Sixth Pharmaceutical Isolator User Group Conference

Sixth Pharmaceutical Isolator User Group Conference

This event is taking place at the Cairn Hotel in Harrogate, United Kingdom from 28th - 30th October 2001.

Statistics
146 delegates
22 speakers

There were a fair number of delegates from outside the United Kingdom.

		Some views of the hotel
		A typical room, with ensuite bathroom, remote controlled TV and telephone. Tea and coffee making facilities also available.
		Some scenes from Harrogate, including Betty's Tearoom and the memorial.

Sunday, 28th October, 2001

The first session was essentially a refresher session - introducing isolator technology to beginners, classification of isolators and transfer devices (including some new classifications), validation and operator training.

There was an introduction to the concept of SHE - Single Hole Equivalent and how to calculate it. This will be discussed further in another session.

Isolators intrinsically leak - do we protect the operator or the product ?
Can we prepare hazardous materials in a positive pressure isolator ?
What about the hazards caused by evaporation of cytotoxics ?
Is a HEPA filter adequate or do we need a carbon filter or do we vent isolators to roof level ?

Some of the questions to be addressed in the sessions to come.

Monday 29th October, 2001

Brian Midcalf began by welcoming the delegates and speakers and outlined the objectives of the Conference. He gave an overview of the User Group and the latest progress of the 3rd edition of the "Isolators for Pharmaceutical Applications" - this had been intended to be ready for this conference, but there were a couple of sections that required adding or modification in the light of recent research. The Committee had decided that it was better to release an up-to-date version at a later date, rather than to release first and then make amendments later.

There was an overview of the Isolator User Group's web site and an introduction to the Exhibitors demonstrating products at the Conference.

Exhibitors
Amercare Faulding Pharminox
B.Braun Helapet Steris
Biotest La Calherne

The next session was given by Didier Meyer, La Calherne, discussed PDA Technical Report No. 34; Design and Validation of Isolator Systems for Manufacturing and Testing of Health Care Products - (PDA = Parenteral Drug Association), comparing it with existing and forthcoming guidance documents.

Following that, Colin Davy, from the Health and Safety Executive, discussed the important factors in the consideration of operator protection. Under COSHH, isolators are "engineering controls" but were also classified as personal protective equipment. He went on to discuss some research performed at two sites, using positive and negative pressure isolators. In the study, by Mason et al, they discovered that there was a low level of cytotoxic contamination found on surfaces, in the air and in the operators urine. However, they discovered that there was no significant difference between positive or negative pressure isolators.

Colin Davy went on to add that if there was a major cytotoxic spillage and a breach of isolator integrity, then there could be a problem with positive pressure isolators.

In another study, involving gloves and pesticides, they discovered that the greatest risk came from the way gloves were changed, rather than the glove material. However, this was not to say that glove material was irrelevant. In conclusion, he said that training, supervision and regular safe glove replacement was paramount.

Colin went on to explain some areas of future work - contamination of the vial/ampoule surfaces with cytotoxic agents; glove contamination and breakthrough and the influence of "wash solutions".

In the final session of the morning, Andrew Bill, Medicines Control Agency, talked about the siting of isolators. Following the extensive liaison between the MCA and the NHS a working party was set up to study isolator operations, configurations and background environment. A draft guidance document had been produced and this was currently with the NHS Quality Control Committee.

This document gives guidance on the siting of pharmaceutical isolators. In essence, the table shown during the session, indicated that negative pressure isolators should be sited in rooms meeting a minimum of Grade D - Using closed systems, a Type D transfer device & "so long as it is managed properly". It was also mentioned that a jet stream effect, produced by pinholes in the fabric of a negative pressure isolator, would not be deflected by the use of either uni-directional air flow or turbulent air flow.

For negative pressure isolators, Andrew Bill advocated the use of sanitised garments with impervious sleeves. In order to protect the product, clean room gloves need to be changed at least every 4 hours for both positive and negative pressure isolators.

The ball was thrown back into the court of the employer:- ".... it is possible to use either positive or negative pressure isolators and to maximise drug protection and minimise operator exposure ... Factors commensurate with worker health and drug protection should be taken into account by means of a risk assessment .... Pharmacy workers and their representatives should be involved in these processes."

It was important to make sure that there was no "re-use" of air from rooms used to undertake cytotoxic reconstitution in other areas - there should be no recycling.

In the afternoon session, David Watling, Bioquell Pharma, explained the basis of hydrogen peroxide sanitisation - is it a dry gas process or is micro-condensation involved ? It was established that the micro-condensation effect was the one responsible for the activity against spores and micro-organisms. However, in order to achieve this effect, there are many factors to take into consideration - humidity of the air, temperature etc.

The mass of hydrogen peroxide required and the time required for decontamination depended on the load present.

There was then an appraisal of different sporicidal gassing agents by James Drinkwater, also from Bioquell Pharma. The disadvantages of formaldehyde, peracetic acid and chlorine dioxide were highlighted and the advantages of using hydrogen peroxide was discussed.

The use of a dry hydrogen peroxide process vs a wet process was highlighted - eg dry process gives sporicidal effect in 1-2 hours, whereas the wet process is more rapid, at 10-30 minutes.

It was noted that adequate circulation was required to enable the hydrogen peroxide to sanitise properly.

In the next session, John Neiger, Envair, reviewed parts of the forthcoming 3rd edition of:- "Isolators for Pharmaceutival Applications". The design, siting and transfer device classification of isolators was covered. Under the transfer device section, the new classifications were discussed - the old Type A is now reclassified as Type A1. A new A2 type was created to allow for "mousehole" type positive pressure isolators, where there was a conveyor belt type system. What used to be Type B has been reclassified as Type B1. A new B2 type had been created to allow for an airlock (where gas or vacuum purging is required). Type D has been completely changed - it now classifies a double filtered transfer chamber for positive and negative pressure isolators. What used to be classified as Type E transfer device has been reclassified as Type F. The new Type E is for double filtered transfer chamber with a gassing facility.

Finally, David Stribling, Flowmerics, demonstrated the use of Computational Fluid Dynamics in order to assess clean up times in isolators. There were some visual demonstrations of various scenarios - allowing for experimentation in the "What if we do this ?" situation without having to build prototypes.

There was then a seminar session demonstrating some of the manufacturer's gizmos.

Envair demonstrated their "Vari-height" isolator - gives a 14" height adjustability, by using flexible exhaust ducting. There was also the chair with a HEPA filter fitted into the seat, so as to minimise the risk of unfiltered air being expelled from the seat when the operator sits down. The seat also had a tilting facility.

A mention was made about their new flexible film window which allowed the operator greater freedom of movement.

They also mentioned about their cable seal, which allowed electrical equipment to be used within the isolator whilst preserving the integrity.

Amercare presented their isolator with angled transfer chambers, comfortable glove ports, no door housings, angled roof, lightweight vacuum-sealed door, simple pressure testing method and plastic coated foot-rest. The isolator also has no lip between the transfer chamber and the workzone, and is low-profile to allow cleaning the top of the isolator.

Shield Medicare demonstrated their new isolator cleaning tool pads - 100% polyester cover, but now available in a lint-free version. They now produce B-D syringes in packs of 5, double-bagged, gamma irradiated. Additionally, there are vaporised hydrogen peroxide resistant foil packs of various disposables, which should be listed in their latest catalogue.