What is formation of glass lamellae in sterile dosage form containers, how formation of glass lamellae can be eliminated.
Current good manufacturing practices > requirements< for finished drug product requires that a parental dosage form must to be sterile and pyrogen free, as well as must be free from particulate matter.See 21 CFR 210
There are certain incidence where the container it self accounted for addition of particles in the sterile liquid later on storage. The glass vials of small unit dose of injectables were found to be adding its minute glass flakes later after filling and sealing and the glass particles shed during filling and sealing could not be detected by visual inspection due to its transparent characteristics the condition which we are referring is called as formation of formation of glass lamellae. Glass lamellae are glass flakes shed from inner surface of glass vial, there are several reasons for formation of glass lamellae.
One of the reason for formation of glass lamellae is localised solubilisation of alkali over the glass surface followed by localised supersaturation, the process is enhanced by heat.
1. Glass vials produced with high temperature method (tubing process) are not resistant as glass vials formed by process of molding
2. Characterics of filled solution an highly alkaline solutions and buffers like citrate and tartarate are found to induce glass lamellae formation
3. The time period for which the solution will be in contact with the glass that is storage time , more is the self life better quality of glass should be chosen.
4. Storage temperature, the glass vials congaing drug product stored at room temperature are more likely to form glass lamellae.
5. Product vials sterilized by the method of terminal sterilization are more susceptible for formation of glass lamellae later.
Numbers of products were recalled due to the formation of glass lamella. c gmp guidelines are mandatory and indicate that the product container should be inert and should not alter the characteristics of a drug being packed within and should not be additive means should not add any fiber or particulate matter of any kind to the product packed within.
Up to now there is no serious effects reported due to glass lamellae, but it has potential danger of causing thromboembolic condition or embolism and other vascular complications like phlebitis and can cause, immunogenicity, irritation and granuloma formation at the site of injection.
What should be done to avoid glass lamellae in injection vials
1.The finally packed sterile dosage form ampoules and vials must be checked periodically for any glass lamella formation and the products susceptible for formation of glass lamellae should be identified.
2.Selection of high quality borosilicate glass.
3.Periodic in process inspections while filling and packaging as well as during shelf life of the product.
4.Conducting supplier manufacturing process and facility audit, to ascertain good quality raw material is used for production of glass vials and ampoules for injecatble dosage form. injectable dosage form manufacturer should do qualification of glass vial and ampoule vendor by periodic examination of vendor quality assurance systems.
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