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Case Study: Holoclar

Learning from a successful experience

Holoclar is one of the few Advanced Therapy Medicinal Products (ATMPs) that have been granted marketing authorisation in Europe. Here we collated existing information about each stage of development for Holoclar, from early-stage research to approval, to serve as a guide for the research community to learn about the development process, the keys to success, the challenges and how developers overcame them.

Holoclar was developed based on more than twenty years of research by a team of internationally renowned scientists in the field of epithelial stem cell biology. It is an ex vivo expanded autologous human corneal epithelial cells containing stem cells, capable of restoring eyesight of patients with severe cornea damage due to ocular burns, and is classified as Tissue Engineered Product (TEP).  Holoclar was brought to the clinic by an Italian team led by Professor Michele De Luca and Professor Graziella Pellegrini, both from the Centre for Regenerative Medicine (CMR) at the University of Modena and Reggio Emilia, and Andrea Chiesi, Director of R&D Portfolio Management of Chiesi Farmaceutici S.p.A. and CEO of Holostem Terapie Avanzate, an University spin-off located in the CMR. The authorization process for Holoclar has been long and complex, but in 2015, Holoclar received conditional marketing approval in the EU.

Read the following resources to learn more:

Key Resources

Review Articles

Holoclar: first of its kind in more ways than one

  • This paper describes the regulatory pathway Holoclar took to achieve Marketing Authorisation.

Navigating Market Authorization: The Path Holoclar Took to Become the First Stem Cell Product Approved in the European Union 

  • An in-depth description on Holoclar manufacturing processes and quality requirements for marketing authorization

From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU

  • An overview of the development process and recent developments, from early stage research to manufacturing.
  • Contains an executive summary of key considerations and challenges at various stages.   

    Regulatory viewpoints on the development of advanced stem cell–based medicinal products in light of the first EU-approved stem cell product

    • A report on the regulatory and scientific framework for stem-cell-based products in Europe.
    • Holoclar is used here as an example

    Approaches for Effective Clinical Application of Stem Cell Transplantation

    • Describes problems related to translation of ATMPs (including Holoclar and 2 others) from early stage research to clinical translation.

    Other Articles

    Incentives, IP and smaller companies – the story of Chiesi and Holostem

    • This article discusses the financial incentives Chiesi and Holostem Terapie Avanzate utilised in Holoclar development.

    Regulatory tools and measures applied pre-authorisation

    ATMP Classification: Holoclar is classified as Tissue Engineered Product (TEP)

    • This EMA report provides information on ATMP approvals, classifications, and more.

    Orphan designation: Holoclar was designated as an orphan medicinal product for the treatment of corneal lesions, with associated corneal (limbal) stem-cell deficiency, due to ocular burns

    Paediatric Investigation Plan (PIP): Information on Holoclar's PIP

    EMA Authorisation Details

    Summary of the European public assessment report (EPAR) for Holoclar

    • This summary explains how EMA assessed the medicine to recommend its authorisation in the EU and its conditions of use

    Holoclar, INN-ex vivo expanded autologous human corneal epithelial cells containing stem cells

    • Holoclar product information document contain information including: summary of product characteristics, manufacturing authorisation holder responsible for batch release, conditions of the marketing authorisation, labelling and package leaflet. 

    Holoclar received a conditional marketing authorisation

    • This means that further evidence on this medicinal product is awaited.

    HTA Evaluation

    Holoclar for treating limbal stem cell deficiency after eye burns

    • Guidance by NICE
    • Contains information on: recommendation, evidence, summary of committee discussion.

    HOLOCLAR (cellules souches limbiques autologues amplifiées), cellules souches pour transplantation autologue

    • Opinion from the French Transparency Committee at the Haute Autorité de Santé (HAS) on the reimbursement of Holoclar by the French National Health Insurance System
    • A summary of the opinion in English is available here

    Delivering Holoclar

    A case study by ATTC on the Importation of Holoclar.


    Published: 23/05/2023


    Hsin-Yu Kuo, EuroGCT Information Officer - ATMP Product Development Pathway

    Reviewed by Aurélie Mahalatchimy, EuroGCT WP4 Convenor, UMR 7318 DICE CERIC, Aix-Marseille University, CNRS, Aix-en-Provence- France

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