Process Analysis of Breakage and Cracks in Pharmaceutical Vials Using DMAIC Problem Solving Methodology

Pharmaceutical industries are using glass vials to fill in the vaccines that they manufacture at their facility. The filling/finish department of the organizations are faced with an issue in their filling line which has become a serious threat to the product quality, safety, and the business reputation. When a vial cracks, it leads to contamination of the pharmaceutical product or the vaccine that is filled in the glass vials. This leads to the growth of the bacterial or fungus contaminations in the product. When these contaminated vaccines are intravenously administered, the contaminations directly enter the blood circulation of the human body. The contaminations circulate through the blood and affect different parts of the body, it might enter the heart or brain leading to an individual’s coma or even death. In the past, there has been a lot of recalls regarding the contamination of vaccine due to the presence of vial cracks. All these incidents have led to creation of more stringent quality gates and more advanced technologies to prevent escaping of the cracked vials into the market. Despite the presence of the advanced technologies and stringent quality gates, there is still occurrence of vial breakage inside the filling line. When a breakage occurs, it causes production down time of 8 hours. The reason for this huge downtime of 8 hours, is that the entire filling process of this vaccines take place in a sterile environment and breakage of glass vials in this environment requires cleaning of the broken glass vials from the sterile environment and resterilising the whole environment through standard sterilization techniques. This is a heavy business loss as the time, money and resources utilized in manufacturing of those vaccines are ultimately scrapped when the vial breakage occurs. The fundamental job of packaging material for the capacity and conveyance of pharmaceutical product is to prevent contamination and loss of sterility. This is particularly significant for glass vials, as loss of sterility or contamination can bring about coma or even death. comprehensive assessment of the process has been performed and to understand all the factors that will contribute to vial cracking, DMAIC (Define, Measure, Analyse, Improve, & Control) problem solving methodology is used. The Analysis Part of the DMAIC approach consists of two phases. Phase I of this research focused on the statistical analysis of the empty glass vial visual inspection machine rejection rates. Rejection Rates for the past 2 years has been collected and hypothesis testing is used which showed that the visual inspection machine rejection rate is within the target limits and Box plots show that the rejection rate increases with the increase of vial size. Also, the Visual inspection machine was subjected to Repeatability MSA analysis to control and judge the measurement process. Phase II of this research examined the combined effects of impact force and thermal exposure in the glass vials. A combination of tools was used to identify the magnitude of stresses developed in the vials due to the impact force and thermal exposure including: numerical methods which establish the impact force the vials are subjected to and those calculated values along with the thermal exposure value ( in °Celsius) are applied in 3D modelling CAD/Simulation software such as Solid works and Ansys. This Analysis is done for all the vial sizes (50 ml, 100 ml, 250 ml, & 500 ml) that are used in the production facility. The magnitude of stress which was calculated in the CAD/Simulation software was compared with the SN curve. The SN curve comparison gave the Stress-Cycle at which a typical impact breakage will occur. The combined results of phase I and II pointed out several flaws in the process causing the vial cracks/breakages in the production process. Also, careful study of the Incoming Vial inspection quality procedures is made, and suitable conclusions are derived. Solution for one of the root causes is provided as a design and they are incorporated as part of the project plan that is being proposed. Finally, this paper, proposes a project plan to implement solutions and improvement activities in the production process to eliminate the vial breakage issue in the filling line.