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Which chapter is relevant now?
Work conducted to either <661> or <661.1> / <661.2> is valid now, but you should consider how you use the data, what you are testing (material or container/packaging system), the benefits of each testing approach and when data is needed.
USP <661.1> and <USP 661.2> becomes official on 1 May 2020 (USP 42–NF 37). However, the latest proposed amendment (PF 45 (2)) is that the implementation date will be 1 December 2025.
Until the implementation date, USP <661> still applies or you can adopt <661.1> and <661.2> early. If early adoption of USP <661.1> and USP <661.2> is chosen, then USP <661> doesn't need to be followed.
Where do USP <661.1> and <661.2> apply?
USP <661.1> relates to a plastic material of construction used to manufacture a packaging system, i.e. the resin.
USP <661.2> relates to a packaging system as a whole; conformance to USP <661.2> does not require the materials to also meet USP <661.1> which is is clarified in PF 45 (2).
You apply USP <661.1> or <661.2> depending on whether you seek to evaluate an entire packaging system or an individual plastic material. Plastic materials are considered characterized and appropriate for use if they meet the requirements of USP <661.1> or are used in a packaging system that meets the requirements of USP <661.2>. The material is only considered to be characterized and appropriate for use for a specific packaging system and pharmaceutical product evaluated against USP <661.2>.
Ultimately, if you wish to secure regulatory approval of a packaging system you need to fulfil the requirements of USP <661.2>.
What happens to USP <661> from 1 December 2025 (PF 45 (2))?
USP <661> in its current form, will become obsolete and testing will follow USP <661.1> and <USP 661.2>.
What are the main differences between USP <661> and USP <661.1> and <661.2>?
USP <661.1> and USP <661.2> data packages provide a greater knowledge-base to facilitate an appropriate evaluation for the correct selection of materials and protect patient safety than would be generated for USP <661>. Overall the philosophies link to USP <1661>, <1663>, <1664> and <1664.1> in terms of risk management.
What are the expectations for elemental analysis?
USP <661.1> describes metal limits in the current USP 42–NF 37, however all limits and specific tests have been removed in the proposed revision PF 45(2), acknowledging: “It is the material user’s responsibility to evaluate the need for extractable elements testing”. The user is instead referred to USP <1661>, which also has a proposed chapter revision (PF 45(2)). The proposed revision for USP <1661> links to Elemental Impurities – Limits USP < 232> and Elemental Impurities – Procedures USP 〈233〉, describing an extractables elements testing strategy using ICP-OES or ICP-MS.
What are the expectations for biocompatability testing?
Based on PF 45(2),
biocompatability testing depends on the dosage form. Oral and topical dosage forms do not require either <87> or <88> testing for compliance to USP <661.1>. All other dosage forms require <87> while <88> is also required to obtain plastic classification. USP <661.2> make the same testing distinctions as USP <661.1>, however <88> need only be performed if a plastic designation is required.
Is an Extractable and Leachables study required?
A “Suitability for Use Assessment” (PF 45(2)) is required for packaging systems as described in USP <661.2>. This may include testing especially for those product types that are considered of risk. Extractables and leachables testing is well described in USP <1663>, <1664> and <1664.1>. This is based on “1) the packaging system, 2) its materials of construction, 3) its components of construction, as appropriate, or 4) the packaged drug product”.
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