Bianca Piachaud-Moustakis is lead writer at Pharmavision, Pharmavision.co.uk.

Bianca Piachaud-Moustakis

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Swissmedic is the national authorization and supervisory authority for drugs and medical products in Switzerland whose primary objective is to assesses the quality, safety, and effectiveness of all medicinal products submitted for its approval. In January 2024, the agency announced updated guidance relating to APIs, temporary authorization, and fast-track authorizations.

Changes to the guidance document authorization of human medicinal product with known active pharmaceutical ingredients

In January 2024, Swissmedic announced that it was updating its guidance relating to APIs under the country’s Therapeutic Products Act (TPA). The rationale for updating the guidance on APIs was to reflect the agency’s thinking on how complex or heterogeneous APIs should be reviewed before being granted market access.

According to the agency, “Medicinal products whose known chemical active pharmaceutical ingredient has a complex, heterogeneous structure (or with a formulation of this active pharmaceutical ingredient that is complex and heterogeneous) may be deemed to be medicinal products with a known active pharmaceutical ingredient (known API, with or without innovation)” (1). However, the newly drafted text contains a caveat whereby the agency stipulates that additional documentation requirements may apply in such cases, “depending on the product group or the impossibility of complete chemical/physical characterisation” (1). To this end, the agency may require sponsors to provide additional documentation on the product’s pharmacodynamics, pharmacokinetics, and toxicity to prove that the safety and efficacy data from the reference medicinal product are transferable (2). The guidance also requires that the authorization application must state the reasons for the type of application chosen (known API with or without innovation), and for the amount of data submitted.

The guidance document published by Swissmedic in January 2024 applies to the following types of authorization applications:

for medicinal products for which the indication, pharmaceutical form, route of administration, and dosage recommendation are based on a reference product with the same API that is currently or has previously been authorized by Swissmedic

for medicinal products with an indication, a pharmaceutical form, a route of administration, and/or a dosage recommendation that have not been or are not authorized to date for the reference products with the same API

for variations relating to indication, pharmaceutical form, dosage strength, route of administration, and dosage recommendation for already authorized medicinal products with known APIs

for medicinal product combinations consisting of several known APIs (3).

The guidance document does not, however, apply to:

all extensions and variation applications not listed above

advanced therapies based on gene transfer methods (gene therapy)

medicinal products containing genetically modified organisms (3).

Section 1.1.1. of the guidance document, Authorisation of Human Medicinal Products with Known Active Substance (No: ZL101_00_007, Version 5), has been adapted accordingly and section 5.10 “Requirements for medicinal products with a complex, heterogeneous structure” has been added (3).

Changes to the guidance document temporary authorization of human medicinal products

As part of its package of changes, Swissmedic also updated its guidance about the temporary authorization of medicinal products. At present, all criteria under Article 9a TPA in conjunction with Article 18-22 TPLO [Ordinance of the Swiss Agency for Therapeutic Products of 22 June 2006 on the Simplified Licensing of Therapeutic Products and the Licensing of Therapeutic Products by the Notification Procedure (SR 812.212.23)] must be met cumulatively for a temporary authorization to be granted (4). This applies at the point when an application for a temporary authorization is made and when the application for temporary authorization is subsequently received and completed.

According to Swissmedic’s guidance document, “It is possible for temporary authorisation to be granted under certain conditions defined by law to make medicinal products for the treatment of life-threatening diseases available to patients as quickly as possible” (5). Under these circumstances, the guidance document notes that the submitted clinical documentation, in particular, does not have to be complete for a temporary authorization request to be submitted, and the temporary authorization procedure has an accelerated deadline.

If temporary authorization is to be granted, however, the agency stipulates that one key criterion must be met by the applicant, which is to demonstrate that no authorized, alternative, and equivalent medicinal product is available in Switzerland (Article 9a para. 1 let. c TPA or Article 18 let. b TPLRO) (6). The sponsor is, therefore, obliged to provide details such as the indication, target population, mechanism of action, ease of use, and the risk-benefit profile of the product (2).

Under the provisions of the guidance document published by Swissmedic in January 2024, temporary authorization is possible in the following circumstances provided the criteria per Article 9a TPA in conjunction with Article 18 TPLO are fulfilled:

new authorization of human medicinal products with new active substance (NAS).

new authorization of human medicinal products with known active substance (KAS) if an indication not previously authorized is requested (KAS with innovation).

additional indication for human medicinal products (5).

One of the benefits of the newly updated guidance is that the application process for seeking temporary authorization has been improved. According to Swissmedic, “differing processes will be employed in future, based on the result of the assessment of the documentation submitted with the application for a temporary authorisation procedure … and in particular, Swissmedic will now issue a preliminary decision to reject the application for a temporary authorisation procedure if the assessment reveals that the criteria specified in Article 18 TPLO are not met” (6). In this instance, the applicant will be given the option of submitting a written statement to Swissmedic or participating in an Accelerated Application Hearing (AAA) to request temporary authorization.

According to Swissmedic, the guidance document Temporary Authorisation for Human Medicinal Products has been amended accordingly in sections 5 and 6, along with Annexes 1 and 2, and is valid from 15 Jan. 2024 (5).

Changes to the guidance document fast-track authorization procedure

Also included in its package of updated guidance are streamlined procedures for implementing a fast-track authorization procedure (FTP). Swissmedic will employ differing processes in the future “based on the result of the assessment of the documentation submitted with the application for the implementation of an FTP” (7). In particular, the agency will now issue a preliminary decision to reject the application for the implementation of an FTP if the assessment reveals that the criteria specified in Article 7 TPO [Therapeutic Products Ordinance Package] are not met” (7). In this instance, “the applicant will be given the option of submitting a written statement to Swissmedic or participating in an Accelerated Application Hearing (AAA)” (7).

In accordance with the new FTP guidance, the following criteria must all be met in line with Article 7 of the TPO for a human medicinal product (or any variations thereto), for a medicinal product to be evaluated using a fast-track authorization procedure:

It is a promising prevention against, or treatment for, a severe, disabling, or life-threatening disease.

Treatment using currently authorized medicinal products is either unavailable or unsatisfactory.

A high therapeutic benefit is expected from using this new medicinal product (by demonstrating that the product works in the target population based on clinical studies, there is a high degree of proven effectiveness, and there is strong causality that the treatment works) (2,8).

The new guidance comes into force with immediate effect and forms part of a broad overhaul of guidance regarding multiple aspects of the drug development process and related regulatory processes.

1. Swissmedic. Changes to Guidance Document Authorisation of Human Medicinal Product with Known Active Pharmaceutical Ingredient. 

, 15 Jan. 2024.
2. Al-Faruque, F. Swissmedic Updates Guidances on API, Fast-track Pathway, and More. 

. Regulatory Affairs Professionals Society (RAPS), 15 Jan. 2024.
3. Swissmedic. ZL101_00_007 

Authorisation of Human Medicinal Products with Known Active Ingredients

. Guidance Document, Version 5, 15 Jan. 2024.
4. Fedlex. SR 812.212.23 

Ordinance of the Swiss Agency for Therapeutic Products of 22 June 2006 on the Simplified Licensing of Therapeutic Products and the Authorisation of Therapeutic Products by the Notification Procedure (TPLO)

. Guidance Document, 22 Jun. 2006.
5. Swissmedic. ZL 109_00_001 

Temporary Authorisation for Human Medicinal Products

. Guidance Document, Version 14, 15 Jan. 2024.
6. Swissmedic. 

Changes to the Guidance Document Temporary Authorisation of Human Medicinal Products

. Swissmedic.ch, 15 Jan. 2024.
7. Swissmedic. 

Changes to the Guidance Document Fast-track Authorisation Procedure

. Swissmedic.ch, 15 Jan. 2024.
8. Swissmedic. ZL 104_00_002 

. Guidance Document, Version 10.0, 15 Jan. 2024.

Bianca Piachaud-Moustakis is lead writer at PharmaVision, Pharmavision.co.uk.

When referring to this article, please cite it as Piachaud-Moustakis, B. Updating Swiss Regulatory Processes in 2024. 

Articles

Swissmedic issues updated guidance relating to APIs, temporary authorization, and fast-track authorizations.

Updating Swiss Regulatory Processes in 2024

Landkarte *** Europa | ©beugdesign - Stock.adobe.com

The use of artificial intelligence (AI) in the European Union (EU) will be governed by the AI Act, which is set to become the world’s first comprehensive legal framework for AI. The AI Act forms part of the EU’s digital strategy and was originally proposed by the European Commission (EC) in April 2021. The general approach policy was later adopted by the European Council in 2022, with the European Parliament most recently adopting its position in mid-June 2023. Following these developments, the three bodies will now negotiate the final details before the policy can become law, in a process called “trilogue,” or a three-way negotiation (1).

The AI Act aims to establish harmonized rules for the development, placing on the market, and use of AI in the EU, and its principal aim is to turn the EU into a global trustworthy hub for AI. The scope of the AI Act is very wide, covering systems developed through an array of approaches that are listed in Annex I of the AI Act. These include machine learning approaches that also incorporate deep learning; logic and knowledge-based approaches; as well as statistical approaches, Bayesian estimation, search, and optimization methods (2).

The European Parliament’s priority is “to make sure that AI systems used in the EU are safe, transparent, traceable, prevents bias and discrimination, fosters social and environmental responsibility, and ensures respect for fundamental rights” (3). Crucially, the European Parliament believes that AI systems should be overseen by people, rather than by automation, to prevent harmful outcomes (4).

The parliament also aims to establish a technology-neutral, uniform definition for AI that could be applied to future AI systems. To this end, AI is defined as “software that is developed with one or more of the techniques and approaches listed in Annex I and can, for a given set of human-defined objectives, generate outputs such as content, predictions, recommendations, or decisions influencing the environments they interact with” (1). Interestingly, this definition of AI is focused on its outputs and objectives, rather than its underlying technology or algorithms because the regulation aims to establish a framework for the ethical and trustworthy development and use of AI systems in the EU (5).

As regards intellectual property (IP) rights, the European Parliament has also stressed the importance of addressing issues relating to patents and new creative processes, as well as resolving questions of ownership relating to something that is entirely developed by AI (3).

The new rules follow a risk-based approach so that AI systems can be effectively assessed. Through this methodology, the European Parliament establishes obligations for providers and users depending on the level of risk that AI can generate. Providers are those who “develop an AI system to place it on to the market or put it into service under their own name or trademark” (6). The Act splits AI into the following four bands of risk based on the intended use of a system:

 Under the new proposals, AI systems with an unacceptable level of risk to people’s safety would be strictly prohibited. These include systems that deploy subliminal or purposefully manipulative techniques (such as cognitive behavioural manipulation) to exploit people’s vulnerabilities; systems that are used for social scoring (by classifying people based on their social behaviour, socio-economic status, and personal characteristics); and the use of real-time and remote biometric identification systems, such as facial recognition (7).

 High-risk AI systems are subject to a detailed certification regime but are not deemed so fundamentally objectionable that they should be banned. These systems are divided into two categories:

AI systems that are used in products that come under the EU’s General Product Safety (8) legislation that includes toys, aviation, cars, medical devices, and lifts 

AI systems that fall into eight specific areas that will have to be registered in an EU database:

biometric identification and categorization of natural persons

management and operation of critical infrastructure

employment, worker management, and access to self-employment

access to and enjoyment of essential private services and public services and benefits

migration, asylum, and border control management

assistance in legal interpretation and application of the law (4).

All systems deemed ‘high risk’ will be assessed before being placed on the market and throughout their lifecycle.

 Limited risk AI systems are required to comply with minimal transparency requirements that would allow users to make informed decisions. This category includes AI systems such as chatbots, emotion recognition and biometric categorization systems, and systems generating ‘deepfake’ or synthetic content (6). The legislation stipulates
that users should be made aware when they are interacting with AI and be given an option whether they want to continue using it.

. Minimal risk includes applications such as spam filters or AI-enabled video games for which the commission proposes regulation primarily by voluntary codes of conduct.

The AI Act will also establish a European Artificial Intelligence Board, which will be responsible for overseeing the implementation of the regulation and ensuring uniform application across the EU. The body will be tasked with putting forward recommendations on issues that arise as well as providing guidance to national authorities. According to the legislation, the board should reflect the various interests of the AI ecosystem and be composed of representatives of the EU member states (9).

Implications for the health technology sector

According to Burges Salmon (10), the AI Act is intended to directly affect health technology companies whose AI systems are placed on the EU market, and are subject to third-party conformity assessments (made by notified bodies), as stipulated by the EU’s Medical Devices Regulation (MDR), [Regulation (EU) 2017/745] (11) and 

 Diagnostic Regulation (IVDR), [Regulation (EU) 2017/746] (12). These systems include AI-enabled diagnostic tools, therapeutic devices, or implantable devices such as pacemakers. Furthermore, the AI Act will also affect MedTech companies whose AI systems are not directly affected by the proposed legislation, including AI-enabled general practitioner (GP) apps, patient chatbots, and fall detection systems (assuming that these systems are not already subject to the MDR or IVDR regulations).

For health technology companies whose products fall under the category of ‘High Risk’ AI systems, they will have to meet significant obligations in relation to:

Although the safety risks specific to AI systems are meant to be covered by the AI Act, the overall safety of the product, and how the AI system is integrated, will be addressed by the conformity assessment under the MDR or IVDR regulations, given that the AI Act is intended to “be integrated into the existing sectoral safety legislation [including the MDR and IVDR] to ensure consistency, avoid duplications, and minimize additional burdens” (10).

On 14 June 2023, Members of the European Parliament adopted a negotiating position on the AI Act, with talks now taking place with EU countries in the council regarding the final form of the law. The aim is to reach an agreement by the end of this year, and it is possible that the new legislation could enter into force in 2023. The majority of the provisions will then apply another 24 months later, during which time companies and organizations will have to ensure that their AI systems comply with the requirements and obligations set out in the regulation.

Lynch, S. Analysing the European Union AI Act: What Works, What Needs Improvement. Human-Centred Artificial Intelligence (HAI) Stanford University, hai.stanford.edu, 21 Jul. 2023.

Proposal for a Regulation of the European Parliament and of the Council Laying Down Harmonised Rules on Artificial Intelligence (Artificial Intelligence Act) and Amending Certain Union Legislative Acts.

AI Rules: What the European Parliament Wants.

EU AI Act: First Regulation on Artificial Intelligence.

Taylor Wessing. Introduction on the AI Act of the European Union. Insights (accessed 10 Oct. 2023).

The EU AI Act: A Summary of its Significance and Scope

AI Act: A Step Closer to the First Rules on Artificial Intelligence

Directive 2001/95/EC of the European Parliament and of the Council on General Product Safety

MacCarthy, M.; Propp, K. Machines Learn that Brussels Writes the Rules: The EU’s New AI Regulation. Brookings Institution, Commentary, 4 May 2021.

Whittaker, T.; Slocock, A. The EU’s Proposed AI Act: A Quick Guide for Health Tech. Burges Salmon, Press Release, 25 Jul. 2022.

Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on Medical Devices, Amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and Repealing Council Directives 90/385/EEC and 93/42/EEC (Text with EEA relevance).

 Current consolidated version: 20 Mar. 2023.

Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on In Vitro Diagnostic Medical Devices and Repealing Directive 98/79/EC and Commission Decision 2010/227/EU.


Vol. 35, No. 11
November 2023
Pages: 8–9

When referring to this article, please cite it as Piachaud-Moustakis, B. The EU AI Act. 

The EU’s AI Act is set to become the world’s first comprehensive legal framework for artificial intelligence.

The EU AI Act

Despite the evolution of clinical trial regulation in Europe over the past 20 years, the continuing split in responsibilities across multiple jurisdictions and diverse practices has led to a decline in the number of meaningful multi-state trials taking place across the region. As a result, the European Union (EU) has come to be viewed as a less favourable environment for conducting clinical research (1).

Among the various official responses that have been put forward to address the deficiencies in the European clinical trials landscape is the launch of the Accelerating Clinical Trials in the EU (ACT EU) initiative in January 2022, co-led by the European Medicines Agency (EMA), the Heads of Medicines Agencies (HMA), and the European Commission (EC). ACT EU is described as “a business change initiative designed to transform the EU clinical research environment with top-quality scientific advice and optimized regulatory oversight that is conducive to conducting large trials that deliver decisional evidence” (1).

The new initiative builds on the Clinical Trials Regulation (CTR) (Regulation (EU) No 536/2014), and the related Clinical Trials Information System (CTIS), as well as the EMA/HMA Network Strategy to 2025, and the EC’s Pharmaceutical Strategy for Europe (2).These strategies aim to future-proof the current regulatory framework by supporting industry in promoting research and leveraging decentralized technologies, while at the same time, maintaining the highest level of clinical trial data protection, robustness, and transparency (3).

The ACT EU strategy paper lists 10 priority actions for 2022/2023 (see 

) (4–6). In August 2022, the EC, HMA, and EMA announced a revised ACT EU workplan covering the 2022–2026 period, which outlines in detail what will happen over the next four years (7). The extension of the initiative and the launch of the workplan was, in hindsight, to be expected given the extensive scope and challenge of implementing all of the 10 priorities in just two years. The extended workplan highlights key focus areas such as innovation in clinical trials, robust methodologies, and collaboration across stakeholders. It also makes the targeted objectives more transparent, as all of the priorities and deliverables are described in detail in the revised document.

ACT EU Strategy 10 priority action points (4–6). 

For 2023, the workplan lays out deliverables and timelines that include:

 The aim is to establish a support process specifically targeted at academic sponsors to make the EU a more attractive region in which to conduct clinical research.

 Particular attention will be paid to CTIS and CTR training activities, as well as troubleshooting any issues encountered by clinical trial sponsors.

 This will be established in 2023 to facilitate the evolution of the clinical trials environment through regular dialogue between all stakeholders, including patients, healthcare professionals, and academia, and to find practical solutions that will enable and drive change.

 ACT EU will support not only the adoption but also the implementation of revised EU guidelines in technology and clinical trial design.

Facilitation of innovative clinical trial methods.

 The ACT EU initiative will issue guidance on the conduct of Decentralised Clinical Trials (DCTs) by the end of 2022 and publish a methodology roadmap to identify and prioritize key advances in clinical trial methods (7).

The COVID-19 pandemic served to highlight the discrepancies in regulatory requirements between EU member states and the complications that ensue when submitting multi-state trial applications, especially when many of these applications are processed at a national level. As a result, one of the principal objectives of the ACT EU initiative is to “better coordinate scientific advice as a complement to trial authorisation and to support marketing authorisation and access throughout the medicine life cycle, with the efforts outlined aimed at increasing efficiency through ensuring a clear and unified European position on clinical trials in strategic matters at the international level” (8).

From the end of January 2023, sponsors will have to use CTIS to submit all new clinical trial applications given that from January 2025, the EU Drug Regulating Authorities Clinical Trials database will cease operations, thereby necessitating that all new and ongoing studies will need to be transferred to CTIS. While this will no doubt incur a significant management change, CTIS is a game-changing initiative that will allow for a single submission to be made, and support the flow of information between clinical trial sponsors, EU Member States, European Economic Area (EEA) countries, and the EC (9). It is therefore hoped that the long-term benefits of working with regulatory bodies and having better clarity over submission and approval timelines will outweigh the short-term operating inefficiencies that will ensue as a result of the proposed changes.

1. O’Donnell, P. Playing Catch-up with Europe’s Decline in Attracting Clinical Trials. 

 Online, 17 July 2023.
2. EMA. Accelerating Clinical Trials in the EU (ACT EU). 

, accessed 9 Aug. 2023.
3. Medidata. Accelerating Clinical Trials in the EU (ACT EU): Focus on Decentralised Clinical Trial Innovation. 

. 18 Nov. 2022.
4. HMA. Accelerating Clinical Trials in the EU (ACT EU). Workplan, August 2022.
5. Eglovitch, J.S. EU Adopts 10-part Workplan to Guide the Acceleration of Clinical Trials. 

, RAPS, 30 Aug. 2022.
6. Research Quality Association. EMA—ACT EU: Creating a Better Environment for Clinical Trials Through Collaboration. 

, News Release, 5 July 2023.
7. EMA. Accelerating Clinical Trials in the EU: Publication of 2022-2026 Workplan. News Release, 30 Aug. 2022.
8. Fultinaviciute, U. ACT EU State of Play: EMA’s Headway to Transform Clinical Trials. Clinical Trials Arena, 15 Nov. 2022.
9. Burton, P. 4 Key Priorities for the European Medicines Agency in 2023. Pharma Boardroom, 30 May 2023.


Vol. 35, No. 9
September 2023
Pages: 8–9

When referring to this article, please cite it as Piachaud-Moustakis, B. Accelerating Clinical Trials in the EU. 

The ACT EU initiative aims to develop the European Union further as a competitive centre for innovative clinical research.

Accelerating Clinical Trials in the EU

The Priority Medicines (PRIME) scheme focuses on the development of novel medicines that address an unmet medical need, such as those that offer a major therapeutic advantage over existing treatments, or which benefit patients with no current treatment options for their disease (1). Launched in 2016, the European Medicines Agency (EMA) developed PRIME in line with the European Commission’s (EC) priorities and the common strategy to 2020 for the European medicines regulatory network (1).

PRIME is an entirely voluntary scheme that aims to optimize development plans and speed up evaluations through early and enhanced interaction between the regulator and developers of promising medicines with a view to achieving expedited marketing authorization approval (MAA) in the European Union (EU). The scheme gives medicine manufacturers an opportunity to open communication with EMA’s Committee for Medicinal Products for Human Use (CHMP), or the Committee on Advanced Therapies (CAT) early in the development process (2). Proof of a potential drug’s efficacy must be provided from preliminary clinical evidence which clearly demonstrates that the medicine has the potential to provide a clinically meaningful improvement in effectiveness or that it can improve patient mortality/morbidity rates.

From March 2016 to June 2021, a total of 18 medicines that had received PRIME support were approved in the EU. Among these, 10 received a conditional marketing authorization (CMA), facilitating earlier access to the market; seven are Advanced Therapy Medicinal Products (ATMPs), which have the potential to reshape the treatment of a wide range of conditions, and 16 are aimed at rare diseases (3). In December 2021, the first academia-led development of an ATMP, intended to treat relapsed or refractory acute lymphoblastic leukaemia in adults over 25 years old, was granted PRIME eligibility (3). EMA strongly encourages all academic developers to interact with regulatory authorities to obtain early support for the development and clinical translation of their products.

As of May 2022, the overall approval rate for PRIME sat at 25% of applications, 40% of which were granted to small and medium-sized enterprises (SMEs), 61% to others, and 4% to academia; while in terms of therapeutic area, oncology gained the highest number of approvals at 29% (4). According to the Regulatory Affairs Professionals Society, “PRIME medicines represent significant progress in their therapeutic areas as they include innovative technologies such as CAR T-cells therapies, one-time curative gene therapies, treatments for rare cancers, and a vaccine to protect against the Ebola virus” (5).

In 2022, EMA published a report analysing the experiences of the first five years of the scheme, along with lessons learned (6). Accordingly, the report highlighted some opportunities for further strengthening the scheme, which aims to “facilitate and accelerate the generation of robust and relevant evidence for the evaluation of a MAA, which will give patients earlier access to transformative treatments that can make a real difference” (6). The measures include:

1. Regulatory roadmap and development tracker.

 A roadmap for each PRIME-designated product is being established alongside a product development tracker to optimize the early scientific and regulatory support provided to sponsors with promising medicines in the scheme. Starting as a pilot from March 2023, the roadmap and tracker will replace the PRIME annual update for any products that have not yet been discussed in a kick-off meeting. Under the new guidelines, applicants are required by EMA to maintain and update the regulatory roadmap and development tracker which includes information on planned regulatory submissions and interactions with regulators. The roadmap includes plans for scientific advice/protocol assistance requests and other regulatory interactions, with applicants urged to consider feedback received from regulators, while the development tracker aims to facilitate the efficient tracking of critical development aspects which may arise during the kick-off meeting or subsequent product development (7). The guidance states that “both tools will facilitate the continuous dialogue between regulators and developers as the progress of the development is continuously monitored and as critical aspects for further discussion can be identified throughout the development process” (8).

 Expedited scientific advice can now be provided for PRIME designated products in instances where there are issues with a specific development programme that has already received comprehensive initial advice. To qualify for expedited scientific advice, the new guidance states that all the following criteria must be met:

The initial scientific advice procedure has already been sought on the overall development (in the PRIME indication), that is the request is for follow-up advice.

The advice concerns issues with a specific, well-defined scope (not limited to a single quality/non-clinical/clinical discipline).

The advice is justifiably required more urgently than the standard scientific advice timelines allow (8).

The expedited scientific advice feature is being tested in a 12-month pilot that will run until March 2024. According to EMA, the scientific advice pilot programme is “meant to help significantly expedite the ability of sponsors to get answers to key queries from the agency in a faster timeframe” (8).

 EMA offers a submission readiness meeting with the developer approximately 9–12 months ahead of the applicant submitting their MAA for purposes of discussing the development status and dossier maturity, application type, requirements for post-marketing evidence generation, and potential regulatory challenges (9). Prospective applicants would also be expected to present mature plans for post-marketing evidence generation, as applicable. According to the updated guidance, “applicants are asked to contact their PRIME scientific coordinator about 15 months before their expected application submission date to set up a submission readiness meeting with the PRIME Rapporteur and the assessment team, relevant national experts, as well as the EMA product team” (8).

The experience gained during the COVID-19 pandemic has given EMA greater insight into the types of tools and features that would better assist the acceleration, development, and approval of life-saving medicines. As a result, the new features aimed at bolstering the PRIME scheme are designed to address the perceived shortfalls in tools and support mechanisms needed to enhance and expedite the innovation and development process.

Furthermore, the changes also bring the PRIME scheme into closer alignment with the United Kingdom’s (UK) Innovation Licensing and Access Pathway (ILAP), which was initiated in 2021, and is sponsored by the Medicines and Healthcare Product’s Regulatory Agency (MHRA). The UK’s ILAP initiative more closely mirrors the United States Food and Drug Administration’s Fast-Track process, which enables rolling reviews and allows applicants to submit completed sections for review, rather than waiting until the entire application is complete (10).

With the improvements to the PRIME scheme brought about in 2023, it is hoped that medicine developers throughout the EU can expect a more transparent and easier drug development process, thereby benefiting patients with life-threatening illnesses to have earlier access to medicines. It is also hoped that improvements to the PRIME scheme will help drive greater harmonization across major pharmaceutical markets with regard to scientific advice and regulatory support for innovative products (10).

1. EMA. PRIME: Priority Medicines Fact Sheet. 

, 2023.
2. ProPharma. 5 Benefits of Receiving EU PRIME Designation for Medicine Developers. Article, 20 July 2022.
3. PharmaLetter. EMA Says its PRIME Scheme Enables Earlier Availability of Life-changing Meds. News Release, 4 March 2022.
4. EMA. Recommendations on Eligibility to PRIME Scheme. 

, 23 May 2022.
5. RAPS. EMA Lauds PRIME Priority Meds Scheme and Outlines Potential Revisions. 

, 8 March 2022.
6. EMA. PRIME: Analysis of the First Five Years’ Experience. 

, 2022.
7. RAPS. EMA Updates PRIME Pathway with Roadmaps, Scientific Advice Pilot. 

, 4 April 2023.
8. EMA. European Medicines Agency Guidance for Applicants Seeking Access to PRIME Scheme. Revised Guidance. 

, 30 March 2023.
9. European Confederation of Pharmaceutical Entrepreneurs. New Features Further Strengthen EMS’s Priority Medicines Scheme (PRIME). News Release, 5 April 2023.
10. PharmaLex. Changes Strengthen PRIME Scheme and Bring EMA in Closer Alignment with Innovation Programs in the UK and US. Blog Post. 2 May 2023.

When referring to this article, please cite it as Piachaud-Moustakis, B. Improvements to EMA’s PRIME Designation Scheme. 

Changes to PRIME scheme are set to drive greater harmonization across major pharmaceutical markets.

Improvements to EMA’s PRIME Designation Scheme

Complement Therapeutics (CTx) is a Germany-based preclinical stage biotechnology company focusing on the R&D of novel therapeutic approaches to address unmet needs in disorders that affect the body’s immune system, known as the complement cascade. The complement cascade is a part of the immune system that enhances (or complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane (1). When activated by one of several triggers, the complement system works in conjunction with other components of the immune system to clear invading pathogens (1).

Based on the research of the company’s founders, Simon Clark, Paul Bishop, and Richard Unwin from the University of Manchester, CTx aims to develop innovative and effective therapeutics to address unmet needs in complement-mediated diseases, particularly in the fields of age-related macular degeneration (AMD), kidney disease, and various haematological conditions. Through an extensive programme of translational research, the scientists have gained powerful new insights into the ways the complement cascade works and how it is dysregulated in AMD.

Founded in 2020, CTx has subsidiaries in the United Kingdom (UK), operating as Complement Therapeutics Ltd, and in the United States (US), trading as Complement Therapeutics Inc., as well as research laboratories in Stevenage, UK.

Research conducted by Tracxn Technologies indicates that CTx ranks fourth among 94 active competitors (2). CTx’s key competitors include: CureVac, a Germany-based biopharmaceutical company that develops messenger RNA (mRNA)-based therapeutics focused on prophylactic vaccines, cancer immunotherapies, and molecular therapies. CureVac was the world’s first company to successfully use mRNA for medical purposes (3); Rezolute Inc. (formerly Antriabio), a US-based biopharmaceutical company specialized in the development of drugs for metabolic and orphan diseases. A leading candidate under development is a plasma kallikrein inhibitor (PKI) designed to treat diabetic macular oedema (DME). This oral therapy, formulated to be administered once a day, is designed to reduce inflammation and vascular leakage caused by DME through targeting the kallikrein-kinin system (4); and Visus Therapeutics Inc., a US-based clinical-stage pharmaceutical company that specializes in developing therapeutic solutions for vision care. One of the company’s flagship products includes VT-1051, a novel, injectable, sustained-release delivery system that delivers a Ciliary neurotrophic factor (CNTF) analogue and a FAS/TNF-α inhibitor which has the potential to preserve photoreceptors, prevent programmed cell death, and improve vision in patients suffering from geographic atrophy (GA) (5).

CTx was spun out of the University of Manchester and has raised a total of €77 million over three rounds of financing according to data derived from Crunchbase (6). In 2021, CTx secured initial seed funding from BioGeneration Ventures (BGV), subsequently receiving a further €5 million in Round 2 seed funding from BGV and Forbion in February 2022. With this funding, CTx advanced its lead investigational product, CTx001 through pre-clinical proof-of-concept, and secured an Innovation Passport from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) (7). CTx001 is a highly innovative adeno-associated virus (AAV) gene therapy designed for the treatment of GA secondary to dry AMD, which is a leading cause of blindness, and for which no licensed treatment currently exists.

Through the financing received from BGV and Forbion, CTx also initiated a one-year, natural history non-interventional i-GAIN (investigating Geographic Atrophy Insights) study in patients who have a confirmed diagnosis of GA in one or both eyes in the UK (8). The study is designed to evaluate the relationship between genetics, blood biomarkers, and phenotypic changes in the eye of people with GA. Data derived from the i-GAIN study is designed to support the clinical development planning for CTx001, particularly in enabling the identification and stratification of patients with complement-driven AMD for future interventional studies (8).

More recently in April 2023, CTx announced that it had successfully secured an additional €72 million in Series A financing. The third round of financing was led by Gimv, a Belgian-based private equity and venture capital fund, co-led by Forbion (as an existing investor), and further joined by BGV, Panakès Partners, Cambridge Innovation Capital (CIC), Hadean Ventures and Seroba Life Sciences (9).With this latest round of financing, CTx will continue the development, as well as complete a Phase Ib clinical proof of concept of its lead product CTx001. The novel therapy is expected to have the potential to offer superior efficacy compared to competitive drugs, as well as reduce the burden of treatment among patients through a “one and done” approach (10).

CTx will also use the funds to expand its laboratory-based activities at its site in Stevenage, UK, as well as evaluate its pipeline assets for non-ocular indications. According to Rafiq Hasan, CEO and managing director at Complement Therapeutics GmbH, “the support of this broad syndicate enables us to generate additional data demonstrating CTx001’s unique and differentiated mechanism of action, with the potential to transform the treatment landscape in [GA]” (9).

The financing will also be used to further develop the company’s novel Complement Precision Medicine (CPM) platform, which enables the quantification of over 30 complement cascade proteins from a single systemically drawn blood sample (11). The CPM platform will also facilitate the stratification of patients with AMD and other conditions for enrolment into future clinical trials, and support the subsequent commercialisation of CTx’s assets. According to Cipriani et al. (2021), the CPM platform has been validated in normal human samples and two distinct disease cohorts (12).

Alongside the financing, Michaël Vlemmix (Gimv), Rob Woodman (Panakès), Anne Horgan (CIC), and Roger Franklin (Hadean Ventures) will join the CTx board as new members.

AMD is a chronic and progressive degenerative disease of the macula, the central part of the retina (or the light-sensitive tissue at the back of the eye) that controls sharp, straight-ahead vision (13). AMD is a common condition that blurs a patient’s central vision and is a leading cause of blindness for older adults. Research conducted by Guymer et al. (2023) estimates that AMD is present in 8.69% of the global population, affecting 196 million people in 2020; and its prevalence is expected to increase to 288 million by 2040 (14).

According to the US National Eye Institute (NEI), dry AMD has three stages: early, intermediate, and late, with the disease usually progressing slowly over several years. Also termed GA, there is currently no treatment for late dry AMD, which is driven by a combination of factors including genetic predisposition, natural ageing changes, and lifestyle factors, such as smoking and nutritional intake. Genetic and molecular studies have identified the complement system as a key driver of AMD onset and progression, and there is increasing evidence that complement inhibition can slow the progression of GA (15).

Over the past few years, R&D efforts in the field of complement-mediated diseases have received the support of the US National Institutes of Health (NIH), which has awarded grants worth US$837 million for research in this domain (16). With enhanced funding and growing recognition of the complement system as a multidimensional innate immune surveillance mechanism, it can be expected that more novel therapeutic targets will be discovered in the future. CTx is therefore well placed to take advantage of potential future opportunities by addressing unmet needs in complement-mediated diseases, particularly AMD, to which it can strive to achieve market dominance and leadership position. With the active involvement of big pharma players as well as new entrants, the drug development landscape of complement therapeutics is likely to expand further with the market poised to witness steady growth over the coming years.

Complement Therapeutics. The Complement System. Complementtx.com (accessed 9 June 2023).

Traxcn Technologies Ltd. Complement Therapeutics Competitors. Tracxn.com (accessed 9 June 2023).

CureVac. About Us. Curevac.com (accessed 9 June 2023).

Rezolute Inc. For Patients: Living with DME. Rezolutebio.com (accessed 9 June 2023).

Visus Therapeutics. Product Pipeline. Visustx.com (accessed 9 June 2023).

Crunchbase. Complement Therapeutics Financials. Crunchbase.com (accessed 9 June 2023).

CISION PR Newswire. Complement Therapeutics Secures €72 Million in Series A Financing to Advance Novel Therapies Targeting Complement-Mediated Diseases. PRnewswire.com, 17 April 2023 .

BIA. Complement Therapeutics Enrol First Patient in Non-interventional i-GAIN Study of People Diagnosed with Geographic Atrophy. Bioindustry.org. 8 Feb. 2023.

Complement Therapeutics.Complement Therapeutics Secures €72 Million in Series A Financing to Advance Novel Therapies Targeting Complement-Mediated Diseases. Press Release, 17 April 2023.

Pharmaceutical Technology. Complement Therapeutics Wins Financing for New Therapies Development. Pharmaceutical-technology.com, 18 April 2023

Complement Therapeutics. Complement Precision Medicine (CPM) Platform. Complementtx.com (accessed 9 June 2023).

Cipriani, V.; Tierney, A.; Griffiths, J.R.; et al. Beyond Factor H: The Impact of Genetic-risk Variants for Age-related Macular Degeneration on Circulating Factor-H-like 1 and Factor-H-related Protein Concentrations. Am. J. Hum. Genet. 2021, 108 (8), 1385–1400.

National Eye Institute (NEI). Age-related Macular Degeneration (AMD). Nei.nih.gov. 22 June 2021.

Guymer, R.H.; Campbell, T.G. Age-Related Macular Degeneration. The Lancet. 2023, 401 (10386), 1459–1472.

Armento, A.; Ueffing, M; Clark, S.J. The Complement System in Age-related Macular Degeneration. Cell. Mol. Life Sci. 2021, 78 (10), 4487–4505.

Globe Newswire. Next Generation Complement Therapeutics Market, 2035. Press Release, 4 April 2022.

Bianca Piachaud-Moustakis is a lead writer at PharmaVision.

When referring to this article, please cite it as Piachaud-Moustakis, B. Frontrunner in Therapies for Complement-Mediated Diseases. 

A novel complement therapeutic CTx001 offers a novel approach to treating geographic atrophy. 

Frontrunner in Therapies for Complement-Mediated Diseases

On 22 March 2023, the government of the United Kingdom (UK) published its strategy to promote cyber resilience across health and social care by 2030. The Cyber Security Strategy for Health and Adult Social Care denotes that cyber security is a key aspect of improving patient care and the safety of frontline staff, designed to build trust and in turn, foster innovation (1).

Given that cyber security underwrites public trust in digital services and technologies, the new cyber strategy sets out a vision for reducing the cyber security risk to health and social care organizations across the Department of Health and Social Care (DHSC), National Health Service (NHS) organizations, local authorities, independent social care providers, and suppliers—which includes pharmaceutical manufacturers. The strategy aims to protect patient, service user, and staff data, as well as implement measures to ensure organizations can recover quickly from cyber-attacks when they do occur.

As contained in the government’s policy document, the strategy includes the following five key pillars:

—identifying the areas of the sector where disruption would cause the greatest harm to patients, such as through sensitive information being leaked or critical services being unable to function.

—uniting the sector so it can take advantage of its scale and benefit from national resources and expertise, enabling faster responses and minimizing disruption.

—building on the current culture to ensure leaders are engaged and the cyber workforce is grown and recognized, and relevant cyber basics training is offered to the general workforce.

—embedding security into the framework of emerging technology to better protect it against cyber threat.

—supporting every health and care organization to minimize the impact and recovery time of a cyber incident (2).

The pillars and this strategy’s implementation plan are underpinned by the Cyber Assessment Framework (CAF) (3), which is the National Cyber Security Centre’s (NCSC) standard, designed for organizations responsible for vitally important services and activities.

The growth of technology and the crucial role of effective cyber resilience

In an increasingly digitized health and social care system, technology is transforming how people access health and care services, as well as information. In primary care, technology includes patient booking systems, call and recall facilities, and electronic prescription services. In secondary care, technology includes diagnostic machines such as imaging scanners, and electronic systems that inform hospitals of the number of free beds available. For adult social care organizations, it is technologies such as digital care records and acoustic monitoring systems that facilitate more integrated care.

The DHSC estimates that, in England, there are approximately 950,000 general practice appointments conducted daily, 45,000 major accident and emergency (A&E) department attendances, and 137,000 imaging events recorded (2). Furthermore, it also estimated that more than 40 million people in the UK now have an NHS login, which helps them to book appointments, track referrals, and order medications online; while over 50% of social care providers use a digital social care record, that enables staff to share vital information about the people they care for (1).

While it is unlikely that a cyber incident would bring down all the hundreds or even thousands of separate systems that support direct care, interdependencies between systems imply that the UK government must account for at least some degree of cascading risk, since the scale of impact—both direct and indirect—from a cyber-attack on the health and social care sector has the potential to be far-reaching and large in nature.

Threats to England’s health and social care sector

The Department for Science, Innovation and Technology’s Cyber Resilience Policy defines cyber resilience as “the ability for organizations to prepare for, respond to and recover from cyber-attacks and security breaches … with cyber resilience the key to operational resilience and business continuity” (2).

The health and social care sector encounters cyber threats every day, which include phishing and other malicious emails, automated scanning for common software vulnerabilities, and attempted fraud (4). Of these, phishing and malware are recognized as low-sophistication ‘commodity attacks’ that are used by a wide range of cybercriminals. Data derived from NHS England’s Cyber Security Operations Centre (CSOC), which provides real-time protection against any suspicious activity to approximately 1.7 million devices across the NHS network, estimates that approximately 21 million malicious emails are blocked every month (1).

However, the most significant cyber threat the healthcare sector faces is ransomware, which is used in profit-seeking attacks, often staged by organized criminal groups or state actors (3). Such attacks can cause a complete loss of access to clinical and administrative information technology (IT) systems, resulting in significant disruption in day-to-day operations. This, together with the increasing proliferation and commercial availability of ‘ransomware as a service’, now implies that attacks are not just limited to sophisticated groups. According to the NCSC, ransomware attacks are increasingly seen to include data theft and extortion with a threat of data leaks (3). Furthermore, ransomware and other cybercrime have also become a significant threat to third-party suppliers (which includes pharmaceutical manufacturers), an attack on whom can cause as much, or more damage and disruption as an attack directly on a health or care organization (3). For example, in October 2020, Philadelphia-based company eResearchTechnology, which manufactures software used to develop COVID-19 vaccines and treatments was hit by a ransomware attack (5). Employees were locked out of systems and the attack had a knock-on effect that was felt by IQVIA, the research organization assisting UK pharmaceutical firm, AstraZeneca’s COVID vaccine trial, and US pharmaceutical major, Bristol Myers Squibb, which was involved in the development of a quick test for COVID-19 (5).

According to the UK government’s recently published policy paper outlining the new cyber security strategy, “all these threats pose risk not just to patient and staff safety, but also to public trust in a health and social care system that can and must safeguard people’s data” (2). It is therefore vital that the sector continues to adapt and improve its cyber resilience against these evolving threats and retain the confidence of the public.

The strategy also identifies several other challenges, including:

 The healthcare sector comprises varying working environments and high operational demand with many systems required to run 24/7, presenting a challenge of how to address competing risks, priorities, and pressures.

A strategy on cyber resilience for health and social care organizations has been set out by the UK government.