Regulatory, ethical and technological obstacles for translation of ATMP and especially CAR T cell therapies: a joint CARAT & RESTORE survey

Thanks a lot for your support in advance!
The CARAT and RESTORE teams

more information on the EU initiatives is provided at:
CARAT homepage; RESTORE homepage

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* 1. Background

Please name your Country

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* 2. What is your professional background? Please select most relevant answer.

Researcher (academia)

Clinician (academia)

Manufacturer

Industrial representative (pharma, biotech ...)

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* 3. Describe your previous experience with ATMP/CAR T trial applications: please select the most relevant answer.

PI (principal investigator) in ATMP/CAR T trials

participant (study center) in ATMP/CAR T trials

scientist involved in ATMP/CAR T trials

presently preparing application for ATMP/CAR T clinical trial

no previous experience with ATMP/CAR T trial applications

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* 4. Describe your research interests: several answers are possible.

genetically engineered immune cell therapy (T cells, NK…/CAR, TCR…)

non gene modified immune cell therapy

Genetically modified stem cell therapy

Non-gene modified stem cell therapy

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* 5. Do you regard the following technological challenges as obstacles for translation of ATMP/CAR T cells into the clinics?

	1 (low obstacle)	2	3 (medium)	4	5 (high obstacle)	N/A
Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.)	Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.) 1 (low obstacle)	Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.) 2	Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.) 3 (medium)	Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.) 4	Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.) 5 (high obstacle)	Cell engineering (e.g. vector design, gene transfer technologies, cell expansion, cell activation etc.) N/A
Manufacturing process	Manufacturing process 1 (low obstacle)	Manufacturing process 2	Manufacturing process 3 (medium)	Manufacturing process 4	Manufacturing process 5 (high obstacle)	Manufacturing process N/A
Availability of vector material	Availability of vector material 1 (low obstacle)	Availability of vector material 2	Availability of vector material 3 (medium)	Availability of vector material 4	Availability of vector material 5 (high obstacle)	Availability of vector material N/A
Safety /quality of raw materials	Safety /quality of raw materials 1 (low obstacle)	Safety /quality of raw materials 2	Safety /quality of raw materials 3 (medium)	Safety /quality of raw materials 4	Safety /quality of raw materials 5 (high obstacle)	Safety /quality of raw materials N/A
Quality control (and assays)	Quality control (and assays) 1 (low obstacle)	Quality control (and assays) 2	Quality control (and assays) 3 (medium)	Quality control (and assays) 4	Quality control (and assays) 5 (high obstacle)	Quality control (and assays) N/A
Relevant in vitro preclinical models	Relevant in vitro preclinical models 1 (low obstacle)	Relevant in vitro preclinical models 2	Relevant in vitro preclinical models 3 (medium)	Relevant in vitro preclinical models 4	Relevant in vitro preclinical models 5 (high obstacle)	Relevant in vitro preclinical models N/A
Relevant in vivo preclinical models	Relevant in vivo preclinical models 1 (low obstacle)	Relevant in vivo preclinical models 2	Relevant in vivo preclinical models 3 (medium)	Relevant in vivo preclinical models 4	Relevant in vivo preclinical models 5 (high obstacle)	Relevant in vivo preclinical models N/A

Comments, additional aspects: please insert below.

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* 6. Do you regard the following regulatory aspects as obstacles for translation of ATMP/CAR T cells into the clinics?

	1 (low obstacle)	2	3 (medium)	4	5 (high obstacle)	N/A
Manufacturing license application	Manufacturing license application 1 (low obstacle)	Manufacturing license application 2	Manufacturing license application 3 (medium)	Manufacturing license application 4	Manufacturing license application 5 (high obstacle)	Manufacturing license application N/A
GMP requirements in general	GMP requirements in general 1 (low obstacle)	GMP requirements in general 2	GMP requirements in general 3 (medium)	GMP requirements in general 4	GMP requirements in general 5 (high obstacle)	GMP requirements in general N/A
Documentation for GMP processes	Documentation for GMP processes 1 (low obstacle)	Documentation for GMP processes 2	Documentation for GMP processes 3 (medium)	Documentation for GMP processes 4	Documentation for GMP processes 5 (high obstacle)	Documentation for GMP processes N/A
Clinical trial application approval	Clinical trial application approval 1 (low obstacle)	Clinical trial application approval 2	Clinical trial application approval 3 (medium)	Clinical trial application approval 4	Clinical trial application approval 5 (high obstacle)	Clinical trial application approval N/A
Ethical vote application	Ethical vote application 1 (low obstacle)	Ethical vote application 2	Ethical vote application 3 (medium)	Ethical vote application 4	Ethical vote application 5 (high obstacle)	Ethical vote application N/A
Investigational medicinal product dossier (IMPD)	Investigational medicinal product dossier (IMPD) 1 (low obstacle)	Investigational medicinal product dossier (IMPD) 2	Investigational medicinal product dossier (IMPD) 3 (medium)	Investigational medicinal product dossier (IMPD) 4	Investigational medicinal product dossier (IMPD) 5 (high obstacle)	Investigational medicinal product dossier (IMPD) N/A
Duration of approval process	Duration of approval process 1 (low obstacle)	Duration of approval process 2	Duration of approval process 3 (medium)	Duration of approval process 4	Duration of approval process 5 (high obstacle)	Duration of approval process N/A
General insecurity about regulatory requirements	General insecurity about regulatory requirements 1 (low obstacle)	General insecurity about regulatory requirements 2	General insecurity about regulatory requirements 3 (medium)	General insecurity about regulatory requirements 4	General insecurity about regulatory requirements 5 (high obstacle)	General insecurity about regulatory requirements N/A

Comments, additional aspects: please insert below.

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* 7. Do you regard the following clinical trial related aspects as obstacles for translation of ATMP/CAR T cells into the clinics?

	1 (low obstacle)	2	3 (medium)	4	5 (high obstacle)	N/A
Patient acquisition	Patient acquisition 1 (low obstacle)	Patient acquisition 2	Patient acquisition 3 (medium)	Patient acquisition 4	Patient acquisition 5 (high obstacle)	Patient acquisition N/A
Inclusion criteria, definition of target population	Inclusion criteria, definition of target population 1 (low obstacle)	Inclusion criteria, definition of target population 2	Inclusion criteria, definition of target population 3 (medium)	Inclusion criteria, definition of target population 4	Inclusion criteria, definition of target population 5 (high obstacle)	Inclusion criteria, definition of target population N/A
ATMP manufacturing	ATMP manufacturing 1 (low obstacle)	ATMP manufacturing 2	ATMP manufacturing 3 (medium)	ATMP manufacturing 4	ATMP manufacturing 5 (high obstacle)	ATMP manufacturing N/A
Dosing of IMP	Dosing of IMP 1 (low obstacle)	Dosing of IMP 2	Dosing of IMP 3 (medium)	Dosing of IMP 4	Dosing of IMP 5 (high obstacle)	Dosing of IMP N/A
Dealing with side-effects	Dealing with side-effects 1 (low obstacle)	Dealing with side-effects 2	Dealing with side-effects 3 (medium)	Dealing with side-effects 4	Dealing with side-effects 5 (high obstacle)	Dealing with side-effects N/A
Patient monitoring	Patient monitoring 1 (low obstacle)	Patient monitoring 2	Patient monitoring 3 (medium)	Patient monitoring 4	Patient monitoring 5 (high obstacle)	Patient monitoring N/A
High costs for ATMPs and patient treatment	High costs for ATMPs and patient treatment 1 (low obstacle)	High costs for ATMPs and patient treatment 2	High costs for ATMPs and patient treatment 3 (medium)	High costs for ATMPs and patient treatment 4	High costs for ATMPs and patient treatment 5 (high obstacle)	High costs for ATMPs and patient treatment N/A
Reimbursement e.g. by payers	Reimbursement e.g. by payers 1 (low obstacle)	Reimbursement e.g. by payers 2	Reimbursement e.g. by payers 3 (medium)	Reimbursement e.g. by payers 4	Reimbursement e.g. by payers 5 (high obstacle)	Reimbursement e.g. by payers N/A
Administrative burden	Administrative burden 1 (low obstacle)	Administrative burden 2	Administrative burden 3 (medium)	Administrative burden 4	Administrative burden 5 (high obstacle)	Administrative burden N/A

Comments, additional aspects: please insert below.

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* 8. Do you regard the following ethical aspects as obstacles for translation of ATMP/CAR T cells into the clinics?

	1 (low obstacle)	2	3 (medium)	4	5 (high obstacle)	N/A
Transfer genetically modified cells into humans	Transfer genetically modified cells into humans 1 (low obstacle)	Transfer genetically modified cells into humans 2	Transfer genetically modified cells into humans 3 (medium)	Transfer genetically modified cells into humans 4	Transfer genetically modified cells into humans 5 (high obstacle)	Transfer genetically modified cells into humans N/A
Life-long persistence of genetically modified cells in recipient	Life-long persistence of genetically modified cells in recipient 1 (low obstacle)	Life-long persistence of genetically modified cells in recipient 2	Life-long persistence of genetically modified cells in recipient 3 (medium)	Life-long persistence of genetically modified cells in recipient 4	Life-long persistence of genetically modified cells in recipient 5 (high obstacle)	Life-long persistence of genetically modified cells in recipient N/A
Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD)	Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD) 1 (low obstacle)	Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD) 2	Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD) 3 (medium)	Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD) 4	Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD) 5 (high obstacle)	Side-effects e.g. cytokine release syndrome, neurotoxicity, Graft versus Host Disease (GvHD) N/A
Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products	Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products 1 (low obstacle)	Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products 2	Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products 3 (medium)	Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products 4	Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products 5 (high obstacle)	Socio-economic burden for health care systems through high costs of ATMP/CAR T cell products N/A
Lack of appropriate reimbursement models	Lack of appropriate reimbursement models 1 (low obstacle)	Lack of appropriate reimbursement models 2	Lack of appropriate reimbursement models 3 (medium)	Lack of appropriate reimbursement models 4	Lack of appropriate reimbursement models 5 (high obstacle)	Lack of appropriate reimbursement models N/A
Limited access of patients to novel Advanced Therapies	Limited access of patients to novel Advanced Therapies 1 (low obstacle)	Limited access of patients to novel Advanced Therapies 2	Limited access of patients to novel Advanced Therapies 3 (medium)	Limited access of patients to novel Advanced Therapies 4	Limited access of patients to novel Advanced Therapies 5 (high obstacle)	Limited access of patients to novel Advanced Therapies N/A
Dependency on pharma/biotech industry	Dependency on pharma/biotech industry 1 (low obstacle)	Dependency on pharma/biotech industry 2	Dependency on pharma/biotech industry 3 (medium)	Dependency on pharma/biotech industry 4	Dependency on pharma/biotech industry 5 (high obstacle)	Dependency on pharma/biotech industry N/A
Unrealistic public expectations on therapeutic potential of Advanced Therapies	Unrealistic public expectations on therapeutic potential of Advanced Therapies 1 (low obstacle)	Unrealistic public expectations on therapeutic potential of Advanced Therapies 2	Unrealistic public expectations on therapeutic potential of Advanced Therapies 3 (medium)	Unrealistic public expectations on therapeutic potential of Advanced Therapies 4	Unrealistic public expectations on therapeutic potential of Advanced Therapies 5 (high obstacle)	Unrealistic public expectations on therapeutic potential of Advanced Therapies N/A

Comments, additional aspects: please insert below.

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* 9. Do you regard the following general deficits as obstacles for translation of ATMP/CAR T cells into the clinics?

	1 (low obstacle)	2	3 (medium)	4	5 (high obstacle)	N/A
Lack of templates/blueprints	Lack of templates/blueprints 1 (low obstacle)	Lack of templates/blueprints 2	Lack of templates/blueprints 3 (medium)	Lack of templates/blueprints 4	Lack of templates/blueprints 5 (high obstacle)	Lack of templates/blueprints N/A
Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application	Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application 1 (low obstacle)	Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application 2	Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application 3 (medium)	Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application 4	Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application 5 (high obstacle)	Lack of guidance through the application processes e.g. for manufacturing license or clinical trial application N/A
Lack of funding respectively financing	Lack of funding respectively financing 1 (low obstacle)	Lack of funding respectively financing 2	Lack of funding respectively financing 3 (medium)	Lack of funding respectively financing 4	Lack of funding respectively financing 5 (high obstacle)	Lack of funding respectively financing N/A
Lack of efficacy of cell products	Lack of efficacy of cell products 1 (low obstacle)	Lack of efficacy of cell products 2	Lack of efficacy of cell products 3 (medium)	Lack of efficacy of cell products 4	Lack of efficacy of cell products 5 (high obstacle)	Lack of efficacy of cell products N/A
Lack of safety of cell products	Lack of safety of cell products 1 (low obstacle)	Lack of safety of cell products 2	Lack of safety of cell products 3 (medium)	Lack of safety of cell products 4	Lack of safety of cell products 5 (high obstacle)	Lack of safety of cell products N/A
Lack of research data e.g. on mode of action of CAR T cells or ATMPs	Lack of research data e.g. on mode of action of CAR T cells or ATMPs 1 (low obstacle)	Lack of research data e.g. on mode of action of CAR T cells or ATMPs 2	Lack of research data e.g. on mode of action of CAR T cells or ATMPs 3 (medium)	Lack of research data e.g. on mode of action of CAR T cells or ATMPs 4	Lack of research data e.g. on mode of action of CAR T cells or ATMPs 5 (high obstacle)	Lack of research data e.g. on mode of action of CAR T cells or ATMPs N/A
Lack of transition of ATMPs toward front-line care	Lack of transition of ATMPs toward front-line care 1 (low obstacle)	Lack of transition of ATMPs toward front-line care 2	Lack of transition of ATMPs toward front-line care 3 (medium)	Lack of transition of ATMPs toward front-line care 4	Lack of transition of ATMPs toward front-line care 5 (high obstacle)	Lack of transition of ATMPs toward front-line care N/A

Comments, additional aspects: please insert below.

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* 10. Are there other specific painpoints (personal experiences) for translation of ATMPs/CAR T that you would like to mention?

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* 11. Would you like suggest possible solutions that should be implemented for translation of ATMPs/CAR T cells?

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* 12. Do you have any further comments, questions, or concerns?