Consultation outcome

Consultation on proposed statutory instrument for the Early Access to Medicines Scheme

Updated 2 February 2022

1. Executive summary

The UK Early Access to Medicines Scheme (EAMS) is one of the ways through which a patient with a life threatening or seriously debilitating condition can gain access to a medicine before it has gained approval from the UK’s medicines regulatory authority. This consultation seeks views and comments on the proposed legislative changes to clarify the legal basis for EAMS.

The aim of this proposal is to ensure that EAMS remains an attractive option for patients, healthcare professionals and companies, so that cutting-edge therapies are available for patients where there is an unmet clinical need. We aim to make the legal basis for EAMS supply clear and minimise the burden on those supplying EAMS medicines and for those companies wishing to collect real-world data during the scheme. This will be delivered whilst continuing to ensure the safety of EAMS products through pharmacovigilance (safety monitoring), maximising patient access and benefit.

2. Introduction

2.1 What is the Early Access to Medicines Scheme?

The Early Access to Medicines Scheme (EAMS) aims to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorisation when there is a clear unmet medical need. The scheme was launched in April 2014 following a public consultation and government response. Under the scheme, the Medicines and Healthcare products Regulatory Agency (MHRA, UK medicines regulator) gives a scientific opinion on the benefit/risk balance of using a medicine.

EAMS provides an important regulatory flexibility for early patient access. Significant numbers of patients have benefited in a variety of conditions since 2014. However, changes are now needed to enhance the flexibility of the scheme and maximise benefits to patients and participating pharmaceutical companies, ensuring that EAMS remains an attractive option for companies to provide medicines to patients prior to licensing.

2.2 How does EAMS work?

EAMS is a two-step process. The first step is the Promising Innovative Medicine (PIM) designation. The PIM designation gives an indication that a product may be eligible for EAMS patient access based on early clinical data. The PIM designation is issued by MHRA after an MHRA scientific meeting. When the company has sufficient data to support patient access, they apply to MHRA for the second step - the EAMS scientific opinion. The EAMS scientific opinion considers the risks and benefits of new chemical and biological entities (unlicensed medicines) or new indications of already marketed drugs (off-label use setting), taking into account the assessment of available quality, non-clinical and clinical data. The scientific opinion supports the prescriber and patient in deciding on whether to use a medicine before its licence is approved. Since launch there have been over 100 PIM designation and 50 SO applications.

A positive scientific opinion is only issued if the criteria for EAMS are fulfilled. All EAMS scientific opinion applications are reviewed by the independent Commission on Human Medicines (CHM), an advisory non-departmental public body, sponsored by the Department of Health and Social Care (DHSC). Positive scientific opinions are published on the MHRA webpage alongside a public assessment report and the EAMS Treatment Protocols, describing for healthcare professionals and patients how to use the medicine. More information about EAMS, the criteria and current and past scientific opinions can be found here

2.3 Early Access to Medicines Scheme: An Independent review; 2016

A government sponsored independent review of the EAMS took into consideration prior consultation documents in addition to over 50 in-depth interviews across 42 different stakeholders, an online survey, and three cross-stakeholder workshops with representation across industry, government, and arm’s length bodies. EAMS was seen as an important mechanism in securing early patient access to innovative medicines in areas of clear unmet medical need and with some changes could become an even more effective means to accelerate adoption of these products across the NHS. From the report, there was a collective appetite from industry, government, and arm’s length bodies to build on what EAMS has achieved to date. One of the key features of the vision for a future EAMS process from the report was:

• ‘A robust mechanism to support real world data generation during the EAMS patient access period and beyond’

Early Access to Medicines Scheme: An Independent review

2.4 What problem are the proposals aiming to solve?

There is no UK legislation that specifically covers EAMS. The scheme is entirely non-statutory. Obtaining an EAMS approval from the MHRA is effectively delivering a scientific opinion which supports clinicians and patients when prescribing an unlicensed medicine (a medicine that has not been authorised for use by the medicines regulator) or using a medicine off-label (using a medicine that is already approved but in a different condition or patient group that has not been approved by the medicines regulator). The opinion provides independent reassurance from the medicines regulator that the benefits outweigh the risks.

Since there is no legislative provision that covers or specifically mentions EAMS, there are some aspects that would benefit from clarification in law (see proposals below), providing a legal basis for the delivery of EAMS. We would like to introduce new provisions into the Human Medicines Regulations 2012 (HMRs) to:

• Provide a specific statutory basis for EAMS, therefore improving regulatory certainty regarding this important patient access flexibility and reducing regulatory burden

• Address a key recommendation from an independent review on EAMS on data collection.

2.5 Policy objectives

The proposed legislative changes are designed to ensure that the EAMS remains relevant and attractive following the UK’s exit from the European Union and that patients in the UK are able to access cutting edge therapies in advance of licensing decisions where they fulfil the EAMS criteria. In addition, the proposals on supply and real-world data collection fulfil the goals to reduce regulatory burden and support the UK life sciences agenda in making the UK an attractive place to bring innovative products.

Supply chain aspects are frequently complex, and in the UK will differ depending upon the nature of the EAMS supply (as either an unlicensed medicine or the off-label use of a licensed medicine). A statutory basis is proposed for EAMS that allows manufacture, assembly or importation at sites with any human medicines manufacturers licence. This is intended to simplify regulatory requirements and avoid the current disincentives to a supply chain utilising UK sites.

3. The proposals

We are proposing to introduce a specific EAMS legal provision that will describe the scheme and its goals. This aims to provide legal clarity for those companies who may be considering using EAMS but will also aim to provide a framework on the requirements for safety monitoring and collection of data. Our objective is to reduce regulatory procedural burden where possible whilst supporting earlier patient access in areas of unmet medical need where the benefits have been shown to outweigh the risks, and the risks are monitored. We are considering that the provision will include the following:

3.1 EAMS key principles of operation

To describe the objectives of EAMS and clearly detail its principles of operation, as published in the current EAMS scientific opinion guidance in April 2014. For example, that the EAMS scientific opinion can be withdrawn if the company fails to comply with the requirements of an EAMS approval, and that the company is required to notify the regulatory authority in a timely manner of any information that might impact the benefit/risk decision.

3.2 Simplifying the supply of EAMS medicines

Currently in the UK, the type of manufacturing licences held by the EAMS supply chain differs depending upon whether the EAMS medicine is an “unlicensed” medicine or a licensed medicine being used for an indication which is not currently part of its marketing authorisation (“off-label use”).

A new provision for EAMS medicines is proposed to simplify and harmonise expectations for their manufacture, assembly and importation. In the UK under existing legislation, manufacture and assembly for “unlicensed” medicines require the site to hold a Manufacturing Specials (MS) licence and for licensed medicines, a Manufacturing and Importation Authorisation (MIA). The importation of unlicensed medicines from an EEA member state may be performed under a Wholesale Dealer’s Licence (WDA(H)), however a Manufacturing Specials (MS) Licence is required for importation from a third (non-EEA) country.

However, UK sites involved in the manufacture, assembly and importation of EAMS medicines may not hold an MS or MIA, but instead hold a manufacturing licence for clinical trial supplies (MIA(IMP)).

For a single EAMS medicine supplied for a matter of months, the significant investment in time, cost and administration of obtaining an alternative manufacturing licence for a UK site may not be justified.

We propose a flexible approach, providing a statutory basis for EAMS supplies that avoids the need to classify supply aspects under existing legislation for unlicensed medicines or off-label provision. A simple administrative procedure may be included in legislation and/or guidance and is proposed to permit the manufacture, assembly or importation of EAMS medicines under any manufacturing licence for human medicines, provided that the proposed activity falls within its current scope.

3.3 Provide a supportive framework the collection of real-world data (RWD)

A key recommendation from the Government-commissioned independent review of the EAMS was that EAMS should become a vehicle to support the collection of real-world data.

The benefits of collecting real-world data are increasingly being recognised, where the data can supplement the information derived from clinical studies. However, the collection of real-world data may fall under the requirements of the Clinical Trial regulations and therefore a clinical trial authorisation (CTA) application might be required.

In order to support the collection of real world data, we propose legislation to allow the company who hold an EAMS scientific opinion to be able to collect data in the context of EAMS regardless of whether the product is considered an investigational medicinal product or not. The new provision would allow for real-world data collection without the need for a CTA, as long as the MHRA (following assessment) has no concerns about the collection of that data. Patients must be appropriately consented and have the right to refuse without impacting their ability to join the scheme.

3.4 Clarifying the liability for prescribers and patients

There is some uncertainty about the use of medicines during the EAMS. We would like a provision in legislation to provide clarity around the use of EAMS medicines, in line with the General Medical Council (GMC) recommendations on prescribing unlicensed or off label medicines: * Doctors may prescribe unlicensed medicines where, on the basis of an assessment of the individual patient, it is necessary to do so to meet the specific needs of the patient * Doctors should take responsibility for prescribing the medicine and for overseeing the patient’s care, monitoring and any follow up treatment.

3.5 Pharmacovigilance (safety monitoring) for EAMS medicines

Recommended pharmacovigilance activities provided in guidance for EAMS medicines have generally been adopted satisfactorily by companies providing EAMS medicines. In order to best support safe use and to reassure the individual patient and the healthcare professional when prescribing an EAMS medicine, the following pharmacovigilance requirements are being considered for inclusion in legislation:

• The requirement to operate a risk management system describing appropriate pharmacovigilance and risk minimisation activities
• The requirement to collate and maintain records of suspected adverse drug reactions and report to the MHRA
• The requirement to submit periodic reports summarising the suspected adverse drug reactions for the EAMS medicine
• The requirement to notify MHRA of new information that may impact the benefit/risk balance.

4. Questions

4.1 Question 1

The EAMS has been operational since April 2014. The proposed provisions build on the experience gained during this time and consider recommendations from an independent review of EAMS. Do you agree with the proposed inclusion of the principles of EAMS in the Human Medicines Regulations 2012, as described above? If not, please explain your reasoning.

4.2 Question 2

The proposals above build on guidance that was published in April 2014. The core principle of EAMS remains the same but will be embedded in law. Additional provisions for supply and supporting the collection of real-world data aim to reduce regulatory procedural burden. Are there any concerns or comments with regards to the proposed provisions as listed above?

4.3 Question 3

Are the proposed provisions to support EAMS comprehensive and do they strike the right balance for regulatory oversight of EAMS medicines? Are there additional provisions for EAMS that you would consider important?

5. Annex A – Legal basis and the assessment of the matters set out in section 2 of the Medicines and Medical Devices Act 2021

The Medicines and Medical Devices Act 2021 (‘the Act’) received Royal Assent on 11 February 2021. We propose to make the legislative changes under Part 2 of the Act, which provides powers to make regulations about human medicines.

This consultation is conducted in line with the consultation requirement in section 45(1) of the Act. Section 2 of the Act (power to make regulations about human medicines) states that patient safety must be the overarching objective of the appropriate authority when making regulations. Section 2 also requires that when assessing whether regulations would contribute to the objective of safeguarding public health, the appropriate authority must have regard to three factors:

(a) The safety of human medicines

(b) The availability of human medicines

(c) The likelihood of the relevant part of the United Kingdom being seen as a favourable place which to –

(i) Carry out research relating to human medicines

(ii) Conduct clinical trials, or

(iii) Manufacture or supply human medicines

We have assessed the proposals against each of these factors, outlined below.

5.1 (a) Patient safety: how does this consider patient safety?

Patient safety is at the forefront of the EAMS medicines provision. Prescribers are already allowed to prescribe unlicensed or off-label medicines in certain circumstances. However, EAMS provides a supportive framework for prescribing medicines in the unlicensed and off label settings. There are many advantages that EAMS offers to prescribers and patients over and above simply prescribing outside of EAMS, such as provision of independently assessed and publicly available treatment protocols, consideration of the benefit/risk balance based on quality, safety and efficacy data, and requirements for pharmacovigilance (safety monitoring) and risk management.

5.2 How are the patient benefits shown to outweigh the risks?

An EAMS positive scientific opinion is only issued if the criteria for EAMS are fulfilled following assessment of the EAMS criteria against the quality, safety and efficacy data. This includes that the medicinal product can offer significant advantage over methods currently used in the UK and the potential adverse effects of the medicinal product are considered to be outweighed by the benefits. The assessment includes consultation with the Commission on Human Medicines (CHM). In addition, a pharmacovigilance system for the fulfilment of pharmacovigilance tasks should be in place in advance of an EAMS opinion. EAMS treatment protocols for healthcare professionals and patients provides valuable information on the safe and proper use of the medicine before it is licensed. EAMS operation since launch have demonstrated significant benefits to patients, and the new provisions strengthen the principles of EAMS delivery and provides certainty in the requirements for safety monitoring and risk management.

5.3 (b) Availability

EAMS is an important regulatory flexibility that accelerates the availability of medicines to patients before the drug licence is approved or a current licence is varied. Over 1000 patients have benefited from cutting edge medicines since its launch. These patients have benefit from timely access, and it is expected that the changes proposed will increase the attractiveness of the scheme and thus the availability of important medicines that have the potential to improve and extend patient lives.

5.4 (c) The likelihood of the relevant part of the United Kingdom being seen as a favourable place which to carry out research relating to human medicines, conduct clinical trials, or manufacture or supply human medicines

We consider that the new provision that helps to build a more visible framework to collect real-world data in the EAMS is likely to be an attractive proposition for industry. An independent Government-commissioned report highlighted the opportunity to collect real-world data during the EAMS scientific opinion. Such data could support future decision making for the regulator and other stakeholders such as Health Technology Assessment bodies. The data will also be of value to the company who hold the EAMS scientific opinion in terms of learning more about their medicines in the clinical practice setting, outside of clinical trials. Proposals to provide regulatory flexibilities to the manufacturing licences required for the manufacture, assembly and importation of EAMS medicines will remove current constraints to the use of UK sites, while not impacting assurance of Good Manufacturing Practice.

5.5 Summary

Patients with serious and life-threatening conditions require timely access to medicines. EAMS has demonstrated success in supporting the prescriber and patient in making decisions on using medicines before a marketing authorisation is granted (drug licence) for an unlicensed medicine or variation approved for an established medicine. The scheme is an important regulatory flexibility to ensure that UK patients are some of the first in the world to access new treatments. The proposed provisions build on the experience of EAMS in the first 7 years of operation, providing more certainty and reducing regulatory procedural burden.

6. Annex B - Consultation questions and how to respond

6.1 How to respond

The Government invites responses on the specific questions raised. The questions can be found through the document and are also listed in full in below.

This consultation will close on 17th September 2021.

Please respond through our online consultation survey, on our survey page here.

When responding please say if you are a business, individual or representative body. In the case of representative bodies, please provide information on the number and nature of individuals or firms you represent.

6.2 Consultation questions

1. Do you agree with the proposed inclusion of the principles of EAMS in the Human Medicines Regulations?

2. Are there any concerns or comments with regards to the proposed provisions as listed above?

3. Are there additional provisions for EAMS that you would consider important?

6.3 Background questions

Which best applies to you:

• I am responding as an individual
• I am responding on behalf of an organisation

Where do you live?

• England
• Northern Ireland
• Scotland
• Wales
• Other – please specify

Please tell us the geographical area your organisation covers?

• United Kingdom
• Great Britain
• England
• Northern Ireland
• Scotland
• Wales
• Other – please specify

Name of organisation

Main activities of your organisation

Are you

• a patient
• a healthcare professional
• working for an organisation that could be or has been an EAMS industry applicant
• Other – please specify

Please describe your previous experience(s) with EAMS (if applicable)

6.4 Equality and Rural Screening

In Northern Ireland new policies must be screened under Section 75 of the Northern Ireland Act 1998 which places a statutory duty on public authorities, to mainstream equality in all its functions – so that equality of opportunity and good relations are central to policy making and service delivery. In addition new or revised policies must be rural proofed in line with the Rural Needs Act (NI) 2016 which requires public authorities to have due regard to rural needs.

We do not consider that our proposals risk impacting different people differently with reference to their protected characteristics or where they live in NI. We welcome views on this point.

Do you think the proposals risk impacting people differently with reference to their [or could impact adversely on any of the] protected characteristics covered by the Public Sector Equality Duty set out in section 149 of the Equality Act 2010 or by section 75 of the Northern Ireland Act 1998? If so, please provide details.

6.5 Confidentiality of Information

Information published in response to this consultation, including personal information may be published or disclosed in accordance with the access to information regimes. These are primarily the Freedom of Information Act 2000 (FOIA), the Data Protection Act 2018 (DPA), UK General Data Protection Regulation (UK GDPR) and the Environmental Information Regulations 2004.

If you want the information that you provide to be treated as confidential it would be helpful if you could explain to us why you regard the information you have provided as confidential. Any information not published, including personal information, may still be subject to disclosure in accordance with the Freedom of Information Act. If we receive a request for disclosure of such unpublished information, we will take full account of your explanation, but we cannot give an assurance that confidentiality can be maintained in all circumstances. We will not take a standard confidentiality statement included in an email message as a specific request for non-disclosure.

The MHRA will process your personal data in accordance with the DPA and UK GDPR and in the majority of circumstances this will mean that your personal data will not be disclosed to third parties. However, the information you send us may need to be published in a summary of responses to this consultation.