Purified water in the pharmaceutical industry is a critical component because it is used at various stages of pharmaceutical manufacturing. There are many cases of water system failure in pharmaceutical industries that can be a cause of quality-compromised products. In this article, we shall discuss two different case studies of water system failures in the pharmaceutical industry.
Case Study 1: Microbial Contamination
Background
Once the higher management of a pharmaceutical manufacturing facility situated in Baddi Industrial Area (India) contacted me when they were experiencing recurrent issues of microbial contamination in purified water. This was causing production delays and quality concerns.Issue
The manufacturer was routinely disinfecting the water system but the bacterial contamination and endotoxin were consistently detected in purified water and exceeded the specification limits.Troubleshooting Approach
1. Root Cause Analysis
A throughout investigation was conducted to find the root cause of microbial contamination. A biofilm formation was discovered in the distribution pipeline of the purified water system. It was working as a microbial contamination reservoir that releases the microbes even after routine decontamination.2. System Assessment
The design and operation process of the purified water system were evaluated and found that the system has some deficiencies in design due to which the biofilm was formed. Sufficient flushing of the system was not being done and it contributed to the formation of biofilm.3. Enhanced Monitoring
A laser-induced fluorescence (LIF) system was installed in the water system to monitor the microbial contamination in real-time which allows the microbial contamination immediately. Additionally, regular microbial testing from all user points was implemented to ensure the compliance of purified water with specifications.4. Process Optimization
An enhanced disinfection protocol was implemented that includes periodic chemical cleaning and thermal sterilization of distribution pipelines with hot water (80°C for 4 hours). Some modifications were also made in the water distribution system and reduced the dead legs where biofilm could form.5. Training
Personnel involved in maintaining and operating the purified water system were trained in proper disinfection procedures and biofilm formation prevention strategies.Outcome
By implementing the above corrective actions, the root cause of the issue was addressed and a successful microbial count in the purified water was observed. This removal of microbial contamination from the water system helped the firm to minimize production delays and product quality issues.Case Study 2: Inadequate Water Quality
Background
Another purified water system issue was highlighted by a reputed pharmaceutical company from Egypt. They have issues with water quality that result in the out-of-specification results of purified water.Issue
Routine analysis of purified water showed an increased level of Total Organic Carbon (TOC) and conductivity in purified water. This increased the risk of compromised product quality.Troubleshooting Approach
1. Root Cause Analysis
An extensive analysis of purified water analytical data and system performance and maintenance was done to find the possible causes of increased TOC level and conductivity in the water system. It was found that the reverse osmosis (RO) membrane was compromised and it allowed to pass the organic contaminants during filtration and those were the cause of the increased TOC value and conductivity of purified water.2. Equipment Evaluation
RO membrane of the water system was evaluated for its performance and condition by using a special test of membrane integrity. Some deficiencies in the pretreatment process were also observed that leads to increased carbon levels in the water system.3. Validation Review
Validation documents of the purified water system were reviewed and updated to meet the regulatory requirements required for the pharmaceutical purified water system. Validation of the water system was conducted and corrective actions were implemented to verify regulatory compliance with standards.4. Process Optimization
Suggested corrective actions were implemented to prevent the issues happen with the membrane and pretreatment procedures. The damaged RO membrane was replaced and an enhanced monitoring system was implemented to monitor the increased TOC in an early stage.5. Regulatory Compliance
By implementing the above corrective actions, facility ensured the compliance with regulatory requirements for the purified water system in pharmaceutical and good manufacturing practices. The validation documents and corrective action implementation report were submitted to the regulatory authorities to demonstrate compliance and water quality.Outcome
By implementing the corrective actions, the facility restores the compromised water quality and integrity of the purified water system. Purified water started to meet the regulatory specifications to maintain the product quality during the manufacturing process.
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