Veristat Global Policy Insights Q1 2024

Index: EU ADDRESSING SHORTAGES |  RECENT DEVELOPMENTS: EU | RECENT DEVELOPMENTS: US | Outlook

Topics in focus

USA – Measures to support advanced therapies and orphan drugs

The FDA launches new pilot on cell and gene therapies and a call for its pilot on rare diseases

The FDA announced a new Collaboration on Gene Therapies Global Pilot (CoGenT) at the Alliance for Regenerative Medicine’s Cell & Gene State of the Industry Briefing in January 2024. Although still in the early stages of development, the FDA's pilot will explore the potential harmonization of requirements and collaborative review of applications with international regulatory partners to help facilitate more efficient clinical development. Its goal is to increase the efficiency of the regulatory process, reducing time and cost for agencies and sponsors. It is foreseen that Standing Regulatory Members of the International Council for Harmonisation (ICH) will initially participate in the pilot. Partners will be able to participate in internal regulatory meetings that include the sponsor, and will be able to receive specific regulatory reviews and discuss them. The FDA emphasized that all matters discussed at meetings and shared information will be subject to strict confidentiality agreements.

Earlier this year, the FDA reflected on its achievements in 2023 in relation to rare diseases. It notably reported that more than half of the novel drugs approved in 2023 were in the rare disease field and received an orphan-drug designation. In February 2024, the FDA opened a call for proposals for its Rare Disease Endpoint Advancement (RDEA) Pilot Program. The RDEA Pilot Program supports novel efficacy endpoint development for drugs that treat rare diseases. Sponsors that are successfully accepted into the pilot will be given the opportunity to have extra interactions with FDA experts on endpoint development as well as the associated review divisions. Further calls are expected to be launched later this year, with submission deadlines set on 30 June, 30 September and 31 December 2024.

Veristat is committed to helping its partners and clients in the development and the authorization of innovative medicines, including orphan drugs and cell and gene therapies. Established over three years ago, the Veristat Global Center of Excellence (COE), with focus areas such as Cell and Gene Therapies or Cancer, comprises a multi-disciplinary team of scientific experts who are adept at strategy and execution across this complex clinical development pathway. The Global COE serves as a powerhouse for sponsors and as a mechanism to share insights, successful strategies, and best practices. Through the Global COE and its international team’s expertise, Veristat boasts valuable experience in providing help in areas ranging from clinical trial execution, marketing authorization applications, or post-market obligations.

EU – Addressing shortages and preparing for future health crises

The EU is taking actions to consolidate the European Health Union and strengthen health crisis and shortage preparedness and response capabilities.

The European Commission launched in January a call for interest to join the Critical Medicines Alliance, which is one of the key actions that were announced last October to tackle medicine shortages. The Alliance aims to bring together the Commission, national authorities, the industry and civil society, to identify challenges and priorities for actions to address shortages of critical medicines in the EU. Potential measures include international partnerships to diversify supply chains, investments in European production capacities, a common approach to stockpiling and leveraging available funding. The Alliance, seen as the industrial arm of the European Health Union, will function as a consultative body for the EU and national authorities and a network to support the implementation of the measures. It will focus its work on the medicines on the Union list of critical medicines, released in December 2023. The Alliance is expected to hold its first meeting end of April and to adopt its first recommendations in autumn this year. The project will run for 5 years.

The Commission is also conducting an evaluation of the EU Regulation on serious cross-border threats to health, which is one of the pillars of the European Health Union. The evaluation, foreseen in the Regulation, will focus on the Commission’s preparedness and response activities, including the Early Warning and Response System, the epidemiological surveillance network, the EU reference laboratories, the coordination of preparedness and response activities within the Health Security Committee, as well as the impact of joint procurements. A public consultation was held earlier this year and an evaluation report is expected for Q4 2024

Progress is being made in parallel on the intellectual property package, presented last year, including the revision of the supplementary protection certificate (SPC) and the proposal on compulsory licensing during crises. The European Parliament adopted the SPC report in February, while interinstitutional negotiations are set to begin after the upcoming European elections in June 2024. The texts put forward the following measures:

• Establishment of a centralized procedure to obtain national SPCs for medicinal products authorized through the centralized procedure and covered by a European patent, overseen by the EU Intellectual Property Office (EUIPO),
• Introduction of an EU-wide SPC for medicinal products authorized under the centralized procedure and protected by a European patent with unitary effect, granted by the EUIPO, which would be valid in the countries covered by the unitary patent system,
• Provision of the possibility to use a combined application with the EUIPO.

The Commission proposal for a Regulation on compulsory licensing was adopted by the Parliament on 13 March and will be discussed in a later step with the Council in interinstitutional negotiations.

EU – Further steps taken toward reinforcing AI and cybersecurity frameworks in Europe

The AI Act undergoes institutional negotiations, while the EU Commission is boosting AI cooperation by creating a new AI office and facilitating AI development

The first ever law on artificial intelligence (AI), the AI Act, was adopted by the European Parliament on 13 March and will, after adoption by the Council of the EU, enter into force 20 days after its publication in the official Journal. Similar to the EU’s General Data Protection Regulation, the AI Act has the potential to set a global standard for AI regulation in other regions.

Earlier this year, the European Commission announced a package containing several proposed measures to boost innovation in AI. The Commission established a new AI office to supervise the rules for general-purpose AI systems at EU level, coordinate EU policy on AI and cooperate with EU bodies, Member States, Commission departments and stakeholders, and promote the EU approach to AI governance internationally. As part of this package, an amendment to the High Performance Computing Joint Undertaking (EuroHPC) Regulation was proposed to enable the creation of AI Factories as part of a new pillar for the EU's supercomputers Joint Undertaking activities. Another Commission initiative announced a boost for startups and innovation in trustworthy AI through new funding and investment incentives. The objective is the development of novel use cases and emerging applications in Europe’s fourteen industrial ecosystems, including pharma and biotech. Finally, the European Commission is also establishing, with several Member States, two European Digital Infrastructure Consortiums (EDICs): the ‘Alliance for Language Technologies' (ALT-EDIC) and the ‘CitiVERSE' EDIC.

In March, the European Parliament and the Council of the EU reached a political agreement to better detect, prepare, and respond to cybersecurity incidents and threats. The Cyber Solidarity Act establishes a European Cybersecurity Alert System (network of national and cross-border cyber hubs). It would also introduce a Cybersecurity Emergency Mechanism to ensure the preparedness testing of entities operating in critical sectors such as the health sector, create a new Cybersecurity Reserve from trusted providers ready to act under the Digital Europe Program, and finance the bilateral support assistance of Member States. In addition, the Act foresees the creation of a Cybersecurity Incident Review Mechanism to review and assess large-scale incidents. The Council of the EU and the European Parliament have endorsed the agreement on 20 March. The European Parliament’s plenary is set to vote on the Act on 24 April; should the Parliament adopt the Act without any amendment, the Council of the EU will adopt the Parliament’s position and the Act will be officially adopted.

EU – Ensuring the availability of devices in the EU
Key steps taken to help smoothen the implementation of the IVDR and MDR

Earlier this year, the European Commission released its legislative proposal amending both the In Vitro Diagnostics Regulation (IVDR) and the Medical Devices Regulation (MDR). The proposal addresses two key issues. Firstly, it aims to further extend the transitional period for certain in vitro diagnostics (IVDs) to prevent shortages, especially of high-risk IVDs. Secondly, the proposal aims to implement a phased roll-out of electronic systems into the European database on medical devices (Eudamed), instead of deferring the mandatory use of Eudamed until the last of the six modules is completed.  As a result, the mandatory use of specific modules could potentially start as early as Q4 2025. Three Eudamed modules have been available for voluntary use since December 2020 (Actors) and October 2021 (Unique Device Identifier (UDI)/Devices; Notified bodies/Certificates). Two further modules (Market Surveillance; Post-Market Surveillance and Vigilance) are expected to be completed in Q2 2024. The last module (Clinical investigations/Performance studies) will not be completed before Q3 2026. Separately, the proposal also introduces a new obligation for manufacturers to give prior notice before interrupting the supply of certain critical medical devices and IVDs. Finally, the Commission proposed to postpone until 26 May 2030 the application of one of the requirements for IVDs manufactured and used in health institutions, i.e. the requirements to show that there is no alternative and equivalent commercial device on the market.

Both the MDR and IVDR include provisions that oblige the Commission to assess the application of the regulations and produce an evaluation report at the latest by 27 May 2027. Due to the multiple implementation challenges faced, the Commission will initiate preparatory works for a targeted evaluation already in 2024. The targeted evaluation will assess whether the legislation has delivered results as intended, and whether it is fit for purpose or underperforming in ensuring availability of devices for small patient populations (i.e. ‘orphan devices’) and fostering the development and availability of innovative devices in the EU. The implementation of the prior notice mechanism for monitoring device shortages will deserve special attention in the assessment, as well as costs and administrative burdens stemming from the implementation of the legislation, especially for SMEs.

In February 2024, the Council of the EU reported its endorsement without any amendments of the proposal. The European Parliament is set to vote on the text via the urgent procedure in the week of 22 April. Once approved by the European Parliament and pending linguistic review, the Council will later immediately adopt the Parliament's position and the act will be immediately adopted.

Other recent developments

EU – Global Health Strategy

Earlier this year, the Council approved conclusions on the 'EU Global Health Strategy: Better health for all in a changing world', in which it reaffirms the leading role of the EU and its Member States in advancing global health. The three priorities of the EU Global Health Strategy guide the following efforts:

• The delivery of better health and well-being for people across their life course,
• The strengthening of health systems and the advancement of universal health coverage,
• The prevention of and combat against health threats, including pandemics, applying a One Health Approach.

The strategy will guide EU action in the field of global health until 2030.

EU – Medicine & device update

In December last year, the European Parliament and the European Council reached a provisional agreement on the Regulation on standards of quality and safety for substances of human origin intended for human application. The new EU rules support high safety and quality standards, improve harmonization and access across EU Member States and aim to create conditions for safe, effective and accessible innovation. The Council of the EU endorsed the agreement in January 2024. The European Parliament’s plenary is set to vote on the text on 24 April; should the Parliament adopt the Regulation without any amendment, the Council of the EU will adopt the Parliament’s position and the Regulation will be officially adopted. The Regulation will apply as from 2027.

The European Parliament Committee on the Environment, Public Health and Food Safety (ENVI) adopted on 19 March 2024 compromise amendments on the revision of the EU pharmaceutical, orphan and pediatric legislation. Highlights include, among others, the following:

• The introduction of 7.5 years of minimum regulatory data protection period, which can be extended under certain conditions,
• A one-time 12-month extension of the 2-year market protection period can be granted if the company obtains a marketing authorization for an additional therapeutic indication which provides significant clinical benefits in comparison with existing therapies,
• Market exclusivity of 9 years for orphan medicinal products, 11 years for orphan drugs if they address a high unmet medical need,
• No obligation to launch a medical product in all 27 Member States, but obligation for marketing authorization holders to apply for pricing and reimbursement on request from Member States
• Companies must submit an environmental risk assessment when requesting a marketing authorization application.

The plenary vote took place on 10 April. The European Parliament adopted the compromise amendments in its position on the proposed pharmaceutical legislation. Now the European Council will continue its work to find an agreement among Member States for the negotiating mandate. Trilogues will follow after the EU Parliament elections of 6-9 June 2024.

 In January 2024, the Council formally adopted a regulation to modernize and simplify the structure of fees paid to EMA. The new rules will ensure both adequate funding for the EMA and sufficient support for national competent authorities to undertake their scientific evaluation tasks. The updated regulation implements a shift from a fixed-rate to a fee structure based on costs. It further enhances flexibility and adaptability, incorporating provisions for fee updates and adjustments to evolving circumstances. The regulation will become applicable on 1 January 2025.

The European Parliament and the Council reached a provisional agreement on the urban wastewater framework in January 2024. The agreement introduces new rules on removing micro-pollutants coming from medicines and personal care products. It also strengthens the monitoring of various public health parameters (such as the SARS-CoV-2 virus, poliovirus, influenza viruses and emerging pathogens, antimicrobial resistance), as well as chemical pollutants, including PFAS and microplastics. The agreement further introduces extended producer responsibility (EPR) for medicinal products for human use and cosmetic products to cover the costs of additional treatment to remove micro-pollutants from urban wastewater. The European Parliament and the Council of the EU endorsed the agreement in March. On 10 April 2024, the European Parliament adopted the legislation without any amendment. The Council of the EU now needs to formally approve the agreement before it can enter into force.

The European Commission has rolled out a new data dashboard to provide more transparency in terms of medical device availability across European Union member states and the progression of transitions to the MDR and IVDR. The dashboard is based on data gathered from different stakeholders.

The Medical Device Coordination Group (MDCG) published several documents in the last few months:

• MDCG 2023-7: Issued in December 2023, this guidance focuses on exemptions from the requirement to perform clinical investigations, and associated conditions related to the demonstration of equivalence, for implantable and class III medical devices. The guidance outlines four cases for exemptions.
• MDCG 2021-27 - Rev.1: Issued in December 2023, this revised Q&A document focuses on requirements related to importers and distributors under the MDR and IVDR. New questions were added on the roles of the authorized representative, importer and distributor.
• MDCG 2024-1: Issued in January 2024, the guidance concerns the vigilance system for CE-marked devices pursuant Article 2(64) and (65) MDR and in Article 2(67) and (68) IVDR.
• MDCG 2024-2: Issued in February 2024, the guidance lays out procedure for the annual update of the European Medical Device Nomenclature (EMDN) terms and codes.

The Q&A document for applicants, marketing authorization holders of medicinal products and notified bodies with respect to the implementation of the MDR and IVDR was updated at the end of 2023. The revision concerns an update of question 2.10 regarding Mutual Recognition Procedure (MRP) and the Repeat Use Procedure (RUP). A further, more comprehensive update of the Q&As is currently ongoing and will be published in the near future.

A Team-NB position paper on medical device lifetime issued in December 2023 provides an overview of existing guidance and standards, identifies expectations and illustrates the matter for different device types. The paper concludes that regulations and guidance only very broadly refer to lifetime of a medical device in terms of safe and effective use. The paper recommends that manufacturers’ specifications should correspond to reasonable risk of severity and likelihood of failure modes for the device, and consist of pre-clinical performance testing and clinical data or data from clinical data sources for benefit risk determination. The indication of years of use or number of uses avoids ambiguity in the conformity assessment process for confirmation of applicable supporting evidence for device lifetime.

EU – Swiss relations
The EU maintains personal data flows with Switzerland; both parties kick off bilateral negotiations on their future relationship

In January 2024, the European Commission confirmed the maintenance of the adequacy decisions for the protection of personal data with Switzerland.

The Council of the EU adopted the mandate and directives for negotiations with Switzerland on the future of the framework for Swiss-EU relations on 12 March. The Swiss Federal Council adopted its negotiating mandate on 8 March, after extensive consultations with the Parliament, cantons and civil society. The Swiss negotiating mandate presents a “package approach” and comprises new agreements (e.g. a new cooperation agreement on health) and institutional solutions (e.g. dynamic adoption of legislation or dispute settlement). The negotiations were officially kicked off on 18 March with the meeting of Federal Councilor and President Viola Amherd and European Commission President Ursula von der Leyen in Brussels.

Swiss trade associations in the healthcare sector have emphasized the importance of successful negotiations. Important outcomes that are expected from the healthcare industry’s standpoint include ensuring the update of the mutual recognition agreement for medicinal products, obtaining the update of the mutual recognition agreement for medical devices and IVDs, guaranteeing the free movement of people to allow access to qualified workers, and getting access to EU collaboration programs for research, education and innovation. The negotiations should also deliver the least number of tariffs and non-trade barriers. Failing to conclude Swiss-EU negotiations in a satisfactory manner will likely have a detrimental impact the healthcare industry.

UK – International recognition procedure, future medical device regulation
Launch of the IRP route, revision of the UK regulatory framework for medical devices and strategy against supply shocks.

The start of the UK’s International Recognition Procedure (IRP) was announced by the Medicines and Healthcare products Regulatory Agency (MHRA) in January 2024. Developers of new medicines have been able to submit applications as of beginning this year via the IRP route. The IRP time frame varies between 60 to 110 days to process an application. The MHRA will partner with regulators in Australia, Canada, Japan, Singapore, Switzerland and the USA, as well as the EMA and individual Member States from the EU and European Economic Area. The MHRA issued guidance to the IRP’s two specific application routes and the pre-submission eligibility check. The first approval under this procedure was granted on 29 February 2024

Separately, the MHRA presented an overall time schedule for the revision of the UK regulatory framework for medical devices, announced after Brexit. The future legislation will be rolled out in two steps. First, enhanced post-market surveillance (PMS) requirements will be rolled out through a legislative proposal, which will be presented in the first half of this year and is expected to apply by the end of 2024. Secondly, the government plans to present a proposal in early 2025 on the revision of the future regulation of medical devices after a consultation phase with stakeholders in the course of 2024; the revised legislation is expected to enter into force in the course of 2025.

Earlier this year, the UK Department for Business and Trade launched the Critical Imports and Supply Chains Strategy to secure UK supplies of critical goods such as medicines, minerals and semiconductors. More than 100 UK manufacturers, including the Association of the British Pharmaceutical Industry (ABPI), have contributed to the strategy. Under the strategy the government will provide guidance on risks to key supply chains and how to protect businesses from disruptions. A public-private Critical Import Council will be set up; the Council will be tasked with identifying risks and advising on actions to secure supply. Finally, the strategy will require businesses to report disruptions affecting critical imports

USA – Key updates

Proposed legislation dubbed the "US Biosecure Act" introduced in the Senate in late 2023 and in the House of Representatives in January 2024, which propose to “prohibit federal contracting with certain biotechnology providers connected to foreign adversaries”, is sending ripples throughout the biopharma industry. Companies working with entities under scrutiny could potentially be prevented from accessing US government contracts. Companies concerned by the proposed legislation are Chinese-owned and include BGI, MGI, Complete Genomics, WuXi AppTec, and their family of companies. The legislation, which shows signs of bi-partisan support, could have an important impact and create delays in clinical trials and medicine shortages. 

In early February 2024, an FDA advisory panel debated which medical devices are critical in a public health emergency and should be included in the ‘Mission Critical’ Devices 506J List. The FDA had previously issued a draft guidance in November 2023, which included a list of devices. The Panel discussed the possibility of prioritizing or tiering the list to reflect the variation and severity of different types of public health emergencies. The panel also expressed concerns about the broadness of the product codes and recommended to be more specific on the types of devices within each product code. Members further advised adding specific devices to the list but rejected supply chain resilience as a factor for consideration whether a device should be included in the list.

The FDA published a draft guidance on data monitoring in clinical trials in February 2024. The guidance is intended to assist sponsors of clinical trials in determining the type of monitoring committee and what procedures and practices should be considered to guide their operation.  Once finalized, the guidance will supersede “Establishment and Operation of Clinical Trial Data Monitoring Committees,” issued in March 2006. Comments on the draft guidance can be submitted by 15 April 2024.

Separately, the FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program accepted for the first time a submission of an AI-based and digital health technology for neuroscience. The submission was for an automated depression and anxiety severity measurement tool utilizing multiple behavioral and physiological indices of depression in a machine learning (ML) model. Launched in 2020, ISTAND aims to support the development of novel drug development tools that do not fit into established pathways for evaluation and application to be used in regulatory applications for new medical products.

The FDA’s final guidance for holders of an abbreviated new drug application (ANDA) following revision of the reference listed drug (RLD) labelling  published in January 2024. This guidance provides recommendations on identifying RLD labeling updates and submitting ANDA amendments or supplements to update generic drug labeling. These documents revise older guidance entitled “Revising ANDA Labeling Following Revision of the RLD Labeling” (April 2000). Significant changes from the 2000 version include updates to outdated details about how to obtain information on changes to RLD labeling and how to submit revised ANDA labeling to FDA

The White House Office of Science and Technology Policy (OSTP) released updates in the first quarter of 2024. It published the National Emerging Contaminants Research Initiative Implementation Plan on 19 January 2024, which outline the steps to achieve the strategic goals and metrics to track progress. Separately, in February 2024, the OSTP released an updated list of critical and emerging technologies (CETs) that are potentially significant to U.S. national security. Biotechnologies represent one CET identified, with key subfields including novel synthetic biology, multi-omics, biomanufacturing and bioprocessing technologies and others.

IMDRF

In February 2024, the International Medical Device Regulators Forum (IMDRF) formulated guiding principles for promoting health equity among underrepresented populations in the development, evaluation, and regulation of medical devices. The guidance aims to aid IMDRF working groups in integrating health equity principles into the creation of technical documents, as applicable. These principles are meant to be upheld across the entire lifespan of a product.

Separately, the IMDRF opened a public consultation in February 2024 on its draft guidance on medical device software. The objective of this document is to promote and inform clear and accurate characterizations of medical device software, including intended use/intended purpose statements, and introduce a general strategy for characterizing software-specific risks that leverages the key features of a comprehensive medical device software characterization. Comments may be submitted until 2 May 2024

Switzerland

In an audit report, the Swiss Federal Audit Office evaluated the processes for the regulatory approval and reimbursement of medicines at Swissmedic and the Federal Office of Public Health. The evaluation concluded that, in an ideal scenario, reductions of around 400 days could be possible. The overall process for new drugs currently takes around 900 days for approval and reimbursement. Shorter times could be achieved, among other things, through greater international collaboration, a parallelization of the approval and reimbursement processes and provisional reimbursement directly after regulatory approval.

A new Pharmaceuticals and Health Insurance department was created in the Health and Accident Insurance Directorate of the Federal Office of Public Health as of 1 January 2024. The new department was created to fulfill the complex and increasing tasks related to the reimbursement of medicines through compulsory health insurance more effectively and efficiently.

The Swiss Federal Council announced its political priorities for 2024. These include the following:

• European policy: In 2024 and subject to successful negotiations with the EU, the Federal Council aims to conclude the agreement on the 2021-2027 Horizon package to enable the full participation of Swiss researchers and innovators.  If unsuccessful, transitional measures will be evaluated.
• Digitalization: In 2024, the Federal Council will initiate a comprehensive legislative revision of the federal legislation on electronic patient records (EPDG). The revision aims to improve the framework conditions for the further development of the electronic patient records to increase the benefits of the EPR for all stakeholders.
• Health policy: In 2024, the Federal Council will open the consultation on the implementing provisions for the amendment of the Federal Health Insurance Act (KVG) on the second part of the cost containment package and cost targets. The proposed measures focus on the reimbursement of medical services and medicines so that these can be provided in a more cost-effective manner. Furthermore, in the second half of 2024, the Federal Council plans to initiate the legislative revision of the federal legislation on the fight against communicable diseases (Epidemiengesetz). Findings from the Covid-19 crisis and possible future public health challenges, such as antimicrobial resistance, have been addressed in the revision.

Outlook for Q2/Q3 2024

European Union

• Launch of the Critical Medicines Alliance
• Results of the consultation on the effectiveness/efficiency of HERA (end of consultation on 19 Feb 2024)
• Implementation of revised CTIS transparency rules
• Vote on the pharmaceutical legislation package by the European Parliament committee
• Elections of the European Parliament

United Kingdom

• Legislative proposal to revise the clinical trials framework
• Legislative proposal on post-marketing requirements for devices

Switzerland

• Revision of the Federal Act on the Electronic Patient Record
• Consultations on the partial revision of the Therapeutic Products Act and Epidemics Act
• Finalization of the Federal Council’s draft negotiating mandate with the EU

United States

• CBER's Vaccines and Related Biological Products Advisory Committee Meeting (16 May 2024)
• Legislative CBER's Blood Products Advisory Committee Meeting (09 May 2024)

OUTLOOK: EU | OUTLOOK: US | OUTLOOK: Switzerland | Outlook: UK