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QUALITY MANAGEMENT

European regulation in ART still lags behind clinical progress

EU regulation of clinical practice

Published 18 November 2019

A Campus meeting in October covered a broad range of subjects each aiming to ensure a high-standard framework for ART. Among them was the EU's regulation of clinical practice and its systems of reprovigilance.

While laws governing the regulation of ART have increased patient safety, they are still not keeping pace with innovation and new developments in the blood, tissue and cells sector, according to a recent analysis of the European Tissue and Cells Directive (EUTCD).

Regulation in ART is crucial for the safety of staff and patients, said Edgar Mocanu, consultant gynaecologist at The Rotunda Hospital in Dublin, especially given the incidence of infectious diseases. However, variation exists within and between countries, with one-third still having no legislation for monitoring ART.(1) Within the EU, the EUTCD does provide a regulation framework, but implementation has been slow and remains patchy.

Concerns around cross-border reproductive care, for example, could be resolved by application of a new Single European Code (2015/566/EC) aimed at ensuring full traceability from donor to recipient. This code would be applied to imported tissues and cells. In addition, Mocanu called for a European Reproductive Coding System (ERCS) — by which each ART recipient would be allocated a unique reproductive care code in order for data collection systems to keep pace with emerging changes in clinical practices (eg, the prolonged storage of gametes).(2)

Moreover, changes on the horizon may further affect protections for donors and donor-conceived children. Mocanu reported that earlier this year recommendations from the Parliamentary Assembly of the Council of Europe included a ban on all anonymous sperm/egg donation, and requiring the state to inform donor-conceived children about supplementary information regarding their birth.

Thus, according to Mocanu, for regulation to remain fit for purpose, more robust inspections, authorisations and vigilance are necessary.

This theme of vigilance was discussed further by Paula Nolan, clinical governance lead for the UK regulator the Human Fertilisation and Embryology Authority (HFEA). Her take-home message was that the benefits of vigilance systems are only fully realised when results are communicated effectively, and health professionals receive feedback. Clinics must not create a culture of blame — ‘I know doctors and nurses that have left the profession because they feel unsupported,’ she said.

The limited availability of oocytes and embryos is among several reasons for the importance of biovigilance in ART, she added, and why clinics should consider reporting to regulators any serious adverse reaction (SAR) (eg, transmission of genetic disease) or serious adverse event (SAE) (eg, embryo mix-up). A severity scale can assess if an incident is graded ‘serious’ and should be reported.

Such reporting occurs through EC secure alert platforms — the Rapid Alert for Tissues and Cells (RATC) and Rapid Alert System for Blood and Blood Components (RAB). Nolan described how an e-mail would alert her to an incident, which may often be related to donor gametes. Clinics should ‘act in a timely fashion’, she said, otherwise miscarriage may be a risk.

In 2018, 88 alerts were reported via RATC system, with nearly a third (25) relating to quality and safety defects of tissue and cells. Transmission of genetic disease accounted for the majority of the 221 SAR incidents highlighted in the 2016 Serious Adverse Reactions and Events (SARE) report. These secure alert platforms should work in parallel with existing national vigilance systems.

A useful reference tool recommended by Nolan is the Notify Library, which details adverse occurrences in transplantation, and has reviewed cases to identify general principles supporting detection and investigation. 

Inspection is a key element of clinic regulation as defined by the European Blood Directive (2002/98/EC), with member states required to set up inspection systems by nominating/creating competent authorities (CAs).(3) VISTART (Vigilance and Inspection for the Safety of Transfusion Assisted Reproduction and Transplantation), which provides an audit system to certify authorities, published final inspection guidelines in 2018 for EU-based CAs that inspect and authorise blood and tissue clinics.

Gynaecologist and inspector Mauro Costa, from Ospedale Evangelico Internazionale, Genoa, Italy, outlined criteria for ART inspections, which included developing a risk rating for each clinic, questioning staff individually about their roles, and clinic staff providing an overview of the clinic’s quality management system. To ensure inspectors reach a high standard, Costa described how he demonstrates an imitation IVF treatment live in the lab.

From warning systems to inspections, the process of regulation relies on a high degree of competency and knowledge. This evidently must be backed up by directives that progress at the same speed as the sector they are devised to govern. 

 

1. IFFS Surveillance in 2019. Global Reproductive Health March 2019; vol 4. See https://journals.lww.com/grh/Fulltext/2019/03000/International_Federation_of_Fertility_Societies_.3.aspx

2. De Geyter C, Wyns C, Mocanu E, et al. Data collection systems in ART must follow the pace of change in clinical practice. Hum Reprod 2016; 31: 2160–2163.

3. See https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/directive-2002/98/ec-european-parliament-council-27-january-2003-setting-standards-quality-safety-collection-testing_en.pdf