Introduction

The problem of antimicrobial resistance

Antimicrobial resistance (AMR) is one of the most pressing global challenges we face. Already, AMR infections are estimated to cause 700,000 deaths around the world each year. If no action is taken, that figure is predicted to rise to 10 million by 2050.

No new classes of antibiotics have been discovered since the 1980s. This, together with the prescribing patterns of the drugs already in circulation, means we are heading rapidly towards a world in which our current antibiotics are no longer effective.

The difficulty of developing novel antimicrobials

For most antimicrobial products, there are few replacements or alternative products in development and even fewer that target priority pathogens.

This is partly because investment in novel antimicrobials by the pharmaceutical industry is widely seen as commercially unattractive. The ideal scenario would be for companies to develop and manufacture new antimicrobials that were not released into circulation until needed. By restricting use, the development of resistance can be prevented. However, the combination of high research and development costs and low returns because of restricted use makes this an unattractive commercial model for the pharmaceutical industry.

Addressing the market failure

The UK government’s national action plan for antimicrobial resistance 2019-2024 committed to finding solutions to address this market failure.

The NHS has tested an innovative model that pays companies a fixed annual fee for antimicrobials based primarily on a health technology assessment of their value to the NHS, as opposed to the volumes used. We are the first health system in the world to do this.

This subscription-style approach to paying for antimicrobial products can break the link between the payments companies receive and the number of their antibiotics prescribed. We can remove the incentive to overuse antibiotics and reduce the risk of life-threatening infections (such as sepsis and pneumonia) becoming resistant to treatment.

Section 1: Aims and purpose

The purpose of this document is to set out the routes to evaluating and commissioning antimicrobial products through the antimicrobial product subscription model. The model has been designed to allow all 4 UK nations to take part in a single procurement process.

To minimise repetition, the term ‘contracting authorities’ is used to mean NHS England, NHS Scotland, NHS Wales, and Northern Ireland Department for Health, Social Services and Public Safety, where those bodies have chosen to take part in the procurement.

The intention is to give clarity to the roles of contracting authorities and the National Institute for Health and Care Excellence (NICE). The contracting authorities recognise that the characteristics of the market for antimicrobial products – specifically the need for clinical stewardship – undermine the normal business model for pharmaceutical companies.

The purpose of the subscription model is to create sufficient commercial incentives for companies to develop new products while continuing to support good stewardship. The UK government and the NHS are committed to evaluating and paying for selected antimicrobial products in a different way from other medicines.

This document sets out the commissioning route for antimicrobials that offer exceptional value based on meeting a set of clear clinical criteria, where payments are delinked from volumes used and contractual requirements guarantee surety of supply. This will ensure antimicrobial product availability at the right time and right place to meet need and demand.

The contract evaluation will attribute different scores for antimicrobial products depending on the value they offer to the NHS and place them into 1 of 4 value bands. Not all products will qualify for a subscription style contract. For products that do not qualify, the standard routes to market for launching a medicine in the UK should be followed.

Please note: in England, this document sits alongside the NHS commercial framework for new medicines, which outlines the purpose and principles on which NHS commercial medicines activity are based.

Section 2: Roles and responsibilities

This section sets out the roles and responsibilities of different organisations within the UK health system.

The contracting authorities

The national bodies for the NHS in each devolved nation set out the commissioning strategy and clinical priorities for the health systems in their jurisdiction.

For the commissioning of antimicrobial products, where each nation of the UK chooses to participate in the subscription model, these organisations will nominate the contracting authorities of the procurement process through which subscription styled contracts will be tendered.

Initially NHS England will act as the lead authority running the procurement process and issuing the invitations to tender.

The contracting authorities of the devolved administration can be listed within the tender documents and will be responsible for the decision to issue a contract for their nation and for the payments within their respective jurisdictions.

NICE

While contracting authorities will have overall responsibility for the process to award subscription style contracts, they will commission NICE to support key clinical input to the process, through the 3 main areas below:

The eligibility panel

NICE will provide representatives for the eligibility panel, established by the authorities, to assess the suitability of an organisation and its product for a contract award, based on clinical and non-clinical criteria before it progresses to the award stage.

The representatives provided by NICE will include clinical experts from the evaluation panel (see below).

Recommendations of scope

The eligibility panel may also recommend the population(s) within the marketing authorisation indications to be included within the scope of the award stage and assessed against the award criteria.

Applicants will be advised of the proposed scope, which must be accepted as a condition of progressing to the award stage.

The evaluation panel

On behalf of the authorities, NICE will establish a standing panel of experts from across the UK to evaluate each product against clear award criteria, known as the ‘evaluation panel’.

The panel will be recruited, hosted and implemented by NICE, with input from the authorities as appropriate.

For example, recruitment of panel members will adhere to typical NICE processes for committee recruitment, with representatives from the authorities also involved in assessing applications and agreeing appointments.

Section 3: Public contract regulation compliance

Compliance with the public contract regulations (PCRs) is a legal requirement for all UK authorities seeking to award a contract with a value above threshold. To deliver the antimicrobial products subscription model, in compliance with PCRs, interested organisations will be able to express interest in the advertised selection process.

The selection process proposed will be open to all interested organisations and consist of 2 stages:

• Stage 1: an eligibility stage, where potential suppliers will be required to demonstrate that they satisfy minimum eligibility criteria to be awarded a subscription style contract.

Subject to passing stage 1, eligible suppliers will be invited to stage 2:

• Stage 2: an award stage, where potential suppliers will be required to provide evidence for assessment by the evaluation panel, to demonstrate the extent to which their product satisfies the award criteria.

Stage 2 will determine if a supplier is awarded a subscription style contract and the quantum of the associated annual fee. Further details are set out in section 5.

The eligibility and award criteria, together with the subscription style contract terms and process instructions for suppliers, will be published when the opportunity is advertised. The precise eligibility criteria will be considered and set each year as part of the invitation to tender documentation.

While there will be no opportunity for potential suppliers to vary the criteria or contract terms, there will be an opportunity to seek clarification about the process and associated documents.

Use of a PCR-compliant approach also provides a mechanism to select a limited number of products from those available, should there be a limited number of subscription style contracts available.

We have considered the potential procurement routes available within the regulations and when awarding subscription type payment contracts, we consider use of the restricted procedure to be the most appropriate.

The principal reasons for proposing the restricted procedure are:

1. it facilitates the proposed 2-stage approach (eligibility and award)
2. it is a relatively simple, well understood and quick (6-8 month) process from advertising the opportunity, completing the eligibility and award stages and having signed contracts in place
3. based upon the learning from the pilot procurement process and management of the two initial contracts:
   • we currently do not see the need for detailed dialogue with suppliers during the procurement process
   • we have already developed a tried and tested form of subscription style contract
4. the existing contract and proposed award process will enable suppliers to respond to the NHS requirements.

The authority will publish documentation that includes all the information needed for companies to make an informed decision to participate and to submit a response to the invitation to tender (ITT).

Where it adds value, these documents will be published with a prior information notice (PIN) that will signal the start of a pre-market engagement period and will allow potential suppliers early sight of the proposed requirements and to provide feedback prior to the launch of the tender.

The documentation will include the eligibility and the award criteria. These will be reviewed each year before notice of the tender is given. Where the material in the documentation is changed, the authority will look to hold a pre-market engagement to inform companies of the details in the tender.

Section 4: Eligibility criteria

Only products that meet the published eligibility criteria will be considered for full evaluation for a contract. These criteria will be clinically led and focus on areas recognised by the World Health Organization (WHO) as areas in need for new antimicrobial treatment options.

Clinical criteria

WHO priority pathogen

Products that are active against pathogens on the WHO priority list will be eligible. The key target will be products that treat infections caused by pathogens designated as ‘critical’ on the WHO priority list.

Table 1: WHO priority pathogens list for research and development of new antibiotics

The tender documents published with the contract notice will confirm the focus of the eligibility criteria for that year’s procurement. From time to time, the criteria may be restricted to 1 or more of the categories depending on the clinical priorities of the NHS.

Other criteria

Confirm agreement to the model contract terms

1. Surety of supply:

• contractual requirements for companies to provide assurance that they will always have supply, ensuring antimicrobial product availability at the right time and right place to meet need and demand

2. Antimicrobial stewardship:

• sales force stewardship: reinforce appropriate organisational behaviours, delinking remuneration incentives for company sales representatives from antimicrobial sales
• promotional activities: activity on use of products should be informative and educational. For products with a subscription style contract, companies must keep the NHS informed of the activities they intend to undertake through the year.

3. Performance:

• key performance measures and reporting requirements.

4. Payment terms.

Environmental standards

Companies must demonstrate, via independent assessment, compliance with specified antibiotic manufacturing standards that aim to reduce the development of resistance and ecotoxicity in the environment because of manufacturing operations.

Economic and financial standing

It is a standard requirement of all public sector contracts that companies demonstrate they have a sufficient economic and financial standing to justify award of the proposed contract.

Probity

Companies must demonstrate they do not trigger any of the requirements that would make them ineligible to be awarded a public contract.

Social value

Companies must demonstrate their commitment to specified social value requirements; for example, achieving Net Zero carbon emissions.

The assessment of eligibility is largely administrative. The scoring for these criteria is normally ‘pass’ or ‘fail’, depending on whether than company submits the specified information and demonstrates a minimum financial standing.

The inclusion of a section on the willingness to agree to the terms of the model contract on supply, stewardship and promotion is intended to draw the attention of applicants to these terms at an early stage.

Limited to products that either:

• have received marketing authorisation in the UK since the previous invitation to tender for antimicrobial subscription contracts
• are from companies which can demonstrate they expect the product to receive marketing authorisation in the UK within a specified period stated in the invitation to tender, for example within 12 months or the end of financial year.

For the procurement opportunity in 2024, products that met the eligibility criteria for the pilot project will also be considered. The opportunity documentation will give more details.

Section 5: Route to commissioning

The route to commissioning antimicrobial products differs from other medicines. New branded pharmaceuticals in England are expected to undergo an appropriate NICE health technology assessment (HTA) unless there is a clear rationale not to do so.

In the standard route to market for antimicrobial products, a NICE HTA is not normally undertaken. For all antimicrobial products, whether in the standard route or otherwise, companies are required to apply for market authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) and seek a list price from the Department for Health and Social Care (DHSC) in the same way as other medicines.

In this new model, in addition to products already launched (including products that have been granted a marketing authorisation since the previous procurement opportunity), companies with products that are expected to receive marketing authorisation within 12 months of the tender invitation launch date can apply for a subscription style contract, subject to meeting the eligibility criteria.

Companies will need to demonstrate that the timeline for marketing authorisation is realistic. NHS England and NICE will be liaising with the MHRA to verify the timeline.

Subject to available funding, a product that meet the eligibility criteria and demonstrate sufficient value against the award criteria will be offered a contract reflecting the product’s assessed value.

The contract length will be for an initial period of 3 years. The authorities will have the option of extending the contract for a period of up to 3 years per extension, up to a maximum total period of 15 years to cover the exclusivity period of the product. The intention is that the contracts will be extended up to the loss of patent or regulatory exclusivity but not beyond.

It is possible that the product could change between value bands (in either direction) during the contract term, depending on how the value of the product to the NHS evolves over time. The authorities also reserve the right to terminate a contract should it determine that the value of the product to the NHS no longer warrants a subscription contract.

The window for considering new products will be open periodically (for example once a year).

Products that do not meet the eligibility criteria for a subscription style contract will still be able to access the NHS market via the standard route mentioned above.

Ongoing clarification

Companies will have the opportunity to seek clarification from the lead authority to help them fully understand the requirements. Any clarification information provided to a company in response to a question received from one company may be shared with all companies applying for a contract to make sure the process is as transparent as possible.

Step 1: Advertise opportunity and publish tender documents

Each opportunity will be advertised via a prior information notice and/or contract notice. These will provide information on where to access the relevant tender documents and how to submit an expression of interest.

The contract notice will also confirm the participating contracting authorities and the lead contracting authority responsible for the procurement process.

Companies which have launched products since the previous opportunity, or which expect to receive marketing authorisation for their product within 12 months of the contract notice being published, may apply for a subscription style contract.

The tender documents will include instructions for potential suppliers, the eligibility criteria, the award criteria, and guidance on the evidence that companies will need to provide, together with the contract terms.

Step 2: Completion of application

Companies wishing to apply for a subscription contract will need to complete an application responding to the contract notice.

The application will require submission of documentation and evidence to demonstrate that the company and product meet the eligibility criteria, which will include both clinical and non-clinical requirements.

Step 3: Eligibility assessment

An eligibility assessment panel will assess the documentation provided by the company against the eligibility criteria. Companies which meet the criteria will be informed of the assessment decision by the authority and invited to progress to the next step of the process.

During the eligibility stage, the assessment panel may request companies to clarify details included in their application. No additional evidence or data may by requested or provided at this stage; clarification requests will be restricted to questions to help with the panel’s interpretation and understanding of the evidence already submitted.

Step 4: Scoping

After the eligibility assessment decision has been communicated to the companies, the lead authority will confirm the population(s) and/or marketing authorisation indications to be included within the scope of the award stage and assessed against the award criteria.

This will be recommended by NICE based on input from clinical experts on the eligibility assessment panel.

Each applicant will be advised of the proposed scope when they are invited to submit evidence for the product evaluation (see step 5), which must be accepted as a condition of progressing to the award stage.

Companies may be invited to submit information about the scope of the use of the product within the marketing authorisation as part of their initial application to the eligibility assessment.

Companies may also be invited to comment on a draft scope before it is finalised.

Step 5: Evidence submission

Companies will be invited to submit evidence showing how the product performs against pre-specified award criteria. The award criteria will be published as part of the opportunity documentation and will include guidance on the evidence requirements for the assessment.

The evidence submitted by companies will be reviewed and quality assured by representatives of the evaluation panel. Companies may receive a request for clarification about the evidence submitted before the product is scored (see step 6).

This review and clarification process is designed to allow the authorities, NICE, the evaluation panel and companies to reach a common understanding of the evidence provided.

Step 6: Award stage – product evaluation using award criteria

A UK panel of experts, convened by NICE to provide recommendations to the contracting authorities, will meet in private to assess the documentation provided by the company against the award criteria, which include a points-based scoring system.

The product’s points score will determine the value band of the contract offered by the authority to the company. The score given will depend on the evaluation panel’s view of the strength and quality of the evidence provided by the company.

The evaluation panel can recommend 1 of 4 possible contract ‘value bands’ (see Table 2) – or none if a product scores insufficient points. The lowest category is for products with relatively low clinical value but value nonetheless from controlling their use, and the top band is for innovative breakthrough products that offer exceptional value.

The value of the bands shown in the table are for England only. Each nation will determine the values that will apply for their health system. The table also shows the proportion of the points needed from the evaluation process for a product to be placed in each contract band. The values for each nation and points will be reviewed each year and published in the documentation that accompanies the tender opportunity.

Table 2: Value bands, linked to the award criteria scoring system

Step 7: Results and contract awarding

Once the evaluation process has been completed and the authority has approved implementation of the recommendations from the evaluation panel, companies will be informed of the proposed value of the contract based on the assessment against the award criteria. The evaluation panel’s recommendations to the authorities will not be subject to consultation.

Following the decision to award, the authorities intend to publish information on the organisations awarded a contract. This will include the value band agreed for the product, the scores awarded for each criterion, and an account of the evaluation panel’s rationale for awarding each score. At its discretion, NICE may also publish stewardship statement for the NHS on the optimal use of the product.

Publications of these documents will happen only after the contract has been awarded. This is in line with best practice under public contract regulations.

Subject to the agreement of the companies, NHS England and the devolved governments, at their discretion, will offer a contract in the relevant value band.

The antimicrobial products subscription model will use a model contract based on the standard NHS contract. This will include key performance indicators to support surety of supply and will be published as part of the procurement documentation.

Once companies have been informed of the contract award outcome, the authority will observe the public contract regulations mandatory minimum standstill period of 10 days before entering into a contract with the successful applicant(s).

Any applicant may seek clarification or raise any concerns about the award outcome with the authority during this period. Applicants will have up to 30 days to accept the award, if offered, by the authority.

Publication reference: PRN01167