Frequently Asked Questions on Food Contact Notifications
A Brief Tutorial on the U.S. Food Contact Notification System
As the U.S. Food and Drug Administration's Food Contact Notification (FCN) system has reached twenty-one years of operation, a step back to review the program is fitting. Since January 2000, the FCN program has been the principal instrument by which FDA has cleared “food additives” that qualify as “food contact substances.” Our response to “frequently asked questions” below addresses both basic information for the newcomer to the program, as well as some of our insights into the particularities of FDA’s implementation of the FCN system. Keller and Heckman, as one of the leading proponents for the FCN system when first considered by Congress in the mid-1990s, as well as serving as legal counsel for the preparation and submission of more successful FCNs than any other single entity over the program’s history, has had a ring-side seat into FDA’s evolving thinking on implementation of the Food Contact Notification process.
What is the Food Contact Notification program?
The Food and Drug Administration Modernization Act of 1997, which was enacted in 1997, amended the Federal Food, Drug, and Cosmetic Act to provide, inter alia, for the submission of notifications for food contact substances in lieu of Food Additive Petitions and Threshold of Regulation submissions. FDA began actual operation of the FCN program in early 2000, converting a backlog of several pending food additive petitions into FCNs.
Under the FCN program, a manufacturer or supplier of a food contact material may submit an FCN to FDA providing the chemical identity and use of a new food contact substance (FCS), along with information supporting the conclusion that the substance is safe for the intended use.
Is FDA required to respond to an FCN within a certain time frame?
If, after receipt of a complete filing, FDA does not object within 120 days to the substance’s use based on safety grounds, in writing, the submitter and its customers may legally market the substance for the uses set forth in the notification. The FCN is effective on Day 121.
If FDA finds an FCN submission to be “incomplete,” it will send a letter to the notifier asking for data that it views as critical to the determination of whether the particular substance is appropriate for use in the intended food contact application. FDA colloquially refers to these missives as “deficiency letters.”
Who may rely on an FCN?
Unlike Food Additive Petitions, notifications are proprietary and may be relied upon only by the listed manufacturer/supplier and its customers. Note that the statutory language that created the FCN program makes the notification effective for the listed “manufacturer/supplier,” not the listed “notifier” if this entity is different. FDA’s guidance document makes it clear, however, that a company that supplies a substance to itself may be considered a “supplier” and may submit a notification for a substance that they do not, in fact, manufacture.
Are the existing Food Additive Regulations and Threshold of Regulation exemption letters still valid?
Most definitely. FDA’s Food Additive Regulations and Threshold of Regulation letters remain effective, unless and until revoked by FDA. However, expansions of existing clearances in most cases will be obtained through the FCN process.
How many substances can a single FCN cover?
Aside from original FCNs, which were allowed to become effective in place of existing petitions, FDA usually permits an FCN to cover only one FCS. If a company is interested in using a product that contains more than one uncleared substance, a separate FCN must be filed for each uncleared FCS. Not all components of an FCS, however, require separate FDA clearances (e.g., substances needed to make a basic resin, such as catalysts); the question of which components need clearance is addressed by FDA on a case-by-case basis.
Further, it may be possible to obtain a single FCN for a class of polymers that are closely related.
“Formulation FCNs” are addressed separately (see below) and presume existing clearances for all components of the formulation as a prerequisite to consideration by the Agency.
What types of data are required for FCN filings?
FCNs must contain sufficient scientific information and data to demonstrate that the FCS is safe, which FDA defines as a “reasonable certainty of no harm” and is the safety standard that FDA applies to all food additives. This same safety standard was used in the original petitioning process for food contact materials. The requirements for an FCN are substantially similar to those for a Food Additive Petition. Generally speaking, the notification should include information on:
- The chemical identity of the FCS and its impurities and residual reactants from the production of the FCS, including the chemical and structural formulas and CAS Registry Numbers;
- A robust description of the manufacturing process for the substance, including manufacturing specifications used to ensure consistency in the process;
- The FCS’s intended conditions of use;
- The quantity and identity of substances likely to become components of foods under the intended use conditions;
- An estimate of the concentration of the additive in the daily diet;
- Toxicology data demonstrating the safety of this intake level; and
- An environmental assessment (in some instances)
Submitters must calculate the cumulative estimated dietary intake (CEDI) of potential migrants from all sources, not just the product in question, and provide supporting toxicity studies for substances with cumulative exposures above 0.5 ppb in the diet.
How detailed must the manufacturing process description be?
FDA’s guidance documents indicate that notifiers must include a complete description of the manufacturing process used to make an FCS, including purification steps, as well as the chemical equations for all stages of the synthesis of the FCS. FDA expects the manufacturing process to include a list of reagents, solvents, catalysts, purification aids, etc., the amounts or concentrations used, the intended function of each substance, and their CAS Registry Nos. FDA requires this level of detail so that it may ensure that the resulting exposure to all impurities of the FCS are safe. In the case of polymers, FDA expects to receive details on the concentrations of residual monomers in the polymer of interest, together with validation data supporting these levels. Where such information is missing, FDA will likely request these details in a “deficiency letter.”
What types of toxicity data must be submitted?
In general, where the cumulative dietary concentration:
- Is below 0.5 ppb? - no toxicity data need be generated, but all available toxicity data that is relevant must be submitted;
- Is between 0.5 ppb and 50 ppb? - two genotoxicity studies (a bacterial mutagenicity assay plus an in vitro cytogenetic damage or mouse lymphoma assay) must be submitted;
- Exceeds 50 ppb but is below 1 ppm? - a third genotoxicity study (in addition to the two noted above) in the form of an in vivo chromosomal aberration study is required, as are two subchronic studies (two different species);
- Is in excess of 1 ppm? - a full range of toxicity studies is generally required, including chronic (two-year) toxicity/carcinogenicity studies in rats and mice, a one-year feeding study in dogs, and multigeneration reproductive studies in rats.
Where cumulative dietary exposure exceeds this 1 ppm level, FDA may request the filing of a Food Additive Petition instead of an FCN. A Notifier may find it helpful to consult with FDA prior to commencing subchronic or chronic studies to support an FCN.
Are food contact materials used to prepare, package, or serve food to infants handled differently than such materials for the general consumer?
Yes. Beginning in 2013, FDA began regularly imposing limitations on uses of a food contact material with infant food, ingredients, and breast milk unless specifically addressed in an FCN submission. At that time, the Agency publicly indicated that, due to differing body weights and food consumption patterns, the potential dietary exposure of an infant to a particular food contact substance is likely to be significantly different than the exposure for an adult consumer to the same substance. Therefore, to account for these differing exposures (and the potential for different toxicology data requirements associated with the same), the Agency began imposing limitations on the permitted uses of food contact substances when infant uses were not specifically addressed in the FCN.
What data is necessary to cover infant food contact applications?
In 2019, FDA issued a separate guidance document regarding the preparation of FCNs for food contact substances that are intended to come into contact with infant formula -- both liquid (concentrates and ready to feed) and powdered formula -- and/or human milk. FDA noted that the types of food contact substances that are covered by the guidance include materials used in packaging infant formula, as well as materials used to manufacture baby bottles, bottle inserts, and nipples. The guidance contains detailed chemistry, toxicology, and administrative recommendations for preparing and submitting FCNs for substances intended to contact infant food.
“Preparation of Food Contact Notifications for Food Contact Substances in Contact with Infant Formula and/or Human Milk: Guidance for Industry” (May 2019)
Can an FCN still be filed that does not cover use with infant food contact applications?
Yes. Although guidance concerning these infant applications is now available, Notifiers may elect to file an FCN without considering the potential infant exposures if limitations concerning such uses are acceptable to the Notifier.
When infant exposures are not specifically addressed in an FCN filing, FDA currently includes the following language in the “Limitations/Specifications” of the FCN clearance language:
The FCS is not for use in contact with infant formula and human milk. Such uses were not included as part of the intended use of the substance in the FCN.
When is environmental impact assessment required?
FDA requires submitters to include an analysis of the potential environmental impacts resulting from the use and disposal of the food contact substance. Impacts related to use of the FCS may include sites of production of food contact materials and articles that will utilize the FCS if there is potential for the environmental release of the FCS at that site. Any environmental impacts concerning the production of the food contact substance, per se, are outside the scope of the Environmental Assessment (EA); for example, FDA does not require details regarding compliance with air or water permits for production of the FCS.
FDA has adopted categorical exclusions from the need to file an EA for substances that are 5% or less of finished articles by weight (if that article is a food packaging material), components of coatings, and components of repeated-use articles. Although FDA has, in the past, considered substances that are used at 5% or less in food contact articles generally to be categorically exempt from the need to file an EA, FDA’s current interpretation of the regulatory language addressing categorical exclusions is that this particular categorical exclusion applies only to additives used in food packaging materials and not all food contact substances generally.
Where can I find more information about data requirements?
Details regarding FDA’s data requirements can be found in FDA’s guidance documents implementing the FCN program, available on FDA’s Web page as follows:
“Guidance for Industry, Preparation of Premarket Notifications for Food Contact Substances: Chemistry Recommendations” (made final, April 2002, updated December 2007)
“Guidance for Industry, Preparation of Premarket Notifications for Food Contact Substances: Toxicology Recommendations” (April 2002)
“Guidance for Industry, Preparation of Premarket Notifications for Food Contact Substances: Administrative” (June 2000, updated May 2002)
“Preparation of Food Contact Notifications for Food Contact Substances in Contact with Infant Formula and/or Human Milk: Guidance for Industry” (May 2019)
FORM 3480, FORM 3479, and FOOD MASTER FILES
What is Form 3480?
Form 3480 is the U.S. government form that summarizes the basic data found in the FCN. FDA’s regulations specify that this form is a required element of an FCN, which must be used by notifiers.
What are Food Master Files?
Food Master Files are a means to submit information directly to the Agency to support review of an FCN. Typically, this might be manufacturing information or the impurity profile of an FCS supplied by a different company than the notifier, where the manufacturer of the substance is not willing to share such information directly with the notifier filing the FCN. Note, although an FMF is one step removed from the FCN, there is no presumption of confidentiality for the information in an FMF. Namely, all information in an FMF is subject to the same government disclosure obligations found in FDA’s Freedom of Information Act requirements. More on this below.
What are the logistics of relying on a Food Master File?
Typically, an FMF holder will authorize the Notifier to reference the FMF in an FCN submission. This letter of authorization is included in the FCN submission.
Are Food Master Files confidential?
Maybe, maybe not. Importantly, as stated above, no presumption of confidentiality exists with the contents of an FMF. FDA will follow its Freedom of Information Act regulations at 21 CFR Part 20 (Public information) in determining whether specific information in an FMF is confidential, and is subject to release under the FOIA, or not. In other words, information considered essential to the identity and safety of the FCS will be disclosed to the public, even if submitted to FDA in an FMF. Confidential business information and trade secrets will not be disclosed under FDA’s FOIA requirements.
How are formulations addressed?
FDA accepts notifications for “FCS formulations” if and only if all of the formulation’s components are already explicitly cleared for the intended application. See 21 CFR § 170.106(a). A special form – Form 3479 – is used for such submissions. Of course, a form 3479 submission is not literally required under the law, as all components of the blend are ostensibly already cleared for the application at hand. Furthermore, the submissions are relatively stream-lined (and frankly rare). Since the formulation represents a mixture of already cleared substances, FDA’s review is limited to assessing whether the clearance status of each component has been adequately supported – no new safety review is conducted. Additionally, FDA has stated that the statutory 120-day review period does not apply to formulation FCNs because the process is optional and not mandated by federal law.
What are Pre-Notification Consultations?
Pre-notification Consultations (PNCs) are a mechanism to seek FDA’s advice or input on any issue prior to filing an FCN – the testing conditions, the toxicity data needed, the current cumulative dietary intake to a substance, the assigned Acceptable Daily Intake to a substance, to name a few examples.
By going to FDA with certain questions first, this can sometimes help to avoid questions during review that might lead to FCN withdrawal later. This said, FDA is under no obligation to respond to a PNC within a particular time frame. It ultimately may be more efficient to proceed directly with an FCN and forego seeking FDA’s prior input on an issue. The risk of receipt of a “deficiency letter” versus delays in an FDA response to a PNC must be weighed.
FDA assigns “PNC” numbers to any submissions to the Agency for tracking purposes, even if not in anticipation of a future FCN.
Furthermore, any information obtained during a PNC with FDA staff only represent the staff’s current thinking on a particular matter at the time of the consultation, is subject to change over time, and is never legally binding on the Agency.
When is an FCN submission considered accepted by FDA?
FDA conducts “initial” reviews of FCNs (which currently take six to eight weeks from receipt of the filing) to determine whether any basic information is missing, and will request additional information by email and accompanying letter. If the request for simple, clarifying information is answered in a satisfactory way, typically within ten business days, then FDA will issue a letter acknowledging receipt of the FCN, with the 120-day period ordinarily running from the original date of receipt. On occasion, however, FDA has issued acknowledgment letters only a few weeks in advance of the effective date of the notification. Receipt of an acknowledgment letter is certainly a very good sign that the FCN is well on its way to a positive result, but FDA may still ask substantive questions at any point prior to the 120-day mark.
What if FDA asks for more data?
FDA may request new, substantive data to bolster the original filing’s data package. If FDA’s request is met within the ten-day timeframe, FDA may, even so, determine to “re-start” the FCN review clock where the data submitted is not merely clarifying, but is instead substantive.
If supplemental information cannot be provided quickly, the FCN will need to be withdrawn or FDA will send a letter refusing to accept the FCN for filing. The FCN notifier also may choose to leave an FCN pending to draw a formal objection from FDA. This will set the stage for judicial review of FDA’s decision.
Where will FDA publish effective notifications?
Effective notifications are listed on the Agency’s Web site. No other publication is provided.
Will FDA issue a written letter indicating that the FCN is effective?
FDA currently sends such letters identifying the notification, including a description of the substance and any limits on its intended conditions of use, and the date on which the notification became effective.
FDA is not under a statutory mandate to issue such letters; however, the Agency has indicated that it plans to continue providing these “Effective” letters unless the administrative burden in sending them becomes too great.
WHO CAN RELY ON AN FCN?
Does an effective FCN grant an exclusive proprietary right?
One feature of an FCN that differs from a Food Additive Petition is the proprietary nature of an FCN. Namely, an FCN is proprietary to the listed manufacturer/notifier, and may be relied upon by the manufacturer/supplier and its customers.
Unlike a patent or trademark, however, a manufacturer/supplier’s proprietary right to an effective FCN is not necessarily truly exclusive. Another party or competitor can submit an FCN to FDA for the same substance and, provided FDA does not object, obtain its own notification after the requisite 120-day review period. But until this “Me-Too” FCN (our term, not FDA’s) is filed and effective, the original FCN is proprietary to the listed manufacturer/notifier and its customers.
The FCN process can be repeated multiple times by anyone who collects and submits adequate chemistry and toxicology data demonstrating that the substance is safe. A subsequent notifier can obtain and rely on the non-confidential data submitted by previous notifiers – including migration and toxicology data.
Can a notifier transfer or assign its FCN to a third party?
In the event of the sale of a business, a change in corporate control, or a change in the name of the notifying company, the company should be able to transfer an FCN to the successor organization simply by informing FDA of the change and providing authoritative documentation of the legal basis for the transfer.
Nothing in the statute or in FDA’s implementing regulations provides that a notification can be assigned or transferred to a competitor absent a sale of the business or technology. Certainly, a competitor can rely on the data the original notifier has submitted to file its own FCN and prove the safety of the competing product if it can show that the characteristics of its product are the same.
Can a notifier’s proprietary right to an FCN expire?
FDA has the power to rescind an FCN if, at any time after the FCN becomes effective, FDA becomes aware of information calling into question the safety of the FCS.
To consider an FCN to be no longer effective, FDA must follow a process in its regulations (i.e., 21 C.F.R. Section 170.105) that provides the notifier an opportunity to respond to FDA’s safety concerns. If the notifier cannot adequately respond to the Agency’s concerns, the regulation calls for FDA to publish a notice in the Federal Register indicating that the notification is no longer effective. This action is considered final agency action that is subject to judicial review.
AFTER THE FCN IS EFFECTIVE. . .
What if changes are made to an FCN? For example, what if a manufacturer makes changes to a Food Contact Substance’s manufacturing process?
FDA states in its Administrative Guidance document for FCNs that a new notification should be submitted “if changes are made in the manufacturing method that result in substantive changes in the identity of the product or its impurities, and/or level of impurities.” In addition, the Agency states in its letters to notifiers announcing the date that a notification will become effective that the notifier should inform FDA of any modification in the food contact substance limitations/specifications or any alteration to the manufacturing process that would result in a change in the impurities of the food contact substance.