Public Consultation GAP on AMR - European Commission Page 1

Consultation on a draft Global action plan to address antimicrobial resistance

EUROPEAN COMMISSION and its agencies (EFSA, EMA and ECDC)

The questionnaire is divided into four sections. The questions are broadly framed and intended to

give you the opportunity to enter into some depth and explain your organization's viewpoint. While

only questions marked with * are mandatory, we would appreciate answers to as many as possible.

Where a choice of answer needs to be selected please highlight your answer.

Before answering the questions, please refer to our list of supporting documents.

http://www.who.int/drugresistance/amr-consultation/en/index.html

1. Name of individual respondent*

(deleted)

2. Email address* (preference for official email addresses)

(deleted)

3. Are you authorised to represent your organization or interest group?* Yes

4. Organization Name*

European Commission including its agencies: the EMA (European Medicines Agency), the EFSA

(European Food Safety Authority) and the ECDC (European Centre for Disease Prevention and

Control)

5. Address of the organization*

B-1049 Brussels, BELGIUM

6. Organization website (if available)

http://ec.europa.eu/

7. Country*

Belgium

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8. Type of Organization*

• Government department, ministry or agency

• Development or aid agency, foundation, trust or other funding authority

• International developmental organization

• Academic institution

• Civil society

• Private sector

• Other non-governmental organization (NGO)

• Other (please specify): International Institution

9. Main sector of interest:

• Human health

• Animal health

• Finance/economics

• Agriculture or food

• Environment

• Communication, education and community

• Other (please specify): All these sectors, including Research and Innovation, Development

and Cooperation

10. Would you like to be added to our mailing list to receive updates on the development of the

global action plan?* Yes

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General questions

1. From the perspective of your organization, what are the most important areas of concern

in AMR?

To contain the rising threat from Antimicrobial Resistance a holistic approach, based on the "One

Health" concept, with engagement from all relevant sectors, including human and animal health,

agriculture, environment and research, is needed.

Measures in all areas (for example the promotion of the appropriate use of antimicrobial agents in

human and veterinary medicine, the prevention of microbial infections and their spread, the

development of new antimicrobials and alternatives for treatment or diagnostic tools, the

harmonisation of surveillance systems, the establishment of education and training programs and

early warning systems and trend watching) need to be implemented in parallel in order to effectively

address AMR.

These can only be achieved if a multi-sectorial approach is adopted with involvement and

commitment of all governments and concerned stakeholders.

2. Is your organization currently involved in work related to AMR? If Yes, How?

Yes. Over the past decades, the European Commission has developed a series of EU-wide policy and legislative initiatives for the prevention and control of AMR. Some examples are: In human medicine, the 2001 Community Strategy against AMR called for EU initiatives in the fields of surveillance, research, prevention and international cooperation. This led to the adoption of EU-wide recommendations and guidelines against AMR to be implemented by EU countries. In order to collect data on AMR, EU wide surveillance systems were set up to monitor the spread of AMR and the consumption of antimicrobial agents. In 2008, the EU launched the European Antibiotic Awareness Day. This annual event aims at increasing awareness on AMR and promoting the prudent use of antimicrobial agents. In animal husbandry, a ban on the use of antimicrobials for growth promotion was introduced in 2006. In the veterinary field, EU law calls for the harmonised monitoring of zoonotic AMR (resistance transmissible between animals and humans). It also focuses on monitoring the use of antimicrobials in animals. Authorisation requirements for human and veterinary medicines, and other products such as food enzymes, probiotics and decontamination agents, with possible effects on the development of AMR are also kept in focus. EU-funded research: During the last 16 years, the European Union has awarded nearly €950 million to transnational collaborative projects on antimicrobial resistance, most in the area of human health, but also in the areas of animal health, food and environment. This includes around €155 million for AMR research supported via the Innovative Medicines Initiative (IMI). This is supplemented by a €165 million contribution from the pharmaceutical industry.

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Stronger international cooperation against AMR: the EU has been working actively with international organisations such as Codex Alimentarius, FAO, OIE or WHO. Bilateral contacts have also been set up. In 2009, the EU and the United States of America set up a Transatlantic Task Force against AMR (TATFAR). A progress report has been published.

To further strengthen its commitment, the European Commission launched in November 2011, a five

year Action Plan against the rising threats from Antimicrobial Resistance. The Plan is based on a

holistic approach, in line with the "One Health" concept, involving all sectors and aspects of

antimicrobial resistance. Prudent use of antibiotics in human and veterinary medicine, enhanced

surveillance systems, development of new antimicrobials and prevention of infections are

implemented in parallel to effectively address AMR. The Action Plan substantially reinforces the

measures already in place and introduces an additional set of rigorous measures to prevent and

control the further spread of resistance, preserve the ability of antimicrobial agents to combat

microbial infections and securing the availability of new antimicrobial agents.

The plan describes 12 detailed concrete key actions in 7 different attention areas, both in the human

and veterinary field.

The actions put forward in the plan aim to:

Mitigate the risk of developing antimicrobial resistance in humans by ensuring appropriate

and prudent use of antimicrobials both in humans and animals;

Introduce new effective measures to prevent microbial infections and their spread;

Develop effective antimicrobials or alternatives for treatment of human and animal

infections;

Join forces with international partners to contain the risks of spreading antimicrobial

resistance from international trade and travel, and via the environment;

Harmonise surveillance systems (use of antimicrobials and antimicrobial resistance);

Reinforce research to develop the scientific basis and innovative means to combat AMR;

Improve communication, education and training.

The detailed Action Plan (Communication from the Commission to the European Parliament and the Council,- Action plan against the rising threats from Antimicrobial Resistance; COM(2011)748 which has been translated into the official languages of the EU) includes the description of the 12

actions. A Road Map detailing the operational objectives and the concrete activities and deadlines for

each of the 12 specific actions described in the plan, as well as other information such as research

activities, conferences, legislation, etc. are publicly available at the websites of the European

Commission (DG Research and Innovation, DG Health and Consumers) and its agencies (EFSA, EMA

and ECDC). In October 2014, the European Commission will publish a progress report on the

implementation of the Action Plan.

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Questions about the draft global action plan outline document

Before the WHA resolution was adopted, two WHO AMR Strategic Technical Advisory Group (STAG)

meetings were held in anticipation, which included members plus a large number of representatives

from other organizations. These meetings identified key issues, concerns and led to the

development of a draft outline.

As this consultation progresses and stakeholder meetings are held, the secretariat will harvest and

incorporate the input into the draft global action plan.

1. How would you rate your understanding of WHO’s intention in the development of a

global action plan to address AMR?

Very good

Additional comments

2. From the perspective of your organization, are the major issues relating to AMR outlined

in the draft global action plan? Yes

If No, what additional issues need to be addressed?

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Questions on the ‘Building blocks’ described in the draft outline.

You will notice, the global action plan has been constructed around “building blocks” in recognition

that different countries will have different starting points. In this situation, countries can choose

building blocks to concentrate upon. Each building block specified has been identified as a key area

where specific attention, planning and work are needed to achieve progress in addressing AMR.

Through questions in this section, we would like to hear your opinions on these building blocks in

more detail.

I. Building block-1: Increasing awareness and understanding about AMR and of the actions and

changes needed

a) What do you consider to be the main issues under this priority?

Political and societal awareness on the threat of AMR is needed to ensure the implementation of measures to combat antimicrobial resistance, especially the inappropriate use of antibiotics, and to drive research and innovation. Global estimates are that more than 50% of all medicines are prescribed or dispensed inappropriately, i.e. with a wrong indication, dose, or duration. In addition, about half of all patients do not take their medicines as directed. This has serious health and economic consequences. For example, inappropriate use of medicines increases the risk of adverse medicine events and contributes to the increase in antimicrobial resistance worldwide. Improving antimicrobial use by educating the general public and the healthcare professionals of the importance of prudent use of antimicrobial agents is key to address the issue. More particularly, raising awareness of the problem of antimicrobial resistance and encouraging realistic public expectations for the prescriptions of antimicrobial agents. Furthermore, producing, harmonising and disseminating guidelines for infection prevention to decrease the transmission of bacteria that are resistant to antimicrobials in healthcare settings. In general, investment by the pharmaceutical industry in promoting their products is much higher than investment by governments in promoting rational use of medicines or providing independent medicines information. b) What are the main actions that needs to be done -- and who are the main actors/stakeholders

who need to take action -- to go beyond the status quo?

Awareness rising is a key element in order to minimize the development of AMR. In the human field, awareness needs to be increased in public health and healthcare facilities, targeting both consumers and health care professionals. Regular and periodically updated local, national, regional and global public information campaigns on the importance of prudent antibiotic use targeting the general public, healthcare professionals (e.g. primary care/hospital prescribers, nurses etc) and involve other relevant stakeholders with a view to educate and raise awareness on the threat of antimicrobial resistance. These campaigns should include strategies to address behavioural aspects. This could be done by using social marketing principles and techniques and/or involving behavioural scientists to support awareness campaign planning and material. The impact

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of those campaigns should be regularly evaluated and monitored. Good level of coordination of activities could be reached by promoting the creation of mechanisms such as e.g. national organising committees with all relevant stakeholders. The creation of a national operative committee, made up of key stakeholders in the area of AMR and HAI, who report to the Ministry of Health in each country with the mandate to make this operative, “inter-sectoral committee” mandatory with the goal to harmonise practices and ensure their implementation in each country. Furthermore, the prudent use of antimicrobial agents should be included in the training curriculum of healthcare professionals. Auditing best practices and indicators with feedback to frontline healthcare workers and healthcare settings. In the veterinary field, all involved parties (farmers, veterinarians, professionals involved in animal production, universities, pet owners, etc.) need to be correctly informed by regular campaigns. The active involvement and support of the relevant networks and stakeholders associations are essential in order to guarantee the success of such campaigns. The competent authorities should include the campaigns in their national strategies. The campaigns should not be limited to the distribution of information but should include practical tools to encourage the implementation of all the actions/behaviour aimed at reducing AMR. The campaigns may include (national) guidelines and education programmes to encourage hygiene practices, infection prevention or transmission, correct treatment, appropriate use of antimicrobials. Examples: treatment guidelines for veterinarians, seminars or post-graduation programs for health professionals, posters, social media, etc. Campaigns should also be targeted at consumers to strengthen their knowledge and their willingness to demand food produced in systems requiring as low an amount of antimicrobial agents as possible. In developing countries there is an extensive body of research on strategies to address inappropriate medicine use. The most effective interventions are those with multiple components addressing prescriber and patient education and supervision, and community case management (Holloway K et al: Medicines use in primary care in developing and transitional countries; Results from studies reported between 1990-2009; Presentation at the Third International Conference on Improving Use of Medicines; Turkey 2011). Advocate for ethical medicines promotion in developing countries by originator and generic companies should be also considered. The use of the results of the Access to Medicines Index ranking in public fora could provide an incentive to industry to improve their ranking.

c) What steps have already been taken to address this priority? (please provide references where

possible)

See Road Map and progress report of the EU Action plan, and the internet sites of DG SANCO, EFSA,

EMA and ECDC.

See for example, the results of the Eurobarometer 2013, some conferences or other events on

Antimicrobial Resistance organized or supported by the European Commission and its agencies, the

European Antibiotic Awareness day, etc. The EC will publish by the end of 2014 Guidelines for prudent

use of antimicrobials in veterinary medicine; this document will include an annex with practical

examples of national strategies in the EU Member States to combat antimicrobial resistance in the

veterinary sector. An ongoing study funded by the European Parliament (“Antimicrobial resistance

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and causes of non-prudent use of antibiotics in human medicine”) will identify key factors that drive

the sales and non-prudent use of antibiotics in human medicine obtained without prescription, assess

the level of enforcement of the legal prescription-only requirement for antimicrobial agents in the EU,

and document best practices aimed at strengthening a more prudent use of antimicrobial agents.

Building upon several very successful public information campaigns in EU Member States (e.g. France

and Belgium) which have resulted in a decrease in antibiotic prescriptions, European Antibiotic

Awareness Day (EAAD) was launched in 2008 as a European health initiative coordinated by the

European Centre for Disease Prevention and Control (ECDC). This annual initiative takes place every

year on 18 November in all EU Member States and beyond with several non-EU European countries

participating. This initiative is also coordinated with other key international similar initiatives

(WHO/Europe, USA, Australia, Canada, etc.) . As part of this campaign, fully referenced template

materials and supports countries with press and media toolkit including ECDC latest data and

information on antimicrobial resistance and healthcare-associated infections, TV spots, infographics

etc. are prepared.

Ethical promotion is included as an indicator in the Access to Medicines Index which scores adherence to the International Federation of Pharmaceutical Manufacturers & Associations’ marketing code, extension of this code to sales agents, processes for monitoring and enforcement, and disclosure of enforcement and breaches. Generic companies are not yet included amongst the companies surveyed. d) What are concrete and measurable indicators of progress for this priority? (Including, for

example, global and national goals to be achieved within 2, 5 and 10 years)

Number of campaigns per country/sector

Number of countries participating on a Antibiotic Awareness Day/Week (eventually number of social media events organised, participation, etc.). Number of national organising inter-sectoral committees with all relevant stakeholders/country – 5 years

Coverage – number of people reached, type of audience reached (e.g. socio-professional category) – 2 years

Evolution of the level of awareness of and understanding on the threat of antimicrobial resistance (Regular enquires or surveys showing/comparing the impact of the campaigns, the level of understanding of professionals, the level of understanding of the public, etc.)Behaviour change – 10 years

Evolution of antimicrobial agent prescriptions and consumption – 5 to 10 years

Evolution of antimicrobial resistance – 5 years

Level of implementation and compliance to national/international guidelines and practices – 5 to 10 years

The Access to Medicines Index ranking could be use to evaluate ethical promotion of medicines.

•II. Building block-2: Identifying the most important approaches for preventing development of

infections and the steps needed to move beyond guidance to more effective implementation of

such approaches

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a) What do you consider to be the main issues under this priority?

The deficit in effective and comprehensive prevention measures to avoid acquisition and transmission

of infections in the first place a major issue here.

To address this in the public health sector, this necessitates

optimal infection control programmes in healthcare settings (incl. long-term care facilities)

aiming at decreasing the frequency of healthcare-associated infections and the containment

of antimicrobial resistance in acute care facilities.

implementation of infection control programmes in healthcare settings.

availability of adequate numbers of specialised infection control staff in healthcare settings

adequate healthcare building structure and capacity for correct implementation of infection

prevention measures, e.g. single rooms with dedicated bathrooms, negative pressure rooms

and placement of alcohol-based hand rub at the point of care.

continuous education for all healthcare staff for evidence-based infection control practises

and guidelines.

availability of adequate material resources for implementation of infection prevention

policies, e.g. for contact precautions (gloves, masks, respirators), UV lamps, negative Global

cooperation framework on cross-border patient transfer.

Global cooperation on cross-border patient transfer.

b) What are the main actions that needs to be done -- and who are the main actors/stakeholders

who need to take action -- to go beyond the status quo?

In the veterinary domain, the prevention of infection is also the best way to reach a reduction in the usage of antimicrobials. As a consequence of a reduction in the incidence of animal disease and zoonotic infections, the impact of outbreaks is minimised, thereby minimising also the need for and the consumption of antimicrobials. Main actions should include:

• Implementation of hygiene and biosecurity measures including the prevention of the introduction of infections (separate dedicated clothes and boots to be used per unit, limited access, hand washing and hand disinfection facilities including liquid soap, hot and cold water close to the workplace, quick removal and prevention of access to dead animals, all-in/all-out per unit, cleaning, disinfection, verification of disinfection, etc); Clear protocols should be written for infectious disease prevention, infection control and hygiene and these should be available at the farm.

Introduction of herd specific health plans aiming for a consequent stepwise improvement of herd health. Avoid health programmes in which animals are systematically treated with antibiotics in a prophylactic way.

(National control) Programmes to control specific animal diseases (viral and bacterial), including but not limited to vaccination;

Improvement of husbandry systems/farming practices including:

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- ensuring proper ventilation and appropriate environmental conditions for the animals, - appropriate and clean facilities for transport (lairage area, vehicles, etc.), - integrated production systems which avoid buying and mixing of populations and transport of animals with unknown disease status. - use of quality feed and water. - recommend adequate density of animal populations and other zootechnical conditions to decrease antimicrobial consumption.

Incentives for farmers which would lead to measurable improvement in animal health by means of effective preventive measures, improvement of welfare standards (in the broad sense of animal welfare) and monitoring of pathogens and their sensitivity at the herd level with the ultimate objective to ensure evidence based use of antimicrobials in individual herds in line with the prudent use principles.

Introduction of systems to reward a decrease in use of antimicrobials and to penalise an inadequate increase in such use.

Increase of R&D activities (in human and veterinarian field) in infection prevention, such as development of vaccines and other new interventions to prevent infection/acquisition/transmission.

Improvement of therapeutic approaches and development of new diagnostics.

Research on the effectiveness of prevention strategies and their effective implementation in various settings.

In the public health domain, infection prevention should likewise be a priority. Main actions should therefore include

Creation of infection control committees and programmes in healthcare settings which are comprised of all relevant stakeholders (e.g. physicians, nurses, epidemiologists, microbiologists, hospital administrators and infection control specialists).

Empowerment of infection control team or infection preventionists to implement and enforce infection control good practices and guidelines in healthcare settings.

Development of an infection control committee that meets regularly.

Direct involvement of hospital administration (e.g. Director or CEO) in the infection prevention committee.

Direct reporting of rates of healthcare-associated infections to the healthcare administration with feedback to healthcare workers or wards.

Development of performance and structure indicators and evaluation of infection prevention and control interventions/programmes.

Training in infection control and the epidemiology of healthcare-associated infections.

Availability of guidance on infection prevention and control for healthcare professionals.

Development of repositories of existing guidance and other documents on the prevention and control and assessment on these existing guidance to obtain a core of key measures.

Support the assessment of training needs for infection control with a view to develop basic training strategies and core competencies in infection control.

Assessment of the real burden and cost of antimicrobial resistance and healthcare associated infections, across sectors and to societies globally (see block 6).

Ensuring the availability of appropriate resources to correctly implement and comply with infection prevention practices, e.g. gloves, gowns, masks, respirators, alcohol-based hand rubs, and UV lamps.

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Construction of healthcare facilities (including laboratories) that will allow and make possible the correct implementation of infection control practices, e.g. with regard to natural ventilation, negative pressure rooms, work flows.

Audit and feedback of compliance of healthcare workers with infection control practices: e.g. hand hygiene compliance, compliance with the infection prevention bundles and contact precautions.

Identifying high-risk patients in a timely manner in order to implement necessary infection prevention measures and to prevent spread of multidrug-resistant organisms (e.g. active screening on admission, pre-emptive isolation, patient isolation, implementation of contact precautions).

Systematic surveillance and reporting of antimicrobial resistance and healthcare associated infections in each healthcare settings (knowing local epidemiology).

International agreements against which infection control and antimicrobial stewardship indicators (process indicators and outcome indicators) are then monitored.

c) What significant work has already been done to address this? (please provide references where

possible)

In the veterinary domain, the principle “prevention is better than cure”, is the basis of the new Commission's proposal for a Regulation on Animal Health (currently undergoing the ordinary legislative procedure in the European Parliament and the Council). The legislative proposal introduces clear responsibilities for:

- animal keepers and other operators for the health of the animal under their care, to ensure the required level of biosecurity measures and to have basic knowledge in animal diseases, including interaction between animal health, animal welfare and human health.

- veterinarians and other health professionals for appropriate measures to prevent the spread of pathogens and to raise awareness as well as to ensure the early detection of diseases by carrying out proper diagnosis and differential diagnosis to rule out or confirm a disease before symptomatic treatment is commenced.

- competent authorities who not only must be capable to protect animal health, human health and the environment through reduction of the risks arising from pathogens but also support operators in acquiring basic knowledge in animal health and inform the general public of the nature of the risk and the measures taken.

It also provides for an assessment, prioritisation and categorisation of diseases or disease agents, including where appropriate, the capacity to generate resistance to treatment (e.g. antimicrobial resistance) as criterion to decide about appropriate measures. It contains all the possible measures related to pathogens which can be equally applicable to AMR pathogens (e.g. notification, surveillance, eradication, etc.). All the above mentioned elements alone and in combination have the potential, and are expected to deliver a more proactive and preventive approach in the EU towards better animal health, i.e. for the control of major transmissible animal diseases. Furthermore, they also contribute to a better husbandry, less pathogen pressure and indirectly, to the reduction of infections in animals. As a result this would lead to a possible subsequent reduction of the need for the use of antimicrobials. The Transatlantic Taskforce on Antimicrobial Resistance (TATFAR) resulting from the EU-US Summit Declaration of 3 November 2009 with the goal of improving cooperation between the U.S. and the EU has identified three key areas one of which is focussing on the prevention of health care- and community-associated drug-resistant infections.

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See also road map AMR, and the upcoming progress report for more details on the EU policy, as well as details as to the EU agencies’ work in these areas. See also block 4 and 5 as regards the health research projects on this field funded by the European Commission under the 7th Framework Programme and included in the scope of the Joint Programming Initiative (JPI). d) What are concrete and measurable indicators of progress for this priority? (Including, for

example, global and national goals to be achieved within 2, 5 and 10 years)

Number of member countries /sectors with appropriate guidelines or protocols

Level of implementation of the protocols/guidelines/legal requirements

Decrease of specific infectious diseases

Decrease of antimicrobial consumption III. Building block-3: Optimizing the use of existing antimicrobials for human and animal health and

in agriculture

a) What do you consider to be the main issues under this priority?

Antibiotics are a precious global source that should be managed on a sustainable basis. Therefore

guidance should be put in place for prudent (responsible, appropriate) use, together with appropriate

measures to ensure compliance in both the human and veterinary sector. The main challenge will be

to establish in all regions in the world packages of measures resulting in a similar 'AMR safety level'

(a similar level of risk of development and spread of antimicrobial resistance by the use of

antimicrobials).

In the human sector, irresponsible use of antibiotics including over- or under dosing, use of the wrong

type of antibiotic, e.g. the use of antibiotic to treat infections that are not caused by bacteria, and

poor-quality antibiotics are major issues. Main actions needed include

Improving prescribing and improving use of antimicrobial agents to minimise selective

pressure and preserve effectiveness of these dwindling agents.

Estimate the risk to man of the antibiotic use in animals known to select antimicrobial

resistance whether through direct infection by resistant bacteria or by the transfer of

resistance determinants to other bacteria.

Banning over the counter sales of antimicrobial agents.

Ensure multidisciplinary and multi-sectoral cooperation between public health, food safety

and animal health stakeholders in promoting and implementing prudent use of antimicrobial

agents in a “One Health approach”.

Ensuring high quality of antibiotics so that they contain the minimum required level of active

substance.

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In the veterinary domain, guidance should balance the need to minimise the risk to man arising as a

result of use of antimicrobials in animals with the need to ensure sufficient availability of

antimicrobials to treat infectious diseases in animals. Whilst the overall use of antimicrobials in

animals should be reduced, care needs to be taken that antimicrobials are still available to treat sick

animals as "healthy animals make healthy food".

Main issues in developing countries/LMIC

Existing evidence suggests that low and middle income countries are disproportionately affected by

substandard and/or falsified medicines available on the market. Reasons that may influence this

growing problem are:

Complex international supply chains, including for manufacturing components;

Weak regulatory oversight in some countries (inadequate capacity of National Medicines

Regulatory Agencies (NMRAs);

Possible access to affordable medicines in non-formal markets

Lack of public awareness on health risks of AMR

Lack of access to information/information sharing on identified substandard and falsified

medicines (including between developed and still developing NMRAs).

Even if the 2012 MGD Gap Report notes that access to medicines in some regions has hardly

improved in the recent years, unavailability of medicines in some developing counties is still a

problem. Reasons for unavailability of medicines include:

Regulatory barriers (e.g. costs for preparation of registration; lack of incentives for

registration, long registration processing times)

Lack of incentives to market (low volume products)

Inefficient public sector procurement & supply management systems

Fragmented supply chains (including the use of different international procurement agencies

by different donors; many intermediaries)

Unreliable/delayed release of funding (donors & government)

Difficult to reach areas (geographical, seasonal)

The role of NMRAs in developing countries: Governments are responsible for protecting the health of

their people. Governments therefore establish NMRAs with the mandate to safeguard public health

by ensuring that pharmaceutical products available on the market are safe, effective and of assured

quality. This also applies to the majority of developing countries, where NMRAs have been set up

either as autonomous agencies or within the Ministry of Health institutional set up. However, these

authorities tend to suffer from a lack of political and financial support by their governments

contributing to the overall capacity constraints impacting fulfilment of their mandate ( See e.g. The

World Health Organization: Assessment of medicines regulatory systems in sub-Saharan African

countries - An overview of findings from 26 assessment reports; WHO, Geneva, 2010).

b) What are the main actions that needs to be done -- and who are the main actors/stakeholders

who need to take action -- to go beyond the status quo?

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Countries should be encouraged to develop and implement global national strategies or action

plans for countering AMR and to ensure the prudent use of antimicrobials. The strategy should

consist of a comprehensive set of actions including prevention of disease, surveillance programs,

risk communication strategies, risk management measures, regulatory measures, research, etc.

The strategy/plans should take into account the specific situation in the country (e.g. infectious

diseases, prevalence of food borne pathogens, patterns of resistances, etc.).The national

strategies may include targets or appropriate indicators to monitor achievements.

Ensure at a global level that antimicrobials are only supplied by professionals with sufficient

training in the responsible use of antibiotics; this will require training those actually delivering

health products at the point of need (nurses, animal health auxiliaries).

Development of guidance for prudent use of antimicrobials at all levels in the human and

veterinary sectors; whilst general guidance can be created at international, regional and national

level, specific guidance can only be developed at regional/local level to take into account the

characteristics of the health and farming system and local patterns of resistance and availability

of antimicrobials.

Put in place harmonised monitoring systems for the sale and use of antimicrobials in both human

and veterinary medicine.

Put in place surveillance systems for the harmonised monitoring of antimicrobial resistance in

humans, food and animals,

Secure the supply chain for antimicrobials to prevent entry onto the market of poor quality or

counterfeit medicines.

Ensure the prudent and appropriate use of antimicrobials for the purpose of treating and

preventing infections.

Support the development, implementation and assessment of hospital antimicrobial stewardship

programmes. For instance, hospitals should establish a multidisciplinary antimicrobial

management (AM) team (including surgeons, anaesthesiologists, nurses, pharmacists, infection

control specialists, and clinical microbiologists) who should develop and implement a protocol of

appropriate perioperative antibiotic prophylaxis (PAP) .

Promote the use of appropriate diagnostic tests to improve diagnostic and antimicrobial

prescription

Support educational programme for healthcare workers aiming at improving understanding on

the problem of antimicrobial resistance and healthcare associated infections.

Promote appropriate use and prescriptions of antimicrobials

Addressing over-the-counter sale of antimicrobials and the issue of antimicrobial drug self-

medication (i.e., use of left-overs)

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Information campaigns to promote prudent use of antimicrobial agents – see above.

Discourage marketing related impact on prescribing habits irrespective of diagnosis or best

practice.

Availability of antimicrobial utilisation and treatment guidance

Strengthened laboratory capacities to be able to follow trends of antimicrobial resistance,

discover new trends of resistance and enable prescribers to make informed antimicrobial choices.

Multidisciplinary and multi-sectoral (One Health Approach) cooperation between public health,

food safety and animal health stakeholders in promoting and implementing prudent use of

antimicrobial agents.

Enforce/improve quality control programmes for antibiotics, so that no sub-optimal products

reach the market.

Strengthen procurement or simplify procurement to prevent stock outs.

Ensure availability of a wide range of different classes of antibiotics to enable design of adequate

multidrug treatments (e.g., for tuberculosis). This requires the registration of antibiotics and

adequate procurement mechanisms

Public information campaigns to educate and inform the public (see also block 1).

Coherent participation in the WHO Substandard/spurious/falsely labelled/ falsified/counterfeit

medical products (SSFFC) member states mechanism: Develop a joint Member States position in

support of the WHO SSFFC member states mechanism that is based on promotion of public

health and de-linkage from intellectual property issues, and recognises capacity constraints of

developing countries. Ensure that the final work programme of the SSFFC mechanism will include

capacity building of developing countries regulatory authorities.

In the context of budget support use political and policy dialogue to put NMRA capacity

strengthening on the agenda (including provision of financial resources and adequate staffing

plans). Prioritising NMRAs in national health strategic plans could be made conditional for

budget support.

c) What steps have already been taken to address this priority? (please provide references where possible)

Detailed information on the EU activities is described in the Road Map and the progress report of

the EU AMR Action Plan.

See specific activities under Action 1, 2, and 3. See also GRACE and APRES research

projects funded by the EC.

See block 1 for activities on information/communication campaigns

Concrete and measurable indicators of progress for this priority may include:

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Number of regions and countries with legislation controlling the supply and use of

antimicrobials in human and veterinary domains.

Number of countries or regions that have developed and implemented global national

strategies for prudent use of antimicrobials in humans and animals.

Number of regions and countries with prudent use guidance in human and veterinary

domains.

Number of regions and countries with systems in place for monitoring sales and use of

antimicrobials in man and animals.

Number of regions and countries with surveillance systems in place for the harmonised

monitoring of antimicrobial resistance in humans, food and animals.

Number of regions and countries not allowing the use of antimicrobials as growth promoters

in animals.

Volume of global and national antimicrobial sales

Number of countries where access to antimicrobials is regulated and over-the-counter sales

forbidden

Number of education and training programmes in place – presence of antimicrobial

resistance and healthcare-associated infections in the curriculum of the healthcare workers.

Availability of national treatment guidelines and evaluation of the adherence to the

treatment

Setting up of multidisciplinary and multi-sectoral cooperation platforms/initiatives

Development of new rapid diagnostic tests

Presence of a multidisciplinary antimicrobial management (AM) team which is responsible

for developing, implementing and regularly updating perioperative antibiotic prophylaxis

(PAP), for regularly updating the local AB protocol and regularly analysing and auditing

compliance with appropriate PAP.

Rate of compliance with the administration of the perioperative antibiotic prophylaxis within

60 minutes.

Rate of compliance with indication, selection and dosage of PAP according to protocol before

incision.

Continuing antibiotic prophylaxis after the end of surgery is not recommended*.* Hospitals

should use a reminder/stop order system (e.g. computer system, checklist) in order to

encourage appropriate duration and dosage of PAP. – 2- 5 years

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Ratio of broad-spectrum antibacterials to narrow-spectrum antibacterials for the treatment

of community pneumonia

Evolution of the level of awareness of and understanding on the threat of antimicrobial

resistance

Behaviour change

Evolution of antimicrobial resistance

Use of diagnostic tests before deciding on use of antimicrobials

Compliance to correctly perioperative prophylaxis performed

IV. Building block-4: Identifying and closing critical gaps in knowledge needed to address AMR

1) What do you consider to be the main issues under this priority?

Availability of comparable and reliable global data on antimicrobial resistance, antimicrobial

consumption and healthcare-associated infections.

Availability and quality of surveillance data and gather reliable and comparable data for

antimicrobial resistance, antimicrobial consumption and HAI.

Increasing number of reports of extensively drug-resistant Gram-negative healthcare-

associated infections (or colonised patients) and emergence of the first properly described

cases of pandrug-resistant healthcare-associated infections (or colonised patients), i.e. the

responsible bacteria will be resistant to all available antibiotics.

Identify the knowledge gaps in understanding the transmission to man of antimicrobial

resistance arising as a result of the use of antimicrobial drugs in animals and to the

development of effective intervention measure to prevent this transmission including the

development of alternative drugs.

Non availability of drug susceptibility tests for newly introduced drugs (e.g. bedaquiline and

delamanid)

2) What are the main actions that needs to be done -- and who are the main

actors/stakeholders who need to take action -- to go beyond the status quo?

An ever-increasing range of drugs to treat infections caused by bacteria, parasites, viruses

and fungi are losing their effectiveness. It is crucial to find ways to use these valuable drugs

more wisely, understand the mechanisms and transmission of resistance and to develop new

drugs and treatments to cure resistant infections

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AMR represents a serious threat to global public health, and new resistance mechanisms

emerge and spread globally. This implies that global action across all sectors and society is

needed.

AMR threatens human health, but also animal health and the environment. A One-health

approach is needed since this problem cannot be successfully tackled through isolated

sectorial efforts.

Prevention of infectious diseases is key to reducing the use of antimicrobials and to combat

AMR. Vaccination and identifying ways to reduce health care associated infections can

support prevention.

As regard the use of antimicrobials in veterinary medicine, it is not clear to which extent

resistant organisms originating from use of antimicrobials in animals represent a threat to

human health. Better understanding of this transmission process should help to identify

those links in the chain where interventions can be most effective.

Joint working between human and veterinary sectors to analyse the risk chain and identify

critical points and the types of intervention that break transmission.

Reliable and comparable data on AMR and on the use of antimicrobials in human and

veterinary medicine is essential for evaluating the trends and sources of AMR, both for the

risk assessment process and research purposes and for the evaluation of the effectiveness of

the measures in place. For this purpose, the establishment of integrated surveillance systems

for the monitoring of AMR in humans, animals and in the food chain, including the creation

of an (official) network of laboratories and a database is essential. The results provided by

the surveillance systems should be based on internationally standardised methodologies and

clear internationally standardised interpretative criteria.

Global cooperation to develop national/regional surveillance systems and strengthen and

ensure the sustainability of existing surveillance systems on antimicrobial resistance and

antimicrobial consumption in human medicines and healthcare associated infections

Global cooperation to develop and/or share surveillance common methodologies and

approaches for surveillance of antimicrobial resistance, antimicrobial consumption and

healthcare-associated infections to ensure comparability and reliability of data.

Strengthened laboratory capacities to be able to follow trends of antimicrobial resistance,

discover new trends of resistance and enable prescribers to make informed antimicrobial

choices.

Multidisciplinary and multi-sectoral (One Health approach) cooperation between public

health, food safety and animal health stakeholders globally.

3) What steps have already been taken to address this priority? (please provide references where

possible)

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EFSA, EMA and ECDC have published in the last years several publications on AMR. The

complete list of these publications will be provided in the annexes of the progress report

mentioned before, to be published in October 2014.

The Joint Opinion on antimicrobial resistance (AMR) focused on zoonotic infections (ECDC,

EFSA, EMA, SCENIHR, 2009), provides a chapter on the areas where innovation and research

should be encouraged in order to address existing problems caused by AMR.

The European Commission has prioritised research to combat antimicrobial resistance over

three successive Framework Programmes for Research starting from FP5 in 1999 through to

FP7 and Horizon 2020 today. The EU has awarded nearly €950 million to transnational

collaborative projects on antimicrobial resistance, most in the area of human health, but also

in the areas of animal health, food and the environmental. This includes around €155 million

for AMR research supported via the Innovative Medicines Initiative. This is supplemented by

a €165 million contribution from the pharmaceutical industry. The research priorities address

all pathogens ( bacteria, virus, fungal and parasites) and takes a "One Health" approach in

addressing the following aspects:

o Understanding the mechanisms and transmission dynamics of resistance;

o Development of diagnostics;

o Development of therapeutics and alternatives including vaccines;

o Improved surveillance systems;

o Understanding the role of the environment, animals and the food chain in the

development and spread of AMR;

o Development of interventions to prevent acquisition and transmission of AMR

pathogens.

With support from the European Commission a Joint Programming Initiative on AMR

(JPIAMR) has been set up, bringing together 17 European countries, Israel and Canada to

coordinate their research efforts.

The first transnational joint call of JPIAMR was launched end of January 2014, and under its

research and innovation funding programme, Horizon 2020, the EC plans to support a

transnational research call of the JPIAMR via the ERA-NET co-funding scheme.

In April 2014 the JPIAMR launched its strategic research agenda identifying 6 priority topics

for research to combat AMR. These could serve well as a model for research priorities for the

WHO GAP.

Surveillance networks of antimicrobial consumption in humans and animals have been

established in the EU. Annual reports on the results of the surveillance systems provided by

the Member States are published by the relevant EU agencies (ECDC and EMA).

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Surveillance networks of antimicrobial resistance in human, animals and in the food chain

have also been established in the EU.

In order to improve and harmonise the surveillance systems in the veterinary and food sector,

the Commission has laid down, based on an EFSA opinion, the legal requirements for the

harmonized monitoring and reporting of AMR in zoonotic and commensal bacteria.

Annual reports on the data obtained by the surveillance systems and the harmonized

monitoring provided by the Member States are published by the relevant EU agencies (EFSA

and ECDC).

In the EU, an official network of laboratories for Antimicrobial resistance has been created

for the monitoring of AMR in the food chain. The network is composed of the European

Reference Laboratory for AMR (EURL-AR) and the National Reference Laboratories appointed

by each Member State.

At international level, the international guidance on risk assessment related to transmission

of resistance through foodstuffs of animal origin has already been developed by Codex

Alimentarius.

Likewise, guidance on the pre-approval information for registration of new veterinary

medicinal products in relation to AMR has been developed by the International Cooperation

on Harmonization of Technical Requirements for Registration of Veterinary Medicinal

Products (VICH).

EU surveillance data on antimicrobial resistance, antimicrobial consumption and healthcare-

associated infections are made available through ECDC surveillance systems on antimicrobial

resistance (EARS-Net) and antimicrobial consumptions (ESAC-Net) and ECDC standardised

methodology and framework for national surveillance of healthcare-associated infections

(HAI-Net), and the joint ECDC/WHO Europe annual report Tuberculosis surveillance and

monitoring. Those systems allow for the gathering of reliable and comparable data which are

presented in regular ECDC reports and made available through interactive database from

ECDC website.

In order to ensure comparability of data across Europe, the methodology of EARS-Net is

already being used by WHO/Europe (CAESAR) in close collaboration with ECDC with a view to

enable joined reports of antibiotic resistance for all 53 countries based on the same

standards and methodologies in the future.

The EU/US Task Force on Antimicrobial Resistance (TATFAR) has identified cooperation on

surveillance activities and the gathering of reliable and comparable data as a priority. The

TATFAR has agreed on the addition one recommendation, aiming to identify the knowledge

gaps in understanding the transmission to man of antimicrobial resistance arising as a result

of the use of antimicrobial drugs in animals and to the development of effective intervention

measure to prevent this transmission including the development of alternative drugs.

With regard to multi-sectoral cooperation:

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ECDC and EFSA publish an annual European Union Summary Report on antimicrobial

resistance in zoonotic and indicator bacteria form humans, animals and food

ECDC – EFSA – EMA are working on a joint report on consumption of antimicrobials and

antimicrobial resistance in animals, food and humans (JIACRA)

4) What are concrete and measurable indicators of progress for this priority? (Including, for

example, global and national goals to be achieved within 2, 5 and 10 years)

See also building block 5:

The development and implementation of national research strategies

Further increase in research funding to tackle main priority areas

Number of publications and patents generated

A widening participation and increased investment in the JPIAMR (In this context it is

important to note that Australia, Argentina, India, and South Africa have already expressed

an interest in participation).

An increase in the number of antimicrobial drugs, vaccines, alternative treatments and

diagnostics reaching the market

Development of harmonized surveillance systems able to provide reliable and comparable

data on the on the use of antimicrobials in human and veterinary medicine and on the

occurrence of AMR in humans, animals and in the food chain.

Number of countries implementing such surveillance systems, including laboratory capacity.

Availability of surveillance data

Quality and comparability of data at national/global levels

Number of countries using similar/comparable surveillance methodologies and approaches

V. Building block-5: Developing an innovative and sustainable approach to develop and distribute

critical products and technologies needed to address AMR

a) What do you consider to be the main issues under this priority?

Overall, to guide political action/regulatory action, the global burden and cost of healthcare-

associated infections and antimicrobial resistance (e.g. number of cases, number of deaths, economic

impact).

b) What are the main actions that needs to be done -- and who are the main actors/stakeholders

who need to take action -- to go beyond the status quo?

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Industrial investment in antimicrobial drug development has declined considerably over the

past decades. Public and private partners need to work together to revitalise the drug

development pipeline.

Novel business models are needed which incentivise investment in antibiotic R&D while

delinking it from sales volumes to promote responsible use.

Clinical trials should be optimised and clinical trial capacity should be increased to support

drug development.

Novel and rapid diagnostics are needed to promote a better use of current and new

antimicrobials.

Support to translational research is relevant in this context.

Availability of estimates on the human and economic burden of antimicrobial resistance

c) What steps have already been taken to address this priority? (please provide references where

possible)

A number of partnerships and tools have been implemented by the Commission under the EU

Framework Programme for Research and Innovation to stimulate the development of new product

and technologies such as;

1. Public-Private partnerships: The Innovative Medicines Initiative

a) The Innovative Medicines Initiative (IMI), a Joint Undertaking between the European Union,

represented by the European Commission (DG RTD) and EFPIA is the biggest public–private

initiative in Europe. Within the IMI, the New Drugs for Bad Bugs (ND4BB) programme was

launched in May 2012 as a rapid response to the launch of the EU Action Plan.

b) The ND4BB is a programme in which academic and other public partners, SME’s and the

pharmaceutical industry join forces to spur the development of new antibiotics1. Since the

launch of this programme, seven ND4BB projects with a total committed budget of more

than € 600 million have either started or are under development.

c) ND4BB Topic 4 focuses on the urgent need to develop a new business model for antibiotic

development that will reinvigorate investments in this vital area while also addressing the

issue of the responsible use of antibiotics. This new project will develop concrete

recommendations for new commercial models that provide industry with an incentive to

invest in this area while ensuring that new antibiotics are used wisely. The project is under

development and will be launched in 2014.

2. Specific funding schemes to boosting AMR research in SMEs

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a) Seven of 15 AMR research projects launched last year specifically harness the potential of

small and medium enterprises to develop novel antibiotics, vaccines or alternative

treatments for drug resistant microbial infections.

b) The 15 new projects directly support the work of 44 innovative SMEs.

3. Public–public partnerships

a) Joint Programming Initiative on AMR (JPIAMR). See building block 4. The first call under JPI

aims at developing new drugs;

b) EDCTP

The European & Developing Countries Clinical Trials Partnership (EDCTP) a public –public

partnership between the EU, 15 European countries and 9 Sub Saharan Countries aims to

accelerate the development of new or improved drugs, vaccines, microbicides and

diagnostics against HIV/AIDS, tuberculosis and malaria, with focus on phase II and III clinical

trials in sub-Saharan Africa.

4. Inducement Prizes

To foster innovation in the area of research in diagnostics, the Commission will launch at the

beginning of 2015 one of the first inducement prizes under Horizon 2020 aimed at boosting the

development of a rapid point of care test to identify patients with upper respiratory tract infections

that can safely be managed without antibiotics.

4) What are concrete and measurable indicators of progress for this priority? (Including, for

example, global and national goals to be achieved within 2, 5 and 10 years)

The development and implementation of new business models that accommodate for cheaper

and faster routes for drug development;

The development of clinical trial networks to support drug development;

The increase in the number of pharmaceutical companies which return to this field;

The increase in the number of SME's which work in this field;

The increase in the number of antimicrobial drugs, vaccines, alternative treatments and

diagnostics reaching the market;

The increase in the number of countries/regions with global access to life-saving novel

antibiotics.

Availability of estimates on the human and economic burden of antimicrobial resistance

VI. Building block-6: Assessing the long term economic, developmental and social costs and

implications of AMR as a basis for sustainable investment and action

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Antimicrobial resistance leads to the loss of many advantages in medical care that antimicrobials

have enabled (for example cancer therapy). Health services and systems will be substantially

impacted if resistance becomes endemic and effective antibiotics are lacking.

Antimicrobial resistance is not solely a public and animal health threat, it has also a global economic

impact. Firstly, AMR impacts health systems by increased morbidity and mortality from untreatable

or difficult to treat infections, secondly by its impact on human health affecting labour productivity,

output and economic growth. Overuse or misuse of antimicrobials (co)-financed by public health

systems is also an unnecessary cost.

Insufficient data exist on potential economic and social costs of AMR. Better estimates of AMR's

current and estimated economic impact can provide an appropriate base for determining the proper

level and balance of required investments and measures to counteract AMR by governments and

society; in particular it will help to evaluate the cost/effectiveness of measures to address AMR. The

hard data to result will also help galvanize long-term commitment globally.

The establishment of a global agreement on model(s) to estimate the economic and social impact of

AMR is one of the main actions to be done in this field and one of the concrete indicators of progress

for this priority.

The Commission is assessing the possibilities of having an OECD study on the economic and social

impact of AMR in OECD countries.

Data about the cost in Europe of AMR can be found at the Technical report The bacterial challenge:

time to react of ECDC and EMA of 2009.

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Concluding questions

3. What contribution would your organization be able to make in implementing the global

action plan?

The EU and its 28 Member States have warmly welcomed the Resolution WHA67.25 adopted by the

67th World Health Assembly calling the WHO to lead the process to develop a Global Action Plan

(GAP) to address AMR.

As expressed during the WHA of May 2014, the EU will engage actively and constructively in the

process of developing the plan, sharing our experiences and supporting capacity building wherever

possible. It is the Commission’s firm commitment to ensure optimum implementation of the future

GAP.

The specific contribution as well as other details of the Commission´s participation in the

implementation of the GAP could be bilaterally discussed with WHO in order to ensure the best

support.

4. Additional input that you feel would facilitate development of the GAP.

See question 3.