The latest version of this guidance issued on May 21, 2002. Below is an earlier version.

Guidance for Industry
Preparation of Premarket Notifications for Food Contact Substances: Administrative

Additional copies are available from:
Office of Premarket Approval (OPA), HFS-215
Center for Food Safety & Applied Nutrition (CFSAN)
Food and Drug Administration (FDA)
200 C. St., SW.
Washington, DC 20204
(Tel) 202-418-3080
(See updated contact information.)

U. S. Department of Health and Human Services
Food and Drug Administration
Center for Food Safety and Applied Nutrition (CFSAN)
June 2000

Table Of Contents

1. Introduction

2. Scope of the PMN Program

1. Who May Notify

2. Uses of substances that may be the subject of a PMN

3. Uses of substances that should not be the subject of a PMN

4. Simultaneous submission of a food additive petition and a PMN

5. Scope of an effective premarket notification

6. Fiscal Requirements

3. Format of a PMN for an FCS

4. Electronic submissions

5. Disclosability of information in a PMN

6. FDA response to a PMN

1. Acknowledgment of a PMN

2. Nonacceptance of a PMN

3. Objection by FDA

4. Final letter

5. Inventory of effective PMNs

7. Withdrawal without prejudice

8. Determination that a premarket notification is no longer effective

9. Conversion of existing food additive petitions and threshold of regulation requests

10. Presubmission meetings

11. Inquiries concerning FCSs

1. Identity

2. Use level and conditions of use

3. Appropriate regulation, exemption, or notification

12. Format of a PMN for a Food Contact Substance Formulation

• FDA FORM 3480


• FDA FORM 3479


• INTERIM Guidance for Preparing an Environmental Assessment
1. For uses specified under categorical exclusion 21 CFR 25.32(i), (j), (k), (q) and (r).
2. For uses not covered above.

1. Introduction

   Section 309 of the Food and Drug Administration Modernization Act of 1997 (FDAMA) amends Section 409 of the Federal Food, Drug, and Cosmetic Act (FFDCA) (21 U.S.C. 348) to establish a premarket notification (PMN) procedure as the primary method by which the Food and Drug Administration (FDA) regulates food additives that are food contact substances (FCSs). An FCS is any substance that is intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use of the substance is not intended to have any technical effect in such food.

   Notifications for an FCS must contain sufficient scientific information to demonstrate that the substance that is the subject of the notification is safe for the intended use (21 U.S.C 348(h)(1)). Because the safety standard is the same for all food additives, whether subject to the petition process or the PMN process, information in a PMN should be comparable to that recommended for inclusion in a food additive petition.

   This guidance has been prepared by the Office of Premarket Approval of the Center for Food Safety and Applied Nutrition (CFSAN) at the Food and Drug Administration in accordance with FDA's "Good Guidance Practices" (62 FR 8961; Feb. 27, 1997). The purpose of this document is to provide general guidance for the format and content of information that should be included in a PMN for an FCS. This guidance represents FDA's current thinking on the format and content of information for a PMN. It does not create or confer any rights for or on any person and does not operate to bind the Agency or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute and regulations. For situations not addressed in this guidance, notifiers are advised to consult FDA. Periodically, FDA will update this guidance in light of new information.

   
   

2. Scope of the PMN Program

   1. Who May Notify

      Anyone may submit to FDA a notification for a new use of an FCS. However, a notification for an FCS will be "effective" only for the manufacturer(s) identified in the notification. (See II.E.1.)

   2. Uses of FCSs that may be the subject of a PMN

      Only "food contact substances" that are food additives require premarket authorization by FDA. An FCS is defined as any substance that is intended for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food if such use is not intended to have any technical effect in such food (21 U.S.C. 348(h)(6)). FDA believes that the definition of an FCS encompasses a broader range of substances used in contact with food than those that have been regulated as food additives. For example, FDA believes that a substance that is GRAS or prior sanctioned for its intended use in contact with food may also be an FCS, and may be the subject of a PMN, even though authorization under the PMN process is not required for the FCS use.

      1. Food additives that are FCSs

         In the past, FDA has informally characterized a food additive as being a "direct additive" if it was intended to have a technical effect in food, a "secondary direct additive" if it was intended to have a technical effect on food during food processing but not in the finished food as consumed, or an "indirect additive" if it was intended to have a technical effect in a food contact material. Even though each of these types of food additives is regulated in a separate section of Title 21 of the Code of Federal Regulations (i.e., direct food additives are listed in 21 CFR Part 172, secondary direct food additives are listed in 21 CFR Part 173, and indirect food additives are listed in 21 CFR Parts 175-178), no definitions for direct, secondary direct, or indirect food additive exist in the codified regulations or the statute. PMNs will be accepted for unapproved uses of food additives that meet the definition of an FCS regardless of the location in the Code of Federal Regulations of any related codified listing regulation. FDA expects that most PMNs will be submitted for the use of substances that are intended to have a technical effect in food contact materials (so-called indirect additives). However, FDA also expects some substances that are intended to have a technical effect in food during processing (processing aids) but not in the finished food may also be the subject of a PMN.

      2. Other FCSs

         FCSs that may be the subject of a PMN but that are not food additives include substances that are GRAS or prior sanctioned for their intended use, substances that, under their intended conditions of use may contact food but are not reasonably expected to migrate to food, and substances that FDA has historically considered constituents of food additives. FDA recognizes that accepting a PMN for an FCS that is not a food additive under its intended conditions of use may be valuable in clarifying the conditions of safe use for the FCS. Therefore, FDA expects to accept PMNs for FCSs that are not food additives under the intended conditions of use that are the subject of the notification. FDA recommends that potential notifiers for the use of such substances consult with the Agency prior to the submission of a PMN in order to ensure that the safety of the FCS is adequately addressed in the PMN.

      3. Notifications requiring FDA consent

         Section II.C.2. lists circumstances in which the Agency currently does not believe a PMN is appropriate but that a petition would be required. However, there may be some situations in which a petition would not be required even if one or both of the circumstances in Section II.C.2. are met (proposed 21 CFR 170.100(c)). For example, FDA may determine that a notification is appropriate for an FCS even if the cumulative estimated dietary intake (CEDI) is >1 ppm. The following are examples of four situations where FDA expects that a notification would be appropriate even if the cumulative estimated dietary intake is > 1 ppm.

         1. ) There is an existing acceptable daily intake (ADI) for the FCS and its constituent(s). In such case, the notifier should contact the Agency to determine the applicability of the ADI for the cumulative dietary concentration of the FCS, before submitting a PMN. FDA expects to make publicly available on its internet site http://www.cfsan.fda.gov a database of ADIs and CEDIs for regulated, exempted, and notified FCSs to assist potential notifiers in preparing notifications and petitions for FCSs.
         2. ) A large database is available on close structural analogs of the FCS and its constituent(s), and the analogs have been regulated by the Agency. In such cases, the following toxicological tests are recommended to demonstrate the degree of toxicological and metabolic similarity between the FDA-regulated analogs and the FCS and its constituent(s): a subchronic oral toxicity study in a rodent or non-rodent species and comparative absorption, distribution, metabolism, and elimination studies.
         3. ) The FCS and/or its constituent(s) is poorly absorbed or is not absorbed from the gastrointestinal tract (e.g., the substance is a high molecular weight polymer or is a highly charged substance at gastric pH). Such assertions should be supported by relevant scientific information or data.
         4. ) The FCS undergoes chemical or metabolic transformation solely to products known to be of little toxicological concern at the estimated level of cumulative dietary concentration. Such assertions should be supported by relevant in vivo or in vitro data.

         FDA recommends that, prior to submission to the Agency, potential notifiers discuss any other scientific bases for FDA to accept a notification rather than a food additive petition.

      4. Notification for a mixture of FCSs

         FDA believes that there are two types of mixtures of FCSs that may be the subject of a notification. The first type of mixture is an FCS formulation where all the FCSs in the mixture may be legally marketed for their intended use. Notifications for these formulations are discussed further in Section XII. The second type of mixture is a mixture containing one or more FCSs that may not be legally marketed for their intended use at the time FDA receives the notification for the mixture because one or more of the FCSs are unapproved food additives. FDA believes that a notification for a mixture of FCSs containing only a single new FCS or a single new use of a lawful FCS may be submitted under section 409(h) of the act. A notification for a mixture of FCSs containing one or more new FCSs would be comparable to a FAP for the use of an indirect food additive in combination with a particular polymer or other food contact material. In this case, the types of polymers with which a petitioned substance is regulated for use represent a limitation on the conditions of use for which the petitioned substance is authorized. Therefore, FDA currently believes that the conditions of use for an FCS that is the subject of a PMN could include detailed specifications on the other FCSs that may be used in combination with the notified FCS. FDA is concerned that it could be burdensome for FDA to review within 120 days a notification for more than one new FCS. Thus, FDA believes that a separate notification should be submitted for each new FCS in this second type of mixture. In other words, a mixture containing two or more unauthorized FCSs should be the subject of two or more companion notifications. FDA believes that this approach will permit the Agency to better manage its resources and its statutory obligations concerning the review of notifications for FCSs.

         When a food additive petition for an FCS is submitted without prior consultation with the Agency, FDA will conduct a prefiling review of the petition to determine whether the petitioned use should instead be the subject of a PMN. If so, FDA will not file the petition and will so notify the petitioner.

   3. Uses of substances that should not be the subject of a PMN

      1. Regulated and exempted uses

         In accordance with proposed 21 CFR 170.100(b), FDA will prohibit the submission of a PMN for any use of an FCS that is already permitted by a regulation in 21 CFR Parts 173 through 186, or that is the subject of an exemption under 21 CFR 170.39.

      2. Uses for which a petition is required

         Section 409(h)(3)(A) of the act states that the PMN process shall be utilized for authorizing the marketing of an FCS except where FDA determines that the submission of a food additive petition is necessary to provide adequate assurance of safety. Section 409(h)(3)(B) authorizes, but does not require, FDA to promulgate regulations describing those circumstances in which a food additive petition would be required prior to marketing an FCS. In making this determination, section 409 of the act states that FDA should consider criteria such as probable consumption and potential toxicity.

         Under proposed 21 CFR 170.100(c), FDA would require the submission of a petition in either of the following situations: 1) When the use of the FCS will increase the cumulative estimated daily intake (CEDI) of the FCS from both food and food-contact uses to a level greater than 1 part per million (ppm) (i.e., 3 mg/person/day) or, in the case of a biocide, to a level greater than 200 parts per billion (ppb) (i.e., 0.6 mg/person/day), or 2) When existing data include one or more bioassays on the FCS that the Agency has not already reviewed and such studies are not clearly negative for carcinogenicity.

      3. Agreement that a petition may be submitted

         Under section 409(h)(3)(A), FDA and a notifier may agree that a petition may be submitted to authorize the use of an FCS. If a notification was submitted prior to this agreement, the notification shall be deemed to be withdrawn in accordance with proposed § 170.103. FDA recommends that persons wishing to submit a petition contact the Agency prior to making such a submission to obtain FDA's agreement. Under proposed § 171.1(i)(1)(c), FDA will decline to file a food additive petition for a use of an FCS that the Agency believes should be the subject of a PMN.

   4. Simultaneous submission of a food additive petition and a PMN

      Section 409(h)(3)(A) of the act states that the notification process shall be utilized for authorizing the marketing of FCSs except where FDA determines that submission and review of a food additive petition is necessary to provide adequate assurance of safety, or where FDA and a sponsor agree that a petition may be submitted. Therefore, simultaneous submission of a food additive petition and a notification for the same use of an FCS by the same person will not be permitted.

   5. Scope of an effective premarket notification

      1. For whom is a notification effective?

         Section 409(h)(2)(C) of the act states that a premarket notification is effective for the manufacturer, the FCS, and the conditions of use identified in the notification and not effective for a similar or identical substance produced or prepared by a manufacturer other than a manufacturer identified in the prior notification. ⁽¹⁾ Therefore, FDA believes that, for example, a new notification should be submitted in the following situations:

         1. ) for a manufacturer other than the manufacturer specified in a prior notification; or

         2. ) if substantive ⁽²⁾ changes are made in the specifications for the FCS; or

         3. ) if changes are made in the manufacturing method that result in substantive changes in the identity of the product or its impurities, and/or levels of impurities ⁽³⁾ (Notifiers should be aware that identity information in the notification apply to the FCS whether or not they are specifically included in the description of the FCS in an acknowledgement letter or in FDA's inventory of effective notifications); or

         4. ) for conditions of use or levels of use not included in the prior notification.

      2. Who may rely on an effective notification?

         Since a PMN is effective only for the manufacturer, substance, and intended use identified in the notification, any person wishing to rely on a PMN will generally need to demonstrate that the FCS being marketed has been manufactured by the manufacturer identified in the PMN and is being used under the conditions that are the subject of the PMN. The following is an example that illustrates how these principles are applied for a particular notification.

         There is an effective notification for polymer antioxidant X produced by manufacturer A and intended for use without limitation in polymer Y.

         A supplier of antioxidant X may rely on that notification if the supplier can establish that the antioxidant was produced by manufacturer A and the supplier is marketing antioxidant X for the intended use that is the subject of the notification.

         A manufacturer of polymer Y may rely on the notification to use antioxidant X if the polymer manufacturer can establish that the antioxidant X was manufactured by manufacturer A and the antioxidant X is being used under the conditions described in the notification.

         A manufacturer producing food packaging from polymer Y containing antioxidant X may rely on the notification to market such food packaging if the packaging manufacturer can establish that the antioxidant X was produced by manufacturer A and has been used under the conditions described in the notification.

      3. Conformance with Section 409(a)(3)

         Section 409(a)(3) of the Act states that a food shall not be deemed adulterated by reason of bearing or containing a food additive that is a food contact substance if there is a notification in effect relating to such food additive and such notification has not been revoked pursuant to section 409(i).

         Under the food additive petition process for food contact substances, FDA would commonly receive a food additive petition from a chemical manufacturer that produced a chemical used to manufacture a food additive that was a food contact substance. An example of this would be a manufacturer of a chemical intended for use as a monomer in a polymeric food contact material. In the past, in response to such a petition, FDA has regulated the polymeric food contact material as the food additive and has considered the monomeric starting material as a constituent of the food additive. However, FDA currently believes that such a monomeric starting material could be considered an FCS and thus could itself be the subject of a notification.

         FDA believes that chemical manufacturers may wish to notify the Agency about the use of monomeric starting materials in order to preserve the proprietary nature of the authorization under the notification process. Therefore, FDA has accepted and expects to continue to accept notifications for monomers and other constituents of food additives where the constituent and the food additive are both FCSs under section 409(h)(1). Such notifications must demonstrate the safety of the constituent under its intended conditions of use in the production and use of the food additive. In order to demonstrate the safety under the intended conditions of use, the notification must demonstrate the safety of the additive that is manufactured using the notified constituent.

         In cases where FDA does not object to such notifications for a constituent of a food additive and the safety of the food additive under its intended conditions of use has been demonstrated, the Agency believes that the effective notification for the constituent may meet the requirements under section 409(a)(3) of the Act to permit the food additive to be legally marketed. Thus, separate notifications for constituents and food additives produced from constituents will not be necessary.

   6. Fiscal requirements

      In accordance with Section 409(h)(5)(i) of the act, the premarket notification program shall not operate in any fiscal year for which the program is not funded as described in section 409(h)(5). FDA currently believes that, in order to use resources effectively, the Agency must be able to object to a notification if any portion of the 120 days after FDA's receipt of the notification falls within a fiscal year for which the program may not operate in accordance with section 409(h)(5) of the act. Accordingly, proposed § 170.104(c)(3) would permit FDA to object to a premarket notification solely on the basis that some portion of the 120-day review period occurs during a period when the PMN program is not in operation.

3. Format of a PMN for an FCS

   FDA is requesting that 5 copies of a PMN be submitted. Special instructions for submitting an electronic copy of a notification are presented below. PMNs should be submitted to:

   Notifications Control Assistant,
   Office of Premarket Approval, HFS-200
   Center for Food Safety & Applied Nutrition
   Food and Drug Administration
   200 C. St., S.W.
   Washington, DC 20204 (See updated contact information)

   Because of the short time provided for the Agency to review a PMN, it is important that the PMN be well organized. The Agency recommends the following organizational format for PMNs:

   Format items within the PMN should be presented as distinct units or chapters within the submission. This may be accomplished most easily by inserting dividers between the different sections of the submission. In addition, an overall table of contents should be provided identifying each of the required format items within the submission and individual data units within the submission that form the basis for the notifier's safety determination.

   A PMN may reference data in a food additive master file. If data have been submitted as a master file by a manufacturer other than the notifier, the notifier may refer to the master file, if and to the extent that the notifier obtains written permission from the manufacturer to do so. The manufacturer may authorize specific reference to the data without disclosure to the notifier.

   Notifiers are advised to consult FDA's guidance documents on recommended chemical and toxicological information for PMNs before submitting a PMN. The guidance documents are available on FDA's web site at http://www.cfsan.fda.gov. In addition, notifiers are urged to contact FDA regarding questions not addressed in the guidance. In accordance with proposed § 170.101, a PMN for an FCS should include the information listed below.

   1. Comprehensive Summary

      A summary and comprehensive discussion of the basis for the notifier's determination that the use of the FCS is safe within the meaning of Section 409(c)(3)(A) of the act, including a comprehensive discussion of all information and data submitted in the notification.

      The summary should address cumulative dietary exposure to the FCS and any potential impurities, the results of toxicity studies, and any ADI derived from those studies. For such a discussion to be deemed comprehensive it should address all safety data in the notification. Although a notifier's discussion of every study or test need not be exhaustive, a notifier should include a thorough discussion of safety data deemed pivotal to the determination of safety. The comprehensive summary should include the safety narrative (See "Guidance for Industry: Preparation of Premarket Notifications for Food Contact Substances: Toxicology Recommendations") and may reference the comprehensive toxicological profiles for the FCS and its constituents. To ensure a balanced evaluation of existing data, the notifier should include a comprehensive discussion of any information that appears inconsistent with the determination that the use of the FCS is safe. Under this proposed scheme, if FDA determines that a notifier's discussion is not sufficiently comprehensive to show that the notifier has considered all relevant facts, the Agency will object to the notification on the basis that the notification does not demonstrate that the use of the FCS is safe.

   2. Chemical Identity

      Detailed information on the chemical identity of the FCS and the impurities and residual reactants from the production of the FCS, including the chemical and structural formulas and CAS Registry No. , "Guidance for Industry: Preparation of Premarket Notifications for Food Contact Substances: Chemistry Recommendations".

   3. Intended Conditions of Use

      Detailed information on the intended conditions of use of the food contact material(s) manufactured with the FCS (e.g., maximum use temperature, type of food that the substance is intended to contact, duration of the contact, and whether the food contact material is intended for repeated or single use application), "Guidance for Industry: Preparation of Premarket Notifications for Food Contact Substances: Chemistry Recommendations".

   4. Intended Technical Effect

      A statement of the intended technical effect of the FCS and data to establish the minimum amount of the substance that will achieve the intended technical effect, "Guidance for Industry: Preparation of Premarket Notifications for Food Contact Substances: Chemistry Recommendations".

   5. Estimation of Intake

      Sufficient data to enable FDA to calculate the estimated daily intake (EDI) resulting from the notified use of the substance, including information on levels of residual reactants and impurities and the notifier's estimate of the CEDI from all food uses of the FCS, "Guidance for Industry: Preparation of Premarket Notifications for Food Contact Substances: Chemistry Recommendations".

   6. Environmental Information

      Either an environmental assessment (EA) or a claim for categorical exclusion from the requirement of an EA.

      A claim of categorical exclusion should be made by completing Part IV. of FDA Form No. 3480. FDA recently published a direct final rule amending 21 CFR part 25 to add the action of allowing a PMN to become effective as an action that would qualify for the categorical exclusions in §§ 25.32 (i), (j), (k), (q), and (r). Until that final rule becomes effective, all PMN actions will require an EA under § 25.40, see Interim guidance for preparing EAs for PMN actions.

   7. FDA Form No. 3480

      A completed and signed FDA Form No. 3480.

      The name and address of the notifier should be reported on FDA Form No. 3480, as well as a summary of the chemical, toxicological, and environmental information submitted with the notification.

4. Electronic submissions

   Electronic copies of notifications must meet the requirements of 21 CFR Part 11. Electronic submissions should be submitted to FDA on a CD-ROM or disk compatible with IBM-clone personal computers. Files should be provided in so-called "portable data file" (PDF) format or in a common word-processor format (e.g. WordPerfect or Word). FDA recommends that information addressing each format item above should be saved as a separate file.

5. Disclosability of information in a PMN

   Under section 409(h) of the act, FDA is not permitted to disclose any information in a PMN for 120 days after receipt of the PMN by FDA. Under proposed § 170.102(c) FDA's conclusion regarding the review of a PMN will be publicly available once the Agency has completed its review. For the purposes of this section, FDA's review will be completed when either 120 days have passed after receipt of a PMN or FDA has issued a letter objecting to the PMN.

   Under proposed § 170.102(e), at the completion of FDA's 120-day review period, the information in a PMN, including all safety and functionality data and information incorporated by reference, will be publicly available with the exception of trade secret and confidential commercial information. However, under proposed § 170.102(d), by submitting a notification, a notifier waives any claim to confidentiality of information required to adequately describe the FCS and the intended conditions of use that are the subject of the notification.

   For those PMNs that the notifier chooses to withdraw prior to completion of FDA's review, FDA will maintain the confidentiality of the information in the PMN under proposed § 170.102(b).

   FDA recommends that a notifier submit an additional copy of its notification identifying those portions that the notifier considers to be trade secret or confidential business information (i.e., a redacted version of the notification). FDA may not agree that all identified information is protected from disclosure under 21 CFR Part 20.

6. FDA response to a PMN

   1. Acknowledgment of a PMN

      FDA intends to acknowledge receipt of a premarket notification in writing within 30 days of receipt. This acknowledgment will serve two purposes. First, the acknowledgment will inform the notifier of the date of receipt of the notification by FDA, and thereby the effective date of the notification if FDA does not object to the marketing of the substance. Second, the acknowledgment will identify the substance and use that is the subject of the notification. Notifiers should review the description of the FCS and intended conditions of use in the acknowledgment letter carefully because this will be the description and intended conditions of use that FDA may ultimately list in its inventory of effective notifications. (Notifiers may wish to provide language for the acknowledgement as part of the information on identity and intended conditions of use.) During the course of review of a PMN, FDA may find it necessary to revise or correct the description of the FCS or intended use. In these cases, FDA will inform the notifier as soon as possible of any changes in the description of the FCS or conditions of use. If the notification becomes effective, FDA will place information on the identity of the substance, manufacturer, and conditions of use that are the subject of the notification in the publicly available inventory of effective notifications.

   2. Nonacceptance of a PMN

      If any component of a notification required under proposed § 170.101 is missing, FDA will not accept the notification for review. In addition, under proposed § 170.100(b), FDA may choose not to accept a notification for a use of an FCS that is the subject of a regulation in parts 173 through 186, or that is the subject of an exemption under 170.39. In cases where the Agency does not accept a notification based on deficiencies in information, FDA expects to inform the notifier in writing within 30 days of receipt of the submission.

   3. Objection by FDA

      The bases for FDA's objection depend in part on the provisions of the final rule implementing Section 409(h) of the Act. Under the proposed rule implementing Section 409(h), FDA may object to a PMN if:

      1. ) The notification does not comply with the general criteria for a PMN in §170.100.

      2. ) FDA does not agree that the notifier has demonstrated that the substance is safe under the intended conditions of use. In this case, FDA will inform the notifier in writing that FDA objects to the marketing of the substance for the use that is the subject of the notification, and describe the basis for the objection, as well as any additional information that would be required to support the safety of the substance for the intended use.

      3. ) A portion of the 120 days after FDA's receipt of the notification occurs within a fiscal year for which the premarket notification program does not operate in accordance with section 409(h)(5) of the act.

   4. Final letter

      FDA is not required to issue a letter if it does not object to the marketing of the notified substance. However, FDA realizes that such a letter may serve to bring the review process to closure. Therefore, FDA expects to issue a letter to the notifier that includes information identifying the FCS that is the subject of the notification and the date on which the notification became effective.

   5. Inventory of effective PMNs

      In order to provide for efficient enforcement of the act, FDA maintains an inventory of effective premarket notifications. FDA expects that this inventory will be the primary vehicle for informing the public of effective PMNs. The inventory contains information on the identity of the substance that is the subject of the notification, the conditions of use shown to be safe, any limitations on the use of the substance, specifications for the substance, the manufacturer or supplier for whom the notification is effective, the date on which the notification became effective, and a tracking number. The inventory is publicly available on FDA's internet site at http://www.cfsan.fda.gov.

7. Withdrawal without prejudice

   In accordance with proposed § 170.104, a notifier may withdraw a PMN for an FCS, without prejudice to a future submission, at any time prior to the completion of FDA's review. For the purposes of this section FDA's review will be considered complete if either 120 days have passed since receipt of the PMN and FDA has not objected to the notification, or FDA has issued an objection letter. Such withdrawal would be effective when FDA receives written authorization from the notifier.

8. Determination that a premarket notification is no longer effective

   In accordance with proposed § 170.105(a), FDA may declare that a premarket notification for an FCS is no longer effective if the data available to the Agency no longer demonstrate that the intended use of the substance is safe. FDA may use information other than that submitted by the notifier in determining whether a PMN should continue to be effective. As stated in proposed §170.105(b), if information becomes available that demonstrates that the use of an FCS that is the subject of an effective notification can no longer be considered safe, FDA will inform the notifier in writing of its tentative conclusion and provide the basis for that tentative conclusion. Under proposed § 170.105(b), the notifier would be given an opportunity to adequately address the information raising FDA's concerns. The FDA will establish a time frame for the notifier to respond to the Agency's concerns. If the notifier is not able to adequately address FDA's concerns within that time, FDA will publish a notice in the Federal Register stating the Agency's conclusion that the notification is no longer effective and the reasons for such conclusion. After publication of such notice, the notification will no longer be effective (proposed § 170.105(c)). Under proposed § 170.105(d), the Agency's determination that a notification is no longer effective shall be final agency action subject to judicial review.

9. Conversion of existing food additive petitions and threshold of regulation requests

   When the PMN program began to operate on October 25, 1999, the Agency had an inventory of pending food additive petitions for the use of FCSs and pending threshold of regulation exemption requests (under § 170.39). Nearly all of these petitions and exemption requests are for uses that would meet the criteria for a food contact substance notification under section 409(h) of the act. On October 25, 1999, FDA issued letters to all submitters of food additive petitions and exemption requests for FCSs, advising them of the possibility of converting their submissions to PMNs.

   Existing food additive petitions or threshold of regulation requests for the use of an FCS may be withdrawn and resubmitted as a PMN. If a petitioner does not withdraw the petition and submits a PMN for the same use, the petition would be deemed withdrawn under proposed § 171.7(c) for the use or uses described in the notification. Likewise, if a sponsor does not withdraw the threshold of regulation request and submits a PMN for the same use, the request would be deemed withdrawn. FDA encourages petitioners and requestors under the threshold of regulation process to contact the Agency, prior to withdrawal of a petition or threshold of regulation request, to obtain specific guidance on conversion to a PMN. Petitions and threshold of regulation requests for the use of an FCS not converted to PMNs will continue to be reviewed as petitions or under the threshold of regulation process.

   When the notification program began to operate, FDA was awaiting additional information necessary to the safety determination for some of the food additive petitions and threshold of regulation requests in the Agency's inventory. Any such information is still necessary to establish the safety of the intended use of the FCS even if a petition or request is resubmitted as a notification.

10. Presubmission meetings

    If present guidance is not completely applicable to a given situation a presubmission meeting between the notifier and FDA may be advisable. The Chemistry and Toxicology PMN guidance documents describe certain circumstances under which a presubmission meeting is recommended. Generally there are three circumstances where FDA recommends a presubmission meeting. First. In all cases, FDA recommends that a presubmission meeting be held prior to the submission of a petition for a use of an FCS. Such a meeting may be used to verify that petition is required and that an appropriate level of information is supplied in the petition. Second, FDA recommends a presubmission meeting when there are uncertainties about how scientific data may be interpreted and those uncertainties are of such magnitude that they may affect the outcome of the overall safety determination. For example, if the EDI is close enough to the acceptable daily intake (ADI) that different choices for the no effect level may cause the resulting ADI to be larger or smaller than the EDI, a presubmission meeting is recommended. Third, a presubmission meeting is recommended when different interpretations of available data would result in different conclusions regarding whether a notification or a petition should be submitted. For example, a meeting is recommended if different interpretations of data in a bioassay could change the conclusion regarding the likely carcinogenicity of the substance.

    In order to make the most of the usefulness of presubmission meetings, relevant information should be provided to FDA sufficiently in advance of the meeting to permit Agency personnel to familiarize themselves with the information to be discussed.

11. Inquiries concerning FCSs

    Companies that produce, market, and use FCSs are responsible for the compliance of such materials with applicable regulations, exemptions, or notifications. Therefore, such companies should be aware of the regulatory status of any FCS that they produce, market, or use. In addition, Section II.B above specifies that the submission of a PMN for the use of an FCS will be prohibited for any use that is adequately covered by a regulation or an existing exemption under § 170.39. Information on the regulatory status of an FCS may be obtained by inspection of §§ 170-199 or searching the GPO (Government Printing Office) website at http://www.access.gpo.gov/nara/cfr/index.html. In addition, information on effective PMNs or existing exemptions for an FCS may be obtained through the FDA website. If, after consulting the above information sources, a company is still uncertain about the regulatory status of an FCS, FDA should be consulted by either telephone (202-418-3080), E-mail (OPAPMN@cfsan.fda.gov), or letter (Food and Drug Administration, HFS-215, 200 C Street, SW, Washington, DC 20204). (See updated contact information)

    When contacting FDA concerning the regulatory or notification status of an FCS, the following information is generally pertinent and should be readily available when contacting the FDA by telephone. This information should also be included in a letter or E-mail inquiry to minimize delays in response.

    1. Identity

       Identify the individual FCS, or components of a formulation, by their chemical names, structural formula and CAS Registry No., if available. FCSs are not listed in the regulations or notifications under trade names, nor does FDA maintain a list of such names. Therefore, FDA cannot review materials identified only by trade names. Additionally, give the weight percentages of each component of a formulation.

    2. Use level and conditions of use

       Identify the maximum use levels of the FCS in the food contact article, the most severe anticipated conditions of use of the food contact article (i.e., time-temperature conditions), types of foods to be contacted, and whether the article is intended for single or repeated use. Include information on the intended technical effect of the FCS for each component of a formulation

    3. Appropriate regulation, exemption, or notification

       List the specific regulation section(s), if known, that are believed to authorize the use of the FCS or formulation under the desired conditions of use. For effective notifications, list the specific notification number, if known, and the identity of the notifier.

       In the event that the Agency determines that any of the individual substances, or components of a formulation, are not authorized by a regulation, effective notification, or existing exemption for the proposed use, a PMN or petition will need to be submitted to provide for the proposed use.

12. Format of a notification for food contact substance formulations

    FDA is proposing under 21 CFR 170.106(a) to accept notifications for food contact substance formulations where all of the components of the formulation are already authorized for their intended uses. FDA has serious concerns regarding the potential burden that accepting notifications for formulations could place on the Agency should the number of notifications become unexpectedly high. Therefore, proposed § 170.106(b) states that the Agency may prohibit the submission of notifications for food contact substance formulations at any time by publishing a notice in the Federal Register stating that the Agency does not have sufficient resources to review such notifications.

    Such notifications are to be distinguished from PMNs in two ways. First, notifications for food contact substance formulations are for a particular mixture of two or more food contact substances. Second, each of the substances in the formulation is already authorized for its intended use. Thus, FDA's evaluation of such notifications consists of a review of the basis for compliance with section 409 of the act. Because all substances in a notification for a food contact substance formulation should already be authorized for their intended uses, such notifications would not be required under section 409 of the act.

    FDA's current view is that notifications for formulations would not require resubmission of the information supporting the safety of the intended use of each food contact substance in the formulation. FDA tentatively believes that a notifier for a formulation would ordinarily submit only a completed FDA form 3479 and any additional documentation required to establish that each of the components of the formulation is authorized for its intended use. In cases where the basis for compliance of an individual FCS in a formulation is an effective notification, a notifier of the formulation should establish that he could rely on the notification cited and that such notification is effective for the intended use in the formulation.

    FDA is requesting that two copies of notifications for formulations for food contact materials be submitted. A notifier may submit the second copy of the notification in an electronic format. Special instructions for submitting an electronic copy of a notification are presented in Section IV. Notifications for food contact substance formulations should be submitted to:

    Notification Control Assistant,
    Office of Premarket Approval, HFS-215
    Center for Food Safety & Applied Nutrition
    Food and Drug Administration
    200 C. St., S.W.
    Washington, DC 20204. (See updated contact information)

Content last updated by emw/hrw on 2004-JAN-06
Hypertext updated by emw/ear/kwg/dms/cjm/hrw 2004-JAN-06