Advanced therapies, hospital exemptions & marketing authorizations: the UK’s emerging regulatory framework for point-of-care manufacture

Hospital-centred manufacture, which consists in producing therapies close to the patient, within a hospital or in a nearby unit, is becoming increasingly viable and necessary. There are at least two modalities of this kind of manufacture: in what we name bedside manufacture, therapy production relies on hospital infrastructure and facilities, products can have all sorts of shelf life, and a small number of hospitals is involved; in the emerging modality called point-of-care manufacture, there is great reliance on portable manufacturing devices taken to the hospital, products have short or very short shelf life, and a large number of hospitals may be involved. The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has proposed a new regulatory framework dedicated to point-of-care manufacture. A large range of products can be manufactured this way, including some Advanced Therapy Medicinal Products (ATMPs), which are medicines based on cells, genes or tissues. Bedside manufacture has been traditionally overseen via regulatory exemptions. In the European Union (EU), the manufacture of ATMPs in hospitals or for hospitals has been covered by the “Hospital Exemption”. In the UK, another exemption, known as the Specials scheme, has been used. Both exemptions are grounded on the specificities of hospitals and clinical needs. The MHRA’s current regulatory proposal introduces a new rationale in which point-of-care manufacture will be subject to a flexible and proportionate framework while following the regulatory pathway now valid for commercial products, including the conduct of clinical trials and the issuance of marketing authorisations. This brings about a market route that will coexist with the clinical route of exemptions. This article analyses the implications and uncertainties of the UK’s possible move from regulatory exemptions (bedside manufacture) to marketing authorizations (point-of-care manufacture) for hospital-produced ATMPs. It also sheds light on strategic issues triggered by the MHRA’s proposal.