From 25 to 29 January 2022, the 150th session of the World Health Organization’s (“WHO”) Executive Board (“EB”) took place in Geneva, Switzerland. Two years into the COVID-19 pandemic, a central theme for this session was the management of global health emergencies. This post briefly outlines the main take-aways for pharmaceutical companies.
On 20 January 2022, the National Institute for Health and Care Excellence (NICE) announced major changes to the processes and methods by which it assesses the cost-effectiveness of medicines and other health technologies.
NICE is an independent expert body tasked with appraising the cost-effectiveness of medicines and recommending whether a product should be funded by the National Health Service (NHS). NICE is therefore considered the gatekeeper for medicines reimbursement; a positive recommendation obliges the NHS to fund a product.
NICE has announced a suite of detailed changes, which mark the culmination of a two-year-plus long “methods review”. NICE will implement the changes in new guidelines. They are due to take effect from February 2022.
Some of the new innovations affect the process by which NICE appraises medical technologies. Perhaps most importantly, they also affect the manner in which NICE reviews submissions and its criteria for issuing positive recommendations. Many of the changes are technical in nature.
NICE considers these changes “will give patients earlier access to innovative new treatments by allowing greater flexibility over decisions about value for money and consideration of a broader evidence base.”
The following are some headline points we noted:
- Evolution of a Well-Established Framework. Although the changes are significant, NICE’s fundamental framework remains largely the same. NICE appraisals will continue to focus on a technology’s incremental cost-effectiveness ratio (ICER) against an existing reference based on the quality-adjusted life year (QALY). These are established health economic concepts that seek to quantify the relative utilities of a technology. NICE’s baseline ICER for approving a product will remain broadly the same (e., below £20,000 or £30,000). These thresholds have remained broadly unchanged for a number of years. They can prove to be a major hurdle for higher-cost innovative medicines.
- Flexibility for Disease Severity and Health Inequalities. NICE will have the flexibility to recommend technologies with ICERs higher than its traditional thresholds, depending on disease severity. Products that treat the most severe diseases might receive a positive recommendation, even if their ICER exceeds the £30,000 upper limit (potentially up to £50,000). Previously, this flexibility was reserved for end-of-life treatments. NICE will also have some discretion for treatments that help to reduce health inequalities.
- New Approaches to Evidence Review. NICE has committed to “enhance and expand upon” how it assesses real-world-evidence submitted as part of a review. NICE has also given its appraisal committees additional discretion when reviewing products for which it is inherently difficult to generate sufficient clinical evidence (g., paediatric indications, rare diseases or complex cases). NICE’s aim is to “to consider uncertainty appropriately and to manage the risks to patients and the NHS while preventing inappropriate barriers to valuable innovations.”
- Clearer and Potentially More Expansive Approach to Highly Specialized Technologies. NICE has historically maintained a separate review programme for “Highly Specialised Technologies” (often medicines that treat rare diseases that have a heavy disease burden for patients). Highly Specialized Technologies benefit from far higher ICER thresholds that apply to conventional therapies; reflecting the high-cost of developing rare-disease treatments. The most recent changes streamline the entry-criteria for the Highly Specialized programme. In principle, this may allow more products into the programme. It may also help companies plan better, with clarity over whether a particular product qualifies.
- Earlier Engagement and More Clarity Promised for Managed and Commercial Access. NICE has for some time had the ability to make interim positive recommendations, to enable companies to gather further data about a product’s cost-effectiveness. Similarly, NICE may approve a product subject to a “commercial deal” the company has struck with the NHS. NICE has committed to earlier engagement with the NHS and companies, when these situations arise. The changes also ought to make it clearer when NICE can make these types of contingent or interim recommendations. Notably, NICE declined to establish a standalone review system for these situations (which many in the pharmaceutical industry had called for).
It is worth noting that the ambition behind, and trajectory of, these changes go towards clarifying, speeding up and de-cluttering the review of the most promising and innovative technologies. This ties together with other post-Brexit innovations to improve access to medicines. These recent innovations include the new Innovative Licensing and Access Pathway (ILAP), which seeks to co-ordinate and streamline marketing authorization and market access reviews for innovative treatments. They also include the creation of a new NHS Innovative Medicines Fund (IMF) in England.
No doubt, commentators, market access experts and industry will pore over the details of the changes over the coming days and weeks to survey the new landscape for health technology appraisals.
Whether the changes will have their desired effect remains to be seen. Many of the innovations give appraisal committees more flexibility and discretion. How committees exercise these new tools will be the critical point; and that will only become clear once we start to see the results of appraisals under the new system.
The Italian Legislative Decree 196/2021 (“Italian Decree”) implementing the Single-Use Plastic Directive (“SUPD”) will enter into force on January 14, 2022. The Italian Decree diverges from the SUPD on significant aspects: it provides a more flexible definition of plastic; delays the entry into force of the ban on prohibited SUPs; and exempts from such ban specific biodegradable and compostable materials. The Decree also imposes specific return obligations on waste plastic bottles.
While the Italian Decree provides companies with additional flexibilities to market their SUPs in Italy, companies should carefully assess the risks that may arise if EU Courts finally hold that the Decree is not compatible with EU law.
Following the federal election in September 2021, Germany will soon be led by a new three-party coalition, the so-called “traffic light coalition”, composed of the Social Democratic Party (SPD), the Liberal Democrats (FDP) and the Green Party (Die Grünen). This new federal government led by the new chancellor Olaf Scholz from the Social Democrats will replace the Merkel administration and will be in office for four years. On November 24, 2021, the new coalition has presented their coalition agreement with their plans for the next 4 years. The agreement needs to be approved by the respective party committees and it is expected that all three parties will approve it.
The new government’s roadmap foresees reforms in the healthcare and life sciences sector that will have a significant impact in particular on pharmaceutical and medical device companies but also healthcare providers and technology companies focusing on the healthcare and life sciences sector.
The coalition agreement has an own chapter for the healthcare and life sciences sector that among other things envisages changes to the regulation of pharmaceuticals and medical devices. In particular, there will be far-reaching cost-containment measures by amending the drug pricing and drug reimbursement rules. The new government also plans legislative changes in the areas of supply of medicines, vaccines and medical devices. Moreover, the enhanced digitalization of healthcare is a particular goal of the new coalition. With respect to digitalization, Germany generally and especially its healthcare sector starts from a rather low development stage (e.g., still widespread use of fax machines) so that significant investments will be needed.
It is also important that the new Ministry of Health will be a politician from the Social Democratic Party. This Ministry was led by a politician from the Christian Democratic Union for the last 8 years.
The new government also intends to enact changes to other areas of the broader life sciences industry, such as food advertising and the regulation of cannabis, alcohol and tobacco. The responsible ministries of Environment/Consumer and Agriculture/Food will be led by a politician from the Green Party.
Among other things, the roadmap of the coalition parties includes in particular the following plans with respect to the life sciences sector:
Pharmaceutical and Medical Device Companies
- Pricing procedure. The coalition parties wish to amend the drug pricing and market access procedure (AMNOG). The AMNOG procedure starts with the market launch of a new medicine and can be divided into two procedural stages, namely the benefit assessment by the Joint Federal Committee (“G-BA”) and the negotiation of the reimbursement amount with the top association of the health insurances (“GKV-Spitzenverband”). Under the current regulations, the pharmaceutical companies are entitled to a period of free pricing for 12 months after the product launch. The coalition parties now plan to reduce this free pricing period for new drugs from one year to six months. According to their plans, the negotiated reimbursement price (Erstattungsbetrag) will apply from the seventh instead of the 13th month after launch. This will cut in half the period of free pricing for pharmaceutical companies. This measure is intended to increase cost-containment options for the statutory health insurance (SHI) fund.
- Further cost containment measures to limit drug prices. The new government has also announced that it will generally strengthen the possibilities of the health insurances to limit the prices of medicines. The coalition agreement does not further elaborate on this important point so that it remains open which instruments the new government plans to provide the healthcare insurances with. In any event, the coalition agreement quite clearly and repeatedly speaks out the plan of the new coalition to limit drug prices and contain the expenditures of the healthcare insurances for drugs. The pharmaceutical industry needs to be prepared that the new government will employ several different measures to reach this goal.
- Price freeze. Among the more concrete measures to limit drug expenditures, the new government plans to prolong the existing and quite controversial price freeze (Preismoratorium) for medicines. The price freeze was introduced back in 2010 and allows only very limited (inflation-reflecting) reimbursement of price increases for medicines. Following the most recent extension in 2017 for another five years, the price moratorium was expected to expire in 2022. This has now become very unlikely so that the industry needs to be prepared to a perpetuation of this significant cost containment measure which undoubtedly has a severe impact on pharmaceutical companies in Germany. The prolongation of the price free may trigger a new discussion around the legality of this legislative prohibition.
- Federal Joint Committee. The new coalition parties plan to reform the rules governing the Federal Joint Committee (G-BA) to speed up its decisions. Among other things, the G-BA is responsible for conducting health technology assessments, i.e., assessing the (added) benefit of new drugs in the above mentioned AMNOG procedure for the market access of new drugs in Germany. The G-BA is also involved in health technology assessments of new medical devices and treatment methods and is also the key decision maker with respect to many other healthcare related matters (e.g., the exceptional reimbursement of off-label-use treatments). Therefore, the new government’s plan to “reform the G-BA” may have significant ramifications for life sciences industry companies.
- Patient Rights and Patient Involvement in Market Access. Patient centricity appears to be another special concern for the new German government. The coalition agreement sets forth that the new government will strengthen the structures for independent patient counseling and enhance their independence. As part of the above mentioned reform of the G-BA and the market access rules, the new government will enhance the representation of patient groups in the G-BA. Further, the new coalition plans to make reforms to the exiting liability rules to improve the position of patients in medical liability matters. In that context, the new coalition also wishes to establish a new hardship fund.
- Supply Security and Reshoring. The new coalition parties wish to prevent any shortages in the supply of medicines and vaccines. Among others, the parties want to take measures to relocate and re-shore the manufacturing of pharmaceuticals back to Germany or the EU. This includes reducing the bureaucratic burden, examining investment subsidies for production sites, and considering subsidies to ensure security of supply. In addition, a Health Security Act (Gesundheitssicherstellungsgesetz) is intended to ensure the efficient and decentralized stockpiling of medicines and medical devices, as well as regular emergency exercises for health risk personnel.
- More Transparency and “Sunshine laws” against Conflicts of Interests. Germany has not yet enacted so-called “Sunshine laws” and does not require drug and device companies to disclose payments and transfers of value they make to healthcare professionals. The coalition agreement now announces that the new government will create more transparency about financial contributions made to healthcare professionals to avoid conflicts of interests. Hence, the new German government appears to consider new Sunshine legislation for the healthcare and life sciences sector in Germany.
- Pharmacies. The new coalition envisages various changes and legislative amendments in the rules governing pharmacies and pharmaceutical services.
- Digitalization. The coalition parties especially emphasize their goal to improve the digitalization of the German healthcare system. Among the many goals, they want to provide more telemedical services to patients on a regular basis. They also plan to accelerate the introduction of the electronic patient record (elektronische Patientenakte) as well as the connection of all relevant players to the telematics infrastructure. All insured persons in Germany should be provided with an ePA in compliance with the GDPR but its use will be voluntary (opt-out). In this context, Gematik, the agency currently tasked with the roll-out of the ePA, is to be expanded into a digital health agency.
- Research Use of Health Data. The new German government also plans to enhance the possibilities to use health data for scientific research purposes by public and private entities. Insofar, a new act on the use of health data is envisaged (Gesundheitsdatennutzungsgesetz) as well as a new act governing registries (Registergesetz). These goals are also embedded into the broader healthcare digitalization strategy.
Beyond these specific changes affecting the pharmaceutical and medical devices space, the new government also plans further changes in the broader healthcare area which will have direct and indirect implications for life sciences companies. In particular, there will be changes in nursing care, hospital care and financing and health insurance.
Food industry and cannabis, alcohol and tobacco companies
- Food. The coalition parties intend to create scientifically based reduction targets for sugar, fat and salt that are tailored to target groups. In addition, they want to prohibit advertising directed at children for foods with high fat, sugar and salt (HFSS) content in TV shows and other formats for under-14-year olds. Further, they want to develop further an EU-wide Nutriscore in a scientific and generally understandable way. The parties intend to strengthen plant-based products and advocate for the approval of innovations such as alternative protein sources and meat substitutes in the EU.
- Cannabis, alcohol and tobacco. Germany plans to further liberalize Cannabis. In addition to the already legal provision of cannabis for medical purposes, there will also be controlled supply of cannabis to adults for recreational purposes in licensed stores in the future. This approach seeks to control the quality, prevent the distribution of contaminated substances and ensure the protection of minors. With regard to alcohol, tobacco and cannabis, the parties want to toughen the regulations for marketing and sponsoring.
Whistleblowing, Class Actions, Corporate Sanctions and other Plans
- Whistleblowing Laws. The new German government has announced that it will implement the EU Whistleblowing Directive (EU) 2019/1937 into national law. In doing so, the new coalition plans to adopt national whistleblowing laws, which go beyond the scope of the EU Whistleblowing Directive and also include protection for whistleblowers that report breaches of national law and not only EU law violations. The implementation of the Whistleblowing Directive by companies will in any event require the establishment of local whistleblowing systems and procedures as it will not be sufficient to only refer to a corporate-group-wide whistleblowing system.
- Class Actions and Collective Redress. The new German government plans to expand the currently available collective redress options for consumers. It will implement the new EU Directive on representative actions for the protection of the collective interests of consumers and the coalition agreement states that this will be implemented in a “user friendly” manner. Small companies should also benefit from the new “class action” options.
- Corporate Sanctions and Compliance Programs. The new government plans to “protect honest companies from unlawful competitors” which will probably lead to amendments of the respective commercial laws. The coalition also wishes to revise the rules on corporate sanctions, including the level of sanctions, in order to improve the legal certainty of companies with regard to their compliance obligations. The last government had attempted to reform the existing German laws and enact new rules on corporate criminal liability. In that course, the companies should also be incentivized to implement robust compliance programs. In the last government, the SPD had pushed this legal reform idea. As the SPD is now the strongest party in the new government, it can be expected that the new government will soon present similar reform plans.
- Internal Investigations. In conjunction with the reforms of the corporate sanctions rules, the new German government also plans to create a new legal framework for internal investigations by companies.
- English as Court Language. The new government plans to establish English-speaking special chambers at German commercial courts.
The envisaged reforms of the coalition parties will have significant direct and indirect implications for life sciences companies. Therefore, all companies in this sector should closely monitor the upcoming legal developments in Germany.
Between 29 November and 1 December 2021, all member states of the World Health Organization (WHO) will convene for an extraordinary session of the World Health Assembly (WHA). There is only one agenda item: whether or not to commence negotiations towards a legally binding, global instrument on pandemic preparedness and response. Since it was first proposed by the European Union (EU) in November 2020, significant momentum has built towards some kind of International Pandemic Treaty (IPT). The project is currently backed by the EU and more than 25 countries, though sceptics include the U.S., Russia, Brazil and China.
The IPT will be directly relevant to all pharmaceutical companies developing medical countermeasures (e.g. vaccines, diagnostics, and therapeutics) to most infectious diseases with epidemic or pandemic potential. This blog summarizes key points that pharmaceutical companies should be aware of.
1. Public-private collaboration in the global system to detect and assess health threats
On 30 January 2020, the WHO Director-General declared the COVID-19 pandemic a “Public Health Emergency of International Concern” The timeliness of this declaration has been under significant criticism. As a result, there is consensus that the existing 2005 International Health Regulations (IHR) need to be reformed, and that a new system will be organized to rapidly detect and share information on outbreaks of “disease with pandemic potential.”
High-ranking officials at the WHO expect that this new monitoring system may function comparably to the existing Global Influenza Surveillance and Response System (GISRS). This network of laboratories has been monitoring seasonal influenza for decades, as well as influenza with pandemic potential under the WHO’s Pandemic Influenza Preparedness (PIP) Framework since 2011. Since early 2020, the GISRS network of infectious disease experts has been instrumental in the global response to coronavirus.
It is uncertain whether the IPT’s new monitoring system would absorb the GISRS. In any case, the key message for industry is that most pharmaceutical companies can, will and even must interact with the new monitoring network under IPT. For instance, under the PIP Framework, pharmaceutical manufacturers have been obliged to sign a Standard Material Transfer Agreement (SMTA) in order to be allowed to receive virus samples as well as sequence or epidemiological information. In that context, the obligation to conclude these SMTAs was relevant mostly for manufacturers of influenza vaccines, a relatively small and well-defined group. For the future IPT, it appears likely that its scope will comprise all pathogens “with epidemic or pandemic potential.”
These SMTAs will likely become the key legal instrument to organize public-private collaboration under the future IPT. Importantly, their drafting is already underway in the context of a SARS-CoV-2 pilot project called the WHO BioHub System. Without awaiting the outcome of the upcoming WHA Special Session, the WHO Secretariat already started chiseling away at the building blocks for the future IPT. We zoom in on this BioHub and its draft SMTA, since they provide insight into key topics that will be central to the upcoming WHA Special Session: global equity, intellectual property, and funding the IPT.
2. Equity for global health: concrete impact for industry?
To prepare the Special Session of the WHA, a Member States’ Working Group was convened in July 2021, chaired by Indonesia and the United States. The group published a so-called “zero draft” already on 28 October 2021, stating that equity is “at the core of the breakdown in the current system” and that equity is “ideally suited for negotiation under the umbrella of a potential new instrument.” Much can be covered by the umbrella of equity, and pharmaceutical companies are well advised to monitor discussions on e.g. (i) equity as regards access to and distribution of medical countermeasures, and (ii) equity as regards intellectual property, technology transfer and empowerment of local and regional manufacturing capacity during emergencies. There are many moving parts, but it is clear that what happens at the Special Session later this month will be connected to parallel discussions and outcomes at the WTO on the TRIPS waiver.
At a more granular level, the SMTAs will likely be the legal instrument to organize the equitable contribution of the pharmaceutical industry under the IPT. Companies that wish to develop medical countermeasures relating to pathogens of “epidemic and pandemic potential” will likely require physical samples for their R&D, or will need access to the information developed by the global monitoring system. In order to obtain access to these materials and information, the SMTA will require companies to become “qualified entities” by WHO and agree to “benefit-sharing.” The pilot phase of the WHO BioHub contains a draft SMTA “for the Sharing of Biological Materials with Epidemic or Pandemic Potential (BMEPP) with a Qualified Entity for non-commercial public health use.” Article 4 of this SMTA states that “[i]n the event that the use of BMEPP results in the creation of such material benefits, the Qualified Entity will engage with WHO to distribute and provide such benefits on a fair and equitable basis.” While there is no clarity yet on what ‘benefit-sharing’ would be expected of companies under an International Pandemic Treaty, the existing regime for pandemic influenza is likely to be an inspiration. In the SMTAs relating to pandemic influenza, companies have been given the option to agree to e.g. donations of vaccines, antivirals, medical devices and diagnostic kits; affordable pricing; transfer of technology and processes; granting of sublicenses to WHO; and laboratory and surveillance capacity building.
Last but not least, a point on funding. A consensus has emerged that the cost of the new system should be shared between private and public actors. Aside from the need for “sustainable resourcing”, there is little detail. Currently, it is envisaged that the WHO would have a technical and convening role, with support from e.g. the International Monetary Fund (IMF) and the World Bank. It is worth recalling that under the Pandemic Influenza Preparedness Framework, pharmaceutical companies pay a so-called “Partnership Contribution” which between 2012 and 2021 totaled to more than 227 million USD, on top of the “benefit-sharing” agreed through the SMTAs. In practice, the contribution itself has not been too controversial, but rather issues such as transparency and accountability on how the monies have been spent by WHO to contribute to pandemic preparedness and response.
3. Next steps
The “zero draft” of 28 October 2021 states front-and-center that “the status quo is not acceptable to anyone.” Though the legal nature and exact content is in flux, it is most likely that a new international system will emerge, and that pharmaceutical companies should pay close attention.
Covington intends to publish another update once the dust from the Special Session has settled. In the meantime, do get in touch with Bart Van Vooren, partner in Covington’s life sciences practice.
With the assistance of Kolahta Ioab Asres, intern on global health policy.
On 27 October 2021, the U.S. Food and Drug Administration (“FDA”), Health Canada, and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (“MHRA”) (together the “Regulators”) jointly published 10 guiding principles to inform the development of Good Machine Learning Practice (“GMLP”) for medical devices that use artificial intelligence and machine learning (“AI/ML”).
AI and ML have the “potential to transform health care” through their ability to analyse vast amounts of data and learn from real-world use. However, these technologies also pose unique challenges, given their complexity and the constantly evolving, data-driven nature of their development. The Regulators formed the guiding principles to “help promote safe, effective, and high-quality medical devices that use . . . AI/ML” and to “cultivate future growth” in this fast paced field.
The Regulators predict that the guiding principles could be used to: (i) adopt good practices from other sectors; (ii) tailor these practices to the medical technology/healthcare sector; and (iii) create new practices specific to the medical technology/healthcare sector. The Regulators expect these joint principles to inform broader international engagements as well.
The 10 Guiding Principles
The guidance published by the Regulators set out the 10 principles in full; however, in short, they recommend:
- Leveraging multi-disciplinary expertise throughout the total product life cycle
- Implementing good software engineering and security practices
- Ensuring clinical study participants and data sets are representative of the intended patient population
- Making training data sets independent of test sets
- Basing selected reference datasets upon best available methods
- Tailoring the model design to the available data and ensuring it reflects the intended use of the device
- Placing focus on the performance of the human-AI team
- Ensuring testing demonstrates device performance during clinically relevant conditions
- Providing users with clear, essential information
- Monitoring deployed models for performance and managing re-training risks
These principles cover the entire life cycle of devices with the aim of ensuring safety and efficacy. The Regulators have focused on use of appropriate datasets and carrying out sufficient testing before marketing AI/ML-based devices. These guiding principles set out an ongoing recommendation to manage risks, which will involve monitoring and potentially re-training AI/ML-based devices after deployment.
These principles are merely a starting point. The Regulators stated, “[a]s the AI/ML medical device field evolves, so too must GMLP best practice and consensus standards.”
Possible Impact & International Considerations
AI and ML are clearly top priorities from a global health regulatory perspective. The Regulators expect this collaboration to lead to further and broader international collaborative work. As noted above, the Regulators expect these guidelines to evolve and emphasize the importance of “strong partnerships with [their] international public health partners.”
As one example, the guiding principles identify areas of possible collaboration for the International Medical Device Regulators Forum (“IMDRF”), international standards organizations, and other collaborative bodies. These areas include “research, creating educational tools and resources, international harmonization, and consensus standards.”
This collaboration is important as it follows on from the individual work each agency has been doing in this space. For example, MHRA has consulted on the future regulation of medical devices in the UK, including by developing a Work Programme for Software and AI-based Medical Devices (which we previously discussed in our blog post). FDA has also been active in the AI/ML space, and several more FDA digital health developments are on the horizon for 2022. Through this international regulatory collaboration it appears the Regulators are working towards a united front through close alignment on best practice and international regimes. It also shows, for example, that the UK is considering international regimes broadly, rather than simply aligning with the European Union.
In sum, it appears there is an appetite for further international regulatory collaboration, so watch this space for the potential development of more detailed and sector specific international standards and practices for AI/ML-based technologies.
The Medicines & Healthcare products Regulatory Agency (“MHRA”) has published a “Consultation on the future regulation of medical devices in the United Kingdom” (the “Consultation”), which will run until 25 November 2021. The consultation sets out proposed changes to the UK medical device regulatory framework with the aim to “develop a world-leading future regime for medical devices that prioritises patient safety while fostering innovation.”
Separately, the MHRA has published a work programme on software and AI as a medical device to deliver a regulatory framework that makes sure that the UK is the home of responsible innovation for medical device software. Any legislative change proposed by the work programme will build upon the wider reforms to medical device regulation being consulted upon as a part of the Consultation.
The MHRA intends that any amendments to the UK medical device framework will come into force in July 2023. This aligns with the date when UKCA marking will become mandatory in the UK and when EU CE marks will no longer be recognized. The MHRA has made clear that it will provide adequate transition periods before adopting any new requirements.
All interested parties are encouraged to contribute to shaping the future regulation of medical devices in the UK by responding to the MHRA’s consultation before the deadline (25 November 2021).
The MHRA’s overarching objectives are to develop a regime for medical devices that enables:
- “Improved patient and public safety;
- Greater transparency of regulatory decision making and medical device information;
- Close alignment with international best practice, and;
- More flexible, responsive and proportionate regulation of medical devices.” (emphasis added)
The Consultation sets out a proposal for a future UK-wide regime to regulate medical devices, which would run in parallel to existing or future EU rules. However, the consultation acknowledges that the MHRA seeks “…greater alignment with … international regimes rather than bringing in higher regulatory burdens.”
The Consultation sets out four “significant areas” that the new regime will focus on, namely:
- “creating new access pathways to support innovations
- a unique, innovative, and ambitious framework for regulating software and artificial intelligence as medical devices
- reforming IVD regulation
- becoming a sustainability pioneer – through safe reuse and remanufacture”
The MHRA has further split these areas into 15 Chapters, which cover: (1) the scope of the regulation; (2) classification; (3) economic operators; (4) registration and UDI; (5) approved bodies; (6) conformity assessments; (7) clinical investigations/performance studies; (8) post-market surveillance, vigilance and market surveillance; (9) in vitro diagnostic medical devices; (10) software medical devices; (11) implantable devices; (12) other product specific changes; (13) environmental sustainability and public health impacts; (14) routes to market; and (15) transitional arrangements.
For each of these chapters, the Consultation indicates how the MHRA proposes to update the UK regulatory framework in line with the overarching objectives detailed above. Many of the principles appear to align with those in the EU Medical Devices Regulation 2017/745 (“MDR”) and EU IVD Medical Devices Regulation (EU) 2017/746 (“IVDR”), which is not surprising given the UK was a key player in the development of the MDR and IVDR. It is clear, however, that the UK intends for broader alignment with international standards (e.g. the IMDRF) rather than simply aligning with the EU regulatory framework.
Impact on Software and AI
The MHRA acknowledges that software and AI are developing fast and play an “increasingly prominent role within health systems” and that UK device regulation needs to be updated to both protect patient safety and also keep up with technological advances.
Chapter 10 of the Consultation sets out proposed changes for “Software as a Medical Device (SaMD), including AI as a medical device (AIaMD).” The Consultation provides a detailed overview of changes, including defining software, introducing requirements for persons selling SaMD via electronic means, adopting the IMDRF Risk Categorization for SaMD and defining specific requirements for AIaMD (amongst others).
Separately, the MHRA published details of an extensive work programme to inform regulatory changes for software and AI devices. These aim to ensure that:
- “The requirements for software and AI as a medical device provide a high degree of assurance that these devices are acceptably safe and function as intended, thereby protecting patients and public
- That the requirements are clear, supported by both clarificatory guidance and streamlined processes that work for software, as well as bolstered with the tools to demonstrate compliance, for instance, via the designation of standards
- That friction is taken out of the market by working with key partners such as the National Institute for Health and Care Excellence and NHSX to align, de-duplicate, and combine requirements, ultimately providing a joined-up offer for digital health within the UK.” (emphasis added)
The programme includes 11 work packages over two workstreams. The work packages relate to: (1) qualification; (2) classification; (3) pre-market; (4) post-market; (5) cyber secure medical devices; (6) innovative access; (7) SaMD airlock; (8) mobile health and apps; (9) AI rigour; (10) AI interpretability; and (11) AI adaptivity.
The MHRA plans to deliver these work packages between autumn 2021 and summer 2023. It is anticipated that much of the reform from the work packages will be in the form of clarificatory guidance, standards, or processes rather than secondary legislation. Any legislative change proposed by any work package for software/AI will build upon wider reforms to medical device regulation being consulted upon as a part of the Consultation.
Following the UK’s departure from the EU, the UK Government has been exploring ways to leverage its new regulatory freedoms. In particular, the life sciences sector has been a key Government priority. As early as January 2021, for example, the Government granted the MHRA powers to fast-track approvals for innovative medicines. More recently, two reports from Westminster bodies have proposed a new regulatory regime for so-called “nutraceuticals” (products that are part drug, part nutritional) to encourage investment.
Taskforce on Innovation, Growth and Regulatory Reform Report
On 16 June 2021, the UK’s Taskforce on Innovation, Growth and Regulatory Reform (“TIGRR”) published a report setting out their vision for the UK’s approach to regulation post-Brexit. In this report, TIGRR makes 120 recommendations covering three broad areas: a new UK regulatory framework based on core principles of UK law; specific regulatory reforms in high-growth sectors; and proposals for how these regulatory reforms could be delivered. The report focusses heavily on principles that the UK should adopt post-Brexit. The overarching theme of these ambitions is removing unnecessary regulatory burdens, boosting innovation and the UK’s long-term competitiveness, and a departure away from the EU model of regulation.
As part of the UK Government’s renewed scrutiny of current regulations, TIGRR’s report explores new possibilities for food and drug regulation post-Brexit. One of the report’s recommendations is to introduce a separate regulatory regime for nutraceuticals. TIGRR explains that a new pathway is necessary to fill the gap between food and pharmaceutical regulation and to help the fast-growing sector “realise its potential.” In particular, they propose fixing the current lack of a clear regulatory framework for assessing, verifying and authorizing medicinal claims for nutraceuticals.
All Party Parliamentary Group on Access to Medicines and Medical Devices Report
In July 2021, the growing need for separate nutraceutical regulation was highlighted again by the Parliamentary Group on Access to Medicines and Medical Devices. In a report, the group summarizes and comments on stakeholder views on potential improvements to the MHRA. Stakeholders proposed a licensing process review and a clearer regulatory framework for “nutri-foods.” The Parliamentary Group appears to agree, citing the similar calls made by TIGRR and the current backlog of borderline products for review, which it says stifles innovation.
These reports are significant as, beyond nutraceuticals, they more generally signal a departure away from the EU model of regulation for medicines, medical devices and borderline substances. The proposals also include adaptive approaches to medicines regulation and the use of artificial intelligence in healthcare. Industry should keep abreast of these developments and the opportunities they present, in particular for regulator, policy and corporate investments.
Covington lawyers have a well-established nutraceutical practice in the UK (e.g., R (otao Blue Bio) v MHRA) and the EU, having represented clients before the English courts and the European courts on borderline matters, and working with the appropriate regulators to agree appropriate branding and ingredients.
On 6 May 2021, the European Food Safety Authority (“EFSA”) published its updated safety assessment on titanium dioxide as a food additive (E171). EFSA examined new evidence on nanoparticles and found that there was uncertainty about E171’s ability to accumulate in the body and damage genetic material in cells; i.e. genotoxicity. The agency could not calculate an Acceptable Daily Intake (“ADI”), nor could it determine a safe cut-off value for particle size and distribution. On that basis, it could not confirm the safety of E171 in food. However, since it found no evidence of acute toxicity, an immediate ban is not warranted. France previously initiated a national ban in 2019/2020; following EFSA’s revised opinion, the EU is likely to adopt an EU-wide ban early 2022. In this blog, we briefly review the planned EU-level response and the developments in the Netherlands, Germany and the UK.
On 18 May 2021, the Commission Working Group on Food Additives discussed EFSA’s revised assessment and its follow-up. According to a report on the meeting by the Dutch delegation, all Member States indicated they could support a ban on E171. An official from the European Commission has confirmed that the Commission foresees a transitional period to give operators time to phase out the use of this additive in food and replace it where needed. However, reportedly, the Commission wishes for this transition period to be as short as possible. The Member States will provide feedback on this as soon as possible. As a reference, France suggested that a transition period of 8 months was applied without any problems with the French (national) E 171 ban in 2019/2020. The Commission expects to table a proposal by the end of July to be voted on at the Plants, Animals, Food and Feed Standing Committee meeting on Toxicology & Novel Food (SCoPAFF Tox & NF) scheduled for 28 September 2021. If adopted, the proposal could enter into application at the beginning of 2022.
Titanium dioxide is also permitted as a coloring agent in other products, such as pharmaceuticals, animal feed, food contact materials and care products. The relevant agencies have been informed and will consider for themselves whether the EFSA opinion has consequences for the use of titanium dioxide in their area. For its part, EFSA also concluded on 16 June 2021 that titanium dioxide can no longer be considered safe to use in animal feed.
II. The Netherlands
It is currently unlikely that the Netherlands will impose a national prohibition on the use of titanium dioxide as a food additive. In the Dutch minutes for the Commission Working Group on Additives on 8 February 2021, the Netherlands reportedly indicated that European legislation exists for a reason and that national bans are undesirable. The National Institute for Public Health and the Environment (“RIVM”) webpage on E171 confirms that any decision on banning titanium dioxide is to be taken at EU-level.
Similarly, there are no developments in Germany that suggest it will adopt a national E171 ban.
The Federal Minister for Food and Agriculture and the Federal Institute for Risk Assessment have both issued press releases on titanium dioxide on 6 May 2021. Both of them refer to actions to be taken at EU level. Federal Minister Klöckner stated in her press release that she has asked the Commission to take action. The Federal Institute for Risk Assessment also issued a press release stating that it has reached comparable conclusions to the EFSA. It subsequently updated its Q&A on the additive and indicated it expects action at the EU level.
The emphasis on EU-level action suggests that an initiative at the national level is rather unlikely.
The UK is still considering its stance on the additive, suggesting no immediate national ban is to be expected, but further action cannot be ruled out.
Following the publication of the EFSA opinion, a spokesman for the UK Food Standards Agency (‘’FSA’’) said its independent scientific advisory committees would scrutinize EFSA’s revised assessment alongside existing evidence. This review would inform next steps and future policy.
The FSA also discussed the issue during its board meeting on 26 May 2021, where it concluded it would “put the EFSA opinion through the risk analysis process” and that “devolved administrations have been informed and we are considering implications for Northern Ireland.”
In short, an EU-wide ban on the use of titanium dioxide could be put to a SCoPAFF Tox & NF vote in September 2021 and come into effect by January 2022 with a relatively short transition period of 6 to 9 months. We await the outcome of the UK FSA scrutiny of the EFSA assessment and expect no further national action in the Netherlands and Germany.
On 1 July 2021, the new French rules on early access to unauthorized medicinal products and off-label use of authorized medicinal products entered into force. The rules were introduced by the Social Security Financing Law for 2021 (LOI n° 2020-1576 du 14 décembre 2020 de financement de la sécurité sociale pour 2021 or “LFSS 2021”, available here). The reform seeks to simplify existing rules, make early access and off-label use more predictable for all users, and ensure the sustainability of these programs for the public health insurance system. In this blog, we present an overview of the new rules.