First published in our Biotech Review of the Year publication (Issue 10).

Since that article, the European Commission has published a detailed proposal for a Regulation on standards of quality and safety for substances of human origin (SoHO) intended for human application (the Proposal) which will repeal the twin Directives currently in force[1]. In this follow-up piece, we take a detailed look at the Proposal and the key changes it will bring to SoHO regulation in Europe. We also look at what is happening in Great Britain (GB).

Legislation

The Proposal was adopted by the European Commission in July 2022 and is currently being discussed by the European Council and the European Parliament. Once the final text is agreed and adopted, it will come into force with a two-year transition period for most provisions and a three-year transition period for a few specific provisions.

The Proposal is the culmination of a project that has been ongoing for several years. In 2019 the European Commission conducted an evaluation that identified several gaps and shortcomings in the existing legislation on quality and safety of BTC. The twin Directives on BTC have been in force for nearly 20 years and the European Commission concluded on the basis of a public and stakeholder consultation that they no longer address the scientific and technical state of the art. The introduction of a new EU Regulation to repeal and replace the old Directives continues the recent life sciences legislative trend in the EU of favouring Regulations (which have direct effect) over Directives (which require Member State implementation). Indeed, this approach takes on the views expressed as a result of the consultation that a common EU Regulation would avoid the diverging national interpretations and implementations that can arise under Directives. At present, these deviating approaches result in unequal levels of safety and quality and in barriers to the exchange of BTC across the EU, barriers that were exacerbated by the pandemic.

Key changes

Scope

The proposed Regulation covers all substances of human origin, except for solid organs for transplantation, which will remain regulated by the existing Directive. The old Directives regulated BTC only, so the scope of regulation is being both expanded and consolidated.

SoHO encompasses not only BTC, but also substances invoking similar safety and quality concerns, such as human breast milk and microbiota, which are currently unregulated. In addition, other SoHO that may be applied to patients in the future will automatically fall within the scope of the proposed Regulation.

Standards

SoHO must be prepared and treated according to specific standards to ensure safety. High-level standards on SoHO will be written into the proposed Regulation. These standards will protect recipients of SoHO and will be extended to protect both offspring born from medically assisted reproduction and donors of SoHO. The proposed Regulation will provide for a hierarchy of rules for the implementation of standards to facilitate efficient and responsive uptake of the most up-to-date guidelines.

Scientific expert bodies

At present, industry consensus is that the technical standards set by the existing BTC Directives lag behind innovation. The consultation established strong industry support for SoHO safety and quality standards to be set jointly, with technical guidelines written into the legislation but developed and updated by nominated expert bodies.

The new approach will involve standards being set by the European Commission, with some written into the text of the proposed Regulation and others set by implementing acts, and nominated expert bodies such as the European Directorate for the Quality of Medicines & HealthCare and the European Centre for Disease Prevention and Control. In the absence of a technical guideline from an expert body it will also be acceptable for establishments to set their own technical methods, taking into account international standards, evidence and risks.

Registration

All entities conducting activities that will affect the safety and quality of SoHO will be required to register, either with a national SoHO competent authority or with a central EU SoHO platform. The new platform is intended to reduce administrative burdens on national authorities and the European Commission by facilitating the secure transfer of information (such as safety data and alerts) between those authorities and the Commission.

Reporting

The 2019 evaluation identified vulnerability to interruptions in supply of some BTC as a key shortcoming of the existing legislation. The EU is highly dependent on importing BTC from third countries, especially the US. The current legislation does not contain concrete measures to protect or increase supply of BTC, and this has not been proven adequate to protect against the risk of shortages or sudden supply disruptions. To address this, the proposed Regulation will introduce increased reporting requirements for SoHO entities, including the reporting of annual activity data, to allow Member States to implement measures to improve donation collection rates when needed. Entities working with critical SoHO (SoHO for which an insufficient supply will result in serious harm or risk of harm to patients) will be required to alert the relevant competent authority in the case of a sudden fall in supply and must also put in place emergency plans for such situations.

Oversight

One of the fundamental revisions that the proposed Regulation introduces is to both strengthen and harmonise oversight with a view to facilitating better exchange of SoHOs between Member States and improved access for patients.

The proposed Regulation achieves this goal through the introduction of common measures on oversight and the joint regulation model described above. The common oversight measures include new and more-efficient practices such as joint inspections, risk-based oversight approaches such as risk-based inspections, and EU level support such as EU auditing of oversight systems and training courses for competent authority personnel.

The package of common oversight measures aims to increase mutual trust and facilitate collaboration between Member States.

Position in the UK

In September 2022, the Department for Health and Social Care (DHSC) published a policy paper on the proposed regulation. The paper considers the impact of this regulatory change on Northern Ireland (NI), as when it is introduced the Regulation will apply in NI. DHSC acknowledge that the intention of the proposed Regulation is to increase the safety, quality, innovation and supply of SoHO within the EU, and therefore the Regulation is likely to have a positive effect in NI. However, the paper also discusses the consequences of regulatory divergence between NI and GB, which could include supply chain disruption since NI is reliant on importing SoHO from GB.

It seems clear from the paper that the UK government wishes to harmonise some aspects of the UK framework with that of the proposed EU Regulation. Remarkably, given the nature of government Brexit rhetoric, the paper stresses the importance of maintaining minimum standards with the EU to allow the movement of NI and EU SoHO into GB. DHSC expects to conduct a targeted stakeholder consultation (but not a public consultation) to inform policy decisions. Overall, this paper suggests that overarching harmonisation between the UK and EU life sciences regulatory frameworks may be a theme that will continue.

Conclusion

Finally, it is interesting to consider some of the potential points of revision that were consulted on but did not make it into the proposed Regulation, especially the borderline between the BTC framework and other regulatory frameworks. This area proved particularly contentious during the consultation and the explanatory memorandum to the proposed Regulation states that the Proposal will: (a) reinforce cooperation among the other adjacent regulatory frameworks; and (b) feed into the ongoing and separate evaluation and revision of the pharmaceutical legal framework.

The explanatory memorandum suggests that the issue of regulatory delineation between the BTC sector and the pharmaceutical sector will be considered as part of this wider legislative review as “the delineating criteria are set by definitions in the pharmaceutical framework and are not altered by this proposal.”

The wider life sciences industry eagerly awaits the much-anticipated outcome of the review of European pharmaceutical legislation, which is now due to be published in the first half of 2023. With almost every aspect of pharmaceutical regulation currently under review, it will be fascinating to see whether there is appetite to alter the definitions affecting this delineation. However, we cannot but welcome the new Regulation, which will hopefully bring a much needed harmonisation and will bring the legislation in line with the state of the art.

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[1] Directives 2002/98/EC and 2004/23/EC