Assessing Compliance with EU Food-Contact Regulations: Technical Considerations

By Keller and Heckman's Scientific Staff

The overarching regulation governing food-contact materials (FCMs) in the European Union (EU) is the Framework Regulation, (EC) No. 1935/2004. This regulation governs all FCMs and is in force in all the Member States. Article 3.1 of this Regulation establishes the general principles that FCMs must be manufactured in accordance with good manufacturing practice so that they do not transfer their constituents to food in quantities that (a) could endanger human health, (b) bring about an unacceptable change in the composition of food, or (c) bring about a deterioration in the taste or odor of food.

To achieve these objectives, the European Commission (EC) has adopted the Good Manufacturing Practice (GMP) Regulation[1] as well as specific measures for certain classes of FCMs.

The GMP Regulation sets forth the general rules on requisite practices governing FCMs, such as the establishment of quality assurance and quality control systems and the adequate documentation of those systems. Article 3(a) of the GMP Regulation defines GMP as: 

“those aspects of quality assurance which ensure that materials and articles are consistently produced and controlled to ensure conformity with the rules applicable to them and with the quality standards appropriate to their intended use by not endangering human health or causing an unacceptable change in the composition of the food or causing a deterioration in the organoleptic characteristics thereof.” 

In addition to the GMP Regulation, most FCMs are also subject to compliance with additional, more specific, measures. The most comprehensive of the specific measures currently in place under the Framework Regulation is the Plastics Regulation (EU) No 10/2011, as amended.[2] The Plastics Regulation establishes specific requirements for the manufacture and marketing of plastic materials and articles intended to contact food that fall under the following categories:

• Materials and articles and parts thereof consisting exclusively of plastics;
• Plastic multi-layer materials and articles held together by adhesives or by other means; 
• The above plastic materials and articles when printed and/or covered by a coating;
• Plastic layers or plastic coatings, forming gaskets in caps and closures, that together with those caps and closures compose a set of two or more layers of different types of materials; and
• Plastic layers in multi-material multi-layer materials and articles.[3] 

The Plastics Regulation regulates the manufacture of plastics by establishing a positive list of permissible monomers, other starting substances, macromolecules obtained from microbial fermentation, and additives permitted for use in the manufacture of food-contact plastic materials (known as ‘the Union List’). Despite the establishment of Plastics Regulation, the EC has not achieved full harmonization of the laws governing the manufacture and use of plastic articles throughout the EU. The use of certain components in plastics materials remains outside the scope of the Regulation and, in some instances, subject to specific member state legislation.
 
While monomers and other starting substances, as well as additives intended for use in the production of food-contact plastics, must be included on the Plastics Regulation unless a specific exemption applies, aids to polymerization (ATPs), colorants, and solvents[4] may be used in the manufacture of plastic materials and articles subject to national law. On the other hand, Aids to Polymerization (ATPs) and Non-Intentionally Added Substances (NIAS) are not subject to the positive list requirements of either the Plastics Regulation or Member State legislation; however, as a component of a food-contact article, they remain subject to Article 3 of the Framework Regulation.[5]
   
As a means of introducing further clarity into the regulation of food-contact plastics, the Plastics Regulation includes definitions for additive, ATP, polymer production aid (PPA), and NIAS.[6] These terms are defined in Article 3 of the Plastics Regulation as follows:

• “Additive” means “a substance which is intentionally added to plastics to achieve a physical or chemical effect during processing of the plastic or in the final material or article; it is intended to be present in the final material or article.”
• “ATP” indicates “a substance which initiates polymerisation and/or controls the formation of the macromolecular structure.”
• “PPA” refers to “any substance used to provide a suitable medium for polymer or plastic manufacturing; it may be present but is neither intended to be present in the final materials or articles nor has a physical or chemical effect in the final material or article.” 
• “NIAS” is defined as “an impurity in the substances used or a reaction intermediate formed during the production process or a decomposition or reaction product.”

As identified in the Plastics Regulation, substances subject to the positive list requirements must comply with applicable specific migration limits (SMLs) and the finished FCM must comply with the relevant overall migration limit (OML). For substances outside the scope of the Plastics Regulation which do not require listing, potential migration levels to food are required under the Framework Regulation to be safe.
 
Designing Analytical Studies to Evaluate Compliance

In designing studies that appropriately evaluate the compliance of a food-contact material with the applicable legal requirements, including migration limits, a clear understanding of the intended use(s) of the finished food-contact material is required. For example:

• What types of food is the finished food-contact material intended to contact: aqueous, acidic, alcoholic, fatty, and/or dry?
• What will be the maximum temperature at which the food will contact the substance: room temperature, hot-fill, cooking, etc.?
• Is the food-contact substance expected to be used a single time prior to disposal, such as a food package, or will it be used repeatedly, such as a storage container used in the home?

The answer to these questions will dictate the factors that must be considered in evaluating the compliance of food-contact materials with the technical requirements of the applicable legislation.

The first approach recommended for establishing compliance of a plastic material with the relevant SML(s) is to calculate potential worst-case migration. The purpose of this approach is to gauge the level of a given substance in food, assuming that its entire residual amount migrates to the food. Worst-case migration is calculated based on the residual level in the food-contact article, together with the thickness, density, and surface-to-volume ratio of the material. The advantage of establishing compliance of a given substance using this method is that as it assumes total migration of the residual amount, it would cover all types of food, contact times, and temperatures for the material.

A more refined option for establishing whether an SML is met is by the use of migration modelling, which is based on an understanding of the mass transfer of substances from a plastic material into foodstuffs in accordance with, in most cases, Fick's laws of diffusion. Migration modelling is an accepted screening tool as described in Section 2.2.3 of Annex V of the Plastics Regulation. The EU Joint Research Centre (JRC) has published a guidance document on the conduct of such modeling in which they have compiled the necessary parameters required to utilize modelling for a variety of different polymer types, and for which there is adequate scientific evidence to support the model. As with worst-case migration calculations, migration modeling also requires that the concentration of the particular analyte of interest in the plastic food-contact material be known. Migration modeling also must consider the specific end-uses of the food-contact material (i.e., times and temperatures of any contact with food).
 
When worst-case migration calculations and/or migration modelling are not adequate to establish compliance with the relevant SMLs, testing with food simulants is required. Due to the differences in extractive potential of various foodstuffs, the Plastics Regulation requires that testing with a combination of food simulants be undertaken to simulate contact with all types of food. The recommended food simulants are listed in Table 1 of Annex III. An extensive list of foodstuffs and their assignment to different simulant(s), can be found in Table 2 of the same Annex.
 
Vegetable oil, which is the simulant assigned to represent fatty foods (Simulant D2), is notorious for presenting analytical challenges when testing for substances at low limits. This is why the regulation does allow for the use of two alternative fatty food simulants: 95% ethanol and isooctane. It should be noted that testing in both 95% ethanol and isooctane is required when vegetable oil cannot be used to assess compliance. These simulants are particularly extractive, so depending on the chemical identity of the material being tested, alternative time and temperature conditions may be selected for one of these two simulants as outlined by the JRC. For several specific types of fatty food, migration into fatty food simulants (designated or alternative) may be divided by a factor specified in Table 2, to avoid overestimating migration to a given food – this approach is compatible, to a certain extent, with the use of the Fat Reduction Factor, a correction factor specified in Chapter 4 of Annex V for certain lipophilic substances in Annex I, in which an adjustment to the observed migration level can be made depending on the amount of fat in the food.

When the appropriate food simulant(s) have been determined, it is then time to choose the necessary testing conditions. Annex V of the Plastics Regulation specifies the specific time and temperature conditions recommended for such migration tests. In general, the most severe time and temperature conditions that are foreseen should be tested. Normally, higher temperatures and longer times will automatically cover lower temperatures and shorter times, so often a single “worst-case” set of time and temperature conditions will cover all foreseeable uses of the material.
 
To ensure consistency across industry, the Plastics Regulation does outline some standardized conditions that represent certain universally applicable end uses. For example, a material that is intended to be used for long-term (long-term being defined as more than six months) room temperature storage of food is required to be tested by exposing the material to the required simulant(s) for 10 days at 60ºC. While the majority of the specific testing conditions apply to single-use food-contact articles, the Plastics Regulation also outlines the necessary testing for repeated-use articles.
 
Such articles should be subjected to three consecutive tests (wherein each test simulates a single use of the product). Provided that the stability of the article (i.e., migration in the third test must be lower than in the second; and migration in the second test must be lower than in the first) can be confirmed, compliance is determined by looking at the migration of the analytes of interest in the third extraction. In cases where a substance of interest has a SML of Not-Detectable (ND), compliance must be established in the first extract.
 
For establishing compliance with the OML, recommended test conditions are set forth in Chapter 3 of Annex V. OML testing should also be performed in the food simulants that correspond to the types of food the material will be in contact with.  In contrast to the manner in which SMLs can be assessed, no numerical (i.e., mathematical) models can be used to establish compliance with the OML – testing is required. Only finished articles are required to comply with the OML.

Evaluating the Safety of NIAS

Due to the general safety standard imposed under Article 3(a) of the Framework Regulation, a comprehensive assessment of the compliance of food-contact materials and articles with the applicable requirements in the EU would not be considered complete by the EC authorities without an evaluation of the safety of reaction byproducts, intermediates, and other NIAS that are not otherwise required to comply with specific migration limits and/or be the subject of listings in the applicable positive lists. Experimental assessments of NIAS migrating to food generally follow the SML and OML testing guidelines outlined above.
  
However, while the presence of certain NIAS in food-contact materials may be reasonably foreseeable with knowledge of starting substances and anticipated reaction mechanisms, and specific analytical methods may be developed for assessment of such substances, the indeterminate nature of many other NIAS may require comprehensive screening assessments on finished food-contact articles to determine their presence. Capturing the diverse NIAS that may potentially be present in finished food-contact materials may also require the use of equally diverse analytical methodologies. For example, a comprehensive NIAS screening may require the utilization of the following methods to capture all potential migrants:

• Headspace Gas Chromatography (HS-GC): Analysis of volatiles in the food-contact material, itself
• Gas Chromatography-Mass Spectrometry (GC-MS): Analysis of semi-volatiles in migration extracts
• Liquid Chromatography-Mass Spectrometry (LC-MS): Analysis of non-volatiles in migration extracts
• Inductively Coupled Plasma-Mass Spectrometry (ICP-MS): Analysis of metals in migration extracts

In the absence of specific reference standards for many of these unanticipated NIAS, structurally similar surrogate standards may need to be utilized to aid in the identification of detected compounds and/or to approximate the concentration of these substances in the finished food-contact material or in corresponding sample extracts. However, the use of strategically-selected, structurally representative analytical standards is critical for any reliable concentration assignments that will form the crux of the safety assessments that are mandated under Article 3(a) of the Framework Regulation.

Indeed, a thorough NIAS risk assessment necessarily combines the information gleaned from the above-mentioned analytical testing with toxicological safety data on the specific compounds of interest (or appropriately representative analogs) for the purposes of evaluating the overall safety of the finished food-contact material. While evaluating the safety of the substances based on considerations relating to existing toxicological data collected on that specific substance is preferred, the safety of NIAS of unknown toxicity can be assessed using alternative, but widely-accepted risk analysis principles, such as the threshold of toxicological concern (TTC). However, such evaluations do, nonetheless, require detailed information about the structure and concentration of the individual NIAS.
 
The need for high-quality analytical studies is highlighted by relatively new requirements imposed on manufacturers of intermediate materials by the 15th amendment to the Plastics Regulation. This amendment modified the Annex IV requirements for suppliers of intermediate materials used in food-contact plastic materials and articles to include Declaration of Compliance (DoC) reporting obligations for all substances that are the subject of restrictions in Annex II and disclosure of any substance that is capable of migrating from the final material or article at a concentration exceeding 0.00015 mg/kg food for which genotoxicity has not been ruled out. Similar levels of sensitivity and specificity are also quickly becoming prerequisites of analytical studies used in support of petitions seeking to clear new substances for use in plastic materials and articles contacting food in the EU.

[1] Commission Regulation (EC) No. 2023/2006 of 22 December 2006 on good manufacturing practice for materials and articles intended to come into contact with food, as amended.

[2] Commission Regulation (EU) No 10/2011 of 14 January 2011 on plastic materials and articles intended to come into contact with food. The Plastics Regulation has since been amended on numerous occasions.  

[3] See Article 2, paragraph 1 of the Plastics Regulation.

[4] See Article 6, paragraph 2 of the Plastics Regulation.

[5] See Article 6, paragraph 2 of the Plastics Regulation.

[6] See Article 6, paragraph 2 of the Plastics Regulation.