Attributes for an analytical isolator

Compared to many isolators, those for use in analytical roles need a greater level of flexibility and control. Michelle Frisch, MD at C.O.P.E. (Center of Process Excellence) and Senior Technical Systems Manager at PSL, reviews how to obtain the necessary attributes

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When carrying out R&D activities one difficulty is that the toxicity of the material being developed i­­­s often an unknown quantity and therefore the activities call for stringent requirements such as being able to control the environment in which the work is being carried out.

There could be a risk of dust explosion, cross contamination, unknown compound characteristics or toxicity to the operator. In addition, delicate tasks such as weighing microgrammes may need to be completed.

With the development of an analytical isolator, flexibility is a key factor, along with the assurance that the containment level or operator exposure is kept to a very low level. Most developmental compounds/processes will not have been assigned a toxicity level as yet and so the assumption has to be a worst case scenario.

The best approach to designing the isolator is to first identify the functions that need to take place. Process tasks or functions in typical R&D programmes are:

  • Subdivision
  • Sample taking and testing
  • Finite weighing
  • Powder property testing for flow characteristics
  • Wet chemistry

Dispensing Isolator chamber with weigh scale, hanging shelf and discharging port

Milling/particle analysis

Each one will be considered in turn to determine how it drives the design of an analytical isolator.

Subdivision: Workers need to be able to bring differently sized containers or bottles into the isolator. By providing an airlock prior to the main chamber, containers or bottles can be loaded. The airlock is then purged to ensure any contamination carried into the main chamber of the isolator is removed. The isolator is at a negative pressure compared to that of the room it occupies, with the main chamber being held at slightly less than ¼ inch water gauge.The airlock pressure is slightly higher so that when the internal door to the main chamber is opened, the volume of what could be contaminated air will be pulled into the main chamber and out via the extract system. The container can then be opened and the subdivision process started.

Sampling: With the containers in the main chamber, the operator can pull a sample and either post it out to be taken to another area for testing or the sample can be tested inside this chamber. Provision of a bag-out port or Rapid Transport Port (RTP) allows the operator to post out samples.

Fine weighing: Most compounds used in R&D are in very small quantities and need to be weighed out with an analytical balance to typically 0.0001 of a gram. This type of balance can be affected by air flow and vibration so it can be a challenge in an isolator.

To achieve such fine weighing operations, the isolator has to be equipped with the following attributes:

  • A separate shroud covering the weigh scale
  • A suspended or hammock weighing pan (e.g., Mettler Toledo Safe Weigh)
  • A battery pack weigh scale if the inside of the isolator is electrically classified as hazardous (there is currently no hazard-rated weigh scale on the market)

Weigh scale in lower chamber

The base of the isolator, where the weigh scale resides, needs to be heavily plated to dissipate any vibration. This leads to isolation of the extraction fan; it also means not locating it directly underneath the isolator or on the side walls, as fan vibration can interfere with weighing accuracy.

Powder property testing: This involves the ability to test the energy and friction of a compound for flow characteristics and can be carried out in the main chamber while protecting the operator from exposure to the compound. The size of the “bench room” in the main chamber needs to be fully thought out to ensure there is enough room.

Wet chemistry: Providing removable bars at the back of the isolator, with key hole designs, provides the ability to use reactors and other laboratory glassware for experiments in a controlled environment. The reach of an operator can be critical, so the depth of the isolator has to be carefully considered.

The isolator can be fitted with a side liquid manifold to allow induction of different liquids into the isolator via a peristaltic pump and disposable tubing. Windows that lift up are a must, to allow glass reactors and other equipment to be placed inside the isolator prior to start-up.

Milling/particle analysis: The isolator can be made to accommodate certain mills and integrate an in-line particle analyser. Support plates can be fitted using the key hole design, which is the same principle as the wet chemistry fittings, thus demonstrating versatility.

Other important attributes of an analytical isolator are: cleanability, mobility, different lighting modes, ability to address cross contamination, ergonomics and controlled environments.

Because the isolator needs to be small, adaptable and have the flexability to be moved throughout a lab, the use of pneumatics can be very beneficial. This enables the unit to be connected to compressed air for the extraction pump, nitrogen or compressed air to gain the correct environment control, and 110V/ 240V for the lighting. The latter should be LED-based, as they do not generate heat, and interchangeable diffusion shields can provide amber lighting if required.

To avoid cross-contamination, operators need to be able to wipe down the inside of the isolator or use a wash hose to eliminate any cross contamination. The isolator unit can then by wiped using IPA or other appropriate solvents. The fact that solvents should never be atomised inside the isolator needs to be considered.

Gloves are another area for careful consideration and use of simple over gloves is recommended.

When designing an isolator, thought needs to be given to ensuring the unit offers optimum flexibility and operability. One way to do this is to construct a full size mock-up. This allows items to be placed in the unit, giving first-hand experience of any dimensional constraints.

In summary, clear identification of the processes to be completed within the isolator, along with the construction of a full-scale mock-up, can lead to the optimum design and desired attributes for an analytical isolator.

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