Separative enclosures

This paper sets out to summarise and explain the present draft and then to anticipate whether it will meet the needs of those industries that might be required use it.

The first point to make about the draft standard is that it is generic and not application specific. This is clear from the title itself. Who has ever heard of a separative enclosure? Which industry uses such a device? In fact the word 'separative', which is disliked by spell-check, is defined in the OED as "tending to separate or to cause separation" and was cleverly chosen by the working group for its generic nature. However, just to ensure that the title gives some indication of the subject that the standard covers, it includes in brackets the more application-specific terms 'clean air hoods, gloveboxes, isolators, minienvironments'.

The draft standard characterises a separative enclosure as having three essential elements. These are the separative enclosure itself, the access device(s) which are the means whereby work inside the enclosure is accessed by operators outside, and the transfer device(s) which are the means whereby materials are transferred in and out. There is a strong emphasis on relative levels of leak tightness.

In any standard it is important to understand the scope. In 1.Scope, the point is made that "This part of ISO 14644 specifies the minimum requirements for the design, construction, installation, testing and approval of separative enclosures where they differ from cleanrooms as described in ISO 14644-4 and 14644-5".

With one exception, all the references in 2. Normative references are parts of the two groups of standards being prepared by ISO TC 209, namely ISO 14644 and ISO 14698, most of which are still to be published. The exception is ISO 10648-2:1994 Containment enclosures - Part 2: Classification according to leak tightness and associated checking methods.

Most standards contain definitions. 3. Terms and definitions include the following ones of particular relevance: -

A = ISO Class inside

a = particle size at which A is measured

B = ISO Class outside

b = particle size at which B is measured

Pressure integrity - capability to provide a quantifiable pressure leakage rate under repeatable test conditions

The next two sections are: 4.Specification of requirements, which is a checklist of the items that must be 'defined, agreed and documented between customer and supplier' in the specification of a separative enclosure, and 5. Design and construction, which is another checklist of some of the related design considerations with brief guidance.

The draft continues with 6. Access devices, which is amplified in Annex C. This section explains a number of means whereby processes, products or tools within the separative enclosure may be manipulated by hand operation (e.g. through gloves or gauntlets) or by robotic handling. It is further amplified in annex C. 7. Transfer devices is very brief and is amplified with examples in annex D.

8. Siting and Installating (sic) is another very brief checklist. 9. Testing and Approval is written in the most general terms, making reference to other parts of ISO 14644. For the important aspect of leak testing it refers to the recommendations of annex E.

It is in the annexes that the main interest lies. Annex A introduces the Separation continuum concept and includes a very helpful graphical illustration of the way in which different levels of 'separation means' provide different levels of 'assurance of maintaining separation'. The means range from 'unrestricted air over spill (mass flow)' at the lower end of the graph to ' high integrity/low hourly leak rate enclosures' at the higher end. The means of separation range from aerodynamic at the lower end to physical at the higher end. Application specific examples are given in the most general terms.

Annex B Air handling and gas systems is written in a way that suggests the standard is intended to include inert gas systems and active gas systems within its scope.

Annex C Access devices provides considerable detail on gloves and sleeves, glove materials, and glove change methods. Half-suits are briefly described, but the annex makes no mention of remote manipulation or robotic handling. Annex D Transfer device examples classifies transfer devices according to descriptions and diagrams that originate from Isolators for Pharmaceutical Applications HMSO 1994. However there are some changes and also some additional devices such as the class A2 transfer device - examples of which are: dynamic holes and mouse holes.

Annex E Leak testing describes a number of methods for pressure leak detection and quantitative leak testing. For quantitative leak testing, three methods described in ISO 10648-2 are adopted for separative enclosures, as is the classification according to hourly leak rate. One of the test methods is the oxygen method, which can only be applied to an enclosure that is at negative pressure relative to its surroundings. It works by filling the enclosure with Nitrogen and then detecting changes in the level of oxygen as a result of air entering through a leak. There is a very useful sub-section E.3.1.4. Equation development, which derives a formula for calculating hourly leakage where the pressure differential across an orifice (leak) is known and also links some of the test methods with the combined gas law equation P1V1/T1 = P2V2/T2 where P and T are absolute. The annex also describes a test known as the Parjo test in some detail. The Parjo test indicates the magnitude of a leak by the movement of a meniscus in a tube connected to a reference vessel. If the volume of the separative enclosure, the external barometric pressure and the internal temperature all remain constant for the duration of the test, then the volume displaced by the moving meniscus will represent the actual volume through the leak during the period of the test.

Annex F Design and testing of minienvironments covers ground that appears to be specific to the semiconductor industry. Annex G Calculation of maximum permissible leak rate sets out a rationale and a method for estimating different acceptable leak rates into or out of separative enclosures for different internal or external air change rates by taking into account the dilution effect.

The first possibility is that it will not survive. It could be that separative enclosures at the lower end of the separation continuum will be deemed to be covered by the segregation concepts in ISO 14644-4, and those at the higher levels of pressure integrity by ISO 10648, to the eventual rejection of ISO 14644-7. Interestingly, the scope of ISO 10648-1: Containment enclosures - Part 1: Design principles, which has not been adopted either by CEN or BS, states that it applies to enclosures or enclosure lines intended to be used for work on:

It is not certain that the draft of ISO 14644-7 will be accepted by the semiconductor industry. There is a clue in the inclusion of Annex F. This suggests that, in the perception of that industry, there is something lacking in the remainder of the draft.

Those organisations that manufacture or use anaerobic chambers will have to judge whether the draft standard is likely to be of value or whether they might wish to develop a standard that is more relevant to their own specific needs. Then there is the question as to whether the draft standard will be acceptable to all the nations that are members of ISO. The Australians already have a standard of their own AS 4273-1999 (+ Amdt 1/2000.05.02) called Design, installation and use of pharmaceutical isolators. They may prefer to retain that rather than adopt ISO 14644-7.

The USA healthcare sector has consistently sought to restrict the definition of isolators to those systems that include gaseous sterilisation and in which control of particulates is not an important factor. ISO 14644-7 might not be considered relevant by that sector in the USA. One thing is for sure. That is that being generic ISO 14644-7 will leave room for application specific standards and guidelines. For healthcare applications the one to watch is the comprehensive new edition of the UK guidelines "Isolators for pharmaceutical applications" which is due to be published later this year.

John Neiger is chairman and a founding director of Envair Limited, a leading independent manufacturer of biological safety cabinets, isolators and cleanroom facilities in the United Kingdom. He sits on various standards committees including, for the last two years, ISO TC 209 Working Group 7, which has prepared the draft standard described in this article. He has addressed numerous technical conferences around the world.