What is an Isolator in pharmaceutical manufacturing? how to do validation of Pharma Isolator
As the name suggests, an isolator is an equipment designed to isolate a drug product during manufacturing from the external environment in the clean room. Isolators separate the drug product from the external environment and protect the drug product from getting contaminated. Drug product is contained inside an isolation system in the isolator which not only protects product contamination from the external environment but also protects from risks of personnel handling and contaminations arising from personnel movements. Contentment isolators are isolators which enable us to do processing of highly potent drug products and prevent the contamination of surrounding areas with the potent drug which otherwise could be dangerous to the environment or human. In the bottom of this article we have provided information on Pharma Isolator Validation.
What is the importance of an isolator?
Isolators provide protection to products from getting contamination from an external environment with higher number of particles thereby protecting product from microbial contamination, isolators are used in sterile dosage form manufacturing, where injectable dosage form is required to be sterile. The isolator provided with ULFA filters and the inner air quality have very low particle count below 50 Nos of particles of 0.3-micron particle size, and the viable particle count maintained inside the isolator can be very negligible; almost no viable particle count can be maintained for bacteria and fungus.
Isolators are used in manufacturing of highly potent molecules which if get into an external environment pose risk to humans. Such isolators are called as contentment isolators. Below also information is provided on Pharma Isolator Validation
Principle of working of Isolator?
Isolators are fabricated with stainless steel 316 grade and the inner surface is polished so that easy cleaning and disinfection can be done. Isolator is completely covered, there is a port to put material inside the isolator with a facility to lock on the port. The inner side port is opened from the inner side without exposure to the outer environment and material is transferred inside the isolator and the inner port is closed again.
To handle material inside the isolator glove ports are provided, on these glove ports sterilized gloves are affixed through which one can put their hands inside the glows and handle the material inside the isolator.
These ports can also be used to put media plates inside the isolator during environmental monitoring inside the isolator for viable count, readymade stick plates are available with a box which can be attached readily with these ports. Isolators are provided with Integrated particle monitoring connections and connection for viable and non-viable particle monitoring equipment.
There are two types of isolation techniques based on the pressure inside the isolator, positive pressure isolation and negative pressure isolation.
According to air flow patterns there are two types of isolators: the laminar air flow isolator and turbulent air flow isolator. Automated pressure hold test on-board air compressor.
Validation of isolator and online General Processing Platform Isolators.
During validation requirements of 21 CFR Part 11 are required to consider which are as follows
1.Asses to operation with password to operators, restriction of data access to supervisors with password protection. Restriction for data modification access to manager with password protection.
Data backup and storage, restrictions on modification of data are required, audit trails and automated logs of the activity are required to be captured and stored in data, and whenever required a print in format can be generated.
Following tests are done for validation of an isolator.
- Air velocity test of the air coming from the HEPA or ULFA filters in the air supply.
- Filter leak test for HEPA filters and ULFA filters.
- Pressure differential measuring. Pressure differential between the surrounding area and the inside of the isolator.
- Glove integrity test.
- Particle count inside the isolator, as per the requirements for sterile dosage form manufactured in the isolator requires the isolator qualify for class A.
- Viable Particle count inside the isolator with settle plate method and viable count on the wall and mountings inside the isolator with stick plate method.
- Operability test of isolator system at variable speed at lower speed, at moderate speed, at high speed, after this test a optimum speed to be defined for the equipment.
8.Design qualification, Installation qualification, and operation qualification as done for equipment qualifications and validation to be performed.