5 Access to pharmaceuticals in a globalised world

Question 1

Overview Summary

Answer 1

Ensuring equitable access to quality pharmaceuticals remains a key global health challenge, with approximately one-third of the world’s population lacking access to essential medicines, a figure rising to over 50% in Asia and Africa (Leisinger et al, 2012). Access to safe, effective and affordable pharmaceuticals to prevent or treat illness is an essential part of effective healthcare provision (Seiter, 2010). The availability, accessibility, affordability, and appropriate use of medicines are not assured, and there is growing consensus that any effort to address the issue of access to quality pharmaceuticals must be multifactorial and take into consideration key health system building blocks such as adequate financing, a trained workforce, and regulatory capacity (Frost & Reich, 2008).

Question 2

Overview Aim

Answer 2

The aim of this session is to provide you with an overview of the problem of inequitable access to medicines and its impact on health, with an emphasis on low- and middle-income countries (LMIC).

Question 3

Overview Learning outcomes

Answer 3

By the end of this session, you should be able to: Explain the significance of pharmaceuticals on health systems in terms of financing, disease burden and rational use; Assess the global inequities in access to pharmaceuticals within and across countries; and Discuss the key challenges in ensuring a ready supply of affordable, quality pharmaceuticals in LMIC.

Question 4

Key terms Generic

Answer 4

A pharmaceutical product, usually intended to be interchangeable with an innovator product, that is manufactured without a license from the innovator company and marketed after the expiry date of the patent or other exclusive rights’ (Alfonso-Cristancho et al, 2015).

Question 5

Key terms Pharmaceutical

Answer 5

A chemical substance manufactured for use as a medicinal drug (Oxford Dictionary, 2022).

Question 6

Key terms Product Development Partnership

Answer 6

A public-private partnership focused on improving health in LMIC through product discovery and development (Hoogstraaten et al, 2020).

Question 7

Key terms Substandard medicine

Answer 7

Medical products that fail to meet either recognised quality standards or specifications, or both (WHO, 2018a).

Question 8

Key terms Falsified medicine

Answer 8

Medical products that deliberately/fraudulently misrepresent their identity, composition or source (WHO, 2018a).

Question 9

Key terms Counterfeit medicine

Answer 9

Medicines that are made by someone other than the genuine manufacturer, without authority or right (WHO, 2018a).

Question 10

1. Background

Answer 10

Access to healthcare, including pharmaceuticals, is a fundamental human right as clearly stated in the Universal Declarations of Human Rights in 1948. Essential medicines are a fundamental part of a health system and account for a large share of expenditure on health. Approximately US$1.42 trillion was spent on medicines in 2021, an increase from US$887 billion in 2010. This is forecast to increase to US$1.8 trillion by 2026 (Statista, 2022). Spending on pharmaceuticals is the largest item in household health expenditure in most LMIC (Yadav et al, 2012).

Question 11

1. Background

Answer 11

Although pharmaceuticals are key to adequate health care provision, a study in 2014 found that median availability of essential medicines was 62% globally, with substantial variation in availability across national income levels and WHO regions (Bazargani et al, 2014). Patients living in LMIC with a higher burden of infectious diseases are less likely to have access to adequate treatment for many reasons including lack of adequate funding, lack of infrastructure, and lack of trained staff. This results in preventable illness and death (Kruk et al, 2018). A study examining number of deaths in LMIC found that 5 million deaths in just the year 2016 could have been prevented if people had access to quality healthcare, including necessary drugs (Kruk et al, 2018). In 2021, the UNAIDS annual report stated that ‘under-investment in the HIV responses of low- and middle-income countries was a major reason why global targets for 2020 were missed’ (UNAIDS, 2021).

Question 12

1. Background

Answer 12

Pharmaceuticals were identified as a key component of a number of the Millennium Development Goals (MDGs) and most recently the Sustainable Development Goals (SDGs) (WHO, 2018b; UN, 2022). For example, MDG1 on eradication of extreme poverty and hunger is related to access to pharmaceuticals: access to medicines is linked to a healthier workforce, and a healthier workforce is one of the aspects contributing to economic development. MDG8 included a specific target for access to pharmaceuticals, aimed at providing access to affordable, essential drugs in LMIC in order to improve health. However, this target was deprioritised and dropped from the official report, which suggests that in reality meeting this goal was difficult (see Gotham et al, 2016 for a discussion of this). We will find out why this may have been the case as we go through the session.

Question 13

1. Background

Answer 13

Following the MDGs period, the SDGs were developed to address some of the failures of the MDGs. SDG3 targets improved wellbeing of all people, with a specific target on Universal Health Coverage, including access to essential health care services and to safe, effective, quality and affordable essential medicines and vaccines for all (UN, 2022).

Question 14

1. Background

Answer 14

Pharmaceutical policy is complicated as it transcends national boundaries and goes beyond the health sector (Seiter, 2010). It involves international and transnational policy regimes and agreements on trade, intellectual property, regulation, and industrial policy, and it involves bodies such as the World Trade Organization (WTO), the United Nations, and the World Health Organization (WHO). You will see throughout this session how these multilateral and intergovernmental arrangements are translated into national realities and how patients on the ground are affected by this multi-level policymaking.

Question 15

Activity 1 Do some online research into the elements needed for access to pharmaceuticals to be guaranteed. The relevant WHO webpage is a good place to start: https://www.who.int/our-work/access-to-medicines-and-health-products; In addition to the products themselves, think about system elements required to deliver medicines to those who need them. Make a list of elements;

Answer 15

Summarise and post your findings on the discussion board for feedback from your colleagues and comment on at least one other post.

Question 16

2. The access to pharmaceuticals problem

Answer 16

We can approach the access to pharmaceuticals problem in a systematic manner using a framework adapted from one developed by Frost and Reich (2009). As you’ll see in the figure below, the key aspects of the framework are availability, affordability, accessibility, and acceptability, which we will discuss in more detail in the following sections.

Question 17

2.1 The access to pharmaceuticals framework

Answer 17

It is important to mention that there are some overarching requirements for pharmaceuticals to be accessible, which are part of the ‘architecture’ of the framework. These include: adequate funding to ensure that medicines can reach the intended recipients; a workforce that is sufficient in number and appropriately distributed and trained, to provide advice and support to consumers; strong information systems and the ability to use this information to inform purchasing decisions and broader pharmaceutical policy; and an effective governance system capable of regulating the introduction of new products, ensuring the safety and appropriate distribution of existing products, appropriate enforcement and providing transparent procurement (Frost & Reich, 2008).

Question 18

2.1 The access to pharmaceuticals framework

Answer 18

Many actors and organisations are involved in this framework, including pharmaceutical companies, manufacturers, Product Development Partnerships (PDPs), global health initiatives, governments, funding bodies, the World Health Organization, the World Bank, to name but a few. The roles and responsibilities of these actors will be discussed further in the sections below.

Question 19

3. Availability

Answer 19

All pharmaceutical products must go through the long, expensive process of research and development (R&D) and manufacturing. R&D is profitable because companies can charge monopoly prices under the intellectual property rights system. Central to this system is the concept of patents and the Agreement on Trade Related Aspects of Intellectual Property Rights (the TRIPS Agreement). We will discuss these later in this session.

Question 20

3.1 Research & development

Answer 20

R&D is mostly conducted by and for high-income countries, which, in practice, has the effect that investment is made into diseases that primarily affect populations in high-income countries. This has been highlighted by the issues with production of vaccines for COVID-19, with many researchers suggesting that LMIC should be enabled to make their own vaccines rather than rely on supplies from high-income countries (Maxmen, 2021a). However, pharmaceutical companies are reluctant to do this, stating potential issues with quality and safety. A group of researchers in Africa has started trying to produce existing vaccines, although issues with this include access to technologies and the necessary raw materials (Roelf, 2021).

Question 21

3.1 Research & development

Answer 21

Africa as a whole imports 70–90% of the drugs needed to treat their population (Chaudhuri and West, 2015), which is much higher than the corresponding data for China (5%) and India (20%), despite having comparable populations. Nkengasong and Tessema (2020) point out that Africa needs to develop effective local pharmaceutical manufacturing to avoid unnecessary deaths. For example, anti-retrovirals were first available in high-income countries in 1996, but these didn’t become available in some African countries until 2002. The ability to make these drugs locally would have saved many lives (Nkengasong & Tessema, 2020).

Question 22

3.1 Research & development

Answer 22

Moreover, the availability of drugs to address neglected tropical diseases (NTDs), which disproportionately affect LMICs, is a significant problem (Eisenstein, 2021). In 2021, the WHO produced a roadmap assessing challenges in preventing and controlling these diseases (Casulli, 2021). This roadmap pointed to problems in NTD research associated with lack of funding, lack of R&D, and lack of interest and political will. Until these diseases begin to affect people in higher-income countries, sufficient funding is unlikely to be forthcoming.

Question 23

3.1 Research & development

Answer 23

However, this situation may be changing as a result of several factors: 1. Philanthropic funding from foundations like the Bill & Melinda Gates Foundation (BMGF) and the Wellcome Trust aim to reduce the burden of NTDs through efforts to control, eliminate and eradicate these diseases (BMGF, 2022); 2. Renewed interest by pharmaceutical companies into these diseases, possibly as a result of ‘rewards’ given to companies who participate in this research, e.g., milestone payments or financial prizes and grants based on the impact of the product (Weng et al, 2018); and 3. The creation of new business models and new actors, e.g. PDPs: these are not-for-profit institutions that engage the public and private sectors to conduct R&D into neglected diseases (Hoogstraaten et al, 2020).

Question 24

3.1 Research & development

Answer 24

A good example of PDPs is the Medicines for Malaria Venture (MMV), a not-for-profit organisation created in 1999 to discover, develop and deliver new antimalarial drugs (Medicines for Malaria Venture, 2022). MMV works with multiple partners around the world including multinational pharmaceutical companies, small pharmaceutical and biotechnology companies, universities, and research centres. Overall, this is an example of how PDPs have changed the R&D landscape.

Question 25

3.1 Research & development

Answer 25

Once a medicine is developed and registered, it needs to be manufactured on an ongoing basis. There are some important facts to mention here. First, the lack of manufacturing capacity in low-income countries, which account for only 1% of global pharmaceutical expenditure. Second, some middle-income countries have increased their manufacturing capabilities in the past decades and are now increasingly supplying other LMIC. For example, Indian generic companies manufacture more than 80% of all the antiretrovirals bought by donors (Waning et al, 2010)

Question 26

3.2 Distribution

Answer 26

Once pharmaceutical products are developed, registered and manufactured, the next issues are related to the distribution chain: selection, procurement, distribution and use (Frost & Reich, 2008). At the selection stage, officials at each country’s Ministry of Health need to review the health issues prevalent in their country and identify treatments of choice, considering what individual products and which dosage forms will be available at each level of the healthcare system. During this process, these officials compile a list of Essential Medicines that can satisfy the priority healthcare needs of the majority of the population, with cost of these drugs taken into account. WHO started this concept in 1977, with the Model List of Essential Medicines, which is updated every two years and is used as a template by public health officials (WHO, 2022a).

Question 27

3.2 Distribution

Answer 27

Once essential medicines are selected, the second stage is the procurement of those medicines (Frost & Reich, 2008). Public procurement usually follows certain steps: first medicine requirements for the entire public health system are quantified; then a procurement method is chosen and normally there is a tendering process to guarantee competition under the logic that the higher the competition, the lower the prices. The respective government ensures quality is assured through the Medicines Regulatory Authority.

Question 28

3.2 Distribution

Answer 28

The third stage is the process of transporting medicines from the place where they are manufactured or imported to the health facilities (Frost & Reich, 2008). This process is extremely important for certain products like vaccines which must be kept in certain conditions, such as carefully controlled temperatures to guarantee quality. The process involves numerous steps including clearing customs, transportation to warehouses where products will be stored, transportation to government stores where products can be kept closer to the health facilities and final delivery to drug depots and health facilities. This complicated process can be optimised by using computerised Logistic Management Information Systems to ensure efficient distribution. This distribution process can be managed entirely by the government or can be outsourced (see Bekele & Anbessa, 2021 for an interesting overview of this in practice). The final stage, use, relates to diagnosing, prescribing and dispensing medicines to patients.

Question 29

3.2 Distribution

Answer 29

Challenges to this entire process include the lack of comprehensive procurement policies, fragmented procurement systems, lack of unbiased market information, and poor planning.

Question 30

3.2 Distribution

Answer 30

Other problems like corruption and lack of transparency may affect all stages, especially when private companies are involved in the distribution process. There is the potential for supplies to be ‘held up’ at ports until a ‘tax’ is paid. For an interesting overview of this issue, see this 2016 report by Transparency International (https://www.transparency.org.uk/publications/corruption-in-the-pharmaceutical-sector). There are also problems specific to distribution like vertical and fragmented supply systems; insufficient funding for storage; distribution and inventory management systems; short shelf life; stock-outs when medicines are not available in health facilities; and problems with transportation like a poor cold chain. A cold chain is necessary when a product requires temperature-controlled storage and shipping, e.g., certain vaccines. If the cold chain is broken, the product may become ineffective (Frost & Reich, 2008).

Question 31

3.2 Distribution

Answer 31

When discussing issues related to availability of pharmaceutical products, it is crucial to talk about the procurement funds set up in the past decade. These funds, also called global health initiatives, were created with public and philanthropic funds to subsidise pharmaceutical products for low-income countries and support their supply chain management systems to improve distribution. These initiatives usually fund vertical programmes, which basically means that they focus on certain diseases or certain products (Warren et al, 2013). The most prominent global health initiatives are Gavi, the Global Fund, and PEPFAR. These differ from PDPs as they do not necessarily focus on R&D but have increasingly focused on supporting infrastructure and strengthening health systems in addition to addressing specific diseases (for example, have a look at the PEPFAR website, https://www.state.gov/pepfar-policies/).

Question 32

3.2 Distribution

Answer 32

These initiatives have greatly increased the resources flowing into LMIC for the procurement of pharmaceutical products. The Global Fund invests US$4 billion annually, some of which has gone toward improving access to pharmaceutical products in low-income settings (Global Fund, 2022). However, one main problem is the resultant lack of commitment to strengthening national procurement and distribution networks, as often these vertical programs displace and duplicate country supply chains, creating parallel systems (WHO Maximizing Positive Synergies Collaborative Group, 2009). Increasingly however, more funding is being directed toward health systems strengthening (Global Fund, 2022). You may read more about vertical and horizontal programmes in session 10.

Question 33

3.2 Distribution

Answer 33

COVAX is a recent initiative that stemmed from the COVID-19 pandemic, which sought to support the distribution and availability of vaccines to fight the disease by supporting research, development, manufacturing and the negotiation of prices for every country in the world (Gavi, 2022). It is coordinated by Gavi, the Vaccine Alliance, the Coalition for Epidemic Preparedness Innovations and the WHO. In practice it has struggled to acquire doses and some of its targets, for example distributing 2 billion doses globally by the end of 2021, have not been met (Badr et al, 2021). A report by Nature in 2021 suggested that COVID-19 vaccines would not be available in the least well-resourced countries until 2023, and that only 1% of people in LIC had received a dose (Padma, 2021). Meanwhile, people in higher-income countries at this point had access to at least three doses, which could have been sent to LMIC as first doses for many of their citizens (Maxmen, 2021b).

Question 34

3.2 Distribution

Answer 34

This issue received even more attention during the monkeypox epidemic in 2022. A WHO spokesperson said that there was ‘quite a possible risk’ that high-income countries would bid for monkeypox vaccines and that LMIC would lose out on supplies (Boseley, 2022). For example, despite the number of cases increasing rapidly in Nigeria and the Democratic Republic of Congo, vaccines were being sent to Canada, the UK and the US and not elsewhere.

Question 35

4. Affordability

Answer 35

Affordability of pharmaceuticals is a significant problem throughout the world. This is impacted by many factors, most important of which are the price of pharmaceuticals, lack of sustainable funding, tariffs and the existence of patents. In high income countries expenditure on pharmaceuticals is around 30% of total healthcare expenditure, while the corresponding figure is 60% in LMIC (Maniadakis et al, 2017). Many patients in LMIC cannot rely on a public social security net to cover the costs of their medical treatments and medicines. About 80% of medicines in low-income settings are paid by the patients themselves or by their families. This is an important point because these out-of-pocket payments can result in poverty. For example, in 2017 the WHO estimated that about 100 million people are impoverished each year as a result of out-of-pocket health spending (WHO, 2017a).

Question 36

4.1 Price of pharmaceuticals

Answer 36

As most treatments are financed by patients, we need to consider which factors are associated with lack of affordability of pharmaceuticals and this varies throughout the world.

Question 37

4.1 Price of pharmaceuticals

Answer 37

Questions we should ask include: Are enough competitive purchasing methods in place? Are there multiple manufacturing sources? Is the procurement done properly? Is any tariff (a duty to be paid on goods and services imported from another country) involved? What mark-ups are charged by the producer, by the wholesaler, by the retailer? Do governments have any price regulations? What about taxes like value added tax (VAT)?

Question 38

4.1 Price of pharmaceuticals

Answer 38

The best way to think about this is to look at the distribution chain. The manufacturer’s selling price is the starting point. The final price of the product will include every charge incurred in the distribution chain – such as insurance fees, port fees or import tariffs. Public or private warehouse mark-ups and retail mark-ups also need to be factored in. Finally, it is important to remember that some countries also include VAT whenever the product is sold to the patient. If we include all this, the manufacturer’s selling price could be doubled.

Question 39

4.1 Price of pharmaceuticals

Answer 39

An example from Jordan demonstrates this well: ‘Wholesalers receive 15% on the cost at port of entry plus 4% for expenses, while a pharmacy receives 20% on the wholesale price plus 6% expenses. For imported medicines, other charges include an insurance fee (1%), bank fee (1%), transport and clearance fee (1.5%), added fee (0.2%), VAT (4%), and for some medicines, excluding antibiotics, an import fee of up to 5% is charged depending on the country of origin’ (Kanavos et al, 2018). You may find other examples similar to this in your own countries of origin.

Question 40

4.2 Sustainable funding

Answer 40

Sustainable funding is key to ensuring affordability of pharmaceuticals in many countries, as a Lancet Commission on Essential Medicines Policies found in 2017 (Wirtz et al, 2017). One of the conclusions of this Commission was that governments should provide ‘adequate financing to ensure the inclusion of essential medicines in benefit packages provided by the public sector and all health insurance schemes[…]The aim must be to achieve a benefits package that addresses the population health needs in a way that can be sustainably financed from different sources, in a fair and transparent manner’ (Wirtz et al, 2017).

Question 41

4.2 Sustainable funding

Answer 41

The promotion of sustainable financing mechanisms was addressed by the WHO in 2018 in their global strategy and plan of action on global health (WHO, 2018c). These mechanisms included: i) member states committing to dedicating at least 0.01% of their gross domestic product to basic and applied research relevant to the health needs of LMIC; ii) member states committing to increasing domestic resource mobilisation to implement the health-related SDGs; (iii) member states encouraging the implementation of schemes which delinked product prices from R&D costs; and (iv) member states, supported by WHO, encouraging an increase and diversification of funding for PDPs. However, in practice many countries have not moved to implement these recommendations.

Question 42

4.3 Tariffs and taxes

Answer 42

WHO recommends several ways of pursuing more affordable prices (WHO, 2020). Impartial price information should allow governments to obtain the best price during the procurement process. Competition in local markets is important and can be achieved through tendering of generic products and by allowing therapeutic competition, which is competition between products belonging to the same therapeutic class. Procurement is also extremely important as a way to reduce costs by pulling together pharmaceutical orders and bulk buying. Governments should implement policies to expand the use of generic products as much as possible.

Question 43

4.3 Tariffs and taxes

Answer 43

In some cases, this will not be possible because generics may not exist and so it is important to negotiate prices with the pharma companies. When economically feasible, local manufacturing of essential medicines should be encouraged. Importantly, WHO recommends the reduction or the elimination of any duties, tariffs and taxes for essential medicines and also recommends that mark-ups should be reduced by more efficient distribution and dispensing systems (WHO, 2020).

Question 44

4.4 The TRIPS agreement and the Doha declaration

Answer 44

One of the most important factors related to the price of medicines and pharmaceuticals in general is whether the products are still under patent. While a product is protected by a patent, there is no competition and the originator company has a monopoly (no other manufacturer can produce it). The concept of patents and intellectual property is central to the TRIPS agreement (WTO, 1994). This agreement was negotiated between 1986 and 1994; it relates to trade involving pharmaceuticals but also all tradable goods; and it relates to intellectual property rights. In other words, it involves patents or monopoly rights given to inventors by the different signatories to incentivise innovation and investments in R&D. The TRIPS agreement set the patent life to a minimum of 20 years from the filing date.

Question 45

4.4 The TRIPS agreement and the Doha declaration

Answer 45

After TRIPS was agreed and countries complied with it, it was clear that the agreement had an impact on prices, access to medicines and public health because patents were linked to monopolies, monopolies were linked to high prices and high prices were linked to limited access to medicines. As a result, in 2001 the fourth WTO Ministerial Conference held in Doha, Qatar, issued a declaration on the relationship between TRIPS and public health and basically said that governments had the right to take measures to protect public health, and in particular, to promote access to medicines for all (WTO, 2001).

Question 46

4.4 The TRIPS agreement and the Doha declaration

Answer 46

It made clear that governments had the right to use the TRIPS flexibilities, which are basically three mechanisms to protect public health: 1. Some countries have until 2021 to fully implement the TRIPS Agreement, subject to further extension if necessary. Some countries are not able to conduct R&D in an environment with strong intellectual property protection. Therefore, it was decided that these countries would have some extra time to build core capabilities and skills. 2. Compulsory licensing enables a government authority to license or authorise the use of a patented invention to a third party without the consent of the patent holder but making sure adequate remuneration is given. In other words, if a government does not believe that they are getting a good price for the medicines they are purchasing, and they believe that it is affecting the public health of their population, they can authorise a third party to manufacture the product without the consent of the patent holder. 3. Parallel importation allows governments to import and trade patented products across borders without the permission of the patent holder. Basically, parallel imports take place when there are significant price differences for the same medicine, for the same product, in different markets.

Question 47

4.4 The TRIPS agreement and the Doha declaration

Answer 47

An example of compulsory licensing is the Efavirenz (an anti-retroviral drug used to treat and prevent HIV/AIDS) case in Brazil (Ford et al, 2007). In May 2007, the Brazilian government issued a compulsory license to allow for the manufacturing or purchase of generic versions of Efavirenz, without the consent of the patent holder (Merck). This measure was taken by the Brazilian government after negotiations started in May 2006 to reduce the price of $580 per patient per year failed. Merck initially offered a reduction of 30%, but the Brazilian government wanted a 60% reduction, to reduce the price from $580 to $245 per patient per year. This reduction would align the price the Brazilian government was paying with the price charged by Merck in Thailand (Ford et al, 2007).

Question 48

4.4 The TRIPS agreement and the Doha declaration

Answer 48

Merck did not agree and the government decided to issue a compulsory license. Generic manufacturers then offered to supply the drug at $163.22 per patient per year, which is much lower than the price the Brazilian government was asking Merck for (Ford et al, 2007). The compulsory licence was legal under both international and national trade laws (Alcorn, 2007).

Question 49

4.4 The TRIPS agreement and the Doha declaration Do patients limit access?

Answer 49

Some say no, as most products on the WHO Model Essential Medicines List are off patent (WHO, 2019). Some argue that countries have the right to use the TRIPS flexibilities so they should not worry about patents because they can use these flexibilities to protect public health (Tenni et al, 2022). However, the WHO Model Essential Medicines List does not consider products that are going to be registered. Therefore, if patents do not exist for most products this may be because these products are old and does not mean that new products will not be patented and sold at a high price.

Question 50

4.4 The TRIPS agreement and the Doha declaration Do patients limit access?

Answer 50

A news story in 2022 suggested that patenting and the concomitant financial implications could be driving the development of drug-resistant tuberculosis (TB) in India. This is because the Indian government is rationing prescribing of the two most recommended drugs, bedaquiline (patented to Johnson & Johnson) and delamanid (patented to Otsuka Pharmaceuticals), which are recommended in combination for treatment. Patients should be receiving both drugs to prevent resistance, but this is not happening, so resistance to one of the drugs is likely to increase (Davison, 2022).

Question 51

4.4 The TRIPS agreement and the Doha declaration Do patients limit access?

Answer 51

There were also negotiations around TRIPS and access to COVID-19 vaccines (Mercurio & Upreti, 2022). For example, countries including Germany, Canada, and Chile, among others, implemented emergency legislation that would have allowed compulsory licencing of related medical technologies to produce vaccines, other countries (e.g., India and South Africa) suggested a waiver. The USA also supported a waiver after May 2021. This issue is discussed exhaustively in Mercurio & Upreti, 2022.

Question 52

4.4 The TRIPS agreement and the Doha declaration Responses to intellectual property restrictions

Answer 52

There have been developments to improve access to medicines within the current intellectual property system (see Tenni et al, 2022 for an overview of this entire issue): 1. Differential pricing agreements allow pharmaceutical companies to unilaterally provide special prices to LMIC, charging them based on their income level. However, different income levels exist within the same country and it is difficult for pharmaceutical companies to guarantee that people more able to afford higher prices pay them, rather than paying lower prices. 2. The Medicine Patent Pool for HIV, viral hepatitis and TB treatment. This initiative was established in 2010 to negotiate with patent holders for licenses on medicines for LMIC (Medicines Patent Pool, 2019). 3. Pharmaceutical companies can agree voluntary licensing agreements, allowing generic companies to manufacture products without any patent infringement. 4. Joint ventures between low-income countries that are not yet TRIPS-compliant, with manufacturers from LMIC. One example is the partnership between Cipla, an Indian generics manufacturer, Quality Chemicals, an African generics manufacturer, and the Ugandan government. The African manufacturers gain technology transfer and knowledge, the Ugandan government gets medicines produced locally, creating new jobs, and the Indian generics manufacturer is able to manufacture drugs that are patented in India on African soil (African Financials, 2019).

Question 53

Activity 2 Visit the Gavi Alliance website [http://www.gavi.org/about/strategy/] and familiarise yourself with Gavi Alliance’s main goals and strategy. Consider Gavi’s goals and strategies in terms of the Access to Pharmaceuticals framework (availability, affordability, accessibility, acceptability), focusing on the key challenges to ensuring a ready supply of affordable and good quality vaccines in LMIC. You may want to reflect on and discuss the recent COVID-19 pandemic in your answer.

Answer 53

Summarise and post your findings on the discussion board for feedback from your colleagues and comment on at least one other post.

Question 54

5. Accessibility

Answer 54

Other barriers to access to medicines include factors linked to geographic accessibility, and to good governance of the pharmaceutical supply chain. These are discussed in more detail below.

Question 55

5.1 Geographic accessibility

Answer 55

In LMIC access to health facilities and drug outlets can be a challenge due to poor infrastructure and the remoteness of certain communities, making distribution difficult. This is also the case for rural areas in many high-income countries. Poor accessibility can be evaluated by the number of households located more than 5 kilometres or 1 hour’s journey from a health facility or drug outlet that is expected to have essential medicines in stock. An increase in distance from healthcare facilities is associated with an increase in mortality rates. For example, in rural Malawi the hazard ratio was 1.007 for one additional kilometer [95% confidence interval 1.001 to 1.014]) (Quattrochi et al, 2020). Accessibility is also determined by the average time spent waiting during a visit to a health facility or the average operating hours of the health facility or drug outlet.

Question 56

5.2 Good governance and access to medicine

Answer 56

Accessibility is also determined by the architecture and efficiency of health systems and the pharmaceutical supply chain. Inevitably, accessibility is context-dependent and relies on local capacity and monitoring. It is also important here to talk about ethics in access to medicines and the problems of corruption in the pharmaceutical supply chain. It is estimated that approximately 10–25% of global spending on public procurement is lost to corruption due to weak and un-transparent health systems. The tendering and procurement processes for medicines are susceptible to bribery. Corruption is an important obstacle to social development and to the effective governance of health systems. In 2004, WHO launched an innovative Good Governance for Medicines programme with the goal of reducing corruption in pharmaceutical systems through the application of transparent, accountable administrative procedures grounded in laws and regulation, and the promotion of ethical practices (WHO, 2010). However, weak and non-transparent health systems in low-income countries remain a challenge for access to medicines and for achieving the right to health in general (Langlois et al, 2020).

Question 57

5.3 Measures to improve accessibility

Answer 57

An important development is the recent focus on building health systems in LMIC. Both private and public partners agree on how important it is to improve the supply chain management system and remove other barriers to guarantee as much as possible adequate access to pharmaceutical products. WHO member states adopted the global strategy and plan of action on public health, innovation and intellectual property in May 2008. This strategy was designed to foster innovation and to improve access to medicines for people in LMIC, and focuses on eight main goals including improving delivery and access. A follow-up panel found that these eight goals remain broadly valid but that they have not been implemented as planned, so further priority actions were developed, to be undertaken between 2018 and 2022, including prioritising R&D, building and improving research capacity, promoting technology transfer, and promoting sustainable financing (WHO, 2018c). In addition, WHO agreed on a Medicines and Health Products Programme Strategic Framework (2016–2030) associated with the Towards Access 2030 agenda, which seeks to support Member States to ‘achieve universal access to safe and quality-assured health products and universal health coverage’ (WHO, 2017b).

Question 58

6. Acceptability

Answer 58

The final element of the access to pharmaceuticals framework is acceptability. Acceptability has three main sub-components: quality, which is crucial at the time of manufacture and at the time of consumption by the patient; safety, which relates to identifying as early as possible any unintended consequence of the use of pharmaceutical products; and rational use, which relates to whether patients are taking medicines correctly (see https://www.who.int/activities/promoting-rational-use-of-medicines). These three sub-components are discussed further below.

Question 59

6.1 Quality and safety

Answer 59

Access to adequate and affordable health care is also dependent on the availability and accessibility of affordable, good-quality medicines. The quality of a medical product is evaluated against the product’s intended quality specifications, e.g. purity (or whether it has been contaminated), identity (or the presence of the right active ingredients in the right amounts), dosage (colour, shape, size and consistency), stability or shelf life, or bioavailability (the amount that reaches the blood stream). WHO has a prequalification programme implemented in close cooperation with national regulatory authorities. This programme conducts regular evaluation and inspection activities of manufacturing sites and contributes to building national capacity for manufacturing and monitoring the quality of medicines (see https://extranet.who.int/pqweb/medicines for more information).

Question 60

6.1 Quality and safety

Answer 60

The list of WHO prequalified medicinal products used for HIV/AIDS, TB and malaria is published on the WHO website. It is also possible to report poor-quality medicines after consumption by signalling adverse reactions to specific drugs (pharmacovigilance).

Question 61

6.1 Quality and safety Substandard and falsified drugs

Answer 61

Because the pharmaceutical industry is a very lucrative business, falsified medicines have infiltrated pharmaceutical supply chains. This is a prevalent problem in resource-constrained settings with weak health systems and irregular pharmaceutical quality inspections. Poor quality medicines can be substandard or falsified. Substandard drugs are authorised medical products that fail to meet their quality standards or specifications, or both (WHO, 2018a). Falsified or counterfeit medicines are medical products that deliberately/fraudulently misrepresent their identity, composition or source (WHO, 2018a).

Question 62

6.1 Quality and safety Substandard and falsified drugs

Answer 62

Falsified medicines may contain none or insufficient amounts of the active ingredients and may pose a major threat to public health. Medicine falsification affects both lifestyle and life-saving drugs such as those for TB or malaria. In 2016 a study found that a high proportion of artemisinin-based treatments sold in central Ghana were substandard (Tivura et al, 2016).

Question 63

6.1 Quality and safety Substandard and falsified drugs

Answer 63

Poor-quality medicines can lead to treatment failure or contribute to the rise of drug resistance. These medicines may cause allergies, side effects and adverse drug reactions, or even death due to the presence of toxic products. This is an additional burden on health systems and may have social and economic consequences, such as contributing to a general lack of trust in public health systems (see Choy and Ismail (2017) for an interesting discussion on this topic in southeast Asia).

Question 64

6.1 Quality and safety The role of regulatory authorities

Answer 64

Each country has a medicines regulatory authority which is responsible for several regulatory functions: from licensing premises, practices, and persons and the inspection of manufacturers and distributors to the monitoring of adverse drug reactions. These functions are conducted to guarantee as much as possible that the medicines sold and consumed in a particular market are safe, effective and of good quality. The problem is that regulatory agencies are weak and do not function properly in some LMIC (see Twesigye et al, 2021).

Question 65

6.1 Quality and safety The role of regulatory authorities

Answer 65

While there are noticeable variations between countries, most sub-Saharan nations have limited financial and human resources, affecting their overall capacity to regulate the pharmaceutical market. This lack of a regulatory capacity allows poor quality medicines to enter the supply chain.

Question 66

6.2 Rational use

Answer 66

The WHO describes the rational use of medicines as patients receiving medications that are appropriate to their clinical needs in doses that meet their own individual requirements for an adequate period of time at the lowest cost to them and their community (WHO, 2022b). Irrational use of medicines can occur at different levels: The prescribing level when healthcare professionals prescribe medicines to patients (e.g., the WHO’s Defined Daily Dose Toolkit (WHO, 2022c); The dispensing level when pharmacies are dispensing the medicines prescribed to the patients; and The administration stages when the patients take their medicines on their own.

Question 67

6.2 Rational use

Answer 67

Some examples of irrational use include over-prescription, the most common example of which is the inappropriate prescription of antibiotics: patients may put pressure on their doctors to prescribe as many medicines as possible; this is particularly seen with antibiotics, which are sometimes perceived as the gold standard of care (see Mathew et al, 2020 for an example of this in India).

Question 68

6.2 Rational use

Answer 68

Another example is the prescription of unnecessarily costly medicines, which may be explained by several reasons. Patients might demand expensive medicines in the belief that if a product is expensive, it must be good. Doctors might be encouraged by pharmaceutical companies to prescribe the latest medicine, which may not necessarily be the best or the most cost-effective.

Question 69

6.2 Rational use

Answer 69

Poor adherence might be related to difficult dosage forms, for example when patients are asked to take a medicine every 4 or 5hours or when they are asked to take the medicine for months, like for TB, although measures such as directly observed therapy can be taken to try and address this. Patients may believe that medicines are no longer needed after symptoms resolve. Qualified pharmacists might not be available to make sure administration is appropriate or that products are suitable for patients’ needs due to lack of staffing. Finally, patients may self-medicate, buying medicines over the counter without the advice of a doctor or pharmacist.

Question 70

6.2 Rational use

Answer 70

The consequences of irrational use are multiple. It is not only an inefficient use of limited resources but in many cases morbidity and mortality may increase. In addition, it can encourage the emergence of antimicrobial resistance, which is a problem not just for the patients taking the medicine but for everyone else who may need to use the medicine at some point in the future.

Question 71

6.2 Rational use

Answer 71

WHO lists some policies and recommendations to improve the rational use of medicines, and these go from policies for government to implement to recommendations for health care professionals. Important policies for the government to implement include the identification and promotion of successful strategies that have worked to improve rational use, the strengthening of pharmaceutical regulation in-country and the development of national essential medicines lists and formularies. For health professionals, WHO recommends the development and use of treatment guidelines based on evidence and the implementation of training programmes to better understand the problem of irrational use and its potential solutions.

Question 72

6.2 Rational use

Answer 72

These training programmes are for health care professionals in the public and private sectors, and not just for doctors but also for pharmacists and drug sellers. It is important for consumers to understand and to engage in this process. WHO recommends the creation of a system to empower consumers to take responsible decisions about their health.

Question 73

7. Integrating activity Please conduct some desk-based research on the access to medicines problem for patients with a neglected tropical disease of your choice. Sources could include the Drugs for Neglected Diseases Initiative (www.dndi.org) or Uniting to Combat Neglected Tropical Diseases (www.unitingtocombatntds.org). List one or two main challenges for each of the four components considered here: availability, affordability, accessibility and acceptability. Post your findings on Moodle and check your response with the feedback below.

Answer 73

Your answer will vary according to which disease you chose. Below is an example of a possible answer if you chose an NTD like rabies (see here https://unitingtocombatntds.org/ntds/rabies/):

There is no treatment for rabies, which is fatal, but there is a vaccine. The vaccine can be administered after a bite as well as prophylactically. Some challenges for rabies include:
Availability: lack of a functioning cold chain to transport vaccine to where it is needed, or stock-outs;
Affordability: although the rabies vaccine is often given for free, e.g. in Nepal, travelling to a clinic may be expensive for some people;
Accessibility: although rabies vaccine is available it may not be accessible in remote areas and may cost a substantial amount, both in terms of money and travelling time, to reach a clinic with stock of vaccine, and trained staff may not be present; and
Acceptability: some people may refuse vaccination or deny that it is effective, as has been seen with COVID-19.

Health systems need to be strengthened to ensure that a stock of effective rabies vaccine is always available in clinics, with qualified staff to administer these. It is also important to increase awareness that the vaccine exists, is safe and effective, and that a vaccine is necessary following a bite.

Question 74

8. Summary

Answer 74

We discussed why access to pharmaceuticals is crucial for any health system, including potential effects on a population’s health as a result of lack of access. We covered the wide inequities in access to pharmaceuticals between countries; and how, and why, in certain parts of the world access is extremely limited.

Question 75

8. Summary

Answer 75

We introduced the Access to Pharmaceuticals framework to study the issue of access to pharmaceuticals. This framework shows us how access to pharmaceuticals is impacted by four main elements: Availability: ensuring that pharmaceutical products are produced and delivered, which includes both R&D and distribution activities; Affordability: the relationship between price, patents and additional charges to get the products from the manufacturing plant to the patient; Accessibility: the geographical distance between patients and drug outlets and the efficiency of distribution channels; and Acceptability: safe and effective use of medicines, which includes ensuring that medicines available are of good quality, safe and effective, and that they are used rationally.

Question 76

8. Summary

Answer 76

The session also discussed some overarching factors related to access: sufficient workforce, workable policies, adequate financing, good information systems, and efficient regulation. Finally, we saw how pharmaceutical policy transcends national boundaries and goes beyond the health sector, involving international policy regimes on trade, intellectual property, regulation, and industrial policy.