For the preparation of the notification dossiers by the applicants and their assessment by the advisory bodies and experts, a (non-exhaustive) list of useful guidelines developed by official bodies is listed below.
Because an increasing number of clinical trials with GMOs involve the use of advanced therapy medicinal products (ATMP), the European Commission created a FAQ, a repository of national regulatory requirements, and good practice documents which can be retrieved from the webpages dedicated to ATMP. These documents are endorsed by a large number of countries and aim at streamlining the information that needs to be provided in the context of (multi-centric) clinical trials. In particular, good practice documents have been developed for adeno-associated viral vectors (AAV) and human cells genetically modified by means of viral vectors.
The European Medicines Agency (EMA) has published several scientific guidelines to help applicants prepare marketing-authorisation applications for human medicines and veterinary medicines. Though less detailed or advanced experimental data may suffice depending on the stage of development of the investigational medicinal product and the scale of its release, these guidelines also serve as supporting tools for the clinical trials with GMOs.
Particularly in relation to the environmental risk assessment of GMO medicinal products the following guidelines (non-exhaustive list) can be of interest (links to the EMA website):
- Consideration document: General principles to address virus and vector shedding - 01/06/2009
- Guideline on scientific requirements for the environmental risk assessment of gene therapy medicinal products – 01/11/2008
- Guideline on environmental risk assessments for medicinal products consisting of, or containing, genetically modified organisms (GMOs) – 01/07/2007
- Guideline on environmental risk assessment of medicinal products for human use - 01/12/2006 - Currently under revision
- Guidance on environmental risk assessment for veterinary medicinal products consisting of or containing genetically modified organisms (GMOs) as or in products - 10/03/2006
The following guidelines, related to the quality, non-clinical and clinical aspects, may also be of interest (links to the EMA website):
Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products - 13/07/2018
- Guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells - 03/05/2012
- Guideline on quality, non-clinical and clinical aspects of live recombinant viral vectored vaccines – 10/08/2010
Reflection paper on quality, non-clinical and clinical issues relating specifically to recombinant adeno-associated viral vectors - 08/07/2010
- Guideline on live recombinant vector vaccines for veterinary use - 08/06/2005
- Guideline on development and manufacture of lentiviral vectors – 26/05/2005
The Biosafety and Biotechnology Unit (SBB) also issued scientific publications that are relevant to the biosafety assessment of GMO (investigational) medicinal products, in particular:
- A Baldo, E Galanis, F Tangy, P Herman (2016) Biosafety Considerations for Attenuated Measles Virus Vectors Used in Virotherapy and Vaccination. Human Vaccines & Immunotherapeutics. Published on line.
- A Leunda, A Baldo, M Goossens, K Huygen, P Herman, M Romano (2014) Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations. Vaccines 2(2):463-499
- F Lim, H Khalique, M Ventosa, A Baldo (2013) Biosafety of vectors derived from Herpes Simplex Virus Type 1. Current Gene Therapy 13(6): 478-491
- M Goossens, K Pauwels, N Willemarck, D Breyer (2013) Environmental risk assessement of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Current Gene Therapy 13(6): 413-420
- A Baldo, E van den Akker, H Bergmans, F Lim, K Pauwels (2013) General Considerations on the Biosafety of Virus-derived Vectors Used in Gene Therapy and Vaccination. Current Gene Therapy 13(6): 385-394
- C Verheust, M Goossens, K Pauwels, D Breyer (2012) Biosafety aspects of Modified Vaccinia Virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Vaccine 30(16):2623-2632
- K Pauwels, R Gijsbers, J Toelen, A Schambach, K Willard-Gallo, C Verheust, Z Debyser, P Herman (2009) State-of-the-art lentiviral vectors for research use: Risk assessment and biosafety recommendations. Current Gene Therapy 9(6):459-474