Decision criteria for partial nationalization of pharmaceutical supply chain: A scoping review

Marrone, Patrícia Véras et al. Article Decision criteria for partial nationalization of pharmaceutical supply chain: A scoping review Economies Provided in Cooperation with: MDPI – Multidisciplinary Digital Publishing Institute, Basel Suggested Citation: Marrone, Patrícia Véras et al. (2023) : Decision criteria for partial nationalization of pharmaceutical supply chain: A scoping review, Economies, ISSN 2227-7099, MDPI, Basel, Vol. 11, Iss. 1, pp. 1-21, https://doi.org/10.3390/economies11010025 This Version is available at: https://hdl.handle.net/10419/328652 Standard-Nutzungsbedingungen: Die Dokumente auf EconStor dürfen zu eigenen wissenschaftlichen Zwecken und zum Privatgebrauch gespeichert und kopiert werden. Sie dürfen die Dokumente nicht für öffentliche oder kommerzielle Zwecke vervielfältigen, öffentlich ausstellen, öffentlich zugänglich machen, vertreiben oder anderweitig nutzen. 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If the documents have been made available under an Open Content Licence (especially Creative Commons Licences), you may exercise further usage rights as specified in the indicated licence. https://creativecommons.org/licenses/by/4.0/ Citation: Marrone, Patrícia Véras, Fabio Rampazzo Mathias, Wanderley Marques Bernardo, Marina Feliciano Orlandini, Maria Carolina Andrade Serafim, Maria Lídia Rebello Pinho Dias Scoton, Juliano Marçal Lopes, Sérgio Luiz Pereira, and Eduardo Mario Dias. 2023. Decision Criteria for Partial Nationalization of Pharmaceutical Supply Chain: A Scoping Review. Economies 11: 25. https://doi.org/10.3390/ economies11010025 Received: 3 October 2022 Revised: 23 December 2022 Accepted: 27 December 2022 Published: 12 January 2023 Correction Statement: This article has been republished with a minor change. The change does not affect the scientific content of the article and further details are available within the backmatter of the website version of this article. Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). economies Review Decision Criteria for Partial Nationalization of Pharmaceutical Supply Chain: A Scoping Review Patrícia Véras Marrone 1,* , Fabio Rampazzo Mathias 2, Wanderley Marques Bernardo 3, Marina Feliciano Orlandini 4, Maria Carolina Andrade Serafim 4, Maria Lídia Rebello Pinho Dias Scoton 2, Juliano Marçal Lopes 2, Sérgio Luiz Pereira 2and Eduardo Mario Dias 2,* 1Faculdade de Economia e Administração, and Escola Politécnica de Engenharia, University of São Paulo, São Paulo 05508-010, SP, Brazil 2Electrical Engineering, Escola Politécnica de Engenharia, University of São Paulo, São Paulo 05508-010, SP, Brazil 3Medicine School, University of São Paulo, São Paulo 01246-903, SP, Brazil 4Santos Medical Sciences Faculty, Centro Universitário Lusíada, UNILUS, Santos 11015-300, SP, Brazil *Correspondence: [email protected] (P.V.M.); [email protected] (E.M.D.); Tel.: +55-11-981817800 (P.V.M.); +55-11-30915113 (E.M.D.) Abstract: (1) Background: Any disturbance in the pharmaceutical supply chain (PSC) can disrupt the supply of medicines and affect the efficiency of health systems. Due to shortages in the global pharma supply chain over the past few years and the complex nature of free trade and its limitations when confronted by a major global health and humanitarian crisis, many countries have taken steps to mitigate the risks of disruption, including, for example, recommending the adoption of a plus one diversification approach, increasing safety stock, and nationalizing the medical supply chains. (2) Objective: To scope findings in the academic literature related to decision criteria to guide national policy decisions for the “Partial Nationalization of Pharmaceutical Supply Chain” (PNPSC) from the viewpoints of the three main stakeholders: industry, payers (government and health insurance), and patients. (3) Methods: These consist of a scoping review of the peer-reviewed literature. (4) Results: A total of 115 studies were included. For local manufacturing decisions, five criteria and 15 sub-criteria were identified. Weighting, decision-making, risk assessment, and forecasting were the main data analysis tools applied; (5) Conclusions: The findings could serve as a baseline for constructing PNPSC frameworks after careful adaptation to the local context. Keywords: PSC; pharmaceutical supply chain; healthcare; reshoring; nationalization; local production; API; active pharmaceutical ingredient; pharmaceuticals; drugs; medicines 1. Introduction 1.1. Characterization, Relevance, and Complexity of the PSC According to the IQVIA Institute, drug spending worldwide in 2021 was estimated at USD $1.5 trillion. Eleven (11) markets—USA, Japan, Germany, France, Italy, Spain, UK, Brazil, Canada, South Korea, and Australia—together spent USD $618 billion on medical drugs in terms of hospital and retail sales, amounting to around half of all global medicine expenditure. The global active pharmaceutical ingredient (API) market was valued at USD $300.7 billion in 2021. The API market is segmented on the basis of the molecule, type, type of manufacturer, synthesis, chemical synthesis, type of drug, usage, potency, and therapeutic application (IQVIA 2022). Figure 1is a graphic representation of the PSC showing the different inputs resulting in the manufacture of pharmaceutical specialties distributed in consumer markets. The pharmaceutical industry plays a significant role in providing medicines and saving human lives. The operation of PSC is a crucial element, and any disturbance affecting Economies 2023,11, 25. https://doi.org/10.3390/economies11010025 https://www.mdpi.com/journal/economies Economies 2023,11, 25 2 of 21 supply chains could disrupt the supply of medicines and undermine the efficiency of health systems. Pharmaceutical companies’ supply networks are highly complex, involving the coordination of large numbers of diverse products, markets, processes, and intermediaries in the network, as well as ensuring the timely delivery of products to the right place and to the right customers. Economies 2023, 11, x FOR PEER REVIEW 2 of 22 Figure 1. Generic graphic representation of the PSC. The pharmaceutical industry plays a significant role in providing medicines and saving human lives. The operation of PSC is a crucial element, and any disturbance affecting supply chains could disrupt the supply of medicines and undermine the efficiency of health systems. Pharmaceutical companies’ supply networks are highly complex, involving the coordination of large numbers of diverse products, markets, processes, and intermediaries in the network, as well as ensuring the timely delivery of products to the right place and to the right customers. These companies face a substantial range of risks that Milind and Sriran (2020) described as “…disruptions that occur along the pharmaceutical supply chain, hindering the regular supply of products… mainly caused by a shortage of raw materials, product quality issues, short product life cycles, or sustainable supplier failure… irregularities that may generate lead time loss, late deliveries, backorders, production losses and supply shortages leading to uncertainty in the volume of sales and income”. The pharmaceutical industry is also hampered by fluctuations in demand and uncertainties in the PSC, especially those on the demand side related to quantities and reimbursement prices. PSCs overwhelmingly depend on the rules set by private or public health systems, which not only impact pharma companies’ production and investment decisions, but also play a key role in the criteria used by public health managers when deciding to incorporate a pharmaceutical product into the health system. Stakeholders’ decisions are also directly affected by the complexity and risks of PSC operations. On the supply side, pharma companies need to be able to satisfy the increasing demand for medicines while operating highly complex supply chain structures involving multiple variables and actors. On the demand side, a range of political entities and institutions, often as “intermediate payers”, are involved as stakeholders responsible for decision-making on resource and budget allocations in the healthcare sector. Meanwhile, patients—a third important category of stakeholders in the PSC—need good access to innovative and affordable drugs produced by suppliers (Milind and Sriran 2020). Production fragmentation in the pharma area and other industries increases the systemic risks in supply-chain networks caused by extreme events. Supply and demand uncertainties in the pharmaceutical industry negatively affect its commercial sustainability in both local and non-local markets, and any disruptions in supply chains can seriously undermine the availability of pharmaceutical products in the industry’s target markets. 1.2. Recent Disruptions in the PSC and Actions to Mitigate Them Even before and after the COVID-19 pandemic, the global pharma supply chain has faced shortages in the supply of pharmaceuticals. This is the case for many products that have been listed on the US Food and Drug Administration (FDA) Shortages Webpage (n.d.): https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm, accessed on 11 November 2022. Figure 1. Generic graphic representation of the PSC. These companies face a substantial range of risks that Milind and Sriram (2020) described as “ . . . disruptions that occur along the pharmaceutical supply chain, hindering the regular supply of products . . . mainly caused by a shortage of raw materials, product quality issues, short product life cycles, or sustainable supplier failure . . . irregularities that may generate lead time loss, late deliveries, backorders, production losses and supply shortages leading to uncertainty in the volume of sales and income”. The pharmaceutical industry is also hampered by fluctuations in demand and uncertainties in the PSC, especially those on the demand side related to quantities and reimbursement prices. PSCs overwhelmingly depend on the rules set by private or public health systems, which not only impact pharma companies’ production and investment decisions, but also play a key role in the criteria used by public health managers when deciding to incorporate a pharmaceutical product into the health system. Stakeholders’ decisions are also directly affected by the complexity and risks of PSC operations. On the supply side, pharma companies need to be able to satisfy the increasing demand for medicines while operating highly complex supply chain structures involving multiple variables and actors. On the demand side, a range of political entities and institutions, often as “intermediate payers”, are involved as stakeholders responsible for decision-making on resource and budget allocations in the healthcare sector. Meanwhile, patients—a third important category of stakeholders in the PSC—need good access to innovative and affordable drugs produced by suppliers (Milind and Sriram 2020). Production fragmentation in the pharma area and other industries increases the systemic risks in supply-chain networks caused by extreme events. Supply and demand uncertainties in the pharmaceutical industry negatively affect its commercial sustainability in both local and non-local markets, and any disruptions in supply chains can seriously undermine the availability of pharmaceutical products in the industry’s target markets. 1.2. Recent Disruptions in the PSC and Actions to Mitigate Them Even before and after the COVID-19 pandemic, the global pharma supply chain has faced shortages in the supply of pharmaceuticals. This is the case for many products that have been listed on the US Food and Drug Administration (FDA) Shortages Webpage (n.d.): https://www.accessdata.fda.gov/scripts/drugshortages/default.cfm, accessed on 11 November 2022. In addition to supply shortages, the COVID-19 pandemic exposed the complex nature of free trade and its limitations when confronted by a major global health and humanitarian Economies 2023,11, 25 3 of 21 crisis. The risks of drug supply shortages and disruptions have been suffered by many developing countries traditionally dependent on external suppliers. The inability to meet the growing demand for antiviral agents, for example, caused an unprecedented global shortage of pharmaceutical ingredients, which resulted in higher prices. In recent years, an estimated 80% of all the inputs for medical drug production worldwide were sourced from China and India, while India itself also sourced many ingredients from China according to (Zhu et al. 2020). The lockdown of many Chinese and Indian pharmaceutical producers during the pandemic reduced the supply of key medicines precisely when demand was reaching an all-time high. While China remains a significant supplier of APIs to generic drug manufacturers worldwide, the outbreak of the virus there impeded Chinese pharma factories from working at full capacity to supply the vastly increased demand. To reduce the impact of the lack of strategic medicines for their populations, during the pandemic, some national authorities took deliberate steps to block exports of what they considered to be essential drug-related items. Fearing internal shortages, India, for example, was reported to have stopped exporting at least 26 active drug ingredients normally manufactured there (Rahaman 2021). After the pandemic, this led to a major shift in the Indian Government’s approach to critical medicines production by its decision to promote domestic manufacturing of key starting materials (KSM)/intermediates and APIs, develop its own local sources of materials, and adopt alternative strategies aimed at reducing its dependency on other countries. Meanwhile, the United States FDA, in its turn, belatedly realized that the portfolio of suppliers of many key ingredients to the American market was indeed dependent on this narrow group of Chinese and Indian raw material suppliers. Given that the COVID-19 pandemic exposed the vulnerable modern supply chain logistics to a major disruption in the entire healthcare sector, pharma companies are now, in the post-pandemic era, increasingly aware of the urgent need to build resilient supply chains to weather not only the new strains of the virus, but also to prepare for future events. To mitigate the negative fallout and to protect supply chain operations, several recommendations have been proposed by experts, such as Tang (2006) and Zhu et al. (2020). These include the possibility of pursuing a plus-one diversification approach (i.e., avoidance of dependence on a single supplier), increasing emergency stock, nationalizing medical supply chains, and so on. The main thrust of these and other measures is to seek to alleviate the problems still arising from the crisis and boost the resiliency of pharma companies to withstand potential shortages in the longer term. In the context of this scenario, this scoping review seeks to identify the parameters that must be adopted in a decision of last resort to nationalize production in the event of the inadequacy of the strategies so far proposed for mitigating supply chain disruptions. 1.3. The Option of PSC Partial Nationalization Zhu et al. (2020) have pointed to the need for countries to “shockproof” themselves by reshoring the production of essential medical goods. The “reshoring” approach has gained traction in the USA, India, and other countries, not only to ensure a stable supply of key ingredients, but also to bolster ailing economies. While it is possible for health authorities to encourage the nationalization of off-patent pharmaceuticals (OPPs), providing API and OPP meet the requisite quality criteria, this does not apply to patented pharmaceuticals. OPPs represent between 60% and 80% of the size of the pharmaceutical market in most emerging markets (IQVIA 2022). OPPs are the products that are similar to the innovator product following the expiration of the patent. It is important to remember that the nationalization option stimulated by industrial policy is applicable only to products with expired patents. Given the high costs involved in PSC verticalization, a country’s limited budget for investment, and aspects related to comparative advantages, future attempts by some countries to “shockproof” themselves by nationalizing their pharmaceutical supply chain could well turn out to be partial and confined to a few select APIs. Economies 2023,11, 25 4 of 21 1.4. A Framework to Support a National Strategy for the Selection of Products to Be Nationalized From the standpoint of microeconomics theory, the make-or-buy/vertical integration decision of a firm is the central issue in transaction cost economics. This theory, developed by Williamson (1981), shows how trading partners protect themselves from hazards associated with exchange relationships. The integration of activities by a company is a way to safeguard economic rents, and the institutional arrangements are chosen according to the level of investment protection and lowest transaction cost. There are numerous accounts in the literature describing the efforts and techniques adopted by individual pharmaceutical companies to select drugs to be prioritized from a portfolio of products. Such decision-making processes often depend solely upon the priorities of an individual organization (Hilbert and Blome 2015;Shelanski and Klein 1995;Aurentz et al. 2011). However, we were unable to identify any of the literature referring to methods of prioritization or vertical integration decisions from a ‘collective interest’ viewpoint. This was the gap in the literature regarding this topic of investigation that required a scoping review—a method used to summarize a range of evidence to understand broadly what is known about a phenomenon. The objective of this paper is to scope the three main stakeholders from their PSC perspectives advocated in the academic literature relating to the prospective criteria for the PNPSC. The stakeholders are: industry; payers—government and health insurance; and patients. The identified criteria will be useful to construct a coherent decision-making framework applicable to production decisions in the context of shortage risks, strategic positioning, and pandemic preparedness while considering limited healthcare budgets and the need to minimize environmental impacts. This paper aims to promote a pragmatic approach to industrial policy and point to new areas for policy interventions in the pharmaceutical sector. The paper is structured as follows. Section 2contains the proposed methodology for a scoping review, while Section 3presents the results presenting the key concepts obtained from the literature and responses to the questions raised in the scoping survey. Section 4 focuses on discussion, and Section 5sets out our conclusions. 2. Methodology To facilitate a structured and transparent approach to identifying the criteria for the selection of the products to be nationalized, and contribute to the policy debates, we adopted the method of scoping review for this study. This study was conducted and written according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations (Page et al. 2021). Our work focused on the six phases required for a scoping review: (1) identifying the research question(s); (2) researching relevant studies; (3) selecting studies; (4) mapping, extracting, and tabulating the data; (5) analyzing the data; and (6) presenting the results. The definition of ‘scoping’ reviews is presented below. 2.1. Scoping Review Scoping reviews are a knowledge synthesis method used to summarize a range of evidence to understand broadly what is known about a phenomenon. They differ from systematic reviews in their broad approach to a topic, their purposive sampling frame, and their identification of gaps in the literature (Whittemore et al. 2014). 2.2. Identifying the Research Question The following four research questions originated with the University of São Paulo team of researchers and collaborators. • According to the scientific reference literature, what are the current methods employed for analyzing a product (in any sector) and deciding to manufacture it locally? Economies 2023,11, 25 5 of 21 • What are the criteria and methods practiced by industry and institutions in the health, pharmaceuticals, medical drugs, areas, etc., for selecting pharmaceuticals and APIs for local manufacturing of these products? • What are the criteria used by public health managers in the pharmaceutical sector when deciding to incorporate a product into the health system? •Which are the data analysis tools used to support the above methods? 2.3. Search Strategy With support from experienced researchers, we constructed a comprehensive search strategy for identifying published papers that met the inclusion criteria. Structured search strategies were used in database searches (MedLine, Embase, Google Scholar, and IEEE Xplore) and constructed using PubMed MeSH terms and boolean operators, as described in Figure 2. Economies 2023, 11, x FOR PEER REVIEW 6 of 22 2.2. Identifying the Research Question The following four research questions originated with the University of São Paulo team of researchers and collaborators. • According to the scientific reference literature, what are the current methods employed for analyzing a product (in any sector) and deciding to manufacture it locally? • What are the criteria and methods practiced by industry and institutions in the health, pharmaceuticals, medical drugs, areas, etc., for selecting pharmaceuticals and APIs for local manufacturing of these products? • What are the criteria used by public health managers in the pharmaceutical sector when deciding to incorporate a product into the health system? • Which are the data analysis tools used to support the above methods? 2.3. Search Strategy With support from experienced researchers, we constructed a comprehensive search strategy for identifying published papers that met the inclusion criteria. Structured search strategies were used in database searches (MedLine, Embase, Google Scholar, and IEEE Xplore) and constructed using PubMed MeSH terms and boolean operators, as described in Figure 2. Figure 2. PNPSC Search Strategy. 2.4. Selection Criteria Inclusion and exclusion criteria were developed at the outset of the review. The inclusion criteria covered (a) primary and secondary studies, as well as (b) articles that directly answered the research questions (‘systematic review’) or that would assist a broader understanding of what is known about a phenomenon (‘scoping review’). Papers addressing the following subjects were included: decision-making about investments in the production of and the payment (reimbursement) arrangements for pharmaceuticals in particular countries. Congressional abstracts, letters, editorials, unavailable full-text, and studies presenting subjects in (Figure 3) were excluded. MedLine and Embas e: (Health resource OR Health technology assessment OR HTA OR Health technologies assessment OR Healthcare technologies assessment) AND (Resource allocation OR Resource allocations OR Resource designation OR allocation efficiency OR Resources allocation OR Decision-making OR Decision-making OR Health priority OR Priority setting OR Health policies OR Healthcare policy OR Healthcare policies OR Complexity management OR Portfolio management OR Product data management OR production complexity OR criteria) AND (API OR active pharmaceutical ingredients OR active principle OR finished pharmaceutical product OR finished pharmaceutical products OR active substance OR active constituent OR bulk active OR pharma product OR pharmaceutical products OR pharmaceuticals OR orphan drug OR orphan drugs) IEEE Xplorer: (Portfolio OR Resource allocation* OR production OR criteria OR pipeline OR Manufacture) AND active pharmaceutical ingredients OR active principle finished pharmaceutical product OR finished pharmaceutical products active substance OR active constituent OR bulk active ORpharma product OR pharmaceutical products OR pharmaceuticals) Google Scholar: Health technology assessment, Health priority resource allocation “active pharmaceutical ingredients” Figure 2. PNPSC Search Strategy. 2.4. Selection Criteria Inclusion and exclusion criteria were developed at the outset of the review. The inclusion criteria covered (a) primary and secondary studies, as well as (b) articles that directly answered the research questions (‘systematic review’) or that would assist a broader understanding of what is known about a phenomenon (‘scoping review’). Papers addressing the following subjects were included: decision-making about investments in the production of and the payment (reimbursement) arrangements for pharmaceuticals in particular countries. Congressional abstracts, letters, editorials, unavailable full-text, and studies presenting subjects in (Figure 3) were excluded. 2.5. Study Selection The electronic databases were monitored for the peer-reviewed literature, using filters for English, Spanish, and Portuguese language articles, but none for publication dates. The lack of studies in Spanish and Portuguese selected in our scoping review is due to the non-compliance of such studies to the pre-established inclusion criteria. The studies nevertheless underwent the same selection process as those in English. Reference lists of relevant papers and conference abstracts were manually searched, results were imported into the Reference Manager Zotero TM , and duplicate citations were removed. A detailed breakdown of citations identified from the various information sources is presented in Figure 3(Zotero n.d.). The titles and abstracts that appeared to meet the inclusion/exclusion criteria, or where there was any uncertainty, were screened for relevance and duplication. The full-text articles were then downloaded in Zotero and then screened. Economies 2023,11, 25 6 of 21 Economies 2023, 11, x FOR PEER REVIEW 7 of 22 Figure 3. PRISMA flowchart of the PNPSC study selection process. 2.5. Study Selection The electronic databases were monitored for the peer-reviewed literature, using filters for English, Spanish, and Portuguese language articles, but none for publication dates. The lack of studies in Spanish and Portuguese selected in our scoping review is due to the non-compliance of such studies to the pre-established inclusion criteria. The studies nevertheless underwent the same selection process as those in English. Records identified from: MedLine (n = 8,590) Embase (n = 1,244) Google Scholar (n = 980) IEEE Xplorer (n = 488) Records removed before screening: Duplicate records removed (n = 121) Records removed for other reasons (n = 680) Records screened (n = 10,501) Records excluded (n = 9,517) Reports sought for retrieval (n = 984) Reports not retrieved (n = 584) Full-text articles assessed for eligibility (n = 400) Full-text arti cl e s e xcl uded, wi th reasons (n=285) Main reasons: - Process, chemical and industrial quality aspects - Pharmacovigilance - Regulatory issues - National industrial policies - Environmental risk in the use and dosage of medicines -Pharmaceutical R&D - Pricing policies and payment models for medicines - Specific treatments or diseases - Health professionals’ role in pharma industry Studies included in review (n = 115) Identification of studies via databases and registers Identification Screening Included Industry's Perspective (n = 72 ) Answers to: Question 1: (n=0) Qu es ti o n s 1 a nd 2: (n=3 ) Question 2: (n=34) Question 3: (n=27) Qu es ti o n s 2 a nd 3: (n=8 ) Question 4 (n=0) Government's Perspective Reports of included studies (n = 35 ) Answers to: Question 1: (n=0) Question 2: (n=9) Questions 2 and 3: (n=3) Questions 2, 3 and 4; (n=1) Question 3: (n=20) Question 4 (n=2) Patient's Perspective (n = 6 ) Answers to: Question 1: (n=0) Questions 2 and 3: (n=1) Question 3: (n=5) Question 4 (n=0) Studies purely related to pharma production decision methods that use data analysis tools (n = 10 ) Answers to: Question 1: (n=0) Questions 2 and 4: (n=2) Question 3: (n=0) Figure 3. PRISMA flowchart of the PNPSC study selection process. Economies 2023,11, 25 7 of 21 2.6. Charting, Extracting, and Tabulating the Data The researchers charted key data from the papers selected for inclusion in the scoping study using a data charting form that involved sifting through and sorting data according to key aspects or concepts. The key aspects or concepts were identified a priori and recorded under the following headings: articles evaluated “Yes” or “No”, were selected, or excluded; reason for selection or exclusion; main findings; and conclusion. 2.7. Data Extraction and Synthesis The data were analyzed qualitatively using a general inductive approach. Three researchers carefully examined extracted data (raw text from the tables) to familiarize themselves with the content and potential themes. Initial coding categories representing ‘meaning units’ (themes) were then created. The themes (industry perspective; government perspective; patient perspective), were created to represent the views of the main PSC with influence on the production, consumption, or reimbursement decisions of the PNPSC, as well as the choice of analytical tools (decision models) used to analyze PSC data. Subthemes were added as they emerged during the selection procedure. Each article was also classified according to topic areas (e.g., “Perspective”) and categories withineach area (e.g., “Key Concept”). The synthesis was conducted using acascadingprocess, and the lists of areas and categories were updated as more articles were reviewed. Papers were first checked by a researcher to determine applicability to the research questions, perspectives, and categories. Subsequently, all articles were fully reviewed a second time to check alignment with the respective research question (Questions 1–4). The registered protocol is available at Zenodo (Supplementary Materials). Consulting stakeholders and experts who might propose additional references and/or insights not found in the literature are optional in scoping reviews (Levac et al. 2010), but in the case of the present review, the authors decided not to consult them. 3. Results By October 2021, a total of 11,302 potentially eligible peer-reviewed article listings were identified in the electronic databases. Of these, 121 duplicates were identified and automatically eliminated, and 680 titles were manually eliminated, including congress abstracts, letters, and editorials. 10,501 articles were finally evaluated by title, of which 984 were selected by title, 400 by abstract, and 115 by full text. The selected 115 were each analyzed regarding the theme of PNPSC in terms of the three main perspectives and their respective initial key concepts identified in the literature, as represented in Figure 4: Economies 2023, 11, x FOR PEER REVIEW 9 of 22 Figure 4. Key concepts related to the PNPSC identified in the literature review. 3.1. Analysis and Data Synthesis Table 1 presents the responses to the questions identified in the scoping survey in line with the various criteria and sub-criteria. 3.1.1. What Are the Current Methods Employed in the Scientific Reference Literature for Analyzing and Deciding on the Local Manufacture of a Product (From Any Sector)? Three journal articles addressed methods for analyzing and deciding on the local manufacture of a product in any sector. The main concern highlighted related to economic (supply side) factors or criteria, with the two main sub-criteria identified as “Minimization of raw material and manufacturing costs” and “Maximizing return on investment, profit maximization, and product portfolio optimization”. 3.1.2. What Are the Criteria of the Methods Used by Industry and Institutions (Health, Pharmaceuticals, Drugs, or Inputs Areas) for Selecting Pharmaceuticals and APIs for Local Manufacturing? The selection of pharmaceuticals and APIs for local manufacturing involves a wide range of factors or criteria including economic (supply side), economic (demand for API), technical feasibility, environmental impact, and strategic vision. Ten sub-criteria were identified under this scope in 44 journal articles as being relevant to the decisions of pharmaceutical firms to pursue local manufacturing or not. (Table 1, Question 2 column, highlighted in grey). 3.1.3. What Criteria Are Used by Public Health Pharmaceutical Sector Managers to Incorporate a Product into the Health System? 63 journal articles carried relevant references to the criteria employed by public health practitioners. We selected the scope of four decision factors or criteria: economic (supply side); economic (demand for API); environmental impact; and strategic vision. Concern with “Technical feasibility” was referred to only in the case of vaccine manufacturing. Among the factors or criteria affecting decisions, 12 sub-criteria were identified as being adopted by public health managers. The major concerns were with the projected impact on payers’ budgets in the short/medium term. Other relevant sub-criteria were value assessment of the drug-related to its health gain, affordability and availability, patient preferences, criteria for the subsidization of medicines, environmental risk caused by emissions and waste generation, avoidance of supply interruption risks, risks of shortages, ensuring access to essential and disease-related medicines, and, finally, innovation incentives/scientific spillover (Table 1). Perspective Key Concepts Industry Perspective Industry and Enterprise; Strategy; Volume and Scale; Portfolio and Prioritization; Pricing and Price; Value; Environment and Hazard; Active Pharma Ingredient (API), Production and Manufacturing; Supply; Risk, Future and Trends; Research, Unmet need, Development, and Innovation; Investment; Patents & Intellectual Property; Competitivity. Government Perspective Essential Medicines; Shortage; Crises and Emergencies; Funding and Subsidies; Costs; Plan and Prioritization; Criteria and Decision. Patient Perspective Patient; Affordable; Reimbursement and Payment. Figure 4. Key concepts related to the PNPSC identified in the literature review. Economies 2023,11, 25 8 of 21 Figure 3shows the PRISMA flow chart of the review process and the number of articles at each stage. 3.1. Analysis and Data Synthesis Table 1presents the responses to the questions identified in the scoping survey in line with the various criteria and sub-criteria. 3.1.1. What Are the Current Methods Employed in the Scientific Reference Literature for Analyzing and Deciding on the Local Manufacture of a Product (From Any Sector)? Three journal articles addressed methods for analyzing and deciding on the local manufacture of a product in any sector. The main concern highlighted related to economic (supply side) factors or criteria, with the two main sub-criteria identified as “Minimization of raw material and manufacturing costs” and “Maximizing return on investment, profit maximization, and product portfolio optimization”. 3.1.2. What Are the Criteria of the Methods Used by Industry and Institutions (Health, Pharmaceuticals, Drugs, or Inputs Areas) for Selecting Pharmaceuticals and APIs for Local Manufacturing? The selection of pharmaceuticals and APIs for local manufacturing involves a wide range of factors or criteria including economic (supply side), economic (demand for API), technical feasibility, environmental impact, and strategic vision. Ten sub-criteria were identified under this scope in 44 journal articles as being relevant to the decisions of pharmaceutical firms to pursue local manufacturing or not. (Table 1, Question 2 column, highlighted in grey). 3.1.3. What Criteria Are Used by Public Health Pharmaceutical Sector Managers to Incorporate a Product into the Health System? 63 journal articles carried relevant references to the criteria employed by public health practitioners. We selected the scope of four decision factors or criteria: economic (supply side); economic (demand for API); environmental impact; and strategic vision. Concern with “Technical feasibility” was referred to only in the case of vaccine manufacturing. Among the factors or criteria affecting decisions, 12 sub-criteria were identified as being adopted by public health managers. The major concerns were with the projected impact on payers’ budgets in the short/medium term. Other relevant sub-criteria were value assessment of the drug-related to its health gain, affordability and availability, patient preferences, criteria for the subsidization of medicines, environmental risk caused by emissions and waste generation, avoidance of supply interruption risks, risks of shortages, ensuring access to essential and disease-related medicines, and, finally, innovation incentives/scientific spillover (Table 1). Economies 2023,11, 25 15 of 21 scoping review indicate that multicriteria decision-making theory seems to fit better to decision problems that address collective interests. This was the first effort to scope findings in the academic literature related to decision criteria to guide national policy decisions for the PNPSC from the viewpoints of the three main stakeholders: industry, payers (government and health insurance), and patients. Drug shortages constitute a major public health crisis. This paper presents the first comprehensive review of the available literature on PNPSC-related aspects, which provides a set of criteria on which to build a framework for a shared understanding of the national strategies that can be adopted. Stakeholders, such as industry, health systems, and patients, can benefit from the planning of private and public investments to bring about the nationalization of the supply chain for a selection of drugs needed to deal with epidemics while maintaining an innovative and competitive environment conducive to avoiding drug shortages that negatively affect the delivery of health care. While not all countries can afford to “nationalize the supply chain”, it is a valid strategy for countries or groups of countries with certain levels of population, income, technological development, and innovation capacity. Although the criteria may be adjusted over time, a dependable list of criteria will undoubtedly help establish consistent decision-making, accountability, and transparency in the pharmaceutical market. In this spirit, it is hoped that the present paper will serve as a tool to aid communication between stakeholders. Funding: This research was funded by CC&T—“Center for Science, Technology and Development for innovation in Medicine and Health: InLab Inova HC” “Research project on integrated health information systems, including large databases, big data, artificial intelligence, predictive models, technologies advanced technologies for diagnosis, prevention and treatment in medicine”—Technological Innovation Center, Inova HC—Hospital das Clínicas of the Faculty of Medicine of USP—Polytechnic School of Engineering at USP (POLI), grant number 2021/11905-0. Supplementary Materials: The registered protocol of this scoping review is available at Zenodo, DOI https://zenodo.org/record/6977394#.YwEcG3bMKUk. The data that support the findings of this study are available from the corresponding author, upon reasonable request (Zenodo n.d.). Informed Consent Statement: Not applicable. Data Availability Statement: Not applicable. Acknowledgments: Professional writing and editorial assistance was provided by John Penney (Brasília, DF, Brazil). Conflicts of Interest: The authors declare no conflict of interest. References Abbott, Frederick M. 2004. Managing the Hydra: The Herculean Task of Ensuring Access to Essential Medicines. SSRN Scholarly Paper ID 1913965. Rochester: Social Science Research Network. Afsharmanesh, Gita, Gholamhossein Mehralian, and Farzad Peiravian. 2020. Attributes Development for Pharmaceutical Subsidization: A Qualitative Study. Iranian Journal of Pharmaceutical Research: IJPR 19: 203. [CrossRef] Ahn, Kyungseop. 2017. 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