Marcel Boller
Wenger Vieli, Zurich
m.boller@wengervieli.ch

Introduction

More and more patients are making use of treatments in which tissues and cells of human origin are used, either directly or after (biotechnological) processing.^[1] The use of such cell or tissue preparations in medical care is no longer limited to transplantation.^[2] Cells and tissues of human origin are also used in the treatment of various diseases, such as cancer, diabetes and osteoarthritis. In particular, cell therapies are now known and used in oncology. The therapy uses patients' own cells and equips them with new genetic information. As a result of this new information, the cells can specifically detect and destroy certain cancer cells.

A particular challenge is to correctly qualify such products from a regulatory perspective.^[3] Occasionally, these novel forms are grouped together as 'neuartige Verfahren' (innovative therapies).^[4] Directive 2001/83 and Regulation (EC) No 1394/2007 of the European Union refer to such products as an advanced therapy medicinal product (ATMP).^[5] Additionally, some frameworks are particularly shaped for tissue-based products (TBPs). Legislation in the United States uses the term human cell and tissue products (HCT/Ps).^[6]

Regulatory framework in Switzerland

The EU pioneered the development of a specific regulatory framework by defining a specific classification for ATMPs and establishing a centralised approval procedure for them. The cornerstone of this regulation is that marketing authorisation must be obtained prior to the marketing of ATMPs.^[7] The evaluation of these products is led by a specialised committee within the European Medicines Agency (EMA), that is, the Committee for Advanced Therapies (CAT), which prepares a draft opinion before the Committee for Medicinal Products for Human Use (CHMP) adopts a final opinion and authorisation is granted by the European Commission.

By contrast, Switzerland has not yet issued any specific standalone regulations on ATMPs. Instead, the provisions on ATMPs have been implanted into the existing regulatory framework. The autogenous transplantation of cells has been defined as transplant products.^[8] The definition of transplant products was newly regulated in the Ordinance of 16 March 2007 on the Transplantation of Human Organs, Tissues and Cells (the 'TO'). The TO defines that transplant products are products consisting of or containing human organs, tissues or cells, where the organs, tissues or cells: (1) have been substantially processed; or (2) are not intended to perform the same function in the recipient individual as in the donor individual.^[9]

As a consequence and according to Swissmedic's practice, authorisation is required for the entire manufacturing process regarding autogenous transplantation.^[10] The TA is applicable to transplant products. In Article 49, the TA refers to a vast number of provisions of the Therapeutic Products Act (the 'TPA') that apply by analogy to transplant products.

Transplant medicinal products that are applied to patients in Switzerland require marketing authorisation. For transplant products that are based on an individual patient's cells and can therefore not be standardised, marketing authorisation is granted for the manufacturing process. For the marketing authorisation and application process, Swissmedic refers mainly to the TPA (general duty of care; requirements for marketing authorisation; requirement of a licence for manufacturing, import, export, wholesale, prescription and dispensing; rules on advertising and granting of financial benefits to HCPs; market surveillance and inspections by Swissmedic, and reporting obligations towards Swissmedic; fees; and criminal sanctions). As part of quality assurance, all companies involved in the manufacture of transplant products must be specified in the marketing authorisation application.

Generally, any Swiss company involved in manufacturing medicinal products must hold a manufacturing licence, and any Swiss company involved in the conveyance (ie, acquisition, import, export, storage, offering, transferring or placing on the market of medicinal products, including transplant products or raw material, such as cells) must hold a wholesale or import/export licence, as the case may be.

Reimbursement challenges

In Switzerland, the integration of advanced therapies such as autologous CAR-T cell therapies into the healthcare system has prompted the development of innovative reimbursement strategies to address the high costs associated with these treatments.

On 9 November 2022, the Swiss Federal Council took a decisive step by adopting a framework agreement for the reimbursement of autologous CAR-T cell therapies.^[11] This move aimed to standardise and clarify access to these innovative treatments. The agreement was the culmination of efforts initiated in December 2021 when the Federal Council extended two tariff agreements governing the reimbursement of these cell therapies until the end of December 2022. These agreements were put in place by various tariff partners to regulate compensation for CAR-T cell therapies, which are known for their high cost. The Federal Council also called on tariff partners to find a common solution for the reimbursement of these treatments.

The framework agreement, in conjunction with current and future tariff agreements, outlines the reimbursement for CAR-T cell therapies in the inpatient setting from their authorisation up to their inclusion in the regular tariffication evaluated by the Swiss Diagnosis Related Groups' (the 'SwissDRG') case-based flat rate catalogue. This agreement represents an improvement in terms of uniformity, administration and clarity compared with the previous situation.

The agreement was submitted by key tariff partners, including H+ The Hospitals of Switzerland, santésuisse (the Swiss health insurance association), the purchasing community HSK AG, CSS Insurance AG and SWICA Health Insurance AG, and was approved indefinitely by the Federal Council. This collaboration among stakeholders highlights the Swiss healthcare system's commitment to facilitating access to high-cost, but potentially life-saving, treatments through innovative reimbursement models.

A significant element of the framework agreement for the reimbursement of CAR-T cell therapies in Switzerland is its confidentiality, which has sparked debate over transparency in healthcare pricing.^[12] The Federal Office of Public Health (FOPH) is not required to disclose the actual reimbursed prices for CAR-T cell cancer treatments. This decision was upheld by the Federal Administrative Court following an appeal by a journalist, citing that making these prices public could potentially jeopardise the application of the therapy in Switzerland.

The decision to keep the negotiated prices confidential has broader implications for future reimbursement agreements and the overall landscape of healthcare financing. On the one hand, it could be argued that such confidentiality is necessary to navigate the complex negotiations that enable access to expensive but life-saving treatments. On the other hand, the lack of transparency might raise concerns among healthcare professionals, patients and the wider public about the fairness and equity of healthcare pricing and reimbursement decisions.

Conclusion

Switzerland's approach to regulating ATMPs showcases a distinctive strategy of embedding these regulations within its existing legal framework, in contrast to the EU's centralised procedure. By classifying autogenous cell transplantation as transplant products and mandating comprehensive marketing authorisation focused on the manufacturing process, Swissmedic emphasises quality assurance and patient safety. This pragmatic adaptation highlights Switzerland's commitment to innovation, while ensuring rigorous healthcare standards. The Swiss model offers insights into regulatory adaptability, balancing the advancement of medical technologies with stringent safety measures, and serves as a potential guide for other nations navigating the complexities of ATMP regulation

The Swiss Federal Council's approach to CAR-T cell therapy reimbursement, characterised by innovative agreements and collaboration among key stakeholders, also encapsulates the contentious issue of price transparency. While the current stance supports the notion that confidentiality may be necessary for securing access to innovative treatments, it also invites scrutiny and calls for a nuanced discussion on transparency, fairness and accountability in healthcare financing. As Switzerland moves forward, the outcomes of these debates will undoubtedly influence the evolution of reimbursement strategies for advanced therapies, shaping the future of healthcare innovation and access.

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