A Case Study of Nondelamination Glass Dissolution Resulting in Visible Particles: Implications for Neutral pH Formulations

A Holistic Approach of Extractables and Leachables Assessment of Rubber Stoppered Glass Vial Systems for Biotechnology Products

“…[1][2][3][4] However, various unexpected occurrences including glass delamination and dissolution, metal ions and organic compounds leaching from rubber stoppers have been observed, which could lead to failures for protein therapeutics with respect to product quality or more importantly cause toxicity to the patients. [5][6][7][8][9][10][11][12][13][14][15][16][17] Biopharmaceutical drug products are generally more sensitive to leachables and could possibly be adulterated during storage and transportation, [18][19][20][21][22][23] therefore, high quality vial systems used as primary containers and delivery systems are necessary.…”

Particles in Biopharmaceutical Formulations, Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins, Viruses, Vaccines and Cells

“…137 For an in-depth analysis of particle origin, particle ID techniques, specifically SEM-EDX and FTIR microscopy, are applied in the pharmaceutical industry. 99,127,[144][145][146]148,149 In contrast to liquid SO droplets, glass particles and rubber particles are retained on membranes and filters applied during sample preparation for SEM-EDX or FTIR microscopy, allowing for the analysis of the spectral properties and thus chemical composition of the particles. To date, multiple studies have demonstrated the successful identification of glass particles in placebo formulations or actual therapeutic protein products with the help of both techniques.…”

“…To date, multiple studies have demonstrated the successful identification of glass particles in placebo formulations or actual therapeutic protein products with the help of both techniques. 144,148,149 Mixed particles consisting of protein and silicone rubber particles were identified by Raman microscopy and IFC. 97 Raman microscopy can also be applied for the in situ identification of particles as shown for cellulose fibers and polypropylene particles.…”

Impact of Residual Impurities and Contaminants on Protein Stability

“…Primary glass‐related factors include the glass manufacturing process, surface imperfection/morphology, alkalinity, or treatment . Product‐related factors include formulation pH, composition, and storage temperature and duration . Dissolution and delamination can occur at a neutral or basic pH, especially in citrate, tartrate, or phosphate containing solutions …”

“…[188][189][190] Product-related factors include formulation pH, composition, and storage temperature and duration. 191 Dissolution and delamination can occur at a neutral or basic pH, especially in citrate, tartrate, or phosphate containing solutions. 192 Presence of glass particulates can have a negative impact on product quality/stability, which may lead to product recalls.…”