The articles that we generate are part of our commitment and program to better educate the numerous clients we serve. Much of the content is derived from common questions that we are asked by clients to specific concerns and issues that they routinely face. In many cases, based upon our years of experience and the time we have dedicated to the area of pharmaceutical container testing, we are able to assist clients quickly and easily – we operate and make our living performing container testing so we do see and live it more than the average package engineer. But in addition to our “experience”, there are other sources of information that can assist and support some of the more common concerns and questions regarding USP 661 Container Testing. This article, which was pulled directly from the USP web site, will outline answers to ten common questions that the USP has received specific to the USP 661 chapter.
To prevent any forthcoming outcry of plagiarism, I state again, that the following list of questions and the corresponding answers are taken directly from the USP web site. The link to the relevant page is pasted in below. The purpose of this “reprint” is twofold: (1) we want to share with you this FAQ resource that the USP has published. We encourage you to visit the page and you will see that there are other sections of the USP that are covered with a FAQ section. (2) the common USP 661 questions and the answers are being reprinted in this article as a convenient way for you to quickly see and learn from them.
To access the USP 661 Container Common Questions please visit:
- Within the pharmaceutical industry there are many polymers used to construct packaging systems; however, in <661> there are a just a handful of polymers that are specifically called out with test procedures and specifications. How are polymers that are not specifically called out in the chapter tested to meet the Compendial requirements?
For polymers that are not specifically called out in the chapter (e.g. PVC), they should meet the requirements listed under the Biological Reactivity and Physicochemical section.
- For the identification of polymers, one of the test procedures calls for the use of an IR spectrophotometer equipped with a KRS-5 internal reflection plate. However, this plate is not readily available. Can an alternate plate be used?
An alternate plate can be used if it can be determined that the plate give equivalent or better results (See General Notices 6.30 Alternative and Harmonized Methods and Procedures).
- For a single polymer there are many formulations. The diversity in polymer formulations can lead to minor differences in scans produced by differential scanning calorimetry (DSC) when compared to the USP Reference Standard (R.S.). How should these differences be addressed?
The purpose of preforming the DSC identification test is for the purpose of classification; and thus identification only needs to be sufficiently precise to accomplish this objective. For this reason, the specification in the chapter around DSC material identification states that “the thermogram of the specimen is similar to the thermogram of USP R.S.”
- General Chapter <661> calls for the identification of Polypropylene Copolymer using DSC. Currently, there is no USP Polypropylene Copolymer R.S. Thus, how can identification be sufficiently determined?
Since there is no USP R.S. for polypropylene copolymer, an in-house standard should be developed for this material used during testing.
- Nonvolatile Residue Testing for polypropylene and polyethylene (high density and low density) mentions the use of water, alcohol and hexane as extracting medium. However, it is not clear if the test sample should be extracted in one or all extracting medium.
All three extracting medium should be used in preforming the Nonvolatile Residue Test for polypropylene and polyethylene.
The designation of USP Class VI refers to the biological reactivity or compatibility of a polymer. In <88> Biological Reactivity, In Vivo, there are six polymer classes I-VI. The classification is based on responses to a series of in vivo tests for which extracts, materials, and routes of administration are specified. These tests are directly related to the intended end-use of the polymer.
- Is it required to test each incoming lot of material or component to ensure it meets the Compendial requirements?
The frequency of testing and sampling are left to the preferences or direction of those performing the testing, and other users of USP–NF, including manufacturers, buyers, or regulatory authorities (See General Notices 3.10. Applicability of Standards).
- How will <661> address heavy metals testing of polymeric materials now that <231> Heavy Metals is being omitted from the USP?
The official omission date of <231> Heavy Metals is January 2018. The omission of this standard and alternate testing is address in a proposed revision to <661> that appears in PF 40 (5) Sept. – Oct. 2014. In the proposed revision <661> is split into two chapter, <661.1> Plastic Packaging Systems and Their Materials of Construction Plastic Materials of Construction <661.1>, which contains methods for the testing of extractables metals and <661.2> Plastic Packaging Systems for Pharmaceutical Use, which references <232> Elemental Impurities. The proposed revision of <661> will become official before the January, 2018 omission date of <231>.
- <661> is in the revision process and there seems to be a paradigm shift in the testing requirements and philosophy of the chapter. What is the rationale for the paradigm shift of the chapter and the methods selected?
USP Plastic Packaging General Chapters: An Overview, published in PF 39 (5) Sept.-Oct 2013, provides an overview and rationale for the proposed changes to <661>. The objective of these chapters, Plastic Packaging Systems and Their Materials of Construction <661>; Plastic Materials of Construction <661.1>; Plastic Packaging Systems for Pharmaceutical Use <661.2>,are to delineate a general and chemistry-based approach for establishing the safety and quality of packaging systems and their materials of construction.
- In determining the suitability and safety of a polymer or packaging component for a specific drug product application, extractable and leachable studies are typically preformed. Is there any current guidance in the USP that speaks to extractables and leachable testing?
There are two new General Chapters, Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems <1663> and Assessment of Drug Product Leachables Associated with Pharmaceutical Packaging/Delivery Systems <1664>, which present a framework for the design, justification, and implementation of an extractables and leachables assessment.