Introducing the Alba® Primary Packaging Platform. Part 2: Inorganic Extractables Evaluation.

Sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failure as worst-case scenario.This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, or silicone oil droplets or other particles.The Alba primary packaging platform was designed to have the same interface between the drug and the glass container surface on the different primary packaging containers in order to minimize the emergence of instabilities at later stages of formulation development. Alba containers are internally treated with an innovative cross-linked coating based on silicone oil lubricant, and the additional rubber components have been selected to minimize the possible differences between the container typologies.This paper shows in great detail the reduction of the inorganic extractables released and the comparability of the performances of the different containers obtained using Alba technology.The improvement has been demonstrated by stressing the containers with different extract solutions; Alba-coated containers show a strong reduction of inorganic extractables and of corrosion degree compared to spray-on siliconized and bulk products. The containers included in the Alba platform present comparable results, and this represents a strong advantage during the drug formulation development by facilitating the transition from one container to another.LAY ABSTRACT: The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failure worst-case scenario.This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, or silicone oil droplets or other particles.The Alba primary packaging platform was designed to minimize these problems associated with the interaction between the drug and its primary packaging. This paper shows in great detail and with robust data the inorganic extractables release reduction and the delamination risk mitigation obtained using the Alba technology.

Introducing the Alba® Primary Packaging Platform. Part 1: Particle Release Evaluation.

The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failures as worst-case scenarios. This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, substances coming from the production process, silicone oil droplets, or other particles. The Alba primary packaging platform was designed in order to have the same interface between the drug and the glass container surface on the different primary packaging containers to minimize the emergence of instabilities at later stages during the formulation development. The Alba containers are internally treated with an innovative cross-linked coating based on silicone oil lubricant, and the additional rubber components have been selected to minimize the possible differences between the container typologies. This paper shows in deep detail the subvisible particle release reduction and the comparability of the performances of different containers, obtained using such technology. To demonstrate this improvement, different analytical methods for particle measurement were used on bulk containers, Alba-treated ones and containers from a standard production (spray-on siliconization). Considering that Alba containers are conform to the standard compendial testing and the amount of particles released from Alba-coated syringes was comparable to the bulk syringes for the first two mildly stressful methods, it was decided to develop and apply a more challenging method, such as an autoclave treatment for 1 h at 121°C, to better highlight the performances of this innovative technology. The data obtained, under the most stressful conditions, show a substantial reduction in the released particle concentrations compared to a spray-on siliconized container, with comparable performances for all the containers included in the Alba platform. The latter could heavily reduce drug formulation development timing, facilitating the transition from one container to another.LAY ABSTRACT: The sensitivity of drugs to one or more elements of the primary packaging is a serious concern for the pharmaceutical industry. Biologics in particular are highly sensitive, leading to a higher risk of incompatibility and stability test failures as worst-case scenarios. This potential incompatibility-and the consequent formulation instability due to the interactions between the drug and the primary container surface-may have multiple causes: the intrinsic nature of the container surface, leachables coming from the materials used, or substances coming from the production process, silicone oil droplets, or other particles. The Alba primary packaging platform was designed to solve these problems associated with the interaction between the drug and its primary packaging. This paper shows in deep detail and with robust data the subvisible particle release reduction obtained using such technology.

Delamination Propensity of Glass Containers for Pharmaceutical Use: A Round Robin Activity Looking for a Predictive Test.

Delamination, which is the formation of flakes in drug products owing to specific and localized corrosion of glass vials, is a rare but serious problems, on which the FDA (U.S. Food and Drug Administration) put a warning to the pharma industry in 2011. The Technical Committee (TC) TC12 of the International Commission on Glass (ICG) was created in 2012 with the aim to study the problems related to pharma packaging. The first task of TC12 was to address the problem of predicting the propensity of glass vials to delamination, leaving the study of the mechanism(s) of flake formation as a possible future activity. This paper reports on the results obtained in a round robin test, which involved all the labs of the companies represented in the TC.Five types of vials with different expected delamination propensities were tested using a protocol that includes autoclaving at 121°C of vials filled with NaCl solution adjusted to pH 8 with NaOH solution, a coloration test, and ICP-OES determination of Si, B, and Al.Although there was no flake formation, the results showed that the combination of strong coloration at the bottom of the vials and high silicon concentration in the solution is correlated to an observable morphological modification/corrosion of the inner surface of vials in the bottom region. The test protocol is therefore useful for checking the quality of the vials with respect to the propensity to corrosion. Regarding delamination, no direct correlation with the testing results could be obtained yet. The method allows catching differences in the corrosion behavior, mainly between sets of vials with comparable surface:volume.LAY ABSTRACT: The U.S. Food and Drug Administration (FDA) warned the pharma industry about glass delamination inside primary packaging containers. Delamination is a type of glass corrosion that produces glass flakes, which could seriously affect patient health.Fortunately, delamination is a very rare event. On the other hand, it is very difficult to predict its occurrence. In 2012, the International Commission on Glass (ICG) created a Technical Committee (TC) on pharma packaging-with the initial goal to study an easy and reliable test for predicting the propensity of vials to delamination-involving the most important glass vial producers and pharma companies. This paper reports on the results obtained in a round robin test on different types of vials with different expected propensities to delamination. A specific testing protocol was adopted. In none of the vials, including those with an expected high propensity, glass flakes were observed, demonstrating that delamination is a rare event. However, the test is able to predict the occurrence of morphological modification/corrosion of the inner surface of vials in the bottom region. Therefore, the testing protocol is proposed as a method to evaluate differences in the corrosion behavior mainly between sets of vials with comparable surface:volume.

Delamination propensity of pharmaceutical glass containers by accelerated testing with different extraction media.

The delamination of pharmaceutical glass is a serious issue, as it can cause glass particles to appear in vials, a problem that has forced a number of drug product recalls in recent years. In Type I pharmaceutical glass vials, delamination occurs generally at the bottom and shoulder, where extensive flaming during the conversion process can favor a strong evaporation of alkali and borate species and the formation of heavily enriched silica layers. The contact with parenteral preparations dissolved in an alkaline medium increases the rate of glass corrosion, while the differential hydration of these layers can cause the detachment of flakes. The purpose of this study was to investigate the effect of the pH and the composition of the extraction solutions on the propensity of different glass types to delaminate. Repeated autoclave extractions at 121 °C were carried out on different glass types with different extraction media, including organic extractants like citric and glutaric acid. When vials were in contact with alkaline solutions and similarly aggressive media, an increase in silica extraction values indicated glass corrosion and an increasing risk for further delamination. Under such conditions expansion 33 glass is extensively corroded, showing high silica concentration and heavy flaking as compared to other glass types. Sulfur-treated glass also showed early flaking, even if SiO(2) concentration was very low. A similar ranking was observed with extractions carried out with glutaric and citric acids, but at far much higher SiO(2) concentration levels. Extractions with 0.9% KCl solution can be used as an accelerated test to highlight the propensity of a glass to delaminate, but in no case it can be taken as a guarantee that the glass will not delaminate when exposed to the pharmaceutical drug, whose extraction ability requires case-by-case study. LAY ABSTRACT: How can injectable drug manufacturers prevent glass delamination? The issue of delamination is a serious one, as it can cause glass particles to appear in vials, a problem that has forced a number of drug product recalls in recent years. To combat this, pharmaceutical and biopharmaceutical manufacturers need to understand the reasons for glass delamination. The most recent cases of product recall due to the presence of particles in the filling liquid have involved borosilicate glass containers carrying drugs made of active components with known ability to corrode glass and to dissolve the silica matrix. Sometimes these ingredients are dissolved in an alkaline medium that dramatically increases the glass corrosion and potentially causes the issue. As this action is strongly affected by time and temperature, flaking may become visible only after a long incubation during storage and requires systematic monitoring to be detected at its early stage. If the nature of the filling liquid is the driving force of the phenomenon, other factors are of primary importance. The surface morphology created during vial forming is a key issue, being a function of the forming temperature that is higher in the cutting step and the forming of the bottom. Delamination occurs generally on the vial's bottom and shoulder, where extensive flaming can favor a strong evaporation of alkali and borate species and the formation of heavily enriched silica layers. When these layers are in contact with a solution, they are subject to a differential re-hydration that may result in cracking and detachment of scales. The purpose of this investigation is to identify testing conditions and parameters that can be used as indicators of an incipient delamination process. Extractions with 0.9% KCl solution for 1 h at 121 °C can be used to simulate a long-term contact with aggressive pharmaceutical preparations, while SiO(2) concentration in the extract solution can be taken as an index of glass dissolution. The conclusions developed by this study can provide pharmaceutical manufacturers with information needed to help prevent glass delamination in their processes.