Frequently Asked Questions on Food Contact Notifications: Data Requirements
What information is needed in an FCN regarding polymerization aids used to make a polymer?
It is to be expected that FDA will require sufficient information on catalysts and other polymerization aids (initiators, chain terminators, chain transfer agents, and polymerization solvents, for example) to determine that the intended use of the aids does not make the finished polymer unsafe. This type of information generally was required by FDA to support Food Additive Petitions, at least in recent years. The specific data required on polymerization aids will vary from case to case.
Therefore, once a notification has become effective, changes in polymerization aids are permissible, in our opinion, without notice to FDA, as long as a change does not result "in substantive changes in the identity of the product or its impurities, and/or levels or impurities," in the language of FDA's FCN guidance.
In drafting the FCN, language describing the manufacturing process should provide latitude in using alternative polymerization aids.
What is the impact of a positive (adverse) genotoxicity result where there are other studies and data available to support safety?
There have been circumstances where FDA has allowed an FCN to become effective on a substance with a positive genotox result, but, before doing so, FDA will closely examine the weight of the evidence. A "positive" mutagenicity study may or may not trigger FDA's rejection of the submission, depending on the answers to a number of questions, such as: Are there countervailing genotoxicity studies with negative results? Are chronic studies available that clearly conclude the substance is not a carcinogen? What is the strength of the positive result? What does a structure activity analysis indicate? What is the exposure to the compound of interest? Is it the food-contact substance or merely a constituent of the FCS?
Will FDA accept studies conducted under non-GLP conditions?
Section 170.101(c) requires that all nonclinical laboratory studies be performed under good laboratory practices(GLPs). This provision applies to toxicology or biologically related studies that are indicated under Part 58 of the Food Additive Regulations, "Good laboratory practice for nonclinical laboratory studies." Under Part 58, the studies requiring such GLP attention are identified as in vivo or in vitro studies, but not studies to determine physical or chemical characteristics, i.e., not migration studies.
Section 170.101(c)(3) requires that any data from a toxicity study conducted after 1978, but not conducted in compliance with GLPs in accord with Part 58, must be validated by an independent third party prior to submission to FDA. This latter provision was not required by FDA in the petition process.
Will submission of genotoxicity studies be necessary for polymeric substances, in addition to starting monomers used to make the polymer (where exposure is between 0.5 ppb and 50 ppb)?
The agency has been quite flexible in these circumstances. In several instances, our clients have submitted the required genotoxicity studies on starting monomers, and where these raise no significant issues, FDA has not insisted on the full battery of genotox studies on the polymer per se.
FDA appears to agree with the scientific community that polymers and even oligomers do not pose significant toxicology concerns if their monomers have been tested satisfactorily.