FDA Details CMC Information for Gene Therapies With Microbial Vectors

The FDA is seeking feedback on the chemistry, manufacturing and controls information that it wants drugmakers to include in INDs for gene therapies containing microbial vectors.

Last week’s draft guidance recommends that firms using genetically modified bacteria such as salmonella, listeria or E. coli provide detailed information about the treatments’ composition and development process, including the vector’s seed stock history, genetic and physical makeup and growth properties, the guidance says. Microbial cell bank systems should be recorded and tested, with an in-depth focus on the master cell bank.

INDs should also include information on culturing steps and systems, any antibiotics and animal-derived products used, defrothing agents, cell growth and harvest conditions and monitoring, pH adjustments, ordered purification steps and overall timetables. All final harvests and drug formulas should be spelled out, including cell inactivation and killing with backed-up data, the FDA says.

The agency suggests stability testing through each step for all gene-therapy applications to evaluate the MVGT’s microbial independence, watching for invasive bacterial pathogens, environmental agents and — in early-phase trials when drug manufacturing shares laboratory space — any surrounding microbial products in development.

The FDA suggests creating specific risk-based clinical trial monitoring plans for MVGTs, focusing on the potential for vectors to germinate, regerminate or reseed. For early-phase clinical studies, monitoring for shedding of MVGTs is recommended, the agency says.

The guidance is meant to supplement the FDA’s 2008 Guidance for FDA Reviewers and Sponsors: Content and Review of Chemistry, Manufacturing, and Controls (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs).

Comments are due Dec. 13 to docket no. FDAi-2015-D-3399. Read the draft guidance here: www.fdanews.com/10-13-Gene-Therapy-Guidance.pdf. — Victoria Pelham