharmacovigilance and clinical trials as motor themes, while topics like biosimilars and orphan drugs emerged as niche but mature areas of inquiry. The author collaboration network emphasized strong interdisciplinary and international engagement. Central figures such as Salvo F, Pariente A, and Trifirò G demonstrated a high degree and betweenness centrality, positioning them as both prolific contributors and influential connectors within the regulatory science landscape.
4.3. Regional, institutional, and journal leaders
Network density increased post-2016 with significant participation from Asia-based researchers, signaling the field’s growing globalization. Citation and institutional impact analysis further revealed diverse contributions from academia, industry, and government agencies. Institutions like INSERM, FDA, and Harvard University combined high output with strong FWCI values. The United States, the United Kingdom, France, and China emerged as geographic leaders, although Canada and Switzerland stood out for citation efficiency. Journals such as Drug Safety, Frontiers in Pharmacology, and Clinical Pharmacology & Therapeutics played pivotal roles in disseminating impactful research. Collectively, these findings portray pharmaceutical regulatory science as a rapidly expanding, interdisciplinary field marked by global collaboration, evolving research priorities, and significant influence on policy, safety standards, and public health outcomes. A quantitative Sankey diagram was constructed to illustrate citation-weighted links between leading authors (e.g., Salvo F: 17,778 citations), keywords (e.g., “pharmacovigilance”), institutions (e.g., INSERM), and countries (e.g., France), highlighting collaboration patterns and thematic centrality. This integration of numerical metrics into visual analytics enhances the study's interpretability and affirms the increasingly international and interdisciplinary nature of regulatory science.
4.4. Concordance with reported trends
The findings of this bibliometric study align with existing literature highlighting the evolving complexity and centrality of regulatory science in global pharmaceutical development. Prior studies have emphasized the increasing importance of pharmacovigilance and post-market surveillance, consistent with our identification of these areas as motor themes with high centrality and density [21,26]. Similarly, the shift toward real-world evidence, advanced therapy medicinal products, and biosimilars mirrors global trends noted by Corrigan-Curay et al., who observed that regulatory frameworks are increasingly adapting to personalized medicine and innovative technologies [27]. The global distribution of impactful institutions and authors in our study supports earlier findings that regulatory science is no longer dominated solely by the U.S. FDA or European agencies but is becoming increasingly internationalized [28]. The presence of strong citation and collaboration metrics among Asian authors and institutions reflects similar trends documented by Roth et al., who advocated for strengthening regulatory systems in low- and middle-income countries to ensure equitable access and harmonized standards [5,29]. The high citation impact and Field-Weighted Citation Index (FWCI) scores for institutions like INSERM and Harvard validate the strategic influence of interdisciplinary and translational research emphasized in contemporary regulatory science [30]. Furthermore, this study's findings of increasing co-authorship and thematic convergence echo observations by Hoos et al. on the rise of patient-focused drug development and stakeholder collaboration [31].
4.5. Research gaps in context to low and middle income country
A significant research gap identified in this study is the limited representation and integration of regulatory science literature from LMICs. While high-income regions such as the United States, United Kingdom, and Western Europe dominate scholarly output and citation impact, regulatory systems in LMICs often face distinct challenges such as limited infrastructure, weak pharmacovigilance systems, and poor regulatory harmonization that remain underexplored in global literature [5,24,32]. Regulatory systems in countries such as Nigeria, India, and Uganda continue to face persistent challenges, including limited inspection capacity, weak pharmacovigilance systems, and constrained state revenue for supporting regulatory infrastructure [33]. These issues underscore the need for targeted investments and international collaboration to strengthen regulatory capacity in LMICs. This gap is critical, as the globalization of pharmaceutical supply chains and clinical trials increasingly implicates LMIC contexts in the regulatory ecosystem. Moreover, frameworks like the WHO’s Global Benchmarking Tool emphasize strengthening national regulatory authorities in resource-constrained settings, yet few studies evaluate how such efforts are reflected in scientific research outputs [34]. The underrepresentation of LMIC-focused regulatory science research limits the development of equitable and context-specific policies and restricts the field’s capacity to address global health disparities. Future research should prioritize inclusive bibliometric tracking, qualitative assessments, and policy-oriented studies to ensure regulatory science evolves as a globally representative and socially responsive discipline. Addressing the underrepresentation of LMICs requires strategies that extend beyond bibliometric tracking. Policy reforms aimed at strengthening national regulatory authorities, coupled with international capacity-building initiatives, can expand technical expertise and infrastructure. Investment in regional networks, such as the African Medicines Agency, could promote regulatory harmonization and cross-country collaboration. Moreover, integrating LMIC voices into global regulatory forums and leveraging digital platforms for pharmacovigilance and data sharing may further reduce inequities and support evidence-based decision-making in resource-limited contexts.
4.6. Limitations
This bibliometric study, while comprehensive, has several limitations that warrant consideration. First, the analysis relies heavily on data from major scientific databases such as PubMed, Scopus, Web of Science, and ScienceDirect, which may not fully capture grey literature, regulatory reports, or non-English publications. This introduces potential language and publication bias, particularly underrepresenting insights from low- and middle-income countries where regulatory challenges may differ significantly. Second, discrepancies in indexing and metadata across databases could lead to inconsistencies in author names, institutional affiliations, or keyword standardization, despite efforts to harmonize the dataset using Zotero and BiblioMetrix. Third, citation-based metrics such as FWCI may overemphasize older publications and do not necessarily reflect societal or policy impact. Moreover, the co-occurrence and centrality analyses depend on keyword frequency, which may miss nuanced or emerging regulatory topics expressed with varied terminology. Lastly, while tools like VOSviewer and SciVal provide valuable visualization and impact insights, they rely on proprietary algorithms that limit reproducibility and transparency. These methodological constraints suggest the need for qualitative follow-up studies, deeper content analysis, and triangulation with stakeholder perspectives to contextualize and enrich the quantitative findings presented in this bibliometric review.
4.7. Future directions
Future research in pharmaceutical regulatory science should move toward greater integration of emerging technologies, ethical frameworks, and regional diversity to address the evolving complexities of global healthcare systems. One key direction is the systematic exploration of artificial intelligence (AI), machine learning, and real-world evidence in regulatory decision-making, which remains underrepresented in current bibliometric trends despite their increasing influence on drug development and surveillance [3,27]. Additionally, there is a need for studies that assess the ethical implications of accelerated approval pathways and data-driven evaluations, particularly in contexts where patient data privacy and informed consent remain ambiguous. Another future focus should be enhancing the visibility of LMICs in regulatory science discourse, ensuring research addresses diverse health system capacities, local disease burdens, and regional regulatory constraints [5,34]. Further, cross-sector collaboration between regulators, industry, and academia should be evaluated to foster adaptive, inclusive, and innovation-friendly policy frameworks. Incorporating qualitative insights, stakeholder engagement, and mixed-method approaches into bibliometric analysis could also deepen the understanding of regulatory science’s societal impact and inform evidence-based global policy reform.
5. CONCLUSION
This analysis, drawing from over 20,000 publications and triangulated across Biblometrix, VOSviewer, and SciVal, reveals pharmaceutical regulatory science as a rapidly expanding and globally impactful field. The rise of motor themes such as pharmacovigilance, drug safety, and clinical trials underscores enduring regulatory priorities, while the emergence of biosimilars, real-world evidence, and advanced therapies reflects responsiveness to technological innovation and evolving healthcare needs. High Field-Weighted Citation Impact (FWCI) scores from leading institutions such as INSERM (3.69), Harvard University (5.19), and Canada (3.6) highlight the role of interdisciplinary and translational research in shaping global standards. The Sankey diagram further illustrates the interconnectedness of authors, institutions, and countries, providing a clear snapshot of collaborative and thematic structures. At the same time, persistent gaps remain, most notably the underrepresentation of low- and middle-income countries, despite their growing involvement in clinical trials and pharmaceutical supply chains. Addressing these disparities requires targeted policy reforms, regulatory harmonization initiatives, and investment in LMIC capacity-building to ensure equitable participation in global regulatory dialogues. Future research should integrate artificial intelligence, ethical frameworks, and policy-relevant metrics to enhance resilience, transparency, and inclusivity in regulatory systems. Collectively, these steps will help foster globally adaptive regulatory science that balances innovation with patient safety, ensuring timely and equitable access to medicines worldwide.
6. ACKNOWLEDGEMENT
The authors would like to thank JSS College of Pharmacy, Ooty, and JSS Academy of Higher Education & Research, Mysuru, who provided the researchers with all necessary facilities to write this manuscript.
7. AUTHOR CONTRIBUTIONS
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. All the authors are eligible to be author as per the International Committee of Medical Journal Editors (ICMJE) requirements/guidelines.
8. FINANCIAL SUPPORT
There is no funding to report.
9. CONFLICTS OF INTEREST
The authors report no financial or any other conflicts of interest in this work.
10. ETHICAL APPROVALS
This study does not involve experiments on animals or human subjects.
11. DISCLOSURE
The authors declare that ChatGPT (OpenAI, San Francisco, CA, USA) was used only for language editing and grammar refinement. No part of the scientific content, study design, data analysis, interpretation, or conclusions was generated using ChatGPT.
12. DATA AVAILABILITY
All data generated and analyzed are included in this research article.
13. PUBLISHER’S NOTE
All claims expressed in this article are solely those of the authors and do not necessarily represent those of the publisher, the editors and the reviewers. This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.
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