Guidelines

regulationAdvanced therapies comprise cell therapy, gene therapy and tissue engineering. For the most part, these are considered a special type of medicinal products. The only exception is the cell therapy which is considered as a cell transplant and not as a medicinal product when the cells are not subject to substantial manipulation and are used to carry out their normal function or essential functions.

Below, you can find a selection of the main European and Spanish guidelines and other documents related to this field of study.

 

 

MAIN EUROPEAN AND SPANISH GUIDELINES
UPDATED: NOV. 2022
 
GUIDELINES / REFLECTION PAPERS /
CONCEPT PAPERS		 BASIC AND PRECLINICAL RESEARCH CLINICAL RESEARCH QUALITY/MANUFACTURING
OR PROCESSING		 COMMERCIALIZATION/
CLINICAL USE
Meta-analyses and one Pivotal Study:

CPMP/EWP/2330/99		 X      
Design modifications of GTMP during development:

EMA/CAT/GTWP/44236/2009		 X      
Development pharmaceutics for biotechnological and biological products:

CPMP/BWP/328/99		 X      
Annex to Note for guidance on development pharmaceutic:

CPMP/QWP/155/96		 X      
Guideline on development and manufacture of lentiviral vectors:

CHMP/BWP/2458/03		 X   X  
Use of transgenic animals:

3AB7A		 X      
3Rs (guideline):

EMA/CHMP/CVMP/JEG-3Rs/450091/2012		 X      
3Rs (reflection paper):

EMA/CHMP/CVMP/3Rs/742466/2015		 X      
Potency testing of cell based immunotherapy
medicinal products for the treatment of cancer:

EMEA/CHMP/BWP/271475/2006		 X      
Use of bovine serum:

CPMP/BWP/1793/02		 X   X  
Use of porcine trypsin:

EMA/CHMP/BWP/814397/2011		 X   X  
Non-clinical testing for inadvertent germline
transmission of the gene transfer vectors:

EMEA/273974/2005		 X      
Note for guidance on minimising the risk of
transmitting animal spongiform encephalopathy agents
via human and veterinary medicinal products:

EMA/410/01		 X   X  
Creutzfeldt-Jakob disease and advanced
therapy medicinal products:

CHMP/CAT/BWP/353632/2010		 X   X  
Note for guidance on virus validation studies:
the design, contribution and interpretation of
studies validating the inactivation and removal of viruses:

CPMP/BWP/268/95 o 3AB8A		 X   X  
Quality, non-clinical and clinical aspects of
medicinal products containing genetically
modified cells:

EMA/CAT/GTWP/671639/2008    
CHMP/GTWP/671639/2008		 X X X  
Reflection paper on quality, non-clinical and
clinical issues relating specifically to recombinant
adeno-associated viral vector:

CHMP/GTWP/587488/07		 X X X  
Reflection paper on management of clinical risks
deriving from insertional mutagenesis:

EMA/CAT/190186/2012		 X X    
Stem cell-based medicinal products:

EMA/CAT/571134/2009		 X X X X
Xenogeneic cell-based medicinal products:

EMEA/CHMP/CPWP/83508/2009		     X  
In-vitro cultured chondrocyte containing
products for cartilage repair of the knee:

EMA/CAT/CPWP/568181/2009		   X X X
Genetically modified organisms (GMOs):

EMEA/CHMP/BWP/473191/2006		     X  
Human cell-based medicinal products:

EMEA/CHMP/410869/2006		 X X X  
Clinical aspects related to tissue
engineered products:

EMA/CAT/CPWP/573420/2009		   X X  
Quality, non-clinical and clinical aspects of
gene therapy medicinal products:

EMA/CAT/80183/2014		 X X X  
Plasma derived medicinal products:

CPMP/BWP/269/95		     X  
Minimum quality and non-clinical data for certification of
advanced therapy medicinal products:

EMA/CAT/486831/2008/corr. 		 X   X X
Risk-based approach (RBA):

EMA/CAT/CPWP/686637/2011		 X X X X
Tests on samples of biological origin:

3AB11A		 X   X  
Guideline on safety and efficacy follow-up and
risk management of advanced therapy medicinal products:

EMEA/149995/2008 rev.1 (en revisión)		   X X X
Excipients in the dossier for application for
marketing authorisation of a medicinal product:

EMEA/CHMP/QWP/396951/2006		     X X
Requirements to the chemical and pharmaceutical
quality documentation concerning investigational
medicinal products in clinical trials:

EMA/CHMP/QWP/545525/2017 Rev. 2		   X X  
Interpretation of the principles and guidelines of
good manufacturing practices for medicinal products
for human and veterinary use:

Volumen 4 Good Manufacturing Practice (GMP) guidelines		     X  
Guide to the contents of the technical memory for the pharmaceutical industry:

Version 03. April 2014		     X  
Non-clinical studies required before first clinical use of
gene therapy medicinal products:

EMEA/CHMP/GTWP/125459/2006		 X      
Comparability of Biotechnology-derived medicinal products
after a change in the Manufacturing Process:

EMEA/CHMP/BMWP/101695/2006		 X X X  
Clinical trials guidelines:

Clinical trials guidelines. EudraLex- Volume 10		   X    
Clinical trials in small populations:

CHMP/EWP/83561/2005		   X    
Design modifications of gene therapy medicinal products
during development:

EMA/CAT/GTWP/44236/2009		   X    
GTMP-questions and answers:

CHMP/GTWP/212377/08		 X X X  
Environmental risk assessment of gene therapy
medicinal products:

CHMP/GTWP/125491/06		     X  
Follow-up of patients administered with
gene therapy medicinal products:

EMEA/CHMP/GTWP/60436/2007		   X    
Safety and efficacy follow-up and risk management
of advanced therapy medicinal products:

EMEA/149995/2008		   X   X
Follow-up of patients administered with
gene therapy medicinal products:

EMEA/149995/2008		     X  
Good pharmacovigilance practices (GVP):

EMA/781168/2013		       X
Guidelines on Pharmacovigilance
for Medicinal Products for Human Use:

EudraLex- Volume 9A		       X
Detailed guidelines on good clinical practice specific
to advanced therapy medicinal products:

ENTR/F/2/SF/dn D(2009) 35810		   X    
         
 ICH GUIDELINES BASIC AND PRECLINICAL RESEARCH CLINICAL RESEARCH QUALITY/MANUFACTURING
OR PROCESSING		 COMMERCIALIZATION/
CLINICAL USE
Carcinogenity studies:

ICH S1A - S1C		 X      
Genotoxicity studies:

ICH S2		 X      
Toxicokinetics and pharmacokinetics:

ICH S3A-S3B		 X      
Toxicity testing:

ICH S4		 X      
Reproductive toxicity:

ICH S5		 X      
Biotechnological products:

ICH S6		 X      
Pharmacology products:

ICH S7A-S7B		 X      
Immunotoxicity studies for human pharmaceuticals:

ICH S8		 X      
Nonclinical evaluation for anticancer pharmaceuticals:

ICH S9		 X      
Photosafety evaluation:

ICH S10		 X      
Nonclinical pediatric safety:

ICH S11		 X      
Non-clinical biodistribution considerations for
gene therapy products:

ICH S12		 X      
Stability:

ICH Q1		     X  
Analytical validation:

ICH Q2		     X  
Impurities:

ICH Q3A-Q3E		     X  
Pharmacopoeias:

ICH Q4A-Q4B		     X  
Quality of biotechnological products:

ICH Q5A-Q5E		     X  
Specifications:

ICH Q6A-Q6B		     X  
Good Manufacturing Practice:

ICH Q7		     X  
Pharmaceutical development:

ICH Q8		     X  
Quality risk management:

ICH Q9		     X  
Pharmaceutical quality system:

ICH Q10		     X  
Development and manufacture of drug substances:

ICH Q11		     X  
Lifecycle management:

ICH Q12		     X  
Continuos manufacturing of drug substances and drug products:

ICH Q13		     X  
Analytical procedure development:

ICH  Q14		     X  
Clinical safety for drugs used in long-term treatment:

ICH E1		   X    
Pharmacovigilance:

ICH E2-E2F		   X    
Clinical study reports:

ICH E3		   X    
Dose-response studies:

ICH E4		   X    
Ethnic factors:

ICH E5		   X    
Good Clinical Practice:

ICH E6		   X    
Clinical trials in geriatric population:

ICH E7		   X    
General consideration for clinical trials:

ICH E8		   X    
Statistical principles for clinical trials:

ICH E9		   X    
Choice of control group in clinical trials:

ICH E10		   X    
Clinical trials in pediatric population:

ICH E11		   X    
Definitions in pharmacogenetics / pharmacogenomics:

ICH E15		 X X    
Qualifications of genomic biomarkers:

ICH E16		 X X    
Multi-regional clinical trials:

ICH E17		   X    
Genomic sampling and management of genomic data:

ICH E18		   X    
Safety data collection:

ICH E19		   X    
Adaptative clinical trials:

ICH E20		   X    
MedDRA terminology:

ICH M1		   X    
Estudios de Seguridad
Preclínica:

ICH M3 (R2)		 X      
Common Technical Document:

ICH M4		 X X X X
Data elements and standards for drug dictionaries:

ICH M5		   X    
Gene therapy:

ICH M6		 X      
Mutagenic impurities:

ICH M7		 X      
Electronic common technical document:

ICH M8		 X      
Drug interaction studies:

ICH M12		   X    
         
PHARMACOPOEIA BASIC AND PRECLINICAL RESEARCH CLINICAL RESEARCH QUALITY/MANUFACTURING
OR PROCESSING		 COMMERCIALIZATION/
CLINICAL USE
European Pharmacopoeia     X  
US Pharmacopeia (USP)     X  
         
FDA REGULATION BASIC AND PRECLINICAL RESEARCH CLINICAL RESEARCH QUALITY/MANUFACTURING
OR PROCESSING		 COMMERCIALIZATION/
CLINICAL USE
Current Good Manufacturing Practice (CGMP) Regulations | FDA     X  
U.S. Department of Health and Human Services Food and Drug Administration Center for Biologics Evaluation and Research. Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Application   X X  
FDA Rules and Regulations | FDA   X    
         
DECLARATION OF HELSINKI  BASIC AND PRECLINICAL RESEARCH CLINICAL RESEARCH QUALITY/MANUFACTURING
OR PROCESSING		 COMMERCIALIZATION/
CLINICAL USE
World Medical Association Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects   X    
         
INFORMATIVE NOTES BASIC AND PRECLINICAL RESEARCH CLINICAL RESEARCH QUALITY/MANUFACTURING
OR PROCESSING		 COMMERCIALIZATION/
CLINICAL USE
Guidelines of the Spanish Agency for Medicines and Health Products
on the nomenclature of the active substances of advanced therapy
investigational medicinal products containing cells		 X X X X