Introduction In the pharmaceutical industry, Out-of-Specification (OOS) events can have significant consequences, impacting product quality, patient safety, and regulatory compliance. Effective OOS investigation is crucial to identify the root causes, implement corrective actions, and prevent future occurrences. This blog post will explore various tools and techniques employed in OOS investigations. Essential Tools for OOS Investigations Data Analysis Tools: Statistical Software: Leverage software like Minitab, Excel, or specialized statistical packages for data analysis, trend identification, outlier detection, and process variability assessment. Quality Management Systems (QMS): Utilize QMS software to centralize and manage quality data, facilitating efficient data retrieval, analysis, and reporting during investigations. Electronic Batch Records (EBR): Employ EBR systems to capture and store detailed manufacturing process information, aiding in tracing back steps, identifyi
Pharmaceutical Isolator | Sterility Test Isolator Review
Nowadays pharmaceutical Isolators play important role in the sterile pharmaceutical company. Being sterile production, aseptic conditions are prerequisites for sterile dosage forms. Hence, sterility test isolators are now prerequisites. So to maintain the aseptic environment, Isolators are being used in sterile pharmaceutical industries.
Normally to maintain aseptic environment HEPA filters are used. These filters are providing clean air vertically or horizontally. But due to man and material interference, the external air can contaminate the clean area leading to sterility failure. So to overcome this sterility failure, theuse of Isolators is mandatory. In this post we will come to know that, what are Isolators and how they work.
Sterility Testing Isolator in pharma-
These are required to reduce false sterility test failures. This consists of three modules or cubicles generally one for sterilization of accessories. 2nd for sterility testing and third for material transfer. Usually, it involves glove ports to minimize the manual interventions inside the cubicle.
Isolator for material transfer:
1. Interface isolators, 2. Transfer isolators, 3. Filling machine isolators,
4. Powder charging/handling isolator.
Benefits of Isolator in Pharma industry:
To achieve a clean environment for sterility testing.
To handle dangerous materials.
As per PICS guidance for the installation of isolator, a controlled area is enough. So the cost of maintaining the ISO class area s reduced.
Reduced chances of sterility failure and false results occurrence.
Provides a way to perform aseptic manipulations inside a clean environment.
To maintain positive pressure inside the testing area.
To reduce cross-contamination of microorganisms caused by material handling.
The results are reliable.
In this decontamination procedure is too faster.
As per user requirements, load validation activities can be conducted.
The process
How Isolator Works?
Generally, the isolator is separated from the external environment by using glove ports. Using these glove ports, aseptic manipulation is being conducted. The HEPA filtered air is utilized for maintaining clean air. However, to achieve the sterility assurance level, H2O2 as a sterilizing media is used. During qualification phases, the concentration of H2O2 has to be determined.
The most important is to perform the qualification of the isolator. Many times the procuring party is qualifying the isolator. But the comply with the company set standards again qualification at the site is most important.
The sterility test isolator comes with cubicles. In the 1st cubicle, the accessories and articles used for sterility tests are kept. This is called "load". This load was later sterilized by using H2O2.
The isolators are the same as the bio-safety cabinet. The only difference is that the decontamination provision is available inside the Isolator. But biosafety cabinet has to be cleaned and sanitized routinely with approved disinfectants. For demonstration purpose, the animation video is prepared for the bio-safety cabinet. In the demonstration, only one cubicle was animated; wherein sterility testing activity is conducted. This is to understand the airflow direction in the bio-safety cabinet.
Isolator Qualification Process:
The isolatoris equipment and before utilization of the Isolatorfor routine usage, the Isolatorhas to be qualified. The Isolator qualification process is similar as required for equipment qualification. The stages are mentioned below.
1. URS for Isolator: User requirement specification
This is the first step of procuring an Isolator. Through this document, the user has to mention the detailed requirement of the isolator. In this, the user must specify the required size of the equipment, auto / manual controls, required alarms, procedural requirements, and safety interlocks.
2. Design Qualification of Isolator:
Though the Isolator design is available in the market and we can simply procure by verifying its design, still, FAT and SAT requirement have to be considered for customizable isolators before installation at the site. Through this process, the user has to verify the design requirements of isolator are meeting the user requirements. The party/supplier has to provide detailed design specifications by which the user can compare the design requirements. The requirements for utilizing 21 CFR controls as per (Chapter 11 - Electronic records) have to be assessed through a Computer system validation program.
3. Risk Assessment for Isolator:
Before proceeding for installation, the Risk assessment must be there to evaluate the risk of installation and operation of the Isolator.
4. Installation Qualification of Isolator:
The isolator comes in part. These all parts are assembled at the site by servicing engineer. To operate the isolator utility points are required to maintain the airflow inlet and exhaust. After installation of all cubicles in the area, the installation qualification of isolator can be certified.
5. Operational Qualification Isolator:
To perform operational qualification, first, it is to be cleared that, all the soft switches, software panel operation, alarms challenges need to be completed. The isolator has a pressurized cabinet, which actually prevents the ingress of external contamination. So, leak test of all isolator cubicles to be tested. After satisfactory evaluation of leak test, the filter integrity of HEPA filter provided is to be conducted followed by air velocity test.
The most important part is to evaluate and develop the decontamination cycle using H2O2. The evaluation of the hydrogen peroxide concentration required to kill the existing bioload shall be performed. For that, use of chemical indicators and biological indicators shall be used.
In some cases, hold time of decontamination is required and that can be evaluated simultaneously with operational qualification.
The environmental monitoring i.e. air sampling is to be performed from the cubicle to evaluate after decontamination there is no microbial ingress. During operational qualification, the standard operating procedure shall be developed.
All the details required in the qualification of Isolator are detailed here.
1. HEPA filter integrity testing.
2. Differntial pressure evaluation.
3. Leak testing evaluation.
4. Environmental monitoring.
5. Air velocity measurement.
6. Decontamination cycle development.
7. PLC validation (If applicable)
8. Evaluation of CSV parameters.
9. Airflow direction testing
10. Chamber recovery study.
11. Temperature monitoring.
12. Viable and non-viable particle monitoring.
13. Gloves and glove port integrity testing.
14. calibration of instruments.
15. Utility point evaluation.
All the above parameters shall be challenged deeply during the operational qualification of Isolator. based on the satisfactory results, performance qualification signed off.
6. Performance Qualification of Isolator:
In the scope of performance qualification, the developed cycles are needed to be challenged for 3 consecutive days. based on the satisfactory evaluation of biological and chemical indicator results, the performance qualification of Isolator can be certified.
7. Scheduled Revalidation of Isolator:
After performance validation of Isolatorscheduled revalidation is to be performed for below details;
a. HEPA filter integrity
b. Decontamination cycle validation
c. Leak testing
Review Done By:
Prashant Suresh Devmore
If you want to send a review, kindly send review details to, prashantdevmore@hotmail.com
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