The European Medicines Agency (EMEA) on 24 June 2009 recommended the grant of the marketing authorisation for ChondroCelect, from TiGenix NV. ChondroCelect is the first advanced therapy medicinal product to receive a positive opinion from the Agency’s new Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP)3 under the new EU regulation (i.e. Regulation (EC) No 1394/2007 on advanced therapy medicinal products – the ATMPs Regulation).
The Regulation, which became binding from 30 December 2008, regulates for the first time in the EU in a comprehensive and harmonised manner the authorisation of gene therapy, somatic cell therapy and tissue engineered products (i.e. advanced therapy medicinal products - ATMPs).
ChondroCelect is a cell-based medicinal product consisting of chondrocytes (cartilage cells) grown in vitro. The chondrocytes are taken from a small biopsy of healthy cartilage from the patient, grown outside the body, and then re-injected during surgery. ChondroCelect is intended for use to repair of a single symptomatic cartilage defect of the femoral condyle (the end of the thighbone) in the knee.
As part of the application, the CAT/CHMP have required the company under Article 14(2) of the ATMPs Regulation, to submit a risk management plan with a series of measures, including further studies into the efficacy and safety of the medicine, which are designed to allow for a robust follow-up of the medicine’s efficacy and any adverse reactions.
The scientific recommendation has now been forwarded to the European Commission of the European Union for the possible adoption of a legally binding marketing authorisation decision.
The authorisation in the EU of ATMPs has been extremely difficult over the past few years, due mainly to both technical and legal barriers which, de facto, hindered so far the marketing of these types of products.
From a scientific point of view, these types of products usually failed to obtain a positive opinion under the pre-existing legislation (i.e. Regulation (EC) 726/2004 on the authorisation and supervision of medicinal products for human and veterinary use at European level) essentially due to the lack of adequate and reliable data (i.e. long term efficacy and safety as well as quality data).
As a consequence, these products always failed in the past to meet the legal requirements necessary to obtain a full dossier marketing authorisation or to fall within any of the exemptions (to a full set of data) provided by legislation. Also article 14(7) exception (specific obligations), which provides that in cases of lack of data “an authorisation may be granted subject to certain specific obligations, to be reviewed annually by the Agency”, was deemed inapplicable in cases such as, where, missing the necessary supporting data, benefit-risk assessment was not adequately supported4.
New ATMPs legislation
The pre-existing situation has now changed thanks to new legislation, which provides the regulator with new tools for coping with such issues.
The CAT/CHMP positive opinion on ChondroCelect is based on Article 14(2) of the ATMPs Regulation, which reads as follows:
“Where there is particular cause for concern, the Commission shall, on the advice of the Agency, require as part of the marketing authorisation that a risk management system designed to identify, characterise, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system, be set up, or that specific post-marketing studies be carried out by the holder of the marketing authorisation and submitted for review to the Agency.
In addition, the Agency may request submission of additional reports evaluating the effectiveness of any risk management system and the results of any such studies performed.
Evaluation of the effectiveness of any risk management system and the results of any studies performed shall be included in the periodic safety update reports referred to in Article 24(3) of Regulation (EC) No 726/2004.”
The remarkable change introduced by this new provision is, therefore, that the Commission is now entitled to authorise the marketing of ATMPs requiring companies, as part of the marketing authorisation5, to design specific risk management systems or to carry out specific post-marketing studies whose effective proper implementation might be subject to further assessment by the Agency.
The generation of long-term data in the post-authorisation phase as part of the marketing authorisation allows the immediate marketing of ATMPs, for which quality, safety and efficacy data might have been sufficient to enable a proper benefitrisk evaluation and approval but for which close monitoring of the product by the EMEA is any case required. Any failure to comply with such requirements may eventually result in financial penalties and regulatory measures.
Should the scientific recommendation issued by the CAT/CHMP be followed by the European Commission, it is to be expected that an increased number of ATMPs will be on the market in the near future in line with the aims of new legislation.