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Pharmaceutical Containment

The Pharmaceutical Committee of the Institution of Mechanical Engineers presented a Seminar on Containment and Isolation in Pharmaceutical Manufacture.

A total of 56 delegates attended the IMechE Headquarters in Birdcage Walk to hear a selection of speakers, from end-users, specifiers, designers and manufacturers of containment systems.

Introduction

Containment of solids in the Pharmaceutical sector is as important as it is in any solids handling plant.  Apart from the loss of often very expensive material, there is the cost of clearing it up.  In addition, there may often be hazards concerning the material and if material can get out, undesirable material can probably get in, thus making the product contaminated and useless.

The techniques of containment and isolation also vary widely between primary and secondary manufacture.

The Seminar

The organisers of the seminar brought together speakers from all sides of the pharmaceutical industry: Pharmaceutical Manufacturers; Design Consultants and Contractors; Containment Equipment Designers and Suppliers; to explain the purposes and techniques for containment of product during manufacture, processing or handling and its isolation from external contaminants.  Their presentations: -

  • Promoted understanding of the standards required for containment in pharmaceutical manufacture.
  • Reviewed established and emerging technologies for containment systems.
  • Provided case studies, from the perspectives of both users and suppliers of containment equipment

Handling of high purity, high value, highly toxic or highly active materials is a major issue in the pharmaceutical industry - containment techniques have a profound influence on design and installation costs, operating costs and quality of product in any Pharmaceutical manufacture.

The increasing importance of isolating pharmaceutical ingredients from the environment during manufacture was an underlying theme of this well-supported event.  The presenters provided: -

  • An introduction to the principles of containment and isolation
  • An update on existing and emerging technologies
  • A vision of future developments in containment and isolation

What is Containment?

Containment covers the isolation of material so that is does not come into contact with personnel or the environment.  The material must be contained in such a way that it can be worked upon and sampled without that isolation being compromised.  The needs to achieve reliable levels of isolation and containment are increasing.  Modern drugs are increasingly toxic, in part caused by the demand for lower levels of dosage to the patient.  By their nature most cancer drugs are toxic and vaccines involve the manipulation of live organisms during manufacture.  Many of the manufacturing intermediates are toxic.  This is illustrated by the figures that in 1990 only 5% of drug compounds were considered potent, whilst in 2000, 30% are so classified.

The pharmaceutical industry owes a debt to the nuclear industry in that some of the features of the now common technique of glove boxes, which supplements glove boxes for the more toxic substances, are readily employed.  The exposure limits for antibiotics are between 50 – 2,000, but for anti-inflammatories the permissible level reduces and to between 4 – 20 per million parts and for cytotoxins it is a mere 0.1 per million. 

So, containment for the pharmaceutical sector splits into the two primary purposes of containment for operator safety and containment for sterility.

This can give rise to conundrums.  For example injectable anti-cancer drugs need negative room pressure for operator and environment protection, but positive pressure to keep out contaminants.  The solution lies in a negative pressure enclosure inside a Class 100 room.  Illustrating how pharmaceutical production involves very complex buildings with total environmental control.  This complexity shows up in the costs, where 25m² of production area can escalate from £45,000 to over £250,000 if the highest levels of both operator/environment protection are combined with high needs for sterility protection.

Rooms are designed for high levels of clean air, negative or positive pressures, and with surfaces that are non porous and thus are easily cleaned, sometimes with continuous slopes to one drainage area, with the complex trapping arrangements that drains imply.

Bulk Powders

A similar need to combine several distinct techniques when the pharmaceutical industry manipulates some of it bulk raw materials.  When shipping containers are brought into a storage area they a transferred to a process charging or opening sections where barrier technologies are employed with an airflow that is in an assured, positive, inward direction.

Continuous Safety Monitoring

We are dealing here with the heady mix of environmental protection and operator safety protected by complex multi-discipline engineering systems.  Even with the highest levels of planned maintenance techniques, the regular monitoring of safe performance is an obvious essential.  It is sobering to note that the efficiency of such sampling is often only a small step ahead of the rapid advances that are taking place.  So the need for several levels of protection remains paramount.

Good safety is based on continuing attention to detail throughout the design and operating life cycle.  The design needs to have good ergonomics so that the operator is not stressed physically.  Operators need clear procedures, in which they are thoroughly trained, to work to.  The planned potential flows of material and the acceptable exposure levels need to be thoroughly understood, especially the level of confidence that can be placed upon these figures.  And finally, there needs to be a high level of confidence in the supplier of the entire facility.

Testing of the facility will take place with low hazard, but dusty powders, to prove all the components and practices.  Sophisticated empirical relationships have been developed to verify the boundaries of safe operations with the different design options.

More General Applicability

The Pharmaceutical industry’s need is to contain/isolate relatively low volumes of highly toxic, expensive materials.  More generally, solids handling industry has lower toxicity material, but at much higher volumes.  The damage done with spillage may not be fatal, but can have serious environmental and economic consequences.  So some of the techniques may be worth consideration. 

My mind goes back to a personal recollection of my early years as an engineer, where I was given the task of commissioning a “dust free” rail loading facility.  The loading chutes were meant to retract as the wagon filled, thus reducing the freedom of dust to escape.  However, a constant speed of retraction did not allow for the filling characteristics of a sloping side rail wagon.  Neither did the North-east’s wind help.  Having the tendency to whip up the dust, even on an otherwise still day, depositing it over a wide area and especially on the sliders of the loading chutes.  Oh, for more sophisticated calculated data, linked to variable speed motors!

Case Study

One case study is chosen which illustrates the important gains that can be made if operator fatigue can be overcome by improved design of the facility.

The loading and operating of a centrifuge involving potent material required the operators to wear full air suits for all operations including cleaning and the maintenance and changing of filter media every batch.  The fatigue induced by this cumbersome and laborious environment and the time to de-contaminate was considerable.

The solution lay in part to improving the design between the centrifuge and the existing containment barrier.  Inspections at shutdowns used a remote camera and helped develop the first stage of the solution, which involved the redesign of the centrifuge lid and especially the repositioning of its hinge.  This step allowed the glove ports to be fitted to allow the changing of filter media to take place without full air suits.

The other end of the process at discharge was susceptible to a similar re-design to allow glove ports to carry out the work involved in discharge and transfer the product into shipping drums.

The result of these steps in practice was to divide the machine into four separate controlled environments.  Each environment was protected with its own containment breach alarms.  The need for full air suits was eliminated from routine operations.  They were only required when the containment environments were needed to be opened for cleaning prior to the changing of batch recipes or after and extended period of operation. 

Conclusions

The seminar emphasised that the permissible exposure criteria must be totally understood.  These performance criteria must be explicitly stated in purchase specifications, which will ensure that only competent design consultants and specialist contractors will tender for the work.  Systems would then be engineered to achieve containment and not have it added to an otherwise propriety piece of equipment. 

Tests with safe dusts would initially be carried out on all system criteria to validate the performance of the installed unit. 

Rigorous maintenance procedures and ongoing performance monitoring would then continue through the operational life of the equipment.

 

The Pharmaceutical Committee of the Institution of Mechanical Engineers was formed in June 2000.  The Process Industries Board, recognised that this industry needed mechanical engineers to play a full part in solving its distinct engineering problems in a manner that supported the key industry drivers of: -

  • ·         Regulatory compliance
  • ·         Reduced time to market
  • Pressure to reduce costs

Norman Harris is an independent consultant specialising in Information Management Strategies and Chair of the Pharmaceutical Committee of the Institution of Mechanical Engineers.

Queries can be addressed to consult@20cc.co.uk or visit the websites www.20cc.co.uk or www.imeche.org.uk for further information