Case Study: Holoclar

Long-term restoration of damaged corneal surfaces with autologous cultivated corneal epithelium

Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration

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.

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.

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

• A public summary of positive opinion for orphan designation
• See EuroGCT's resource on: ATMPs and Orphan medicinal products

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

• Learn more about: Paediatric medicines and Paediatric investigation plans
• See EuroGCT's resource on 'ATMPs and paediatric medicinal products'. (sub-entry currently under development.) 

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.

First stem-cell therapy recommended for approval in EU

• EMA's press release on the recommendation of Holoclar.

Holoclar for treating limbal stem cell deficiency after eye burns

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

ex vivo expanded autologous human corneal epithelial cells containing stem cells (Holoclar)

• Assessment by Scottish Medicines Consortium (SMC)

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

A case study by ATTC on the Importation of Holoclar.

• A short video is available here.
• Newcastle pharmacy experts help provide access to sight-saving treatment across England - Newcastle Hospitals NHS Foundation Trust (newcastle-hospitals.nhs.uk)
• The case study demonstrates how regulatory barriers and supply chain challenges can be overcome through private-public collaborations. The approach can be applied to other products, both marketed and investigational ATMPs.

• Interview with Michele De Luca – Epithelial cells and regrowing corneal epithelium
• Interview with Graziella Pellegrini – Using stem cells to cure blindness
• Behind the scenes of the world's first commercial stem-cell therapy