EU decision-making for marketing authorization of advanced therapy medicinal products: a case study

Abstract

A comparative analysis of assessment procedures for authorization of all European Union (EU) applications for advanced therapy medicinal products (ATMPs) shows that negative opinions were associated with a lack of clinical efficacy and identified severe safety risks. Unmet medical need was often considered in positive opinions and outweighed scientific uncertainties. Numerous quality issues illustrate the difficulties in this domain for ATMP development. Altogether, it suggests that setting appropriate standards for ATMP authorization in Europe, similar to elsewhere, is a learning experience. The experimental characteristics of authorized ATMPs urge regulators, industry, and clinical practice to pay accurate attention to post-marketing risk management to limit patient risk. Methodologies for ATMP development and regulatory evaluations need to be continuously evaluated for the field to flourish.

Preclinical Development of Autologous Hematopoietic Stem Cell-Based Gene Therapy for Immune Deficiencies: A Journey from Mouse Cage to Bed Side

“…Developers of gene therapy products not only face challenges in the scientific and technological fields but also experience additional hurdles in the regulatory trajectory, even though the regulatory environment for ATMPs (Advanced Therapy Medicinal Products) has been globally coevolving with the increasing interest in marketing authorization over the past decade [ 171 , 172 ].…”

“…They have been making important steps to define appropriate regulatory standards; however, due to the novelty of this field and the complexity of such products, regulators face scientific issues never discussed before. As a result of this, regulatory requirements for approval for market authorization are not standardized or harmonized yet [ 172 , 174 ].…”

Mitigating Deficiencies in Evidence during Regulatory Assessments of Advanced Therapies: A Comparative Study with Other Biologicals

“…Previous studies have attempted to investigate the evidence in ATMP submissions through the quantification of objections raised by regulatory authorities during the assessment procedure of MAAs. [14][15][16][17] de Wilde et al 14 and Carvalho et al 15 relied on the European public assessment report (EPAR), a document published by the European Medicines Agency (EMA) for all submissions that reach the first stage of assessment, whether approved, refused, or withdrawn. Barkholt et al 16 at the EMA quantified the objections for the first 20 MAAs for ATMPs.…”

Automation in cell and gene therapy manufacturing: from past to future

“…This could be due to many challenges related to manufacturing that are still to be addressed. Marketing and regulatory approval of advanced therapies have two main requirements: (1) to demonstrate the safety and efficacy of the therapy in treating the targeted disease (de Wilde et al 2018) and (2) to demonstrate consistent and rigorous manufacturing to a well-defined product quality (Morrow et al 2017). Automation has the potential to address many of these existing challenges, while facilitating the requirements for regulatory and marketing approval.…”