The primary objective of testing plastic additives is to identify which additives are present in a material and to quantify the levels at which they're present. This information is critical because additives, while essential for imparting desired physical and chemical properties to plastics, are also among the most common contributors to extractables and leachables. These substances can potentially migrate into pharmaceutical products, impacting product quality, patient safety, and regulatory compliance.
Plastic materials used in pharmaceutical applications often contain a variety of additives, including antioxidants, plasticizers, stabilizers, lubricants, and processing aids. While these components are intentionally incorporated to enhance performance, their chemical nature and potential mobility make them important targets for analytical evaluation.
As outlined in USP 〈661.1〉, materials should be tested for all relevant analytes. An analyte is considered relevant if it is either intentionally added during manufacturing or has been detected through analytical characterization. However, no single analytical method is universally capable of detecting all possible additives. Even broadly scoped screening techniques may have limitations in sensitivity, selectivity, or compound coverage. As a result, relying solely on compendial methods may not provide a fully comprehensive profile of all additives present.
Industry best practices emphasize a risk-based, knowledge-driven approach. Information from material suppliers plays a critical role in establishing a complete list of potential additives. Suppliers typically have detailed insight into formulation components, processing aids, and potential impurities which may not be readily identifiable through routine testing alone. At the same time, manufacturers using these materials must evaluate how these additives behave under specific processing and storage conditions, particularly in the context of extractables and leachables studies.
Collaboration between suppliers and pharmaceutical users is, therefore, essential. Leading organizations often implement structured information exchange mechanisms such as technical data packages, quality agreements, or confidential disclosure arrangements. These approaches ensure that all relevant analytes are considered without compromising proprietary information, ultimately supporting more robust material characterization and risk assessment.
In cases where full disclosure is not feasible, alternative strategies may be employed. These include targeted analytical screening based on known additive classes, the use of orthogonal analytical techniques to broaden detection capabilities, and worst-case extraction studies designed to identify unknown or unexpected compounds.
A thorough understanding of plastic additives and their potential impacts is a key component of a robust extractables and leachables program. Identifying all relevant analytes through a combination of supplier knowledge, analytical testing, and scientific judgment helps safeguard product quality and ensures alignment with regulatory expectations for pharmaceutical packaging systems.
Commonly Requested Plastic Additive Testing
Below are examples of frequently requested plastic additive testing for common materials of construction such as polyethylene and polypropylene used in pharmaceutical packaging:
Phenolic Antioxidants
Test A: If the material contains butylated hydroxytoluene and or ethylene bis[3,3-bis[3-(1,1-dimethylethyl)-4-hydroxyphenyl]butanoate] (USP Plastic Additive 1 RS), perform Test A.
Test B: If the material contains one or more of the following antioxidants: pentaerythrityl tetrakis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] (USP Plastic Additive 2 RS); 2,2′,2″,6,6′,6″-hexa-tert-butyl-4,4′,4″-[(2,4,6-trimethyl-1,3,5-benzene-triyl)trismethylene]triphenol (USP Plastic Additive 3 RS); or 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)-s-triazine-2,4,6(1H,3H,5H)-trione (USP Plastic Additive 6 RS), perform Test B.
Test C: If the material contains octadecyl-3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (USP Plastic Additive 4 RS) and or tris(2,4-di-tert-butylphenyl) phosphite (USP Plastic Additive 5 RS), perform Test C.
Nonphenolic Antioxidants
If the material contains dioctyl disulfide (Plastic Additive 8), didodecyl 3,3′-thiodipropionate (Plastic Additive 9), or dioctadecyl 3,3′-thiodipropionate (Plastic Additive 10), appropriate testing should be performed.
Amides and Stearates
Test A: If the material contains stearic acid, perform Test A.
Test B: If the material contains oleamide (Plastic Additive 12) or erucamide (Plastic Additive 13), perform Test B.
CSA Analytical Capabilities
CS Analytical offers plastic additive testing in accordance with 〈661.1〉 and similar testing as per other compendia (such as the European Pharmacopeia), typically applied to packaging systems intended for higher-risk dosage forms beyond solid oral and topical applications.
We have completed compendial method verification in alignment with USP 〈1226〉, ensuring suitability, accuracy, and reliability of the methods used.
The CSA team brings extensive hands-on experience in identifying and characterizing plastic additives in pharmaceutical materials. Our scientists and quality professionals work closely with clients to develop fit-for-purpose analytical strategies tailored to specific materials, ensuring alignment with composition, intended use, and risk profile.
All testing is conducted in a cGMP-compliant, FDA-registered, and FDA-audited laboratory, ensuring data integrity and confidence in the accuracy and reproducibility of results.
Whether you are evaluating additive composition in incoming materials, monitoring batch-to-batch consistency, assessing extractables and leachables risk, troubleshooting compatibility or stability concerns, or generating data for regulatory submissions, CSA provides reliable and compliant solutions for plastic additive analysis.
Contact us today: engage@csanalytical.com
Call us: 888-571-1207