Special Focus

FDA Modification of New Conditions of Use

Dec 2009
Jerome H. Heckman, George G. Misko, Lisa P. Alsobrook

Intended use is a crucial factor in establishing the U.S. Food and Drug Administration (FDA) status of a food contact substance. Intended use may include many elements, but the two most important usually are: (1) the maximum temperature at which a material will be used; and (2) the types of food that will be contacted (i.e., aqueous, acidic, fatty, alcoholic). In April 2006, FDA adopted two new "Conditions of Use" criteria that had implications for existing and future FDA clearances of food contact substances.

Background

Until 2006, FDA recognized the following temperature conditions under which food could be packaged or stored:

• Condition of Use A (High temperature heat-sterilized (e.g., over 212º F));
• Condition of Use B (Boiling water sterilized);
• Condition of Use C (Hot filled or pasteurized above 150º F);
• Condition of Use D (Hot filled or pasteurized below 150º F);
• Condition of Use E (Room temperature filled and stored (no thermal treatment in the container));
• Condition of Use F (Refrigerated storage (no thermal treatment in the container));
• Condition of Use G (Frozen storage (no thermal treatment in the container)); and
• Condition of Use H (Frozen or refrigerated storage: Ready-prepared foods intended to be reheated in container at time of use).

These temperature conditions are listed in Title 21 of the Code of Federal Regulations (CFR), Section 176.170(c), Table 2. Although Section 176.170 is a regulation pertaining only to paper and paperboard food packaging, Table 2 has been used as a convenient reference in many other regulations and, until recently, in food contact notifications (FCNs) for all types of food contact substances.¹ For example, FDA would describe a substance as permitted for use under Conditions of Use A-H, as defined in 21 CFR Section 176.170(c), Table 2.

Since Condition of Use A had no upper temperature limitation (High temperature heat-sterilized (e.g., over 212º F)) as described in the list, a clearance under Condition of Use A was considered to amount to permission to use the covered material at any temperature above 212º F, provided the regulation or notification does not impose an upper temperature limit. The high temperature phase of migration testing to establish a clearance for Condition of Use A is 250º F. This testing is intended to cover retort heat sterilization of packaged food. Where, however, exposure at higher temperatures is expected, it was often advisable to conduct migration testing at the higher temperature for the purpose of establishing that there is not a significant change in the nature or amount of potential migrants.

In April 2006, FDA expanded its list of Conditions of Use to include two additional conditions: I (Irradiation) and J (Cooking at temperatures exceeding 250º F). At that time, FDA did not amend Table 2 in 21 CFR 176.170 or announce the change in a public proceeding. Instead, the new list of Conditions of Use were simply placed on FDA's website. Subsequently, FDA did change the references to permitted Conditions of Use in the Inventory of Effective Food Contact Notifications on its website from Section 176.170, Table 2, to the new list of Conditions of Use on its website.

FDA Updates Chemistry Guidance for Submitting FCNs

In December 2007, a little over a year after adopting Conditions of Use J and I, FDA issued an updated guidance document on chemistry issues related to preparing Food Contact Notification (FCN) submissions, "Guidance for Industry, Preparation of Premarket Submissions for Food Contact Substances: Chemistry Recommendations," which addresses the new Conditions of Use. The previous Chemistry Guidance, published in 2002, had recommended that migration testing be conducted "under the most severe conditions of temperature and time anticipated for the proposed use." The 2007 edition of the Chemistry Guidance is more specific by recommending that migration testing be conducted at the maximum intended cooking temperature for the longest intended cooking time, using a food oil or a fatty-food stimulant. A table describing all of FDA's Conditions of Use categories is included in Appendix V of the 2007 Chemistry Guidance.

A significant change in the 2007 edition of the Chemistry Guidance was the inclusion of an upper temperature for Condition of Use A. In the guidance, Condition of Use A is listed as, "High temperature, heat sterilized or retorted (ca. 121º C (250º F))." However, the description of Condition of Use A as, "High temperature heat-sterilized (e.g., over 212º F)," in 21 CFR 176.170(c) and on FDA's website (link provided above) have not been changed.

The new guidance also contains some updated migration test information on microwave-only containers. In the 2007 Chemistry Guidance, FDA confirms that tests performed for broad coverage under the protocol for Condition of Use H will be adequate to cover microwave-only containers, in addition to conventional oven reheating of ready-to-eat, prepared foods.

Effect of Condition of Use J on Regulatory Status of Food Contact Substances

Since Condition of Use J was adopted outside of a regulatory proceeding, it is only relevant in so far as it describes the types of testing data that FDA requests for an evaluation of an FCN for a product that is intended to be used in cooking applications. FDA has not promulgated an overarching regulation establishing a temperature limitation on any specific food additive regulation. Thus, unless a specific food additive regulation sets out a temperature limit with respect to the substance that is the subject of the regulation, that substance may be used in cooking applications, provided that such use conforms to Good Manufacturing Practice (GMP) requirements in 21 CFR 174.5 (i.e., the substance is used in a manner that does not affect the suitable purity of the finished product for its intended use). That may require some additional testing to establish that no significant migration to food results from the actual intended use.

While the 2007 edition of FDA's Chemistry Guidance references Condition of Use J, little information is provided on the testing required for this condition of use. However, discussions and presentations made by FDA staff provide some direction. For aqueous foods, no further testing should be required if the substance is cleared for use under Conditions of Use A, B, or H. For single service packaging for fatty foods intended to be cooked in a conventional oven at temperatures exceeding 250° F, the packaging material should be exposed at the maximum temperature and time at which it is expected to be used, or, should be tested at 350° F (177° C) for two hours using a fatty food simulant, such as corn oil or Miglyol 812. Testing at 350° F for two hours covers use of the food contact substance at higher temperatures (i.e., not limited to use at
350° F). FDA's recommended test procedure for repeated use food contact articles generally is to extract the samples at the highest use temperature for 240 hours (10 days), and divide the amount extracted by the amount of food that will contact the article over its useful life to determine exposure to the food contact substance.

Some concern has been raised about conditions of use limitations for FCNs that were effective prior to FDA adopting Conditions of Use J and I. At a minimum, submitters of notifications should be able to interpret the notifications as covering the temperatures of use supported by the highest temperature of the migration testing. Companies that have effective notifications may want FDA to add an explicit reference to Condition of Use J if the previously submitted migration data or new data support the higher temperature use. If there are no additional data, then there may be some risk that the clearance will be considered not to include Condition of Use J.

Effect of Condition of Use I on Regulatory Status of Food Contact Substances

FDA's definition of good manufacturing practice for food irradiation (21 CFR 179.25(c)) includes the following: "Packaging materials subjected to irradiation incidental to the radiation treatment and processing of prepackaged food shall be in compliance with Sec. 179.45, shall be the subject of an exemption for such use under Sec. 170.39 of this chapter [the Threshold of Regulation], or shall be the subject of an effective premarket notification for a food contact substance for such use submitted under Sec. 170.100 of this chapter." Sec. 179.45 lists the packaging materials currently cleared for use during irradiation of prepackaged food and the maximum dose levels that are authorized.

Condition of Use I applies only to materials intended to contact food during irradiation of the food, not to food contact substances that are irradiated as part of their manufacturing process. The latter use of irradiation always has been accepted by FDA, subject to the universal good manufacturing practice requirement that all food contact materials must be suitably pure for their intended use (21 CFR 174.5).

The addition of Condition of Use I provides notice that FDA considers migration testing necessary to qualify materials to hold food during irradiation. However, FDA's Chemistry Guidance does not specify the tests to be done. Rather, the Chemistry Guidance states, "We do not have protocols for studies on FCSs [Food Contact Substances] that are intended to be irradiated with ionizing radiation. Please consult with FDA to discuss recommended protocols for this use" (Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances: Chemistry Recommendations, Appendix II. 15).

To date, there are no effective FCNs covering the use of irradiation, but there have been several Threshold of Regulation (TOR) exemptions (see 21 CFR Section 170.38). FDA determined in 2007 that under certain circumstances, prepackaged food can be irradiated without the packaging material being the subject of a food additive regulation or a FCN permitting it to be irradiated. Instead, FDA determined that such materials may be considered exempt from the need for regulation by way of its TOR policy. In a TOR exemption letter for the irradiation of food contact materials incidental to the radiation treatment of prepackaged food, the agency determined that no regulations are necessary for the irradiation of otherwise compliant food packaging materials, provided that the radiation processing is done in compliance with 21 CFR 179; the packaging materials are subjected to radiation not exceeding 3 kGy; and the packaged food is irradiated either in a verifiably oxygen-free environment or while frozen and contained under vacuum. This exemption is applicable to food contact materials listed in 21 CFR 174 through 186, as well as those listed in FDA's inventory of effective FCNs and inventory of TOR exemptions.