Regulatory Assessment of Casgevy for the Treatment of Transfusion-Dependent β-Thalassemia and Sickle Cell Disease with Recurrent Vaso-Occlusive Crises.

Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are hereditary haemoglobinopathies characterized by a reduction in functional β-globin chains. Both conditions cause tiredness and increase susceptibility to infection, which can lead organ failure, significantly reducing life expectancy and typically requiring those affected to undergo regular erythrocyte transfusion. Recently, a novel therapeutic treatment for SCD and TDT was approved by the UK regulatory body (Medicines and Healthcare products Regulatory Agency; MHRA).

Correction to: Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective.

The article [Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective], written by [James W. McBlane, Parvinder Phul, and Michaela Sharpe], was originally published electronically on the publisher's internet portal (currently SpringerLink).

Preclinical Development of Cell-Based Products: a European Regulatory Science Perspective.

Purpose: This article describes preclinical development of cell-based medicinal products for European markets and discusses European regulatory mechanisms open to developers to aid successful product development. Cell-based medicinal products are diverse, including cells that are autologous or allogeneic, have been genetically modified, or not, or expanded ex vivo, and applied systemically or to an anatomical site different to that of their origin; comments applicable to one product may not be applicable to others, so bespoke development is needed, for all elements - quality, preclinical and clinical.

Methods: After establishing how the product is produced, proof of potential for therapeutic efficacy, and then safety, of the product need to be determined.

Preclinical safety testing for cell-based products using animals.

The objectives of preclinical testing include to show why there might be therapeutic benefit in patients and to provide information on the product's toxicity. For cell-based products, given even once, there may be long term exposure and this could imply, unlike for conventional drugs, that all preclinical studies may be needed prior to first human use. The duration of exposure to cells should be studied in animals to guide toxicity assessments.

Regulatory landscape for cell therapy--EU view.

This article addresses regulation of cell therapies in the European Union (EU), covering cell sourcing and applications for clinical trials and marketing authorisation applications. Regulatory oversight of cell sourcing and review of applications for clinical trials with cell therapies are handled at national level, that is, separately with each country making its own decisions. For clinical trials, this can lead to different decisions in different countries for the same trial.

A regulatory perspective of clinical trial applications for biological products with particular emphasis on Advanced Therapy Medicinal Products (ATMPs).

The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible.