Dedicated to barrier technologies, this section explores a number of frequently asked key questions and provides detailed answers.
1. Why should we use an Isolator in aseptic filling processes if the product to be processed is not toxic?
a. Isolators make it easier to achieve GMP Annex 1 requirements than RABS technologies. By implementing more stringent hygienic design solutions and especially by integrating automated decontamination methods. b. Isolators are able to maintain aseptic requirements for a greater duration, thereby enabling longer and more efficient campaigns. c. Isolators can implement temperature, humidity, pressure and pressure cascade configuration requirements that are not possible with other technologies. d. Decreasing costs: class C instead of Class B surrounding the filling area requested for RABS approach.
Lower air-conditioning costs.
Lower gowning time.
Lower cost for gowning material.
Fewer particle and microbiological monitoring requirements.
2. Why should we use an Isolator in aseptic filling processes if the product to be processed is toxic?
a. Unlike closed-RABS, isolators can achieve higher containment levels and be suitable for OEB requirements of 5 or more. b. They can be used more easily in high bio-containment environments such as BSL-2 or BSL-3 facilities. c. They can include automated or semi-automated washing systems for toxic risk reduction at the end of production or automated VPHP-based deactivation solutions in the case of biological products. d. They are equipped with mechanical design, ventilation and sealing systems superior to any closed-RABS.
3. Why should Isolation technology increase product quality?
a. Isolation and RABS technology can physically separate the operators from the filling area, thereby reducing contamination risks. But isolators are able to guarantee protective positive pressure conditions and validated, integrated decontamination able to increase the sterility assurance compared to other technologies.
4. From the operators point of view, the Isolator is a just another “machine” to be managed: can we say that it drastically increases operator procedures?
a. IMA has decided to manufacture complete filling lines, including the isolator. One of the major benefits of bringing all parts design and manufacturing activities under one roof is the resulting harmony between single machines in the line. All the aseptic procedures, as with sterile material introduction into the isolators, are carefully analysed and studied during extensive mock-up activities, decreasing training requirements and increasing risk management.
5. Will size changeover operations be longer than on a conventional line?
a. IMA isolators are equipped with wide, openable windows all along the filling line in order to provide easy and ergonomic access during cleaning and set-up activities of sterile and non-sterile components.
6. Which are the advantages of a VPHP decontamination cycle as opposed to a conventional manual procedure?
a.“SAL 10-6” is achieved by means of a validated and repeatable cycle as requested by GMP Annex 1. b. Results are not dependent on the operator. c. VPHP can be used at the end of production to reduce biohazard risks.
7. Does an isolated filling line have a longer delivery time than a conventional line?
a. Yes, the delivery is generally 2-3 months longer: depending on the actual line configuration.
8. Does an isolated filling line have longer installation and validation activity times compared to a conventional line?
a. Yes, there are additional activities that need to be carried out, linked to the installation of the isolator itself with its own HVAC and the VHP cycle development. Due to the fact that an isolator is used, the installation and validation of the production room is faster (class C instead of class B).
9. Isolators for filling lines are generally very expensive: how can we justify the investment?
a. An isolator is a complex machine, with plenty of expensive components, such as motors, sensors, PLC and so on. It certainly affects the overall investment for the filling line, but at the same time it saves investing extra money in the production room by downgrading the surrounding area from class B to C. As a result, costs are transferred from the production room to the isolator, thereby providing a significant increase in product safety with all relevant economic advantages.
10. Is it possible to quantify the cost-saving operation achieved with an Isolator?
a. The cost-saving is accomplished by virtue of:
Fewer batches being discarded for reasons linked to lack of sterility: this data is not quantifiable, as it is human-dependent and strongly related to the value of the actual products being handled.
A single exercise can be recommended: calculate how much money can be saved if a single batch per year is saved thanks to the isolator.
Investments generated by the environment downgrade (HVAC + gowning time plus material & environmental monitoring): some of the major pharmaceutical companies have declared in public conferences that their savings can be estimated as being between 1 and 1.3 million euro per year (this amount is valid for EU and USA, in other countries it might be different).
All this means that the cost savings entirely pay for the isolator itself after just a few years of operation.