Advanced medicinal products (ATMP)
Advanced therapies or advanced therapy medical products is a term used to describe innovative therapies. International regulators use this term to include gene, cell and tissue therapies.
The European legislation (Directive 2009/120/EC in addition to Regulation (EC) No 1394/2007) uses the following definition for advanced therapies:
Gene therapy medicinal product
Gene therapy medicinal product means a biological medicinal product which has the following characteristics:
(a) it contains an active substance which contains or consists of a recombinant nucleic acid used in or administered to human beings with a view to regulating, repairing, replacing, adding or deleting a genetic sequence;
(b) its therapeutic, prophylactic or diagnostic effect relates directly to the recombinant nucleic acid sequence it contains, or to the product of genetic expression of this sequence.
Gene therapy medicinal products shall not include vaccines against infectious diseases.
Somatic cell therapy medicinal product
Somatic cell therapy medicinal product means a biological medicinal product which has the following char acteristics:
(a) contains or consists of cells or tissues that have been subject to substantial manipulation so that biological characteristics, physiological functions or structural properties relevant for the intended clinical use have been altered, or of cells or tissues that are not intended to be used for the same essential function(s) in the recipient and the donor;
(b) is presented as having properties for, or is used in or administered to human beings with a view to treating, preventing or diagnosing a disease through the pharmacological, immunological or metabolic action of its cells or tissues.
For the purposes of point (a), the manipulations listed in Annex I to Regulation (EC) No 1394/2007, in particular, shall not be considered as substantial manipulations.
Tissue engineered product
“Tissue engineered product” means a product that:
- contains or consists of engineered cells or tissues, and
- is presented as having properties for, or is used in or administered to human beings with a view to regenerating, repairing or replacing a human tissue.
A tissue engineered product may contain cells or tissues of human or animal origin, or both. The cells or tissues may be viable or non-viable. It may also contain additional substances, such as cellular products, bio-molecules, bio-materials, chemical substances, scaffolds or matrices.
Products containing or consisting exclusively of non-viable human or animal cells and/or tissues, which do not contain any viable cells or tissues and which do not act principally by pharmacological, immunological or metabolic action, shall be excluded from this definition.
Cells or tissues shall be considered ‘engineered’ if they fulfil at least one of the following conditions:
- the cells or tissues have been subject to substantial manipulation, so that biological characteristics, physiological functions or structural properties relevant for the intended regeneration, repair or replacement are achieved. The manipulations listed in Annex I, in particular, shall not be considered as substantial manipulations,
- the cells or tissues are not intended to be used for the same essential function or functions in the recipient as in the donor.
‘Combined advanced therapy medicinal product’ means an advanced therapy medicinal product that fulfils the following conditions:
- it must incorporate, as an integral part of the product, one or more medical devices within the meaning of Article 1(2)(a) of Directive 93/42/EEC or one or more active implantable medical devices within the meaning of Article 1(2)(c) of Directive 90/385/EEC, and
- its cellular or tissue part must contain viable cells or tissues, or
- its cellular or tissue part containing non-viable cells or tissues must be liable to act upon the human body with action that can be considered as primary to that of the devices referred to
Regulation of advanced therapies
The European legislative regulates therapeutics consisting of gene, cell and tissue therapies under the Regulation (EC) No 1394/2007 and amending Directive 2001/83/EC and Regulation (EC) No 726/2004.
European Medicines Agency (EMA) guidance
Refer to the following International and EMA guidance on Advanced Therapies:
EMEA/CHMP/SWP/28367/07 Rev. 1: Strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products – Scientific guideline | European Medicines Agency (europa.eu)
EMA/CAT/GTWP/671639/2008 Rev. 1 Corr. : Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells – Scientific guideline | European Medicines Agency (europa.eu)
EMEA/CHMP/410869/2006 : Guideline on human cell based medicinal products (europa.eu)
EMA/CHMP/BWP/271475/2006 rev.1: Potency testing of cell-based immunotherapy medicinal products for the treatment of cancer – Scientific guideline | European Medicines Agency (europa.eu)
All guidelines, reflection papers and concept papers (including those not yet finalized but under public consultation) currently available for ATMPs can be found at: https://www.ema.europa.eu/en/human-regulatory-overview/research-development/scientific-guidelines
Clinical trials
Clinical trials performed in Slovenia that involve ‘unapproved advanced medicinal products’ including gene, cell and tissue therapies, need a clinical trial approval under Regulation (EU) No. 536/2014. The Clinical trial approval involves ethical evaluation by the National Medical Ethics Committee and evaluation of scientific data by the JAZMP, with a focus on safety.
For more information about clinical trial application and approval refer to the Clinical trials of medicinal products – JAZMP
Sponsors are encouraged to contact us at before submitting a clinical trial application. We can provide pre-submission meetings and advice to clarify the regulatory requirements and what data you need in your submission.
Hospital exemption or non-routinely prepared medicines for advanced treatment
Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 amended Article 3 of Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 by adding point 7 to exclude from the scope of that directive advanced medicinal products prepared from time to time, in accordance with specific quality standards, and used in the same Member State, in a hospital institution and under the exclusive professional responsibility of a registered doctor, in order to comply with an individual medical prescription for a tailor-made product intended for a single patient.
Such medicinal products are subject to authorisation by the competent authorities of the Member State, who must ensure that the national traceability and pharmacovigilance requirements, as well as the applicable specific quality standards, are equivalent to those provided for at Community level in respect of advanced therapy medicinal products for which authorisation is required in accordance with Regulation No 726/2004 of the European Parliament and of the Council, of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing the European Medicines Agency.
The field of non-routinely prepared medicines for advanced treatment is regulated in the Republic of Slovenia by the Medicines Act (Official Gazette of the Republic of Slovenia, no. 17/14 and 66/19 ) with Chapter V, with Articles 71 to 86.
