FDA Wants Genetic Products Evaluated for Environmental Hazards

Drugmakers seeking approval of genetically engineered products must begin submitting an assessment with their applications that evaluates whether they would be harmful if released into the environment.

The requirement, laid out in a final guidance, applies to gene therapies, vectored vaccines and related viral or microbial products.

The agency’s concern is with biological products that don’t occur naturally and whose risks are poorly understood. Environmental assessments should consider the degree to which a product’s effects on the environment are likely to be controversial, are highly uncertain or pose unique risks, or might adversely affect endangered species.

In such cases, the FDA will look to see that firms take steps to incapacitate potential pathogens in a product so that they can’t replicate, according to the guidance, which closely follows a June 2014 draft.

To determine if an environmental impact analysis is needed, sponsors need to first determine whether the substances occur naturally in the environment. If they do, such as genetically modified human cells, then an assessment is not needed, the FDA says.

If they are not naturally occurring, then the firm should do an environmental assessment. The analysis should include any metabolites, degradants or byproducts that could be released into the environment, as well as any potential genetic variants that might lead to unintended consequences and measures that might mitigate those risks, the FDA says.

Sponsors of genetically engineered products that have been killed or inactivated via a specific manufacturing step may qualify as naturally occurring, but companies must verify that they are harmless through process validation or lot release testing, the guidance says.

Examples of harmful effects include a product that is capable of transferring antibiotic-resistant genes to other bacteria. While the chance of this happening is small, the impact could be large if the antibiotic-resistant gene spread in the environment to the point that it undermined existing therapies, the agency says.

Sponsors are encouraged to discuss their specific situation with the agency early in development to determine the types of supporting data needed to support a BLA.

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