Document type	Guide & Procedure
Subject	Regulatory & Legal Aspect ; Human Health
Application/Product	Food

This document provides guidance to manufacturers of food ingredients and food contact substances (FCSs), and end users of food ingredients and FCSs, including food ingredients that are color additives. In the remainder of this document, we use the term “food substance” as a general term addressing food ingredients and FCSs.
This guidance is intended to describe the factors you should consider when determining whether a significant change in manufacturing process for a food substance already in the market:
- Affects the identity of the food substance;
- Affects the safety of the use of the food substance;
- Affects the regulatory status of the use of the food substance; and
- Warrants a regulatory submission to FDA.
As with all food substances, this guidance also is intended to recommend that you consult with us regarding a significant change in manufacturing process for a food substance already in the market, irrespective of your conclusion about whether that change affects the safety or regulatory status of the food substance. It is prudent practice for you to do so, particularly when the change in manufacturing process involves emerging technology.
The discussions and recommendations in this guidance document regarding appropriate pathways to gain premarket review by FDA may also be applicable to new uses of food substances.

I. Introduction

II. Regulatory Framework for Food Substances
A. Industry’s Responsibility Regarding the Safe and Lawful Use of Food Substances
B. Food Additive Provisions of the Act
C. Color Additive Provisions of the Act

III. Safety Assessment of a Food Substance
A. Identity
B. Technical Effect
C. Self-limiting Levels of Use
D. Safety Studies
E. Manufacturing Process, including Nanotechnology

IV. Discussion
A. Considerations for Assessing the Impact of a Significant Manufacturing Process Change on the Safety and Regulatory Status of a Food Substance
B. Recommendations

V. References

Appendix 1. Examples of FDA’s Previous Consideration of Changes in Manufacturing Process
A. Carrageenan (21 CFR 172.620)
B. Xanthan Gum (21 CFR 172.695 and GRAS Notice No. GRN 000121)
C. Tartaric Acid (21 CFR 184.1099 and GRAS Notice No. GRN 000187)

Appendix 2. Descriptions of the Principal Regulatory Submissions for Food Substances
A. Petition Process for Premarket Approval of a Food Additive
B. Premarket Notification Program for a Food Contact Substance
C. “Threshold of Regulation” Program for a Substance Used in a Food Contact Article
D. Program to Notify FDA of a Determination that a Use of a Substance is Generally Recognized as Safe
E. Petition Process for Listing a Color Additive

Guide & Procedure (2012)