The U.S. Food and Drug Administration's (FDA) final guidance, Assessing the Effects of Significant Manufacturing Process Changes, including Emerging Technologies, on the Safety and Regulatory Status of Food Ingredients and Food Contact Substances, Including Food Ingredients that are Color Additives, outlines considerations for determining whether significant manufacturing process changes—including ones involving nanotechnology—impact the identity, safety, or regulatory status of a food substance already on the market. It also addresses whether food substances that are the subject of a food contact notification (FCN), a food additive or color additive regulation, or a generally recognized as safe (GRAS) determination warrant a new regulatory submission to FDA.
With respect to manufacturing process changes impacting a food contact substance (FCS) that is the subject of an FCN, FDA's recommendations to manufacturers on what issues to consider are fully consistent with the Agency's long-standing administrative guidance on FCNs regarding "substantive" changes to the identity of the FCS and/or its impurities. That is, FDA recommends that manufacturers take the following steps if an FCS undergoes a significant manufacturing process change:
- Determine what changes have been made to the identity of the FCS as a result of the manufacturing process change, including its physicochemical structure and properties, purity, and impurities;
- Conduct a safety assessment for the use of the FCS, including characteristic properties such as physicochemical structure and properties, purity, impurities, bioavailability, and toxicity;
- Consider whether the substance would remain within the scope of an effective FCN;
- If warranted, consult with FDA about the conclusions concerning the impact of the significant manufacturing change on the safety and regulatory status of the use of the FCS; and
- Make an appropriate regulatory submission to FDA, if necessary.
FDA's guidance notes that a change in the manufacturing process for an FCS to produce components in the nanometer scale that previously were not, or to increase the proportion of nanoscale components in the FCS may well be a "substantive" change that warrants the filing of a new FCN.
With respect to GRAS substances, FDA stated that currently, it is not aware of any food substances intentionally engineered on the nanometer scale for which there are generally available safety data sufficient to serve as the foundation for a determination that their use is GRAS.
The guidance recommends that manufacturers consult with the agency regarding a significant manufacturing process change for any food substances currently being marketed, even when they conclude that the change does not affect the substance's safety or regulatory status, particularly when the manufacturing process change involves emerging technologies, such as nanotechnology.