Designing for Success: Points to Consider in Developing Migration Studies for Packaging Materials
Any use of a new food-contact substance first requires that migration studies be conducted, under the intended conditions of use, to determine if, and to what extent the substance may become a component of the daily diet. A number of important points must be considered in designing and performing migration studies to provide the type and quality of chemistry data that the U.S. Food and Drug Administration (FDA) needs to establish the safety of the intended use of the new substance and to issue an effective Food Contact Notification (FCN).
The same type and quality of chemistry data will also be needed to issue a legal opinion concerning the suitable FDA status of the substance.
Food-contact substances that are anticipated, or have been shown, to become components of food when used as intended must be the subject of: an applicable FDA regulation (found in Title 21 of the Federal Code of Regulations); an FDA Threshold of Regulation (TOR) exemption ; or an effective FCN . In addition, a number of "exemptions" to the Federal Food Drug and Cosmetic Act permit substances not otherwise specifically regulated to be legally used in contact with food.
Clearance of substances under these various regulatory schemes is generally accomplished on the basis of migration studies demonstrating their anticipated concentration in the daily diet when used as intended and adequate toxicology data supporting the safety of these dietary concentrations. Finally, many currently effective regulations were issued with an "end test" requirement to demonstrate compliance of the regulated substance with stated regulatory specifications.
A number of important issues must be considered when designing and performing migration studies for new food-contact substances. For a broad overview of these issues, see FDA's Guidance for Industry: Preparation of Premarket Submissions for Food Contact Substances: Chemistry Recommendations, 2007.
Significant Information Necessary
In designing appropriate migration studies, it is essential that the identity of the food-contact substance be known. The identity includes not only its chemical name, Chemical Abstract Service Registry Number, trade names, molecular and structural formulae, and the identity and quantity of impurities, but also its manufacturing process. This information will dictate, to a great extent, what analytes need to be included as analytes in the extracts when a migration study is done.
Second, a clear understanding of the intended use of the food-contact substance is required. For example:
- Is the substance the food-contact article, per se—such as a film or a coating—or is it used in the manufacturing process for the food-contact article, such as a catalyst, emulsifier, or chain terminator?
- Is the substance a component of the food-contact article, such as a colorant, stabilizer, or plasticizer, and at what maximum level will it be used?
- Will the substance be in direct contact with food, or is it separated from food contact by another material that may serve as a functional barrier to the migration of the substance?
The answers to these and other questions will dictate the type of sample that must be prepared for the migration studies.
Continuing with the intended use of the substance:
- What types of foods will it contact: aqueous, acidic, alcoholic, fatty and/or dry?
- What will be the maximum temperature of food contact: room temperature, hot- fill, cooking, etc.?
- Will the food contact be single use service, such as a food package, or will it be repeated use such as in conveyor belts, coatings for food processing machinery, or tubing/piping?
The answers to these and other questions will dictate the types of food simulating solvents that should be used in the migration studies, the temperature and duration of the migration studies, and the treatment of the developed migration data.
Food-simulating solvents are used in migration studies instead of the actual foods expected to contact the substance. Generally, the food itself is not used in migration studies because food is often compositionally complex, and determining the concentration of trace amounts of the migrating substance into complex matrixes can be extremely difficult. Further, food simulating solvents can be used to represent broad ranges of foods within given food types. For example, all aqueous, acidic, and low- alcohol foods, regardless of their specific makeup and complexity, are represented in most instances by one simple, easy-to-analyze food simulating solvent: 10 percent ethanol in water.
For fatty foods, several food simulants may be employed. Ideally, an actual food fat or food oil can be used, but, as mentioned above, there may be analytical problems associated with such use. For polyolefins, 95 percent ethanol in water can be used as the fatty food simulant. For most other polymers, and for paper and paperboard articles, 50 percent ethanol in water can be used. Finally, heptane can be used in some cases.
What about testing temperatures? FDA has developed a range of food-contact use temperatures from retort canning conditions ("Condition of Use A") to frozen storage ("Condition of Use G"). There is also "Condition of Use H" for precooked food intended to be reheated in the container. Elevated temperature cooking applications covered by "Condition of Use J" (Cooking at temperatures exceeding 250° F) include conventional oven cooking in the package, and susceptor microwave cooking (for popcorn and pizza).
Testing times also vary depending on thermal processing required for the food, as mentioned above, and the polymers used in the testing. For example, any hot fill or retort-type uses require an initial exposure at an applicable elevated temperature (depending on the specific uses), followed by an extended exposure at a somewhat elevated temperature to simulate extended shelf life in the food-contact article at room temperature. In addition, some polymers require only a 10-day extended test exposure at the somewhat elevated temperature to simulate long-term shelf storage of package food at room temperature, while others may require a 30-day test exposure.
Thus, a clear understanding of the intended conditions of use for a food-contact substance is needed before suitable test samples can be prepared and adequate testing can be performed.
After the migration studies are complete, analyses of the test sample extracts must be conducted to determine if, and to what extent, the substance is anticipated to become a component of food when used as intended. Any analytical method may be used provided:
- It has adequate analytical sensitivity, given the needed detection limit based on the known toxicity profile of the food-contact substance, and
- The analytical results can be validated according to specific procedures recommended by FDA.
With regard to analytical method limit of detection, obviously the more potentially toxic the food-contact substance, the lower the analytical limit of detection must be to ensure that the calculated dietary concentration is within the safety parameters for the substance. Finally, the migration study data—and the methods used to generate the data—must be suitably validated; FDA requires validation as a part of its review of an FCN.