Voluntary License Research Articles

Challenges for novel antiretroviral development in an era of widespread TLD availability.

Over 80% of people living with HIV in low-and-middle-income countries (LMICs) take first-line TDF/XTC/DTG (TLD). Due to hard-fought activism, in >100 LMICs TLD now costs under $45pppy under Voluntary License. With final DTG patents expiring by 2029, generic TLD will soon be available globally. We identify seven critical benchmarks underpinning TLDs success which novel ART should now meet, and an eighth for which novel ART should aim. These are superior efficacy; a high genetic barrier to resistance; safety in hepatitis B coinfection; favourable drug-drug interaction profiles including with antimycobacterials; efficacy in HIV-2; safety in pregnancy, long-acting formulation availability and affordable pricing from the outset. We illustrate when generic TLD will become available worldwide and compare this with trial programmes and approval timelines for two case-study novel ART combinations: islatravir/doravirine and cabotegravir/rilpivirine. We demonstrate that currently these regimens and trial programmes will not meet key benchmarks required to compete with TLD.

The politics and governance of drug production in public-private partnerships: Brazil’s response to hepatitis C

ABSTRACT The local manufacture of advanced pharmaceutical products has been a long-standing objective of health and industry policy in many developing countries, including in Latin America. This strategy has been applied to fight epidemics such as HIV/AIDS, malaria, and the COVID-19 pandemic. However, we still know little about the politics and governance that enable such arrangements, especially when there is no consent from the originator company. This study focuses on the case of Brazil, a country that is well-known for its health-industry policy, which includes the local production of direct-acting antivirals (DAAs), a new treatment for hepatitis C. We seek to explain the factors that have contributed to Brazil’s successful production of generic versions of DAAs, and, later, to the decision by the Ministry of Health (MoH) to procure drugs from multinational pharmaceutical companies rather than from local laboratories. A lack of support for domestic production by important stakeholders, the patent holder’s attempt to block domestic production and the MoH’s adoption of more modern treatment guidelines under a different procurement logic all created an unfavourable environment for local production and procurement of DAAs. Our study draws implications for middle-income countries that wish to produce drugs domestically without voluntary license agreements.

International disparities in diagnosis and treatment access for cystic fibrosis.

Elexacaftor/tezacaftor/ivacaftor (ETI) has revolutionized cystic fibrosis (CF) treatment. However, previous research has demonstrated profound global disparities in diagnosis and treatment access. If unaddressed, these threaten to widen existing health inequities. Therefore, in this analysis we aimed to reappraise gaps and evaluate progress in diagnosis and treatment equity in high-income (HIC) versus low- and middle-income countries (LMICs). Estimates of the global CF population were made in 158 countries using patient registries, systematic literature searches, and an international survey of 14 CF experts. Estimates of the global burden of undiagnosed CF were made using epidemiological studies identified in literature searches and registry coverage data. The proportion of people receiving ETI was estimated using publicly available revenue data and a survey of 23 national drug pricing databases. 188,336 (163,421-209,204) people are estimated to have CF in 96 countries. Of these, 111,767 (59%) were diagnosed and 51,322 (27%) received ETI. The undiagnosed patient burden is estimated to be 76,569 people, with 82% in LMICs. ETI is reimbursed in 35 HICs, but only one LMIC. Four years after approval, there are 13,723 people diagnosed with CF who live in a country where ETI is inaccessible. This increases to 76,199 when including the estimated undiagnosed population. Equitable access to CFTR modulators must become a top priority for the international CF community. ETI costs up to $322,000 per year but could be manufactured for $5000 to allow access under a voluntary license. Given the extent of disparities, other mechanisms to improve access that circumvent the manufacturer should also be considered.

SCOPE OF PROTECTION AND DEPENDENCE BETWEEN PATENT RIGHTS

Based on European doctrine and the Author's previous work, the present work intends to illuminate the judicatively complex question of what are the requirements or assumptions whose verification make a invention patented (and therefore a technical solution provided with inventive activity and novelty in relation to the state of the art) “mysteriously” dependent on another previously patented invention, allowing the holder of the latter (dominant patent) to prevent the commercial exploitation of the first (dependent patent) - a situation that is susceptible of being released by entering into a voluntary license agreement or by granting a compulsory license. Basically, taking into account the Portuguese Industrial Property Code, European doctrine and jurisprudence and the European Patent Convention, we seek to demonstrate that the solution to these issues lies in the delimitation of the concrete (technological) scope of patent protection previously registered.

Capitalizing an epidemic: Does voluntary license stabilizes access to patented vaccines and public health crisis?

AbstractThe spread of SARS‐CoV‐2 has paused the entire commercial sector except for the pharmaceutical domain. This highly contagious virus has kept the pharmaceutical domain, and publicly funded research institutions dynamically occupied in the R&D process to achieve the vaccine for the treatment and eradication of the COVID‐19 virus. The key issues are not the incentives for R&D but the accessibility of such vaccines at the ground level amidst voluntary licensing, elliptically, the dilemma encompassing innovations, patent rights, accessibility, and public health emergencies amidst stakeholders with contrasting interests. The voluntary licensing approach promotes a balance between native generic manufactures and international groups yearning to protect their intellectual property (IP) rights while boosting goodwill via better accessibility of such medicine, and concurrently providing pharmaceutical giants a constructive business strategy to set foot in developing markets. Patent rights and more significantly voluntary licensing might have a consequential impact on the public healthcare niche as it would facilitate a grip of patent holders concerning private governance activities over IP‐protected technologies. This paper provides an overview of voluntary licensing and its implications on vaccines in the pandemic.

Application of Parallel Importation and Voluntary License in the Covid-19 Vaccines Patent as a Strategy for Handling the Health Emergency Situations in Indonesia

This article examines how the application of Parallel Importation and Voluntary License in the Application of the Covid-19 Vaccine Patent as a Strategy for Handling Health Emergency Situations in Indonesia. The problem of the Covid-19 vaccine happens in many countries around the world, including Indonesia whos trying to find a vaccine that can neutralize the Covid-19 Virus. As a consequence of the tremendous demand for vaccines, the world pharmaceutical industry is encouraged to provide Covid-19 vaccines for the needs of 7.8 billion. This article uses normative legal research with a statute, conceptual, and comparative law approach. The results showed that mechanisms such as parallel importation and voluntary licenses could be reached to procure the Covid-19 vaccine. If parallel importation and voluntary licenses are not successful, then the Government shall take a win-lose approach, such as Compulsory Licensing and Use of Patents by the Government, or initiate an anti-monopoly lawsuit.

THE IMPACT OF COVID-19 ON INTELLECTUAL PROPERTY LEGAL SYSTEM RELATED TO PUBLIC HEALTH IN CONNECTION WITH TRIPS FLEXIBILITIES IN INDONESIA

In early 2020, countries in the world was shocked by a new virus called Coronavirus Disease 2019 (COVID-19) including Indonesia. The COVID-19 pandemic gives impact to the legal system, including intellectual property (IP). Trade Related Aspects of Intellectual Property Rights (TRIPS) flexibilities on public health in developing countries: Transition Periods, Compulsory License, Government Use, Parallel Imports, Exceptions to Patent Rights, Exemptions from Patentability, Limits on Data Protection, and Implementation of the Paragraph 6 of the Doha Declaration. Research problems: (1) what are the conditions for implementing the flexibilities of TRIPS in facing COVID-19 pandemic in Indonesia and (2) what are the issues that should be anticipated for future IP legal system relating to public health as a lesson from this COVID-19 Pandemic. Government Use is most effective to be used for encounter COVID-19 Pandemic, and voluntary license is recommended tobe promoted for future approach. The study is using a qualitative literature study.

Voluntary return of driver's license and the related activity of a neurocognitive center in Okayama prefecture

Due to the rapid increase in traffic accidents caused by the old populations of ages 65-74 and more than 75 in Japan, the renewal of driver's licenses has become more difficult following the revision of traffic laws in March 2017. As part of the driver's license clinic at Kurashiki Heisei Hospital, the present study investigated the status of voluntary license surrender in Okayama Prefecture of Japan. From March 2017 to December 2019, the number of voluntary surrenders increased from 5,434 to 10,284 cases, or at a rate of 0.42% to 0.80%, among license holders, with the old-old accounting for 68%-77% of voluntary surrenders. The major reasons for surrender were a decline in physical ability (25%-38%), a decline in driving needs (28%-60%), and family's suggestion (14%-17%). The increase in voluntary license surrender over these 3 years was common across all municipalities within Okayama Prefecture, but the surrender rate was closely correlated with the aged-society rate for both old populations of ages 65-74 and more than 75 (r = -0.5508, **p = 0.002 and r = -0.3086, p = 0.110, respectively). The driver's license clinic at Kurashiki Heisei Hospital received 110 visits during the 3-year period, in which MCI (mild cognitive impairment) accounted for 67% of voluntary surrenders (21.8%). The present study suggests that the increase in the rate of voluntary license surrender during the 3-year period was closely related to the aged-society rate in Okayama Prefecture, and that a driver's license clinic provides a detailed dementia status among license holders who have voluntarily surrendered their license.

Regulating the Crypto World - New Developments from France

After the ICO frenzy in 2017 and the turmoil of cryptocurrencies in 2018, will 2019/20 be the year of wisdom where regulators finally accept that it is neither desirable to leave this sphere unregulated nor is it recommended to artificially push it into legal categories that have been conceived for a centralized world and are not necessarily adapted to a distributed environment? Facebook’s release of its white paper on its native currency Libra on 18 June 2019, which has already provoked a lot of reaction from regulators, is likely to be a wake-up call for regulating this evolving environment. But regulating such an evolving and borderless environment is not easy. Fintech and particularly blockchain have a tendency to challenge the scale, scope and the speed of traditional financial system. Through blockchain it is now possible to tokenize almost any asset or right and to transfer and trade it easily. The scope of finance broadens and its borders become blurred. This poses particular challenges for regulators. On the one hand, they need to grasp this evolving environment and its implications for investor protection and financial stability. Regulating this continuously-developing and still quite recent ecosystem too quickly risks hampering its evolution and potential. Regulating it in a disparate way at a national level might favor regulatory arbitrage. On the other hand, regulators cannot let this environment evolve without scrutiny and wake up someday to a private currency like the one considered by Facebook. Furthermore, there are already existing risks favored by the anonymity or at least pseudonimity of crypto-assets, like anti-money laundering (AML) issues, combatting the financing of terrorism (CFT) or general crime, that need to be addressed. However, the ubiquitous nature of blockchain and distributed ledger technology (DLT) poses some challenges for regulators. Thus, the regulatory approach is to target the gatekeepers who allow physical and legal persons to access this environment. Most of the time these service providers are easy to identify. This is precisely what France has tried to do. For better or for worse, France for once did not wait for a wake up call. It enacted a new genre of regulation through a law voted on 22 May 2019 (the ‘PACTE’ law). Putting to one side the preferences of the European regulator, France decided to provide for an optional visa for Initial Coin Offerings (“ICO”) and a mix of mandatory registration for some intermediaries coupled with a voluntary license for all intermediaries. This optional regime (or so it seems) is a new type of regulation: neither totally soft law, nor a default rule, nor totally hard law. Most provisions require an opt-in but once the option is exercised, there are constraining rules that will apply. This carrot and stick method smartly combines a seemingly optional setup with some very persuasive incentives, which in practice makes it anything but voluntary. But the devil is very often in the detail: a smart mix of voluntary and mandatory requirements can only be successful if the advantages outweigh the constraints. The success or failure of the French initiative will also depend on enforcement and in this regard some obstacles still seem to pave the way.

Hit me with your best shot: dolutegravir - a space in the next WHO guidelines?

Hit me with your best shot: dolutegravir - a space in the next WHO guidelines?

Characteristics of Internal Medicine Physicians Disciplined by Professional Colleges in Canada.

Physician misconduct is of serious concern to patient safety and quality of care. Currently, there are limited data on disciplinary proceedings involving internal medicine (IM) physicians.The aim of this study was to investigate the number and nature of disciplinary cases among IM physicians compared with those of other disciplined physicians.Our retrospective study reviewed information from all provincial Colleges of Physicians and Surgeons (CPS) and compiled a database of all disciplined physicians from 2000 to 2013 in Canada. Disciplinary rate differences (RDs) were calculated for IM physicians and compared with other physicians.From 2000 to 2013, overall disciplinary rates were low (9.6 cases per 10,000 physician years). There were 899 disciplinary cases, 49 of which involved 45 different IM physicians. IM physicians comprised 10.8% of all disciplined physicians and were disciplined at a lower rate than non-IM physicians, incurring 5.18 fewer cases per 10,000 physician years than other physicians (95% confidence interval [CI] 3.62–6.73; P < 0.001). They were significantly less likely to be disciplined for: unprofessional conduct (RD 1.16; CI 0.45–1.87; P = 0.001); unlicensed activity (RD 0.78; CI 0.37–1.19; P < 0.001); standard of care issues (RD 1.37; CI 0.49–2.26; P = 0.002); sexual misconduct (RD 1.65; CI 0.90–2.40; P < 0.001); miscellaneous (RD 0.80; CI 0.11–1.50; P = 0.020); mental illness (RD 0.06; CI 0.01–0.12; P = 0.025); inappropriate prescribing (RD 0.74; CI 0.15–1.33; P = 0.010); and criminal conviction (RD 0.33; CI 0.00–0.65; P = 0.048). No significant differences were found with respect to unclear violations, fraudulent behavior/prevarication, or offenses involving drugs/alcohol (all RDs less than 0.32). IM physicians were also less likely to incur the following penalties: voluntary license surrender (RD 0.53; CI 0.37–0.69; P < 0.001); suspension (RD 2.39; CI 1.26–3.51; P < 0.001); retraining/assessment (RD 1.58; CI 0.77–2.39; P < 0.001); restriction (RD 1.60; CI 0.74–2.46; P < 0.001); other (RD 0.52; CI 0.07–0.97; P = 0.030); formal reprimand (RD 2.78; CI 1.77–3.79; P < 0.001); or fine (RD 3.28; CI 1.89–4.67; P < 0.001). No significant differences were found with respect to revocation or mandated counseling/rehabilitation (all RDs less than 0.46).Generally, disciplinary rates among physicians were low. Compared with other physicians, IM physicians have significantly lower disciplinary rates overall and are less likely to incur the majority of disciplinary offenses and penalties.

Strategies for price reduction of HIV medicines under a monopoly situation in Brazil.

ABSTRACTOBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil.METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir.RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership).CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

Existing Provisions on Compulsory Licensing in Countries of Asia-Pacific

If a nation has enacted Patent Legislation and a medicine is patent protected, a generic version of the same can be legally manufactured or imported under the circumstances viz – a) voluntary license by patentee; b) Compulsory License (CL). In Voluntary license, Patent holders may at their discretion, license to other parties, on either exclusive or nonexclusive terms, the right to manufacture, distribute, sell or a drug on agreed fee. While compulsory licensing is invoked when the exclusive rights conferred by a patent are not meeting the reasonable requirements of the public or are anti-competitive in nature. Many Experts consider CL as an effective tool to check monopolies by patent holders in terms of pricing and supply of drugs in a particular market. CL has been used by many countries in the last few years including Indonesia, Malaysia, Brazil and Thailand. The presence of the CL provision in a Country’s Patent Law definitely act as check for innovative pharma companies to price their drugs at affordable level or to further innovate some new processes to bring down the cost of production. The first option is detrimental to these innovative companies as they have to reduce their profits. While the adopting second option involves R&D cost, human resources and risk of failures. The frequent and hassle free grant of the CL will definitely open the door for other generic manufacturer to apply for CL in if such circumstances arise.

Hogrefe OpenMind License

Hogrefe OpenMind License

For-Profit Policies and Equitable Access to Antiretroviral Drugs in Resource-Limited Countries

Unaffordable prices continue to obstruct access to antiretroviral drugs in income-constrained countries. This article explores the fitness of a multi-pronged, incentive-bound, WHO-mediated voluntary license strategy for attuning research, innovation, profit and equitable access to antiretrovirals in under-served markets. The potential of the model was investigated by examining: the predictable effect on current regulatory practices (trade-related aspects of intellectual property rights [TRIPS] and TRIPS-plus measures); the expected benefits, either in terms of equity or safeguarding of the generic and brand name manufacturer’s interests; the interplay dynamics with drug trading policies of deeply concerned countries (China, India, countries in the EU, USA, Brazil, South Africa and Thailand); and the suitability for helping plants for generic antiretrovirals, including home plants in Sub-Saharan Africa, undertake research and development partnerships encompassing innovation, technological catch-up, exploitation of TRIPS flexibilities, as well as raised marketing power and an increase in domestic employment. The explored strategy, although far from being the ideal solution, looks like it would be reliable to help expand equitable and sustainable access to appropriate antiretrovirals in resource-limited populations, as long as it entwines with the WHO’s brokerage. It should also boost know-how, technology transfer, innovation, research and development, as well as national industry plant development and penetration of the wealthy and under-served markets by generic drug enterprises.

What Strategies to Boost Production of Affordable Fixed-Dose Anti-Retroviral Drug Combinations for Children in the Developing World?

No more than 8% of HIV positive children needing treatment in low- and middle-income countries have access to antiretroviral drugs (ARVs). Children presently account for about 4% of all treated patients, while for equitable access they should make up at least 13%. This study explores key issues, implications and interaction dynamics to boost production of easy-to-use and affordable fixed-dose combination (FDC) ARVs for children in the developing world. Potentials for equitable solutions are examined including priority steps and actions, appropriate treatment options and reliable forecasting methods for paediatric ARVs, as well as combination incentives to generic companies against market unattractiveness and enforced intellectual property (IP) rights. Moreover, implementation strategies to enhance the development and production of affordable ARV paediatric formulations and appropriate supply systems to ensure availability are investigated. The current market for FDC paediatric ARVs is already substantial and will only grow with improved and scaled up diagnosis and monitoring of children. This provides an argument for immediate increase of production and development of FDC ARVs for children. These formulations must be low cost and included in the list of Essential Medicines to avoid children continuing to lag behind in access to treatment. Access-oriented, long-term drug policy strategies with the ability to pass muster of governments, the UN system, as well as generic and research-based enterprises are needed to let children gain expanded and sustained access to FDC ARVs. Under the requirements listed above, IP-bound Voluntary License (VL) flexibilities do appear, if coupled with substantial combination incentives to generic firms, as a fitting tool into the needs. Policies must consider enhancing human resource capacity in the area of caregivers and social and health workers aiming to spread correct information and awareness on effectiveness and rationale of FDC ARVs for children. Policies should urge that paediatric ARV treatment programmes entwine with extant interventions on prevention of mother-to-child transmission, as well as with HIV treatment initiatives focused on mothers and household members. Policies, again, should consider centralising functions and pooling resources to help overcome drug supply barriers. WHO's brokering role in VL-based agreements between wealthy and developing country industries, as well as its technical guidance in setting international standards should not be waived while looking for sustained access to optimised ARV treatments for children. Strategies discussed in this paper, while taking unavoidability of marketing and profit rules into account, look closely into the trade and drug policy directions of China and India according to frontier crossing implications of their IP management trends as well as their multi-faceted penetration strategies of both the wealthy and under-served markets the world over.

Affordable Antiretroviral Drugs for the Under-Served Markets: How to Expand Equitable Access Against the Backdrop of Challenging Scenarios?

Threats by enforced Intellectual Property (IP) rights to equitable HIV treatment access by poor populations are impending. India and China's policy directions in the field will be crucial in ultimately affecting the affordability and accessibility of antiretroviral (ARV) therapy in the under-served markets. These directions, together with the exploitation level of IP-bound flexibilities and the evolutionary modelling in partnerships and trade agreements between research-based and generic pharmaceutical industry, will also affect the outcomes of self-sufficiency efforts now at their beginning in the developing world as far as domestic manufacturing of generic ARV drugs is concerned. This paper explores key issues, implications and interaction dynamics across these challenging scenarios while attempting to provide equitable solution glimpses into the near future. Access-oriented long-term drug policy strategies entitled to pass muster of governments, research-based as well as generic industries in both developed and developing countries are needed if equitable access to affordable ARV treatments by poor people has to be achieved despite enforced IP rights. Predictable dynamics between western multinationals and transitional country generic corporations let regard IP-bound Voluntary License flexibilities as a fitting measure into just mentioned needs especially if substantial incentives to generic corporations are concurrently secured. Efforts to equitably expand ARV drug access through exploiting IP opportunities should encompass attainment of self-sufficiency in domestic drug manufacturing whenever basic requirements are in place in the developing world as a whole. A credible industrial potential would act, indeed, as a boosting factor for drawing branded drug producers into technology transfer agreements, the terms of which would let all contractors enjoy substantial advantages. These perspectives consistently bind up with the foreseeable long-term trade and drug policy directions of India and China according to frontier crossing implications of their key IP management trends as well as their multifaceted penetration strategies of both the wealthy and under-served markets worldwide. As coherent with these perspectives, more disbursement by wealthy country governments and donors to basic infrastructure development in sub-Saharan African nations with stable governments in place is urged both as a priority for improving Africa's economy and a prerequisite for allowing domestic industrial plants to take off. Aiming at the targets just underscored, WHO's brokering role in negotiated agreements between wealthy and developing country-based firms as well as its technical guidance in setting international standards have always to be sought if equitable and appropriate end results are to be attained. Overall insights in this paper would mean that, while research-based corporations are to be praised whenever waiving, on humanitarian purposes, part of their profits, the trade and profit rules cannot basically be given up if long-term sustainable results are the goal to look for. Only negotiated agreements securing all contracting parties lasting advantages may ensure shifting of such a goal from mere vision to a really sustainable attainment.