USP <660> - Time for a Change
January 27th of 2023 was a memorable day. That was when the United States Pharmacopoeia (USP) posted a Notice of Intent to Revise in their Revision Bulletins1 that caused a wave of discussion. What was this notice and why was it so remarkable?
Glass is the material most widely used for primary packaging containers for injectables since over a century. But this is not just any glass, it has always been either borosilicate or soda-lime glass, two well-described and well-known glass compositions in the pharmaceutical industry2 . As these have been the only two glass compositions used, regulatory and guidance documents, such as USP and the European Pharmacopoeia (Ph. Eur.) and guidance documents from the International Organization of Standardization (ISO), center around tailor-made tests that are connected to those specific glass compositions. In the USP General Chapter <660> Containers – Glass e.g., there are currently three glass Types described that can be used for pharmaceutical products: “Type I glass” which is defined as borosilicate glass, “Type II glass” which is treated soda-lime silica and “Type III glass” which is defined as soda-lime silica glass.
Within the past years, several new developments in the container arena have come to the market. Not only has the use of high-quality polymer materials, such as COP and COC increased, but also in the glass sector we have seen new developments: Quartz glass as the purest form, combinations of glass with polymer should combine the best of both worlds, or simply a completely new glass composition, such as the aluminosilicate Corning® Valor® Glass from Corning Incorporated®. This glass composition was developed to answer some of the still existing difficulties with the standard glasses on the market, which are delamination and glass breakage. In parallel, the COVID-19 pandemic with its emerging supply chain challenges for certain glass vials has accelerated these new developments.
Now, the United States Pharmacopoeia was faced with a great task: How to include these new developments in a chapter that is over half a century old?
In the meantime, the FDA was also evaluating these new options through their Emerging Technology Program (ETP). Their Office of Pharmaceutical Quality’s laboratory conducted studies on the new “aluminosilicate-type glass to assess if it is more resistant to delamination (i.e., lamellae formation), and two commonly used Type I borosilicate glass products.”3
They finally came to the conclusion that the current USP chapter as it is written now does not provide enough flexibility for pharmaceutical companies to introduce new glass compositions to their primary packaging portfolio. FDA published a letter emphasizing their “recommendation to revise the definition of Type I glass from composition-based characteristics to performance-based characteristics to allow for innovation in the manufacturing of glass intended for parenteral packaging.”4 Further, FDA mentioned that they are “supportive of the use of new glass compositions if they demonstrate equivalent or superior performance characteristics such as improved thermal and hydrolytic resistance compared to the current compendial glass compositions and demonstrate suitability for the drug product; however, restrictive compendial definitions have impeded adoption of new glass compositions with such characteristics.” …” To retain the strict scientific standards for glass packaging while maintaining inclusivity for new glass compositions, FDA strongly recommends that glass be defined by its performance characteristics and not solely on its composition.”
Based on this feedback and interaction with the FDA, USP set out and revised their General Chapter <660> Containers – Glass to disconnect the Type designation from the glass composition. This way, glasses that pass the test for Type I can be used for drugs that require Type I glass as per the packaging section in their monographs.
So, the note that was published on January 27th, 2023, announced this revision:
“To address challenges, the proposed compendial revisions described in this General Announcement would include the following:
- Revisions to General Chapter <660> to remove glass classifications based on composition. Currently, <660> defines: Type I (borosilicate glass); Type II (treated soda-lime silica); and Type III (soda-lime silica). Under the proposal, General Chapter <660> would instead define glass Types I, II, and III by performance characteristics, allowing for additional compositions to be considered Type I, II, and III glass. There are no proposed changes to test procedures or acceptance criteria. Please see the Notice of Intent to Revise for additional details, background, proposed timeframes, and contact information.
- Revisions to 14 monographs that currently prescribe a specific glass type by adding the word “preferably” in the packaging section of the monograph –For example, a current monograph that requires “Type I glass” would be revised to state “preferably of Type I glass.” The addition of the word “preferably” to the monographs at issue means that the use of the glass specified is preferred, but not required. This proposed revision will give manufacturers additional flexibility in their choice of packaging and pave the way for new or different types of packaging to be approved. Please see the Notice of Intent to Revise for additional details, background, proposed timeframes, and contact information.”
This approach is remindful of the way elastomeric primary packaging components are addressed. In the chapter <381> Elastomeric Components in Injectable Pharmaceutical Product Packaging/Delivery Systems there is no definition or formulation description for rubber types, but instead the entire chapter describes tests for physical and chemical performance characteristics.
On March 1st, 2023, the General Chapters-Packaging and Distribution Expert Committee has published the revision proposal to General Chapter <660> Containers – Glass in the Pharmacopoeia Forum (PF) 49(2) [March-April 2023] , with a comment deadline of May 31, 2023. After all the comments have been addressed by the Expert Committee, the final version of the chapter was published on August 25th and was just made official on October 1st 2023.
This just leaves one important question: What does that mean for the current state of global pharmacopoeia harmonization? It is true that now the USP and Ph. Eur. are not harmonized anymore with regards to this specific point. However, the Japanese Pharmacopoeia never had this connection between the glass composition and a type designation. They are describing similar tests as USP <660> and Ph. Eur. 3.2.1 but without any reference to any glass composition. Also in China there are ongoing revisions of their entire pharmacopoeial chapters and industry standards (YBB). So, we can surely expect more to come on this topic in the future.
If you want to learn more about the Corning® Valor® Glass vials, please visit Corning Valor® Glass Vials page.
- USP <660> Containers-Glass, United States Pharmacopeia (2015), Ph. Eur. 3.2.1 Glass Containers for Pharmaceutical Use; European Pharmacopoeia (2019), ISO 12775:1997(E) Guidelines on types of glass of normal bulk-production composition and their test methods, International Organization for Standardization (1997)
Corning® and Valor® are registered trademarks of Corning Incorporated. West Pharmaceutical Services, Inc. iIs the exclusive distributor of Corning® Valor® Glass.