Guidance for establishments on meeting HTA licensing requirements for the procurement of tumour samples to be used as a starting material in the manufacture of an Advanced Therapy Medicinal Product (ATMP).
Certain types of immunotherapies require the use of tumour material in their manufacture. Where the tumour material will comprise part of the active substance of the final product, it will be considered to be starting material for the manufacture of an ATMP. The Q&S Regulations will apply for the donation, procurement, testing and import. Detailed standards are set out in the HTA’s Guide to Quality and Safety Assurance for Human Tissues and Cells for Patient Treatment, which was brought into effect through the HTA Directions 001/2021
The following scenarios have been developed to set out the HTA licensing requirements for these types of materials. They are intended to act as guidance for those seeking assurance about how to demonstrate that tumour material procured for use in the manufacture of an ATMP meets the UK requirements with respect to donation, procurement, testing and import. Any establishment seeking to conduct this type of activity should contact the HTA for further advice.
The primary purpose of removing the tumour material is to obtain starting material for ATMP manufacture.
A HTA human application licence will be required for procurement and testing where this activity occurs in the UK.
If the tumour material is to be imported, then an import licence will be required (see scenario 4 below). If the sample is to be stored, or processed, in the UK prior to transfer to an ATMP manufacturer, then these activities will also need to be licensed by the HTA.
A tumour biopsy is being obtained for diagnostic purposes, or the patient is undergoing surgery for removal of the tumour. At the time of the procedure, it has been identified that the tumour material could be used for the purposes of ATMP manufacture, and a portion of the material is retained for these purposes.
Certain parts of the procurement procedure may not be subject to HTA licensing requirements. This could depend on a number of factors including: the procedure being undertaken to obtain the tumour; and whether the material is transferred directly to an ATMP manufacturer or is held at a tissue bank. In these circumstances, those undertaking the activity should contact the HTA for advice.
Regardless of licensing arrangements, all aspects of the procurement must meet the quality and safety standards required by the Q&S Regulations as set out in the HTA’s Guide to Quality and Safety Assurance for Human Tissues and Cells for Patient Treatment. As a minimum, consideration must be given to: consent; traceability; SAEARS reporting; and packaging and transport.
Donor testing must occur at the time of procurement and this must be performed under the authority of a HTA licence in accordance with the Q&S Regulations requirements.
If the sample is to be stored, or processed, prior to moving to an ATMP manufacturer, then these activities will also need to be licensed by the HTA. In these circumstances, once the material has been removed, it should be transferred to an establishment with a HTA human application licence under the supervision of a Designated Individual (DI).
A tumour biopsy was previously obtained for diagnostic purposes, or the patient underwent surgery for removal of the tumour and the material was retained. At the time of the patient undergoing the procedure, it had not been anticipated that the material would be used as a starting material for ATMP manufacture and the material was not procured, tested or stored in accordance with the Q&S Regulations.
The patient is subsequently identified as being suitable for inclusion in a trial for an ATMP and a portion of the retained material will need to be used for the manufacture of this therapy.
Where the material has been removed prior to determining it will be used for the development of an ATMP, this could mean that it is not possible to work within the licensing framework of the Q&S Regulations.
Once it has been identified that the tumour material will be used for clinical treatment, it should be stored and released in accordance with the Q&S Regulations, under a HTA Human Application licence. Material that has been collected in this way must be subject to a risk assessment identifying areas where procurement and testing has not complied with the requirements of the Q&S Regulations and be subject to a concessional release process, shaped by the outcome of the risk assessment. As part of the concessional release, the ATMP manufacturer must be made aware of any areas of non-conformance. If the sample is to be processed prior to moving to an ATMP manufacturer, then processing will also need to be licensed by the HTA.
An establishment wishes to import tumour samples into the UK from a third country for use as a potential starting material for the manufacture of an ATMP.
The import of starting material from a third country is a HTA licensable activity. The DI will need to ensure that the import of the tumour tissue into the UK meets the requirements of the Q&S Regulations as set out in the Guide to Quality and Safety Assurance for Human Tissues and Cells for Patient Treatment, and all other associated documents.
The DI of the importing tissue establishment will also need to ensure that imported tumour samples meet the standards of quality and safety equivalent to those required for tissues and cells procured and tested within the UK.
If the samples are to be stored, or processed, prior to moving to an ATMP manufacturer, then these activities will also need to be licensed by the HTA.