On Wednesday, October 13, 2015, FDA released a draft guidance entitled “Recommendations for Microbial Vectors Used for Gene Therapy.” The document provides information and recommendations regarding the submission of microbial vectors for gene therapy (MVGTs) in early-phase clinical trials, and is intended to assist sponsors in the process of developing or submitting Investigational New Drug (IND) applications.
In a previous guidance on gene therapy clinical trials (from November 2006), FDA defined gene therapies as “[p]roducts that mediate their effects by transcription and/or translation of transferred genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or genetically engineered microorganisms. The products may be used to modify cells in vivo or transferred to cells ex vivo prior to administration to the recipient.” However, according to FDA’s statement in the recently released guidance, MVGTs meet the regulatory definition of a ‘biological product’, which the agency defines as a medical product that is “made from a variety of natural sources (human, animal, or microorganism). Like drugs, some biologics are intended to treat diseases and medical conditions. Other biologics are used to prevent or diagnose diseases.”
The guidance is focused around chemistry, manufacturing, and controls (CMC) information and, when finalized, will serve as a supplement to the April 2008 guidance entitled “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).” The document provides sponsors with information directly related to the submission of INDs for MVGTs, and provides “provides an overview of preclinical and clinical considerations for these products.”
The draft guidance provides sponsors with various related information, including:
Product Manufacturing & Characterization
- In order to help FDA assess the identity, quality, purity, and potency of the product, the Agency recommends that sponsors include a detailed description of the complete MVGT manufacturing process within IND submissions, including the following areas:
- Sponsors should provide adequate information about pharmacological and toxicological studies of the MVGT on the basis of which they have concluded that it is reasonably safe to conduct the proposed clinical trial. This information must be submitted in the IND (FDA recommendations provided on the selection of appropriate animal species and animal models of disease, as well as the overall design of preclinical proof-of-concept and toxicology studies for investigational products, including MVGT products, in previously issued guidance here). The guidance contains information on the following considerations of preclinical study design for MVGTs include:
- The following issues are unique to the study of MVGT products and can occur during clinical development and early clinical trial design:
- General Considerations
- Prior Human Experience
- Patient Population
- Starting Dose, Dose Escalation, and Dosing Schedule
- Treatment Modifications
FDA has released the draft guidance for the sole purpose of receiving feedback and comments from the industry before beginning to compose the final version. Comments can be submitted either electronically (here) or in writing, and must be done by December 14, 2015, 60 days from the announcement in the Federal Register.
For more details and information, view the full guidance here.
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