FDA Guide for Microbial Vectors used for Gene Therapy

In October, FDA's Center for Biologics Evaluation and Research (CBER) published a draft guideline dealing with the authority's recommendations concerning microbial vectors for the production of gene therapy medicinal products. After its adoption, the new guide entitled "Recommendations for Microbial Vectors used for Gene Therapy" will complement the current guide "Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)".

Nowadays, bacterial vectors such as Salmonella, Listeria or E. coli are genetically modified to express therapeutically relevant compounds like tumour antigens, cytokines, growth factors, therapeutic proteins, etc. for example, such vectors are generated by the modification of chromosomal or episomal genes and the insertion of foreign genetic information. This may also lead to modifications in the therapeutic profile or in the growth characteristics of the organisms.

Now with the new document, the FDA wants to give recommendations to the developing companies and institutions, the investigational new drug application (IND) sponsors, about the information needed with regard to the characteristics, production and control of such microorganisms (Microbial Vectors used for Gene Therapy - MVGTs) for the submission of an IND. Moreover, the document gives an overview of preclinical and clinical aspects.

The guide is composed of the following sections:

PRODUCT MANUFACTURING AND CHARACTERIZATION

• Product Manufacturing – Components
• Product Manufacturing – Procedures
• Product Testing
• Drug Substance
• Drug Product
• Stability Testing
• Additional Testing

PRECLINICAL STUDIES

• Animal Species and Models
• Safety Evaluation
• Attenuation Evaluation
• Biodistribution/ Shedding
• Antibiotic Use

CLINICAL STUDIES

• General Considerations
• Prior Human Experience
• Patient Population
• Starting Dose, Dose Escalation, and Dosing Schedule
• Treatment Modifications
• Monitoring

For more details, please read the complete guidance draft "Recommendations for Microbial Vectors used for Gene Therapy".