Research and Innovation Resource

• Research and development,  European Medicines Agency (EMA)
  • guidance and support on scientific and regulatory information on how to design and run clinical trials, compliance standards, and obligations and incentives for developers of specialised medicines
• Cell-based therapy technology classifications and translational challenges    
• EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation 

Fundamental research

Discovery phase leading to Proof of concept

• Genome-Phenome Analysis Platform (GPAP) for rare disease research, RD‐Connect
  • Related projects and tools: 
    • Solve-RD solving the unsolved rare diseases 
    • NeurOmics for neuro-related disease  
    • EURenOmics project for rare kidney disease 
    • more bioinformatic tools  
• The European Genome-phenome Archive (EGA) 
  • archiving and sharing of all types of personally identifiable genetic and phenotypic data resulting from biomedical research projects 
• Tools & Data Resources, European Bioinformatics Institute
  • free tools and data resources for querying biological data resources  
• Tools and codes, Edinburgh Genome Foundry
  • software to support DNA design and assembly
  • git repo

Three major classes of viral vectors

• adenovirus (AD) (see: paper)  
• adeno-associated virus (AAV) (see: paper)   
• Lentivirus (see: paper)  

Gene editing tools

• Genome engineering with zinc-finger nucleases
  • Review paper on history of ZFN development, summarizes applications that have been made to genome editing in many different organisms and situations, limitations, and prospects.  
• TALENs: a widely applicable technology for targeted genome editing 
  • A review of transcription activator-like effector nucleases (TALENs), TALENs comprise a non-specific DNA-cleaving nuclease fused to a DNA-binding domain that can be engineered to target a specific DNA sequence. 
•  A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
  • Original Dounda and Charpentier CRISPR paper
• Multiplex Genome Engineering Using CRISPR/Cas Systems
  • Zhang’s group modified the CRISPR–Cas9 system to make precise genome cuts in human and mouse cells.
• Reviews: 
  • The next generation of CRISPR–Cas technologies and applications
    • A review of CRISPR (includes variations and technical aspects) and developments in preclinical and translational research.   
  • Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects
    • A review article covering the three gene editing platforms, on structures and mechanism, disease modeling, gene therapy, and clinical trials.

Pre-clinical model 

• Guide on advanced therapy medicinal products - Non-clinical development flowchart and checklist, European Medicines Agency (EMA) 
• Bridging between pre- and clinical, The Academy of Medical Sciences and The Association of the British Pharmaceutical Industry (ABPI) 
• UK Pre-clinical database and commentary, Cell and Gene Therapy Catapult (CGT Catapult)
• The Animals and medicines research booklet, The Association of the British Pharmaceutical Industry (ABPI) 
• Fundamental in Gene Vector Development, NHLBI Gene Therapy Resource Program (GTRP) 
  • This resource is based on a USA perspective 
• Pharmacology and Toxicology Education Information for Gene Therapy, The National Gene Vector Biorepository (NVGB)  
  • The overall objectives of Pharm/Tox studies is to:
    • help establish a safe clinical starting dose and dose escalation regimen
    • help define the risk-benefit ratio of the investigational gene therapy product
    • provide better scientific insight into the activity and potential toxicities following administration
  • This resource is based on a USA perspective

Good Laboratory Practice

• Good Laboratory Practice (GLP), European Medicines Agency (EMA)  
• Good Laboratory Practice (GLP) specific to ATMPs, European Medicines Agency (EMA)  

Non-clinical development (safety and efficacy studies)  

Research on existing collections of samples  

Biobanks

• EuroBioBank 
• UK Biobank
• The European Bank for induced pluripotent Stem Cells (EBiSC)
• European research infrastructure for biobanking (BBMRI-ERIC) network map

Registries

• Human Pluripotent Stem Cell Registry (hPSCreg)

Database for research 

• Database for clinical grade iPSCs, The Global Alliance for iPSC Therapies (GAiT)
  • currently under construction 
• Clinical research metadatabase repository, European Clinical Research Infrastructure Network (ECRIN)
  • free online tool to help researchers find documents and data linked to a clinical research study, and to obtain information on the accessibility of those results
• Search for data and samples, European research infrastructure for biobanking (BBMRI-ERIC)
• UK Biobank research analysis platform
• The European Genome-phenome Archive (EGA)
• RD-Connect online Genome-Phenome Analysis Platform  
• DECIPHER for the clinical community to share and compare phenotypic and genotypic data 

Research on new collections of samples

Manufacturing phase  

Good manufacturing practices 

Chemistry Manufacturing Controls (CMC) 

Clinical Research

• Guide on advanced therapy medicinal products - Clinical development flowchart, European Medicines Agency (EMA) 
• NIHR Clinical Trials Toolkit, National Institute for Health Research (NIHR)
  • It is an interactive colour-coded routemap to help navigate through the legal and good practice arrangements surrounding setting up and managing a Clinical Trial of an Investigational Medicinal Product (CTIMP) 
• ATMP Clinical Study guide, ATMP-Sweden

Clinical Trial 

• Guidance on clinical trials, The International Society for Stem Cell Research (ISSCR)
• Clinical Resource, The International Society for Stem Cell Research (ISSCR)
• Informed consent standard for stem Cell-Based Interventions and practical advice on stem cell-based clinical trials 
• Clinical research metadatabase repository, European Clinical Research Infrastructure Network (ECRIN)
  • free online tool to help researchers find documents and data linked to a clinical research study, and to obtain information on the accessibility of those results 
• Adaptive Platform Trial Toolbox, European Clinical Research Infrastructure Network (ECRIN)
  • a practical and guided toolbox to facilitate planning and conduct clinical trials
• Risk-Based Monitoring Toolbox for researchers, European Clinical Research Infrastructure Network (ECRIN)
• PedCRIN project, European Clinical Research Infrastructure Network (ECRIN)
  • on supporting the setup and the management of multinational neonatal and paediatric clinical trials in Europe
• ECRIN CAMPUS for information about clinical trial regulatory and ethical requirements covering 22 European countries  
• Clinical trial toolbox, Northern Alliance Advanced Therapies Treatment Centre (NA-ATTC)
  • contains organograms of key contacts within NA-ATTC clinical centres, costing guideline, local regulatory approval documentation, and map of clinical referral and treatment networks for exemplar products
  • This toolbox is based on UK context
• Guidance for Good Randomized Clinical Trials, Good Clinical Trials Collaborative (GCTC)
• Clinical Trial application timeline, Paul-Ehrlich-Institut   
• Clinical trials: types, designs and methods, Lung Cancer Europe (LuCE)
• Statistics in clinical trials, Lung Cancer Europe (LuCE)
• UK Clinical database and commentary, Cell and Gene Therapy Catapult (CGT Catapult
• Resource for rare disease research, European Joint Programme on Rare Diseases (EJP RD)
  • Mindmap for accessing EJP RD-coordinated data and services
• Clinical trial guidelines,The Association of the British Pharmaceutical Industry (ABPI) 
• Toolbox (Medicines R&D and Patient Engagement), European Patients’ Academy on Therapeutic Innovation (EUPATI) 
• Clinical trial training resource, NHLBI Gene Therapy Resource Program (GTRP)
  • This resource is based on a USA perspective

Good Clinical Practice

• Good Clinical Practice (GCP), European Medicines Agency (EMA)

Funding  

ATMP certification procedure by CAT  

• Certification procedures for micro-, small- and medium-sized enterprises (SMEs), European Medicines Agency (EMA)

Intellectual Property rights   

Patentability  

• Patenting ATMPs, ATMP-Sweden
• Guidance on IP terms and conditions, Association of Medical Research Charities (AMRC) 

Early interactions with regulators  

EMA- Innovation Task Force Briefing meetings

• EMA- Innovation Task Force 

EMA- Scientific advice and Protocol Assistance  

• EMA Scientific advice and Protocol Assistance  
• EMA and EATRIS Present: Scientific advice for advanced therapy medicinal products (ATMPs): what and when to ask, Webinar by EATRIS and EMA

Early support from national competent authorities 

Parallel advices (EMA/HTA, EMA/FDA) 

• Parallel advices (EMA/HTA)
• Parallel advices (EMA/FDA)
• EMA-EUnetHTA Parallel Consultation 
• To Seek or Not to Seek Parallel European Medicine Agency and Health Technology Assessment Scientific Advice? 
  • see diagram in figure 2. “Regulatory-HTA interface along the product life cycle”