TABLE 5.
Relevant regulatory guidelines applicable for gene editing technologies adapted from the Food and Drug Administration (FDA), US and the European Medicines Agency (EMA), EU.
| Guidance titles | Year published |
| Food and Drug Administration (FDA), USa | |
| Manufacturing Considerations for Licensed and Investigational Cellular and Gene Therapy Products During COVID-19 Public Health Emergency; Guidance for Industry | 2021 |
| Human Gene Therapy for Neurodegenerative Diseases; Draft Guidance for Industry | 2021 |
| Interpreting Sameness of Gene Therapy Products Under the Orphan Drug Regulations; Draft Guidance for Industry | 2020 |
| Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs); Guidance for Industry | 2020 |
| Long Term Follow-up After Administration of Human Gene Therapy Products; Guidance for Industry | 2020 |
| Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up; Guidance for Industry | 2020 |
| Human Gene Therapy for Hemophilia; Guidance for Industry | 2020 |
| Human Gene Therapy for Rare Diseases; Guidance for Industry | 2020 |
| Human Gene Therapy for Retinal Disorders; Guidance for Industry | 2020 |
| Evaluation of Devices Used with Regenerative Medicine Advanced Therapies; Guidance for Industry | 2019 |
| Expedited Programs for Regenerative Medicine Therapies for Serious Conditions; Guidance for Industry | 2019 |
| Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use; Guidance for Industry and Food and Drug Administration Staff | 2017 |
| Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; Guidance for Industry | 2017 |
| Deviation Reporting for Human Cells, Tissues, and Cellular and Tissue-Based Products Regulated Solely Under Section 361 of the Public Health Service Act and 21 CFR Part 1271; Guidance for Industry | 2017 |
| Recommendations for Microbial Vectors Used for Gene Therapy; Guidance for Industry | 2016 |
| Design and Analysis of Shedding Studies for Virus or Bacteria-Based Gene Therapy and Oncolytic Products; Guidance for Industry | 2015 |
| Considerations for the Design of Early Phase Clinical Trials of Cellular and Gene Therapy Products; Guidance for Industry | 2015 |
| Determining the Need for and Content of Environmental Assessments for Gene Therapies, Vectored Vaccines, and Related Recombinant Viral or Microbial Products; Guidance for Industry | 2015 |
| Guidance for Industry: BLA for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System | 2014 |
| IND Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic and Immunologic Reconstitution in Patients with Disorders Affecting the Hematopoietic System – Guidance for Industry and FDA Staff | 2014 |
| Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products | 2013 |
| Guidance for Industry: Preparation of IDEs and INDs for Products Intended to Repair or Replace Knee Cartilage | 2011 |
| Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines | 2011 |
| Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products | 2011 |
| Guidance for Industry: Cellular Therapy for Cardiac Disease | 2010 |
| Guidance for Industry: Considerations for Allogeneic Pancreatic Islet Cell Products | 2009 |
| Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs) | 2008 |
| Eligibility Determination for Donors of Human Cells, Tissues, and Cellular and Tissue-Based Products; Guidance for Industry | 2007 |
| Guidance for Industry: Guidance for Human Somatic Cell Therapy and Gene Therapy | 1998 |
| European Medicines Agency (EMA), EUb | |
| Questions and answers on comparability considerations for advanced therapy medicinal products (ATMP) | 2019 |
| Guideline on quality, non-clinical and clinical requirements for investigational advanced therapy medicinal products in clinical trials | 2019 |
| Quality, preclinical and clinical aspects of gene therapy medicinal products | 2018 |
| Management of clinical risks deriving from insertional mutagenesis | 2013 |
| Risk-based approach according to Annex I, part IV of Directive 2001/83/EC applied to Advanced Therapy Medicinal Products | 2013 |
| Design modifications of gene therapy medicinal products during development | 2012 |
| Quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells | 2012 |
| Creutzfeldt-Jakob disease and advanced therapy medicinal products | 2011 |
| Questions and answers on gene therapy | 2010 |
| Quality, non-clinical and clinical issues relating specifically to recombinant adeno-associated viral vectors | 2010 |
| ICH Considerations: oncolytic viruses | 2009 |
| ICH Considerations: general principles to address virus and vector shedding | 2009 |
| Follow-up of patients administered with gene therapy medicinal products | 2009 |
| Scientific requirements for the environmental risk assessment of gene-therapy medicinal products | 2008 |
| Non-clinical studies required before first clinical use of gene therapy medicinal products | 2008 |
| Guideline on safety and efficacy follow-up and risk management of advanced therapy medicinal products | 2008 |
| Non-clinical testing for inadvertent germline transmission of gene transfer vectors | 2006 |
| Development and manufacture of lentiviral vectors | 2005 |
aAdapted from FDA Cellular and Gene Therapy Guidances: https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/cellular-gene-therapy-guidances.
bAdapted from EMA Multidisciplinary: gene therapy: https://www.ema.europa.eu/en/human-regulatory/research-development/scientific-guidelines/multidisciplinary/multidisciplinary-gene-therapy.