Paper and Paperboard Regulation: Compliance Testing v. Migration Testing
When conducting analytical testing to establish FDA compliance of a particular food-contact material, it is always important to bear in mind any specific FDA requirements that may pertain to the test material. In the case of paper and paperboard food-contact materials—including their additives—there are unique analytical testing issues to consider.
To properly assert compliance with 21 C.F.R. § 176.170, the manufacturer of the finished food-contact paper or paperboard must ensure that it meets the limitations on extractives outlined in 21 C.F.R. § 176.170(c). These "end tests" are intended as a loose quality control measure intended to ensure that the overall migration of cleared additives to food is limited. Compliance of the finished paper or paperboard with these limitations does not, however, relieve a company from the responsibility to ensure that all additives used in the paper or paperboard have an appropriate FDA status for their intended use, i.e., an appropriate regulatory listing in the CFR or on FDA's Food-Contact Notification list, or an applicable exemption from the need for premarket clearance.
For additives that are not the subject of an applicable regulatory listing or exemption, a different type of analytical testing is required. Migration studies, as opposed to "end tests," are intended to simulate the migration of food-contact materials to the contacted food. The results of this type of testing can be used to support an FCN filing or, in some situations, to support a conclusion that a substance is not a "food additive."
There is a specific section in FDA's Chemistry Recommendations that describes the way in which migration studies should be conducted on paper and paperboard. In general, for non-polymer-coated paper, these studies should be conducted at 40°C for 24 hours, using 10% ethanol to simulate contact with aqueous, acidic, and low-alcohol foods, and a food (or synthetic) oil (or, alternatively, 50% ethanol) to simulate contact with fatty and high-alcohol foods. Polymer-coated paper requires testing at an elevated temperature for a short period of time followed by exposure at 40°C for 10 days. These studies are intended to simulate initial heat treatment in the container and subsequent shelf storage at ambient temperature. Testing performed under these conditions will support a clearance for use in contact with all food types under Conditions of Use B through H. (In general, FDA does not consider paper technically capable of being used in Condition of Use A applications.)
It is important to note that this testing will not support a clearance for the use of an additive in microwave susceptor applications. For substances that will be added to paper and paperboard used in microwave susceptor applications, FDA generally recommends testing samples using a food or synthetic vegetable oil in a 700-watt microwave oven for 5 minutes.
In the case of paper additives, these can be added at various stages of the paper manufacturing process. In this regard, FDA makes a distinction between additives that are added prior to the sheet-forming process, often referred to as "wet-end" additives, and those that are added during, or after sheet-forming. Test samples should reflect the intended use of the additive, including the point of its addition and its maximum use level. Accordingly, for additives used solely at the wet-end, samples should be prepared from paper made using the maximum level of the additive. However, prior to doing such testing, it is usually advisable to see if a calculated level of migration can be determined (see below). On the other hand, if the additive will be used in the size press, the sample should be prepared by adding the additive, at the maximum level at which it is expected to be used, to paper at the size press. If the additive will be used in either the size press or the wet end, FDA does not require migration studies on both types of samples. Rather, migration studies performed on size press addition samples can be used to support a clearance for wet end and size press addition of the additive, due to the fact that size press addition is considered by FDA to be a worst-case in terms of migration. In addition, it is important to note that FDA uses 50 mg/in2 as an average paper thickness. Migration studies conducted on 50 mg/in2 samples can be used to support a clearance in paper and paperboard generally, without any limitation on paper thickness. If thinner paper samples are used, the Notifier has the option of factoring up the migration values to reflect migration from a 50 mg/in2 thickness, or limiting the clearance to use in paper and paperboard of the tested thickness (or thinner). For example, if migration studies are conducted on 30 mg/in2 paper, the Notifier has the option of either applying a correction factor of 1.7 to the migration values, or limiting the additive to use in paper with a thickness of 30 mg/in2 or less.
In the absence of migration studies, worst-case calculations can sometimes be helpful in establishing a maximum level of migration. These calculations generally assume that 100% of the additive will migrate to 10 g food/in2. (For microwave susceptor applications, however, FDA assumes a volume-to-surface area ratio of 5 g food/in2.) However, for substances that are added only in the wet end, and are not substantive to the paper and fibers, FDA assumes that 98% of such substances will stay with the process water ("white water"), resulting in a maximum of 2% remaining with the paper. This can be an important consideration in establishing low migration of substances added only in the wet end of paper manufacturing, and may be sufficient to allow an exposure determination to be made without the need for laboratory experiments.
 Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances: Chemistry Recommendations, Dec. 2007 [Editor's note: This article originally referenced the 2002 edition of FDA's Chemistry Guidance; an updated version was published in 2007.]