Stability, Extractables and Leachables: What Plastic Containers Contribute to Product Quality

Abstract

A container is not inert. Plastic walls contain antioxidants, slip agents, plasticisers and colorants, some of which can migrate into a formulation, and the formulation can in turn degrade the polymer. For cosmetic products this is a quality and safety question; for pharmaceutical products it is a regulatory one. This article explains what stability and extractables work actually measures, and how packaging choices influence the effort required to demonstrate compatibility.

What Stability Testing Covers

A stability study places the finished pack under controlled conditions for a defined period and measures the product's critical quality attributes at intervals. For a cosmetic, those attributes typically include appearance, pH, viscosity, color and odor; for a pharmaceutical, they include assay, related substances and dissolution. The container contributes to the result through permeation, sorption and leaching, and through physical changes such as ovalisation of a jar that has absorbed oil. A study that tests only the formula in glass tells you about the formula but not about the pack, which is why finished-pack testing is the only meaningful compatibility evidence.

Extractables and Leachables in Plain Terms

Extractables are the substances that can be drawn out of a material under aggressive laboratory conditions; leachables are what actually appears in the product under real storage conditions. The first is a property of the material, the second a property of the system. Testing extractables involves soaking material samples in solvents chosen to represent the formulation, then analysing the resulting solution for organic and inorganic species. Leachables testing analyses the product itself after storage. The practical value of the distinction is that extractables data can be obtained quickly and used to screen materials before a long stability study begins.

How Packaging Choices Reduce the Burden

Material selection is the most effective lever. Resins with short additive lists, pigments based on well-characterised colorants, and adhesives with known composition produce simpler extractables profiles. Avoiding recycled content in direct-contact layers removes a source of variability that is difficult to characterise. Where a barrier layer is used, it separates the product from the structural material and can dramatically reduce migration. Standardising on a small number of materials across a product range also means one compatibility dossier serves several SKUs, which is a commercial advantage as much as a technical one.

Supplier Documentation

Packaging suppliers are typically asked for material safety data, food-contact or cosmetic-compliance declarations, and in some cases migration test summaries. The quality of that documentation varies widely, and a supplier that cannot state the composition of a liner or an adhesive cannot support a serious compatibility assessment. Buyers should request declarations that name the resin family, list the additive classes and state the regulatory basis for the claim, rather than a generic certificate. Where a formulation is unusual, an early conversation about wetted materials prevents a late discovery that the chosen closure contains an incompatible elastomer.

Practical Sequence

• Define the product's critical quality attributes before selecting packaging.
• Screen candidate materials for additive content and known incompatibilities.
• Run a short pre-study with the actual formula at elevated temperature.
• Confirm with a full finished-pack stability study at ICH conditions where applicable.
• Include a control in glass to separate formula effects from pack effects.
• Test the pack in its worst realistic orientation and at the highest expected temperature.
• Retain samples for the full shelf life plus a margin.
• Document any change of resin or additive as a change requiring re-assessment.

Working With a Packaging Supplier on Compatibility

The most useful conversation with a supplier happens before the tool is ordered. At that point the resin, colorant and liner are still open questions, and a change costs nothing. Once tooling exists, changing resin means re-qualifying dimensions, and changing a liner means re-running stability work. Suppliers can usually name the wetted materials, state whether a liner contains silicone or a slip agent, and describe how a closure was tested for compatibility in similar applications. Asking for that information in writing, and keeping it with the product's technical file, avoids the situation where a compatibility failure is investigated months later with no record of what changed.

Conclusion

Container-product compatibility is demonstrated, not assumed. Stability studies show whether the pack preserves the product; extractables and leachables work shows what the pack contributes. Choosing simple, well-documented materials and testing finished packs early reduces both the technical risk and the cost of the evidence required to support a launch.

References

• ICH Q1A(R2), Stability Testing of New Drug Substances and Products.
• ICH Q3E, Assessment of Extractables and Leachables in Pharmaceutical Products (draft framework).
• USP <1663>, Assessment of Extractables Associated with Pharmaceutical Packaging Systems.
• USP <1664>, Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging Systems.
• EU Regulation No 10/2011 on plastic materials and articles intended to come into contact with food.
• 21 CFR 211.94, Drug product containers and closures. U.S. Food and Drug Administration.