USP has published draft proposals in the Pharmacopeial Forum 52(3) that affect general chapters and reference tables relevant to pharmaceutical packaging and product description. The proposed revisions cover 〈660〉 Containers—Glass, 〈1660〉 Evaluation of the Inner Surface Durability of Glass Containers, and the Description and Relative Solubility of USP and NF Articles reference table.
All three documents opened for commenting on May 2, 2026, with a 90-day comment period, and the chapter revisions are targeted for an official date of August 1, 2027.
The most significant changes are within the glass packaging chapters. USP is proposing to broaden 〈660〉 to cover additional glass compositional families, replace the long-standing Glass Grains Test with a modern X-ray fluorescence identification method, delete the Surface Etching Test, refine the inner surface hydrolytic resistance procedure, and introduce a more sensitive extractable arsenic determination using ICP-based instrumentation.
From a regulatory and GMP perspective, these proposals are important because they redefine how firms identify, qualify, and monitor primary glass packaging used for parenteral and non-parenteral drug products. Several long-established tests are being replaced or repositioned, and the introduction of aluminosilicate and quartz glass into the official chapter expands the compendial framework for glass packaging beyond the traditional borosilicate and soda–lime–silica families.
Overview of the PF 52(3) Draft Proposals
| Chapter / Reference Table | Type | Focus | GMP / Lab Impact |
|---|---|---|---|
| 〈660〉 Containers—Glass | Revision | Retitle to Glass Containers and Their Composition; introduce aluminosilicate and quartz glass; modernize glass identification using WDXRF; revise hydrolytic resistance, arsenic, and spectral transmission sections | Impacts packaging specifications, supplier documentation, CoA/CoC content, incoming QC strategy, CMC references, and container suitability assessments |
| 〈1660〉 Evaluation of the Inner Surface Durability of Glass Containers | Revision | Retitle and expand into a broader chapter on glass manufacture, surface treatments, durability, delamination risk, and predictive screening | Supports risk-based container selection, delamination assessment, extractables/leachables planning, vendor qualification, and formulation-container compatibility studies |
| Description and Relative Solubility of USP and NF Articles | Reference table update | Add two NF entries and clarify the non-compendial-test nature of description and solubility statements | Impacts raw material master data, compendial reference tracking, specification wording, and training around descriptive versus test requirements |
〈660〉 Containers—Glass
Status: Revision
The proposed revision to 〈660〉 is the central scientific change within the PF 52(3) package. USP proposes to retitle the chapter from Containers—Glass to Glass Containers and Their Composition and to substantially restructure the content into two main parts: identification of the glass container based on composition, and performance of the glass container based on hydrolytic resistance, mechanical properties, extractables, and, where applicable, light transmission.
The revised chapter formally introduces aluminosilicate glass and quartz glass into the compendial framework, alongside the existing borosilicate and soda–lime–silica glass families. It also clarifies how the established performance designations—Type I, Type II, and Type III—relate to each compositional family.
Key Revisions
The main elements reflected in the revised draft include:
- Chapter retitle and structural reorganization: The chapter title is changed to “Glass Containers and Their Composition,” and the content is reorganized into numbered sections covering scope, description, and specific tests.
- Introduction of two new glass materials: Aluminosilicate glass and quartz glass are added as recognized compositional families, in addition to borosilicate and soda–lime–silica glass.
- Replacement of the Glass Grains Test for identification: A new test, 4.1.1 Elemental composition by wavelength dispersive X-ray fluorescence, is introduced as the preferred method for glass identification. The Glass Grains Test is retained but repositioned (4.1.2) primarily to distinguish soda–lime–silica glass from the more durable families.
- Deletion of the Surface Etching Test: The Surface Etching Test, historically used to determine whether high hydrolytic resistance is due to chemical composition or surface treatment, is removed from the chapter.
- Revised inner surface hydrolytic resistance test (4.2.1): The autoclaving procedure is described in greater detail, including thermal cycle ramps (heating from 100° to 121° at 1°/min over 20–22 min, holding at 121 ± 1° for 60 ± 1 min, and cooling to 100° at 0.5°/min over 40–44 min), with cross-references to 〈1660〉 for autoclave loading and calibration considerations. The limits table is expanded to include filling volumes ≤0.5 mL.
- New ICP-based extractable arsenic test (4.4): A dedicated extractable arsenic procedure is introduced using ICP–OES, ICP–AES, ICP–MS, or hydride-generation AAS, with calibration recommendations and a limit of 0.1 µg/mL for Type I and Type II containers.
- Revised spectral transmission requirements (4.5): The limits for colored glass containers used for parenteral products are now expressed as a function of nominal wall thickness rather than nominal volume, with a defined calculation for wall thicknesses between 0.45 mm and 1.30 mm.
- New mechanical strength load test (4.3.2): A procedure based on ISO 8113 is introduced to confirm that ion-exchanged glass containers meet the manufacturer’s mechanical strength expectations.
GMP Impact
If adopted, 〈660〉 would meaningfully change how firms identify and qualify primary glass packaging. From a GMP perspective, companies should assess the effect of these changes on:
- incoming material specifications and certificates of analysis
- supplier qualification and audit programs
- analytical method procedures for glass identification and inner surface hydrolytic resistance
- elemental impurity strategies, particularly for arsenic in Type I and Type II containers
- specifications and procedures for colored glass containers, where the move from volume-based to wall-thickness-based spectral transmission limits will require recalculation and possible respecification
- regulatory dossiers, change controls, and technical agreements that currently reference the Glass Grains Test, Surface Etching Test, or 〈211〉-based arsenic determination
The replacement of the Glass Grains Test with a WDXRF-based identification method is particularly significant because it shifts identification from a wet-chemical approach toward instrumental analysis aligned with 〈735〉.
〈1660〉 Glass Containers Used in Pharmaceutical Packaging/Delivery Systems—Manufacture and Evaluation of the Inner Surface Durability
Status: Revision
USP proposes a substantial revision and retitle of 〈1660〉 from Evaluation of the Inner Surface Durability of Glass Containers to Glass Containers Used in Pharmaceutical Packaging/Delivery Systems—Manufacture and Evaluation of the Inner Surface Durability. The proposal expands the chapter from a narrower delamination-focused document into a comprehensive technical reference on the formation, processing, treatment, sourcing, and durability evaluation of glass containers used in pharmaceutical packaging.
The revised chapter is structured into numbered sections that cover: glass composition; formation and processing of molded and tubular glass containers; inner and outer surface treatments; glass container sourcing and supplier qualification; factors influencing container durability during filling operations; glass surface chemistry; classification of glass particles, flakes, and lamellae; delamination mechanisms; evaluation of inner surface durability; extractable elements; and spectral transmission.
Key Revisions
The main revisions reflected in the draft include:
- Chapter retitle and expanded scope: The chapter is reframed to address the full lifecycle of glass containers, from manufacture through processing, sourcing, filling-line behavior, and durability evaluation.
- Coverage of four glass families: The chapter now addresses aluminosilicate, borosilicate, quartz, and soda–lime–silica glass, providing detailed compositional ranges and coefficients of mean linear thermal expansion for each.
- Detailed treatment of inner and outer surface modifications: Combined inner/outer ion-exchange strengthening, dealkalization (including with ammonium sulfate, gaseous sulfuric acid, and 1,2-difluoroethane), plasma vapor deposition coatings, siliconization and silanization, and hot/cold outer-surface treatments are each described with their characteristics and limitations.
- New section on container damage during filling: A dedicated section explains how depyrogenation, accumulation, conveying, capping, and needle alignment can damage the external or internal surfaces of glass containers, and provides practical mitigation strategies.
- Restructured glass surface chemistry section: The reactions between glass and aqueous solutions are presented with revised equations and a discussion of acidic, neutral, and alkaline regimes.
- New classification table for glass particles and flakes: A comprehensive table distinguishes splinters, abrasion-derived particles, precipitation-derived particles, drug–container interaction precipitates, delaminated lamellae, and chemistry-driven flakes, with mechanisms, frequency, location, composition, and corrective actions.
- Refined predictive screening framework: The chapter introduces a clearer distinction between aggressive screening conditions (e.g., 15% potassium chloride/10% sodium thiosulfate at 60° for 8 weeks) and product-specific accelerated screening under conditions linked to actual storage. A worked example of a study protocol is provided for accelerated testing at 40°.
- Detailed discussion of autoclave variability: The chapter expands on critical parameters in the autoclave and titration procedures, supported by a fishbone-style diagram of variability sources, and links these directly to the procedural requirements in 〈660〉.
- Updated extractables guidance: The chapter cross-references 〈1663〉 and 〈1664〉 and provides example extraction conditions across pH and temperature.
GMP Impact
From a GMP perspective, the revision strengthens 〈1660〉 as the principal compendial reference for glass container manufacture, qualification, and durability evaluation. Manufacturers should assess the effect of the revision on:
- delamination risk assessments and supporting documentation for parenteral products
- screening study protocols, particularly those that currently reference the older 0.9% KCl / 3% sodium citrate / 20 mM glycine model systems
- supplier qualification documentation, certificates of conformance, and technical agreements with glass manufacturers and converters
- training materials for QC, validation, and packaging engineering teams
- internal procedures for handling, conveying, depyrogenating, and filling glass containers, especially where line damage and accumulation are known risks
The chapter does not introduce new pass/fail acceptance criteria of its own, since 〈1660〉 remains an informational chapter, but it substantially reframes the conceptualization and documentation of delamination risk and glass durability.
Description and Relative Solubility of USP and NF Articles
Status: Revision
USP proposes to update the Description and Relative Solubility reference table by adding new entries for two NF articles. As USP discontinued routine maintenance of description and solubility information for drug substances starting with USP–NF 2024 Issue 1, the reference table is now primarily maintained for NF excipients and similar articles, with legacy drug-substance descriptions accessible through the “No Longer Official” versions in USP–NF Online.
Key Revisions
The main revisions reflected in the draft include:
- Addition of Benzenesulfonic Acid: Described as a white to light beige powder or crystals with lumps, soluble in water and alcohol, and categorized as a buffering agent, pH modifier, and stabilizer.
- Addition of dl-Lactide and Glycolide (85:15) Copolymer 23000 Hexanediyl Ester: Described as a white to light yellow solid, soluble in a range of organic solvents including acetone, dimethylformamide, dimethylsulfoxide, dioxane, ethyl acetate, hexafluoro-i-propanol, tetrahydrofuran, N-methyl-2-pyrrolidone, dichloromethane, and chloroform, and practically insoluble in water. Categorized as a biodegradable polymer, a polymer for ophthalmic use, and a release-modifying agent.
GMP Impact
The operational impact of this update is limited. It is most relevant for excipient qualification, formulation development, and labeling references where these articles are used. Companies incorporating Benzenesulfonic Acid or the listed lactide–glycolide copolymer into NF-grade formulations should ensure internal specifications and material-handling documentation are aligned with the new descriptive entries once they become official.
Final Thoughts on the PF 52(3) Package
Taken together, these PF 52(3) drafts represent a meaningful modernization of the compendial framework for pharmaceutical glass packaging, alongside incremental maintenance of the NF article description and solubility table.
The 〈660〉 revision is the most consequential part of the package because it changes how glass is identified, expands the compendial recognition of glass families, deletes a long-standing test, and modernizes the extractable arsenic determination. The 〈1660〉 revision provides a substantially more comprehensive technical foundation for evaluating inner-surface durability and delamination risk across all four glass families, with a stronger linkage to the procedural requirements in 〈660〉.
The 90-day comment window that opened on May 2, 2026, provides an opportunity to raise such concerns formally before the proposed August 1, 2027, official date.
