Complete isolation

Simply put, isolators are a means of isolating a process or product for the protection of that process, the product, or both, just as isolators in the electrical sense are used to isolate a portion of an electrical circuit for the protection of people working on that circuit.

The essential difference is that pharmaceutical isolators are used "on-line" and the process is allowed to continue hence the need for a validated system to provide real time protection and with the provision for all elements that will be required during a normal production run and with all contingency measures catered for.

Isolators have been around for many years and are also known as "gloveboxes", where the "glove" refers to an arm length gauntlet, however with the acceptance and increased use of "half suits", thereby providing a significantly larger capacity than a conventional glovebox, the term "glove" becomes inaccurate.

With a number of terms being bandied about, such as absolute barriers, controlled environments, etc, it is easy to understand the confusion on the part of new users, but in essence, the isolator should be a leaktight enclosure with a means of manipulation, equipment entry and exit and a pressure control system to provide the basic requirements of useful isolation.

It should also feature ergonomic understanding of the process and the ability of the human to carry out that process within the confines of the barrier and be backed up with instrumentation and the correct certification and validation documents to allow the user to inspect, validate and certify the installation and to pass regulatory inspections as they arise.

Of course it also needs to fit the pocket and, by and large, the cost of an isolated process is no greater than a conventionally housed one and with significantly lower operating costs and improved personnel gowning regimes and a degree of flexibility that is essential in modern day production.

Wherever you find a new technology, you will find an application for isolators. The third millennium is moving into miniaturisation of products and processes that were previously only dreamt of. Witness flying cameras the size of insects, electronic circuitry of atomic thicknesses, processing of biological cells, gene therapy, human organ replacement techniques, all of these industries will need to control the access to and quality of their production environment to even greater degrees as they evolve.

The excitement, if that is a word that can be used with process equipment, of isolators is the precision of environmental control they permit, such that these new and emerging technologies can be carried out under closely specified atmospheres and hence enable precise levels of control over exposure to bio burdens, particulates, gases, humidity and the like as well as the control of access routes.

It would be easy to see these aspects of isolators as a disadvantage if looked at from the "glass half empty" perspective, but if viewed as half full, the same glass can quickly be a "Cornu Copia" of benefits.

With gloves and half suits providing the means of intervention and restricting the bi-lateral impact of product / human contact, allergic reactions and other side issues of today's pharmaceutical products are removed from the equation, of course there are some of us who are allergic to natural elastomeric products but this list is small. The removal of direct human intervention means that microbiologists and production personnel are in control before hand rather than monitoring after the fact.

The use of isolators and associated equipment can be a revelation if considered in the form of a totally mobile entity – the ability of RTP devices to provide unlimited entry and free up restricted production lines within sites and mobilise product around the world can provide modern industries with the edge they require when trying to introduce globalisation of production. A primary producer in one continent can supply, totally contained and protected, a secondary processor in another, the ability to transfer between sites can now fully utilised existing site staff and equipment strengths without the need for relocation, retraining, revalidation etc.

Of course, with the minimised containment of processes comes reduced wall space and so the opportunities for entry and exits are restricted and the most must be made of the available access points. The restricted access also means that the entry of that forgotten spanner or pump assembly cannot just be thrown in as an afterthought but requires planned workloads.

Thus the critical element of the system is the entry / exit for the supply of equipment to the process, not forgetting the components and tools used within the process, as well as waste exit, sampling and monitoring equipment. With certification and delivery to the user at the precise moment, this list can be a potential nightmare for the production manager, but again if considered creatively it can be turned into an advantage. How many times has the ability to restrict access been thought of as an asset?

As different components have different conditioning parameters and all need to be catered for, and with the large variety of sterilising options available to the modern production pharmacist, a means of control is essential and a validated means a bonus.

Autoclave, steam, gas, vapour, ethylene oxide, irradiation, pulsed light, to name but a few and all with their associated problems and peculiarities, each requiring validation and in a form compatible with the process. Techniques that may not be available on the production site but which can now be considered thanks to the pharmaceutical supply industry evolving to include the supply of pre-sterilised components in the volumes and most importantly, the time required.

Delivery of components on a JIT (Just In Time) basis with full certification, freeing up personnel, capacity, finance and plant within a corporation and allowing those corporations to concentrate on their own particular specialist subjects.

As most major players now need to establish production facilities at significantly reduced costs and time scales and the use of isolators can facilitate this using the specialist services of the equipment supply industry as in the automotive industries where suppliers become partners in production.

Select your components, the quantities, method and time of delivery and place your order. The burden of inspection falls on the supplier for certification and production. Components can now be supplied ready for connection to production lines in pre-sterilised, certificated bulk quantities from FDA approved facilities at the time of your choosing and the quantity of your choosing.

In parallel with the development in the use of isolators is the increased demand from both users and inspectors, for example P.A.T. (process analytical technologies) initiatives coming from the FDA, whereby the process is continuously monitored on-line and does not rely on batch inspection, and the new personnel protection directives such as ATEX.

So as the challenge to production facilities everywhere becomes more acute with increasing demands for quality accountability, certification and continuous monitoring coupled with ever tightening investment budgets and reduced timescales for product to market, isolators themselves are JIT.