Equity in the Pandemic Treaty: Access and Benefit-Sharing as a Policy Device or a Rhetorical Device?

Equity is a foundational concept for the new World Health Organization (WHO) Pandemic Treaty. WHO Member States are currently negotiating to turn this undefined concept into tangible outcomes by borrowing a policy mechanism from international environmental law: "access and benefit-sharing" (ABS).

Selective modulation of monocyte and neutrophil responses with activated protein C in preterm infants.

BACKGROUND: Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease, and necrotizing enterocolitis. Activated protein c (APC) has shown positive immunomodulatory effects. OBJECTIVES: We aimed to study neutrophil and monocyte function in response to lipopolysaccharide (LPS) and APC stimulation ex vivo in preterm infants <32 weeks gestation over the first week of life compared to neonatal and adult controls. METHODS: Peripheral blood was taken on day 1, 3, and 7 and stimulated with LPS in the absence or presence of APC. Expression of toll-like receptor 4 (TLR4) and CD11b and reactive oxygen intermediate (ROI) release from neutrophils and monocytes was examined by flow cytometry. RESULTS: LPS induced neutrophil ROI in adults and preterm infants and was significantly reduced by APC. Baseline and LPS-induced monocyte ROI production in preterm neonates was increased compared to adult and term controls. Neutrophil TLR4 baseline expression was higher in term controls compared to preterm infants. CONCLUSION: Increased systemic ROI release in preterm infants may mediate tissue damage, ROI was reduced by APC. However, due to the high risk of hemorrhage further examination of APC mutant forms with anti-inflammatory but decreased anticoagulant properties is merited.

The COVID-19 Pandemic and the TRIPS Waiver: Patents and Flexibility.

The World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) provides for global minimum standard patents. These patents potentially limit access to products and processes for the surveillance, tracking, diagnosis and treatment of COVID-19. A possible solution currently under consideration is a TRIPS waiver of the implementation, application and enforcement for the prevention, containment or treatment of COVID-19. This article addresses the ways that TRIPS patents might be mediated including through TRIPS flexibilities. The article argues that there are sufficient means of derogating from patents (and potentially copyright, industrial designs and undisclosed information), although they alone will not resolve the access problems. The article concludes that the key patent problem is the transfer of know-how and that developing new ideas about addressing these patent know-how transfers is the presently unaddressed challenge.

Sovereignty, sanctions, and data sharing under international law.

Pathogen samples and scientific data are bargaining chips in a global argument about who gets what in a pandemic.

The future of zoonotic risk prediction.

In the light of the urgency raised by the COVID-19 pandemic, global investment in wildlife virology is likely to increase, and new surveillance programmes will identify hundreds of novel viruses that might someday pose a threat to humans. To support the extensive task of laboratory characterization, scientists may increasingly rely on data-driven rubrics or machine learning models that learn from known zoonoses to identify which animal pathogens could someday pose a threat to global health. We synthesize the findings of an interdisciplinary workshop on zoonotic risk technologies to answer the following questions. What are the prerequisites, in terms of open data, equity and interdisciplinary collaboration, to the development and application of those tools? What effect could the technology have on global health? Who would control that technology, who would have access to it and who would benefit from it? Would it improve pandemic prevention? Could it create new challenges? This article is part of the theme issue 'Infectious disease macroecology: parasite diversity and dynamics across the globe'.

COVID-19 Tests the Limits of Biodiversity Laws in a Health Crisis: Rethinking "Country of Origin" for Virus Access and Benefit-sharing.

The COVID-19 pandemic raises serious questions about the operation of international agreements for accessing and sharing viruses potentially delaying emergency responses. The access and benefit-sharing (ABS) frameworks under the United Nations' Convention on Biological Diversity and its Nagoya Protocol apply to the collection and use of the COVID-19 pathogen SARS-CoV-2. These frameworks aim to ensure countries of origin reap some of the benefits from the use of their resources. Using real-world examples, we demonstrate conceptual and definitional ambiguities relating to "country of origin" that make not only operationalising the ABS scheme for biodiversity conservation and sustainable use objectives difficult but may also undermine public health emergency responses. Understanding how COVID-19 fits (or does not fit) within ABS laws is a valuable exercise for international policy-makers trying to determine how best to operationalise pathogen ABS, an issue currently under examination at the World Health Organization and critical to responding to pandemics.

Building a biofoundry.

A biofoundry provides automation and analytics infrastructure to support the engineering of biological systems. It allows scientists to perform synthetic biology and aligned experimentation on a high-throughput scale, massively increasing the solution space that can be examined for any given problem or question. However, establishing a biofoundry is a challenging undertaking, with numerous technical and operational considerations that must be addressed. Using collated learnings, here we outline several considerations that should be addressed prior to and during establishment. These include drivers for establishment, institutional models, funding and revenue models, personnel, hardware and software, data management, interoperability, client engagement and biosecurity issues. The high cost of establishment and operation means that developing a long-term business model for biofoundry sustainability in the context of funding frameworks, actual and potential client base, and costing structure is critical. Moreover, since biofoundries are leading a conceptual shift in experimental design for bioengineering, sustained outreach and engagement with the research community are needed to grow the client base. Recognition of the significant, long-term financial investment required and an understanding of the complexities of operationalization is critical for a sustainable biofoundry venture. To ensure state-of-the-art technology is integrated into planning, extensive engagement with existing facilities and community groups, such as the Global Biofoundries Alliance, is recommended.

Pediatric Intensive Care: Immunomodulation With Activated Protein C ex vivo.

Objective: Sepsis is major cause of morbidity and mortality in the Pediatric Intensive Care Unit (PICU). PICU patients may develop transient immune deficiency during sepsis. Activated Protein C (APC) has significant anti-inflammatory and cytoprotective effects. Clinical trials of APC in adult sepsis initially showed improved outcome but recent trials showed no benefit in adults or children. We aimed to assess the effects of APC treatment on innate immune responses in children. Design and Subjects: We compared neutrophil and monocyte responses to lipopolysaccharide (LPS) with and without APC treatment in PICU patients at the time of evaluation for sepsis compared with healthy adults and age-matched pediatric controls. We used flow cytometry to examine cell activation (CD11b expression), function [intracellular reactive oxygen intermediate (ROI) release] and LPS recognition [Toll like Receptor 4 (TLR4) expression]. Results: PICU patients had significantly decreased protein c levels and LPS responses compared with adult and pediatric controls for all parameters. APC reduced LPS-induced neutrophil PICU TLR4 and adult ROI (p < 0.05). PICU non-survivors had increased LPS induced neutrophil and monocyte ROI production vs. survivors which was significantly reduced by APC. Conclusion: PICU patients demonstrate significantly reduced endotoxin reactivity which may predispose them to sepsis and alter effective antibacterial responses. APC reduces LPS-induced ROI production in adults and may have a role in treating severely compromised PICU patients especially given that newer APC forms are associated with decreased bleeding risk and enhanced anti-inflammatory effects.

Access by Design, Benefits if Convenient: A Closer Look at the Pandemic Influenza Preparedness Framework's Standard Material Transfer Agreements.

Policy Points Securing access to pathogen samples for research purposes is crucial for pandemic preparedness and responding to infectious disease outbreaks. The Pandemic Influenza Preparedness Framework (PIP Framework) is the only pathogen-specific international access and benefit-sharing (ABS) instrument. This analysis reveals that during an influenza pandemic, the PIP Framework will safeguard access to virus samples but may not be as effective in delivering the associated benefits, like vaccines and antivirals, to countries in need. The PIP Framework's deficiencies must be addressed before an influenza pandemic and before this ABS model is extended to other human pathogens. CONTEXT: The World Health Organization (WHO) adopted the Pandemic Influenza Preparedness Framework (PIP Framework) after being forced to grapple with the demands of developing countries for the fairer distribution of vaccines and antivirals created using influenza viruses isolated from within their territories. Though adopted as a nonbinding resolution, the PIP Framework has been praised for its novel legal approach to access and benefit-sharing (ABS), using Standard Material Transfer Agreements (SMTAs) to create binding terms and conditions on both providers and users of PIP biological materials. The PIP Framework's SMTA1 regulates the movement of influenza viruses with human pandemic potential through the WHO's Global Influenza Surveillance and Response System (GISRS) as it operates to monitor the spread of seasonal influenza and detect the emergence of pandemic strains. Member States give consent to the WHO to transfer their materials to third parties under the terms of a negotiated SMTA2. The SMTA2 details benefits such as vaccines and antivirals to be made available to the WHO for distribution in the event of an influenza pandemic. METHODS: I analyzed the PIP Framework, its SMTAs, and secondary sources to determine whether the PIP Framework will effectively function as an ABS instrument during an influenza pandemic. FINDINGS: The SMTAs do not create any direct or binding agreements between Member States and third-party recipients of influenza viruses. In the lead-up to and during a pandemic, the SMTA1 secures access to influenza viruses for the WHO, and the SMTA2 secures access for commercial users of virus samples, but the SMTA2 may be ineffective in securing tangible benefits for the sovereign providers of those materials. CONCLUSIONS: As the international community starts to consider how to best regulate access to nonpandemic influenza pathogen samples, it is imperative that we first address the shortcomings of the only pathogen-specific international ABS instrument available, and we should do so before it is put to the ultimate test.

Never Mind the Science, Here's the Convention on Biological Diversity: Viral Sovereignty in the Smallpox Destruction Debate.

Since the eradication of smallpox was declared in 1980, debate has ensued over what to do with the remaining stocks of the causative agent, variola virus. For more than three decades the World Health Organization has resolved to destroy the virus isolates, now maintained in high-security laboratories in the Russian Federation and the United States, and each time the deadline has been deferred. The legal facets of this debate have been largely overlooked. As genetic resources, all viruses fall within the scope of the United Nations' Convention on Biological Diversity (CBD) that provides for the fair and equitable sharing of the benefits arising out of the utilisation of genetic resources. This article examines the possible ownership scenarios for variola viruses and concludes that the conservation principles of the CBD and the ambiguous sovereign status of individual isolates may preclude the destruction of the world's remaining variola stocks.

Who Are Indigenous and Local Communities and What Is Traditional Knowledge for Virus Access and Benefit-sharing? A Textual Analysis of the Convention on Biological Diversity and Its Nagoya Protocol.

The United Nations' Convention on Biological Diversity (1992) (CBD) has become the focal point for the regulation of traditional knowledge (TK) held by indigenous and local communities (ILCs). The legally binding CBD is bolstered by a supplementary, non-binding agreement, The Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization (2010) (Nagoya Protocol). Both instruments create the conditions for the access and benefit-sharing (ABS) of genetic resources, and for TK associated with those resources. There has been no consideration as to how TK might factor into virus ABS arrangements. Most of the literature on these issues relates to how the TK provisions of the CBD and Nagoya Protocol should be implemented; there is little guidance as to how to interpret the text itself. This article provides a textual analysis of all provisions of the CBD and Nagoya Protocol that relate to TK and the interests of ILCs. The analysis clarifies the differences in scope between the two instruments and will provide some insights as to how to interpret key terms, particularly indigenous and local communities, traditional knowledge and traditional knowledge associated with genetic resources. This is critical to understanding the obligations that apply to accessing virus samples that are regulated as genetic resources under the CBD.

An Educational Intervention Optimizes the Use of Arterial Blood Gas Determinations Across ICUs From Different Specialties: A Quality-Improvement Study.

BACKGROUND: Overuse of arterial blood gas (ABG) determinations leads to increased costs, inefficient use of staff work hours, and patient discomfort and blood loss. We developed guidelines to optimize ABG use in the ICU. METHODS: ABG use guidelines were implemented in all adult ICUs in our institution: three medical, two trauma-surgery, one cardiovascular, and one neurosurgical ICU. Although relying on pulse oximetry, we encouraged the use of ABG determination after an acute respiratory event or for a rational clinical concern and discouraged obtaining ABG measurements for routine surveillance, after planned changes of positive end-expiratory pressure or Fio2 on the mechanical ventilator, for spontaneous breathing trials, or when a disorder was not suspected. ABG measurements and global ICU metrics were collected before (year 2014) and after (year 2015) the intervention. RESULTS: We saw a reduction of 821.5 ± 257.4 ABG determinations per month (41.5%), or approximately one ABG determination per patient per mechanical ventilation (MV) day for each month (43.1%), after introducing the guidelines (P < .001). This represented 49 L of saved blood, a reduction of $39,432 in the costs of ICU care, and 1,643 staff work hours freed for other tasks. Appropriately indicated tests rose to 83.4% from a baseline 67.5% (P = .002). Less than 5% of inappropriately indicated ABG determinations changed patient management in the postintervention period. There were no significant differences in MV days, severity of illness, or ICU mortality between the two periods. CONCLUSIONS: The large scale implementation of guidelines for ABG use reduced the number of inappropriately ordered ABG determinations over seven different multidisciplinary ICUs, without negatively impacting patient care.

Open Access DNA, RNA and Amino Acid Sequences: The Consequences and Solutions for the International Regulation of Access and Benefit Sharing.

This article addresses how open access to DNA, RNA and amino acid sequences might be reconciled with the benefit-sharing obligations under the United Nations' Convention on Biological Diversity and its Nagoya Protocol, the Food and Agriculture Organization of the United Nations' International Treaty on Plant Genetic Resources for Food and Agriculture, and the World Health Organization's Pandemic Influenza Preparedness Framework for the Sharing of Influenza Viruses and Access to Vaccines and Other Benefits. Tracing the evolution of open access databases, the article posits models for reconciling open access and benefit sharing; the article concludes, however, that none of the proposed solutions ­ monitoring and tracing, the contract model, and the copyright and database right model ­ provides a perfect solution. Each model does, however, suggest that open access to these sequences might be at least partially reconciled with benefit sharing.

Evaluation of the uptake of the Australian standardized terminology and definitions for texture modified foods and fluids.

This paper discusses the uptake of standardized terminology and definitions for texture modified foods and fluids. The Australian dietetic and speech-language pathology associations endorsed national standards in 2007. This project sought to determine the barriers and enablers for use of the national standards in clinical practice. Cross-sectional online surveys were developed, including open- and closed-response questions. The surveys targeted different professional groups in Australia including speech-language pathologists, dietitians, nurses, and food service personnel. Australian accredited universities were contacted to determine penetration of the standards. A total of 574 surveys were received. Sixty-five per cent of respondents indicated full implementation, 23% partial implementation, and 10% no implementation of the standards in their workplace. Speech-language pathologists and dietitians were most likely to have championed implementation of the standards. Barriers to implementation included: lack of knowledge about the standards, time, and resistance to change. Enablers included: encouragement to use the standards and 'buy-in' from stakeholders. Benefits of implementation included: consistent terminology and perceived improvements in patient safety. It was concluded that the standards have been successfully implemented in a majority of facilities and Australian universities. This study provides insight into the complexity of introducing and managing change in healthcare environments.