According to the 2013 House of Lords report on Regenerative Medicine, the term ‘regenerative medicine’ refers to methods to replace or regenerate human cells, tissues or organs in order to restore or establish normal function. This includes cell therapies, tissue engineering, gene therapy and biomedical engineering techniques, as well as more traditional treatments involving pharmaceuticals, biologics and devices.
This could encompass tissues and cells used for human application, such as hematopoietic stem cell transplants, as well as advanced therapy medicinal products (ATMPs).
What is an ATMP?
An advanced therapy medicinal product (ATMP) is a medicinal product which is either:
- a gene therapy medicinal product
- a somatic cell therapy medicinal product
- a tissue engineered product
All ATMPs to be placed on the market in the EU must have a marketing authorisation and are regulated through the centralised authorisation procedure. This is co-ordinated through the EMA.
UK Regulation of Advanced Therapy Medicinal Products
Establishments which manufacture ATMPs from human tissues and cells, work across two pieces of European legislation – the European Union Tissues and Cells Directives (EUTCD) and medicines legislation.
As a UK Competent Authority for the EUTCD, the HTA regulates the procurement, processing, testing, storage, distribution, and import/export of tissues and cells for human application. This is via the Human Tissue (Quality and Safety for Human Application) Regulations 2007 (Q&S Regulations). This includes tissues and cells that will (or may) be used as starting materials for ATMPs.
In the UK, MHRA is the competent authority:
- for clinical trial authorisation for all medicinal products, including ATMPs
- for UK manufacturers or importers of ATMPs
Where a product containing human tissues and cells is classified as an ATMP, the Q&S Regulations will apply for the donation, procurement, import and testing of tissues and cells. The subsequent stages, including manufacture, storage and distribution, will be regulated by the MHRA.
HTA licensing for those working with ATMPs
Where an organisation is involved in the procurement and testing of human tissues or cells, which are to be used in the manufacture of an ATMP, these activities must be carried out under an HTA Human Application licence which covers these activities.
This applies to all tissues and cells which are covered by the Q&S Regulations.
Specific information on the regulation of embryonic stem cell lines.
The HTA and MHRA have also established a joint position whereby the collection of blood as a starting material for an ATMP can be carried out under either a tissues and cells licence or a blood establishment licence.
Establishments which import, export or store tissues and cells intended to be used as a starting material, prior to their transfer to an ATMP manufacturer, may require an HTA licence for these activities. A member of the HTA Regulation Team will be able to advise further on HTA licensing requirements.
Additionally, Eudralex Volume 4, Annex 2 - Manufacture of Biological active substances and Medicinal Products for Human Use - allows that there may be some instances where processing of cells and tissues used as starting materials for biological medicinal products could be conducted under the scope of the EUTCD. Examples of where this could apply would be the derivation of early cell lines or banks prior to establishing a Master Cell Bank (MCB), or the banking of tissue where the future use is unknown but could include the manufacture of an Advanced Therapy Medicinal Product.
Annex 2 also sets out the necessary arrangements that should be in place for the transfer of tissues and cells to be used as starting materials, from a tissue establishment to an ATMP manufacturer. These include: the need for written agreements for transport; traceability requirements from the tissue establishment to the ATMP manufacturer; and, technical agreements between responsible parties. This provides for the for the transport of tissues and cells used as starting material to be covered by legislation outside of the Human Tissue (Quality and Safety for Human Application) Regulations 2007. Where this is the case this activity may be carried out without an establishment being licensed by the HTA for distribution.
External links to resources and other information
The Cell Therapy Catapult has developed a template for a Cell History File