The Antimicrobial Resistance Regulatory Strategy

Table of Contents

Abstract

Table of Figures

Table of Tables

Chapter 1. INTRODUCTION
1.1. Introduction
1.2. Background of the Research
1.3. Justification of the Research
1.4. Aims, Objectives and Scope of the Research
1.5. Outline of the Dissertation
1.6. Summary

Chapter 2. LITERATURE REVIEW
2.1. Introduction
2.2. Antimicrobial History
2.2.1. Microbes and Diseases
2.2.2. Facing Resistance
2.2.3. Global Action Plan Overview

1.1.1. The Three Pillars
1.1.2. Strategy and Timelines
1.1.3. Summary
1.2. The European Union AMR Strategy
1.2.1. Regulatory Institutions and Organizations
1.2.2. The Antimicrobial Regulation in the EU
1.2.3. The EU Enforcement Against AMR
1.2.4. Summary
1.3. The United States AMR Approach
1.3.1. The US Legal Structure
1.3.2. The U.S. National Plan Outline
1.3.3. The US Enforcement Against AMR
1.3.4. Summary
1.4. Comparison of Strategy
1.4.1. National Policy
1.4.2. Antibiotic Stewardship
1.4.3. Incentives, Budgeting and Costing
1.4.4. Outside Aspects
1.4.5. Summary
1.5. Conclusions

Chapter 2. METHODOLOGY
2.1. Introduction
2.2. Research Design
2.2.1. Choice of Research Methods
2.3. Population and Sampling
2.4. Data Collection
2.4.1. Questionnaires
2.4.2. Semistructured Interviews
2.5. Data Analysis
2.6. Validity, Reliability and Bias
2.7. Ethics
2.8. Limitations
Page 4 of
2.9. Summary
2.10. Conclusions

Chapter 3. PRESENTATION AND ANALYSIS OF DATA
3.1. Introduction
3.2. Questionnaire Results
3.2.1. Awareness and Communication
3.2.2. Antibiotic Usage
3.2.3. Changes in Legislation
3.2.4. Summary
3.3. Interview Results
3.3.1. Regulatory Approaches
3.3.2. National Plan Implications
3.3.3. Challenges and Practicality
3.3.4. Out of Scope Aspects
3.3.5. Summary
3.4. Respondent’s Recommendations
3.5. Conclusions

5.1. Introduction
5.2. Discussion
5.2.1. Findings in Relation to the Research Objectives
5.2.1.1. The EU and US Approaches on AMR (RO1)
5.2.1.2. Plan Implementation Impacts (RO2)
5.2.1.3. Challenges and Practicality (RO3)
5.2.1.4. Out of scope Aspects (RO4)
5.2.1.5. Summary of Findings
5.3. Key Conclusions
5.4. Limitations and Recommendations for Future Research
5.5. Research Reflexions
5.6. Final Conclusions

REFERENCES

APPENDICES

Table of Figures

Figure 1 Roadmap Chapter 1

Figure 2 Antimicrobials & Resistance Timeline

Figure 3 Roadmap Chapter 2

Figure 4 Geographical Zones

Figure 5 The GAPAMR 's Five Objectives [[5]]

Figure 6 The Three Pillars

Figure 7 Stakeholders Umbrella [[5]]

Figure 8 Antimicrobial Fight in the EU

Figure 9 EU Institutions [[39]]

Figure 10 Awareness Campaigns in the EU

Figure 11 US Legal Structure

Figure 12 U.S. Task Force

Figure 13 US Awareness Campaigns

Figure 14 2050 AMR Death Projection [[8]]

Figure 15 R&D of Drug Development [[105]]

Figure 16 Roadmap Chapter 3

Figure 17 Research Approaches: Deduction and Induction [[112]]

Figure 18 Phenomenological Data Analysis [[109]]

Figure 19 Roadmap Chapter [[4]]

Figure 20 AMR Awareness

Figure 21 Antibiotics Replacement

Figure 22 Growing population

Figure 23 Roadmap Chapter 5

Table of Tables

Table 1 Microbes Defence Measures [[1]], [[17]]

Table 2 Antibiotics Classification List [[25]]

Table 3 GAPAMR Endorsements [[38]]

Table 4 Guidelines Aiding the Registration of Antibiotics

Table 6 Measures to Reduce Infection Incidents

Table 7 List of Some of the Available Vaccines

Table 8 US National Plan on AMR [[31]]

Table 9 Examples of Antibiotic Stewardship Programs in EU and US [[100]]

Table 10 Cost of funding at national level over 10 years [[8]]

Table 11 Research Principles [[109]]

Table 12 Sampling Criteria

Table 13 Participants Details Questionnaires

Table 14 Participants Details Interviews

Table 15 Interview Process

Table 16 The fight against AMR is well communicated (Qn9)

List of Acronyms

illustration not visible in this excerpt

Abstract

Some years after the first use of penicillin, resistant bacteria emerged. The phenom enon of resistance has continued to show up similarly for almost every marketed antibiotic product, endangering the safety of humans, animals and the environment.

This major threat has been proven to have a worldwide impact. In response, national action plans must be implemented following “antiresistance” guidance: WHO’s Global Action Plan on Antimicrobial Resistance (GAPAMR) in collaboration with FAO and OIE. These plans are to be adopted by 2017, aiding the protection of antibiotic medicines adhering to the approach of One Health.

The aim of the current study was to review the process of such adoptions in the EU and US, understand its practicality, challenges and any out of scope issues.

With the use of a phenomenological approach, this qualitative study found that thanks to the general population’s increment in knowledge and awareness, collaboration and engagement grew stronger, especially among policy makers and pharmaceutical companies, but also healthcare leaders and providers, physicians and veterinarians, and patients.

When trying to discover new antibiotic drugs, serendipity is not an option, therefore, companies must be incentivised to increase their antibiotic pipelines. During the analysis of the inclusion of the plans, a paradox appeared: due to the reduced use of antibiotics, it is difficult to motivate drug developers to increase research in new medicines and alternative forms of treatment. The research concluded, that legislation must be focused on supporting changes that will ease entry of antibiotics to the market (i.e. with a congruent regulatory pathway and/or with financial support of governments) to allow a practical inclusion of the national plans.

CHAPTER 1. INTRODUCTION

1.1. Introduction

Known worldwide for their magnificent contribution to a healthy environment, antibiotics (AM) a have been of much value since their unintended moment of discovery, in 1928. That revolutionary event changed the way infections are combatted, and ultimately, cured. [[1]]

“We can invent things on our own,

but we are likely to find great ideas and innovation just by looking in the dirt”.

Roy Kishony [[2]]

To the contrary, antibiotic resistance (AMR) an inevitable phenomenon that comes hand in hand with antibiotic usage , has been called an “apocalyptic scenario” by Wardle (2016). [[3]] It is one of today’s biggest menaces, carrying substantial implications to the health of humans, animals and the environment, affecting economic, social, and medical aspects, among others.

With the intention of evading a “postantibiotic age”, [[4]] a multisector coordinated action has been called during the World Health Assembly (WHA) in May 2015: The Global Action Plan on Antimicrobial Resistance (GAPAMR). [[5]] The strategy of this plan conveys a way to coordinate the many international sectors and actors. The initial harmonization efforts should be visible by the 2017 WHA.

The race against losing antibiotic efficacy involves a numerous national and international sector, such as governments, private and public healthcare insti tutions and organizations (i.e. the food and pharmaceutical industries), as well as patients. [[3]], [[5]]

a Antimicrobial medicines kill (or stops the growth of) microorganisms. Antibiotics are included in such group. This dissertation equally references antimicrobials and antibiotics; therefore, the acronym AM will refer to any of the two.

This dissertation will examine the potential usefulness of the GAPAMR in the EU and the US, which propagates its global regulatory approach into national plans using its regulatory recommendations, together with the challenges that have been faced.

The following sections provide a description of the background, justification, aims, objectives and scope of the research, as well as an outline of the dissertation and a summary (see Figure 1).

illustration not visible in this excerpt

Figure 1 Roadmap Chapter 1

1.2. Background of the Research

“Resistance is inevitable,

the best we can do is to try to reduce it as much as possible”

Terry Roemer

Despite the steps that some nations (i.e. UK) have taken over the years pro posing and acting in favour of reducing antimicrobial use (AMU), the AMR is a problem that places a mayor burden on international health. [[1]], [[3]] For instance, the UK’s Swan Report of 1969 incited the Food and Drug Admin istration (FDA) Task Force of 1972 to “evaluate the animalhealth and human health implications on feedadditive usage of antibiotics”. In this case, the con clusions stated that the hazards “were neither proven nor disproven” (Hays et al, 1986). [[7]]

These results evidenced the problem of lacking enough data to back up the delivery of a proper solution, hence, the experts of the time failed to acknowledge the resistance situation.

Nevertheless, the fight against AMR had undergone many changes over the years, mostly in terms of international collaboration (which involves the sharing of information). But there are still several necessities promptly indicated in the GAPAMR: awareness, surveillance, reduction of incidence of infection, medicine optimization, and innovation.

Regardless if the tactics taken differ from nation to nation, collaboration is highly important; no individual approach will manage to reach these goals alone. The lifetime costs of not acting are estimated to be unnerving: by 2050, 10 million lives a year will be at risk according to the estimations of O’Neil (2016). [[8]]

With the inclusion of these national action plans the forces united against resistance increased, salvaging antibiotic effectiveness. [[1]], [[2]]

1.3. Justification of the Research

The diminishing efficacy of antimicrobial medicines has led to limited and expensive treatment options. A global state of emergency has been raised due to the millions of deaths caused by bacterial infection that otherwise could have been prevented with existing antibiotics.

The call to implement national action plans in the EU and US, via multidisciplinary teams, is based on the WHA68.7 resolution from WHO, FAO and OIE. Ultimately, both regions pursue different approaches to satisfy the rationale behind their initiatives. It is appropriate to investigate those approaches and evaluate if the inclusion of those national plans is viable.

1.4. Aims, Objectives and Scope of the Research

The aim of the research is to investigate the practicality of the inclusion of na tional action plans in the EU and US. The research objectives and questions are:

Identify, examine and compare the national approaches on antimicro bial resistance in the EU and US.

What is the regulatory status of those regions?

Observe the impact (if any) of the inclusion of national action plans in those regions.

Investigate the practicality as well as the challenges of the national action plans.

What are the pharmaceutical industry perspectives in achieving the national plans’ goals?

What are the foreseeable issues in implementing the national plans?

Investigate what significant aspects lie outside the scope of the GAPAMR and their importance.

In scope are the EU and US national action plans, their inclusion and integration into regional legislation as agreed by the triparty. Other countries are out of scope; some comments might be included on regards to other countries’ approaches, but those will be only demonstrative.

1.5. Outline of the Dissertation

The Antimicrobial Resistance Regulatory Strategy is arranged as follows:[[9]]

Chapter 1 The Introduction addresses the background of the dissertation.

Chapter 2 Presents a critical analysis of the Literature Review to form a context that leads to an evaluation of the research topic.

Chapter 3 Includes the Research Methodology, a process in which the research objectives are going to be answered using a governing philosophy.

Chapter 4 Displays, in a logical flow, the Analysis of Findings obtained from the primary research.

Chapter 5 Poses the Discussion of the findings in a critical and analytical matter, highlighting its significance in accordance with the re search objectives, and presents the Conclusions that recapitu late the plan on which this dissertation was based.

1.6. Summary

This chapter presented the research strategy to be followed to investigate the practicality of the inclusion of national action plans in the EU and US.

It provided the background of antibiotic resistance and the challenges it entails. It also included the reasons why this study was created, in form of a justification, supported by the aims, objectives and questions to be analysed and answered with the use of a strong methodology. It finished with a brief description of the following chapters.

CHAPTER 2. LITERATURE REVIEW

2.1. Introduction

The momentum that brought better healthcare to humanity, animals and the environment was marked by the discovery of antibiotics in the 1940s. But, because of their use, and almost immediately after their introduction, resistant bacteria started to appear (see Figure 2).

illustration not visible in this excerpt

Figure 2 Antimicrobials & Resistance Timeline

The rapid development and proliferation of these microorganisms is today’s cause of a combination of infections that are difficult to treat and extreme cure costs for humanity. In contrast is the excessive consumption of antibiotics for agricultural purposes which can be considered as suitable or not, depending on the viewer. [[10]]

“Bacteria are very promiscuous!

They share genetic elements freely and willingly.” INFECTIONNET [[11]]

This problem is generating a worrying situation on a global scale. [[1]] Today, there are still countries that allow procurement of antibiotics without prescription, which, together with the existing black market which makes drugs easily avail able through the internet are increasing the chances of resistance to flourish.

For this dissertation’s purpose, special attention is given to the inspiring work of the 2015 GAPAMR which is expected to be at least initially implemented by May 2017.

According to O’Neill (2016), those alliances are hoping to achieve the following goals: [[8]]

1. Global public awareness campaigns
2. Global innovation funds
3. Greater market entry rewards
4. Better diagnostic market stimulus
5. Reduction of antibiotics in agriculture

Henceforth, domestic and international work is aimed to prevent, better detect and control diseases by successfully applying the GAPAMR recommended measures.

Failure to achieve these goals could assure the return of frightening times. Times, where 80 years of achievements in medicine could be worthless be cause of a simple cut in the hand that could lead to a severe untreatable infec tion.

This study was concerned with the movement that occurred in the EU and the US particularly, promoting change in the way AMR is viewed. A shifting from hard science to popular science can be observed.

To investigate those changes, this chapter attempts to describe the AM history, together with the significance of what resistance is. Such an outline is some what methodical, but it provides a baseline for an explanation of how AMR works.

In later sections, the past and current situation of the GAPAMR as well as its strategy and timelines are provided, together with an analysis of the application of this global project in both regions, overseeing their legal structures and reg ulations.

Finally, in the last section of this chapter, a comparison of the applied strategy is included: The confronted challenges and some of the outside aspects that might weaken the measures taken against AMR. The following Figure 3 illustrates this chapter’s content.

illustration not visible in this excerpt

Figure 3 Roadmap Chapter 2

2.2. Antimicrobial History

In 1942, the first human use of Penicillin was documented; by 1949, seven years later, an article regarding resistance to it was written (Osteomyelitis producing Staphylococcus aureus). [[12]], [[13]] Resistance continued to appear with the passing of the years (see the previous Figure 2). Today’s difference is the scale of the challenge we face: it has been globalized.

AMR is happening all over the world, and it is having severe consequences for humans, animals and the environment, also called “the three pillars” (GAP AMR, 2015). [[5]] Understanding how resistance functions has been a necessity over the years, and the implications of it have demanded from public and pri vate organizations to achieve, on top of other issues, urgency of action.

2.2.1. Microbes and Diseases

The continuously increasing world population (7.6 billion people today, which is estimated to rise to 9.8 billion by 2050, according to the United Nations) [[14]] is making pathogen transformation easier (with the potential to cause diseases). [[15]] Agriculture another human footprint brings about foodborne contamination (rising as primary source, handlerassociated, or zoonotic). It has been the source of many of the currently existing infectious diseases, i.e. influenza A or rotavirus, among others (see Appendix A).

Some differences in diseasecaused microorganisms derive in the location of their appearance, as shown in Figure 4, the geographical zone (temperate or tropical) have a profound influence on the appearance of diseases. The animal reservoirs and insect vectors, for example, are more frequent in the tropics. Moreover, temperate diseases tend to be rather acute than long last ing, or chronic. [[16]]

illustration not visible in this excerpt

Figure 4 Geographical Zones

The way drug resistance works can be described with the “Evolution of Drug Resistance”. This theory explains the great issue that is AMR (see Appendix B). [[17]], [[18]]

This process is occurring to a variety of fungi, viruses, insects, bacteria and plants, affecting a range of corresponding products: fungicides, antivirals, insecticides, antibiotics and herbicides, respectively. The way microorganisms (also called “Superbugs”) [[19]] protect themselves from these products is listed in Table 1. [[1]], [[17]]

illustration not visible in this excerpt

2.2.2. Facing Resistance

As seen in the previous paragraphs, AMR is a multifaceted situation, and coping with its consequences is turning frightening (Frieden Tom) [[20]]. Global WHO estimations from 2014 showed that 826,000 children (1 to 59 months) that faced AMR did not survive. [[20]], [[21]], [[22]]

In the US, the death toll from the two million people infected per year is 23,000; EU estimations are up to 25,000 deaths. [[23]], [[24]]

The classification of AM (see Table 2) alleviates the situation by advising and controlling product use.

Guidelines adopting these measurements (i.e. 2013 Guideline on the as sessment of the risk to public health from AMR; 2012 FDA Guidance for Industry #209 Judicious use of medically important antibiotic drugs in food producing animals), are exposed to the international regulatory affairs con text aiming for harmonization (like the use for medicines containing “Criti cally Important Antimicrobials, or CIA), especially in the EU, US and Japan.

26, 27, 28, 29

illustration not visible in this excerpt

2.2.3. Global Action Plan Overview

The GAPAMR was born from another international initiative called the One Health approach of 2011, a notion that embraces the holistic idea of preventing the risks coming from the interaction between the three pillars.

By 2014 WHO had used its resources to publish an AMR global report in which it communicated the prohibition of India’s over the counter (OTC) antibiotic products.

The following year, during the 2015 41st G7 Summit in Germany this document was endorsed (see Table 3). [[38]] WHO, FAO and OIE are maintaining the overview and creating the path to achieve extensive worldwide implementation of GAPAMR. [[5]]

illustration not visible in this excerpt

Additionally, the US became a vital participant by committing to save antibi otic’s efficacy; the national government included the “National Action Plan for Combating AntibioticResistant Bacteria” in their agenda in March of 2015. [[31]]

The GAPAMR enlists five objectives (see Figure 5). Governments aim at promoting them to minimize AMU in humans and animals that do not necessarily need them. But the general objective is to maintain the efficacy of antimicrobial drugs by: [[5]]

a) Better management (lowering their demand, reducing their use, and reaching availability for all); and

b) Creating solutions on how to increase the development of new AMs.

illustration not visible in this excerpt

Figure 5 The GAPAMR 's Five Objectives [[5]]

1.1.1. The Three Pillars

The One Health approach acknowledges that wellbeing as well as aggravation of one pillar is intrinsically related to the other two (see Figure 6).

To combat infectious diseases (acquired endogenously or by external fac tors) humans and animals alike, rely on antibiotics: Be it facing surgical pro cedures (prophylactic causes) or other treatment motives (i.e. metaphylactic support).

illustration not visible in this excerpt

Figure 6 The Three Pillars

In addition, the environment also needs protection against environmental bacteria (that stem from the copious quantities of livestock and human waste and circle back to humans and animals), hence the usage of AM’s.

Working according to sanitation and hygiene procedures (like managing the waste of domesticated animals that contaminate the water going into produce fields) can help minimizing the transmission of zoonotic pathogens generating foodborne viruses.

That is not a simple task, because even wild life is contributing to these transmissions (i.e. deer feces contaminating strawberry fields and getting people ill with E. coli). [[15]], [[32]]

In addition, touching back on the point of globalization, the designs supporting the food systems, the food production, and its supplydemand driven culture (necessities of cities like the rapid development in food preservation), incurred in the GAPAMR’s fight to intensify a food production that is safe, sustainable, and widely available. [[33]]

1.1.2. Strategy and Timelines

For the global plan to work out, everyone who either approves, prescribes, utilizes, distributes, manufactures, and/or destroys antibiotics needs to be on board (see Figure 7). Therefore, the most promising strategy is to strengthen alliances and increase trust in each other, with the intention of achieving success executing the GAPAMR’s objectives explained in the fol lowing paragraphs. [[5]], [[18]], [[31]]

illustration not visible in this excerpt

Figure 7 Stakeholders Umbrella [[5]]

Figure 8 illustrates the work performed over the last two decades showing people’s interest in this phenomenon. [[34]], [[35]], [[36]]

Such activities have instigated and complemented the development of the multisector provisions of the GAPAMR. [[29]]

The actual execution is being handled by: a) The Member States (MSs); b) The Secretariat; and c) International and National Partners.

illustration not visible in this excerpt

Figure 8 Antimicrobial Fight in the EU

The following paragraphs show each GAPAMR objective’s significance, and policies for its achievement. All the objectives that need to be escalated into national action plans should be ready for implementation by 2017. [[5]], [[21]], [[37]]

(Objective 1) Awareness and Understanding

Awareness, which is achievable through change in the way AMR is looked at in the human, animal and agricultural sectors. Unfortunately, those sectors do not have an equal way of proceeding. Antibiotics are used too much or too little, and sometimes unwisely.

Understanding the patterns of use start within the professional area’s school curricula, and continue through all their careers with additional training and education. Consumers on the other hand can be informed via public communication programs.

The size of awareness campaigns depends on the budget; but even with moderate funding, they can succeed when properly designed and man aged. [[8]]

(Objective 2) Knowledge, Surveillance and Research

There are several windows of opportunities to improve the current prob lems that involve how the information is gathered, shared and commu nicated. The lack of harmonized standards of reporting and collecting the data throughout the three sectors is also covered in this point.

Countries that have more economic capabilities (like the EU and US), can more easily handle the massive amount of daily data generated from AMU and AMR (i.e. drug resistance rates, and resistance characterization), even if is not homogenously gathered.

Low and middleincome countries lack proper surveillance and offer drugs that are uncontrolled and unmonitored. Those countries can benefit from the work accomplished by international networking.

The data gathered will provide a general overview of pathogens, rates and geographical patterns that can lead to learning on how to characterize new resistant pathogens.

It is important to be able to maintain the existing diagnostic tools upto date by improving them, or developing new ones. A basic and economic research through clinical studies and cost assessments will support that by helping in the identification of alternatives (like vaccines) and the cost/benefit of such interventions. [[8]], [[18]]

(Objective 3) Preventive and Control Measurements

Minimizing AMU can start by stopping infection spreads, which can be controlled better by promoting education and training about control methods to avoid these incidences. [[5]], [[18]]

Firstly, by improving sanitation through better hygiene. Avoiding infections is not only a core task for healthcare facilities; measurements like washing hands and food should be considered everyone’s responsibility. Another control measure in humans is the prevention of infection through sexual intercourse or drug injections.

Secondly, innovating diagnostic tools that are quick, inexpensive and easy to operate will help identify between viral and bacterial strain, and their sensibility to the drug product at hand.

Thirdly, good animal husbandry practices for livestock and aquaculture as well as environmental health for crops, will certainly help reducing antibiotic use.

Vaccination can help achieve these colossal tasks because it can prevent and reduce the occurrence of infection before the use of antibiotic treatment. And, even though vaccines are not effective for all bacterial strains, there are promises for new vaccines to be developed including some that are antibiotic resistance specific. [[1]], [[38]]

(Objective 4) Optimization of Medicines

Optimizing medicine by means of better enforcement of the regulation (like with OTC products, and internet sales of antibiotic medicines), and the generation of rapid diagnosis for prescription.

AM drugs are a public good. In supporting this acknowledgment, this objective helps reinforcing their safety in the way they are made, distributed, and used.

In the same direction as the previous objective, the creation of new di agnostic tools that are quick and cost effective, will support practitioners and pharmacists in issuing accurate and appropriate prescriptions.

(Objective 5) Development of New Medicine and Other Alternatives

The investment for new medicines, and other alternatives like vaccines, needs to be supported with an optimization of the current process for developing and bringing new medicines to market. If this incentive is lacking, the industry will not step forward on this issue.

Companies that aspire to provide customers with a benefit through their products, are also looking at volume of sales and prices. When future revenue is limited by restricting the use of a drug that is taking too long and is too expensive to be put on the market, the development and man ufacturing of antibiotic products will no longer be an enterprise attractive enough to be pursued.

Hence, changes in legislation need to be done to get investment renewed. Forums (i.e. WHO, 2014) have been observing cases, and analysing the impact that the economics have over this point to be able to assess the cost/benefit of development. [[1]]

1.1.3. Summary

In the past decades, microbes developing resistance have let to decreasing efficacy of antibiotic medicines due to:

A continuously growing population that has propagated the use of antibiotics for decades, affecting the way resources like foodproducing animals, and the environment are utilized.

The lack of harmonization for banning antibiotics (i.e. use for growth promotion) have shown the different paths of governments, some of them taking decisions without “thinking global”.

The One Health Summit of 2015 has faced this concern in an integrated multisector approach for the three pillars Humans, Animals, and the Environment in a way of protecting the future population.

Resistance develops, no matter the source and/or path (though the food chain or human transmission) because antibiotics are used irresponsibly, affecting everyone. Luckily, studying the issue has helped come up with solutions on how to tackle it.

In relation to this, the GAPAMR supported by WHO, FAO and OIE, has been designed and put into action by making effective five strategic objectives (awareness, surveillance, prevention, optimization and innovation); ex pected to be internationally in place by the WHA in May 2017. The inclusion of new and updated guidelines, derived from the plan, is assisting organiza tions, private and public, as well as local agencies, in supporting the cause.

1.2. The European Union AMR Strategy

The political structure of the European Union regarding their governing bodies is complex. Nonetheless, the regulatory authorities cope with the singularities of the bureaucracy around their members, and serve as a liaison for finding synchronicity in how they work with organizations, the industry, healthcare pro viders, and other intermediates. That way, the national competent authorities (NCAs, human and veterinary alike) come to an imperative agreement in ac cordance with the global plan. [[1]]

1.2.1. Regulatory Institutions and Organizations

The EU institutions, shown in Figure 9, oversee the legal framework for the creation of the “binding decisions on the authorization of medicines that comply with high quality, safety and efficacy” (EMA, 2017). [[39]]

illustration not visible in this excerpt

Figure 9 EU Institutions [[39]]

In general, the adoption of legislation comes from the resolutions of the European Parliament and the Council. [[40]] Matters concerning communicable diseases such as AMR, are specifically connected through the Employment Social Policy, Health and Consumer Affairs Council (EPSCO).

[...]