Overview
The StepLadder Series is a Steptoe publication focused on discussing food contact regulatory topics in plain language.
There’s no such thing as zero.
"Functional Barrier" is a Subset of "No Migration"
In our recent StepLadder article on Functional Barriers, we discussed how food-contact materials that are completely separated from food are not considered "food additives" subject to premarket approval by the US Food and Drug Administration (FDA), because they aren’t reasonably expected to become a component of food under their intended conditions of use.1 The logic behind the functional barrier approach is straightforward: if a substance can’t get into food, then by definition, it’s not a food additive. The principles underlying a "No Migration" position introduce a further variation on this theme: how much of a food contact substance could potentially migrate into food, when used as intended, before we would consider it to be a food additive subject to premarket approval by FDA? The answer (usually) isn't zero!
How Low Can You Go?
We begin by observing that a "No Migration" position is a self-determination that's made by taking into consideration the identity, intended use, safety profile, and the upper-bound potential (or actual – if measured) migration of a substance from packaging to food. Substances that are properly the subject of a "No Migration" position are, therefore, outside the scope of the definition of a food additive, and do not require premarket approval by FDA. These substances still must be safe when used as intended, however, in keeping with FDA's General Safety Clause and Good Manufacturing Practice (GMP) requirements.
FDA has not provided definitive criteria on how to determine at what specific level of migration a substance may reasonably be expected to become a component of food, so a "No Migration" determination must be made carefully, by taking into consideration the available sources of guidance, including case law in this area. A well-known example of this question was addressed in the Monsanto v. Kennedy case in 1979.2 Here, FDA argued that the mere existence of contact between food packaging and food would result in some conceivable amount of migration of the food-contact substance to food (no matter how small), thereby potentially requiring the need for a food additive regulation for every intentionally added food-contact substance. The court disagreed with FDA's position, and stated instead that, to meet the definition of a "food additive," a food-contact substance must migrate to food in "more than insignificant" amounts.3
Not surprisingly, therefore, the evolution of the "No Migration" position hinges on the interpretation of the word "insignificant" – and there is no shortage of opinions. For example, in 1969, Dr. Lessel Ramsey, then the Assistant Director of Regulatory Programs in FDA's Bureau of Science, circulated a proposal whereby a default migration value of 50 parts per billion (ppb) would be considered insignificant for a "No Migration" determination for those substances with an absence of any specific toxicology concerns. The 50-ppb threshold was chosen based on a combination of the understanding of the toxicology of substances ingested by the oral route of exposure at the time, as well as the ability (or lack thereof) of analytical equipment to reliably detect the presence of a substance at a level below this threshold. While the 50-ppb 'default’ threshold is still accepted in certain instances today, it has largely been replaced by a more individualized assessment of the safety profile of the specific substance or, where such information is not readily available, a read-across approach using structurally similar classes of substances. Of course, analytical methodologies and risk assessment procedures have advanced considerably since that time as well, allowing for the identification of the presence or absence of a substance migrating to food at much lower levels of sensitivity. So, what is an appropriate level of analytical sensitivity for a "No Migration" position today, you might ask? The answer is every lawyer’s favorite phrase: it depends!
How to Support a "No Migration" Position
The determination as to whether a "No Migration" position is appropriate depends on the safety of the substance and how much of the substance could potentially migrate to food. Three generally-accepted principles for assessing the potential or actual migration of a food-contact material to food include:
- Upper-bound (100%) migration calculations: This method assumes that 100% of the substance that is added to (or present in) food packaging and both could and actually does migrate to food under the intended conditions of use. These calculations take into consideration, among other items: (1) the amount of the food-contact substance present in the food packaging; (2) the density of the packaging material; (3) the thickness of the packaging; and (4) the amount of food that contacts a given amount of surface area of the packaging material (volume to surface area ratios are higher, and therefore, more favorable for repeated-use applications than for single-use applications). FDA has established default values for many of these factors, save for the use level. For the calculation of the upper-bound potential migration of polymeric substances to food, one may further refine the calculation to consider only the low molecular weight oligomer (LMWO) fraction, where appropriate.4 Importantly, upper-bound (100%) migration calculations are temperature independent. This means that a favorable mathematical result conceptually covers all temperature Conditions of Use. On the flip side, because these calculations assume that all of the substance added to packaging actually migrates, they are quite conservative and generally overestimate the actual level of migration one would expect in practice. Given the relative simplicity of conducting migration calculations compared to the alternatives below, calculations are typically the first and most commonly employed approach.
- Diffusion modeling: Similar to upper-bound (100%) migration calculations above, diffusion modeling is a "paper exercise" (though usually a computer exercise) by which a number of relevant factors are taken into consideration to mathematically model the potential migration of a substance from packaging to food, using well-established scientific principles such as Fick's laws of diffusion. Diffusion modeling takes many of the same factors described above into account, but further considers the properties of packaging material itself – and more specifically, the propensity of a food-contact substance to migrate through that material and into food. Therefore, diffusion modeling of the migration of "larger" substances with a higher molecular weight will often result in lower estimated migration values than the same modeling of "smaller" substances with lower molecular weights. Similarly, the modeling of the diffusion of the same molecular weight substance from two different polymers may result in different values, with the more diffuse polymer yielding a higher migration value. Diffusion modeling is less conservative than upper-bound (100%) migration calculations, but may still overestimate the actual level of migration one would expect in practice. Therefore, diffusion modeling often is employed as an effective "middle ground" where upper-bound calculations are not sufficient – but actual migration studies are not warranted.
- Actual migration studies: The most accurate (though also most involved) method of measuring the migration of a substance to food is to… measure the migration of a substance to 'food.' Actual migration studies include the preparation of representative test samples of a packaging material that are then subjected to contact with food-simulating solvents, under appropriate time and temperature conditions reflective of actual use. The solvent is then analyzed to determine whether or not the target substance is detected at an appropriate level of analytical sensitivity (or not), using suitable equipment. Studies may be conducted in-house, or at an external laboratory. In the case of migration studies, Steptoe often provides our clients with detailed Migration Test Protocols that describe correct sample preparation, the number of samples needed, how to properly validate the study, and relevant other information to ensure that the results of the study are both accurate and reliable, consistent with FDA's recommendations. When conducted properly, the results of actual migration studies can further be relied upon for other uses, such as in support of a Food Contact Notification (FCN).
The demonstration that a substance could not (in the case of calculations or diffusion modeling) or does not (in the case of actual migration studies) migrate to food at or above the chosen level of analytical sensitivity provides the legal basis for determining that a "No Migration" position is appropriate, and therefore, premarket review by FDA is not required.5
If the outcome of the three approaches described above are unfavorable for a "No Migration" position, all hope is not lost! There are certainly other avenues that remain available to establish a suitable FDA status for the intended use as a food contact substance, both through and by way of exemption from the premarket approval approach. These will be the subject of future StepLadder articles, so stay tuned!
1 See Section 201(s) of the Federal Food, Drug and Cosmetic Act. By "appropriately separated," we mean a true functional barrier (a legal term of art), as discussed more fully in that StepLadder article.
2 613 F.2d 947 (D.C. Cir. 1979)
3 Id. at 955.
4 For polymers, FDA is specifically concerned with the low molecular weight oligomer fraction of a polymer (i.e., the fraction having a molecular weight below 1000 daltons), as this is the fraction of a polymer that would be available to migrate to food and be toxicologically significant from a human exposure and absorption standpoint.
5 In most instances, therefore, the migration study will purposefully be designed such that a result of "not detected" (ND), if achieved, will support a "No Migration" position.
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About the Steptoe StepLadder Series
Steptoe & Johnson LLP is pleased to publish the Stepladder series of articles for our clients, prospective clients, and interested companies as a way of educating attorneys and non-attorneys alike about legal and regulatory principles related to food packaging in meaningful ways. While there are many sources of information available online, the StepLadder series is intended to be accessible to, and understandable by all, to help support business decisions related to food packaging compliance.
This information is provided for educational purposes only, is not legal advice, and does not establish an attorney-client relationship with Steptoe. Our lawyers made us write that. If you have legal questions, please consult an attorney. Preferably from a team well-versed in food packaging regulation – and definitely from a group of attorneys that have a good sense of humor. Because you are what you eat… unless your food packaging isn’t a ‘food additive,' in which case you’re not food packaging.
