1. To whom it may concern
Presentation of professional expertise
Knowledge on high containment
My expertise on the “high containment” topic was acquired in three different kind of organization:
1. Pharmaceutical production company
2. Engineering company
3. Governmental Institute for the safety (Italian National Institute for Safety and Health).
These different working situations allowed me to see the “containment” problem from different
points of view and in a wide range of applications.
The pharmaceutical industry is developing an increasing variety of “highly active ingredients” and,
in addition, there is an increasing attention to industrial hygiene problems. These two factors made
the “containment” topic more and more important in the recent years.
First of all, I was involved in the design of both types of isolators: for personnel protection and for
product sterility preservation. I also saw some situations where both problems had to be considered
at the same time.
In applications in the pharmaceutical industry I was on the design team for both kinds of
production: Active Pharmaceutical Ingredients (API, bulk) and Fill and Finishing (Secondary).
In the API field some examples of the “high containment” technology applications are: loading of
highly active powders into reactors; centrifuges and dryers unloading; filter-dryer unloading;
dispensing of reactants and intermediate; products delumping, weighing and packaging; containers
washing.
Also, in the fill and finishing field there are many unit operations where potent drugs are to be
handled: dispensing; granulation; vial filling; tablet and capsule manufacturing; lyophilizator
loading/unloading; container washing; and many others.
In the Research and Development field there are also many situations where the use of an increased
level of containment is required. In fact the matter of the research (molecules, microorganisms) is
often unknown because it is under development. Very often the data on the long term effects of the
new ingredients are not available. This forces companies to implement the best available
containment level.
Another recent use of the “high containment” technologies is for the security forces (Army, Police,
Fire Brigades). Due to the increased terrorist threat, the security forces personnel is sometimes
required to perform analysis of unknown samples taken where an attack is feared. In this case the
analysis can be done in a safe way for the operators only by using the “high containment”
technologies and following suitable procedures.
I had the opportunity to cooperate with the Italian Army and with the Fire Brigades Dept. in Rome.
I wrote the technical specification of the isolators and other important parts of their mobile
laboratories for the NBC (Nuclear, Biological, Chemical) emergencies. I was involved in this job
because the Institute I’m working for supplies technical assistance to all the governmental
institutions about problems of safety. I also was the speaker for the mobile laboratories presentation
in conferences dealing with safety and security (Orlando-USA, Potsdasm-D, Pisa-I).
About the technology itself, I try to summarize here some relevant points on isolators.
Isolators and their accessories are the most important pieces of equipment in order to get a high
level of containment. There are many kinds of isolators so a deep and detailed study on the process

2. has to be done in order to choose the best alternative. There are “flexible” isolators (done in plastic)
suitable for temporary utilization or for production in short “campaign”. In case of more “stable”
processes or with large quantities of material to be handled, the “classical” solution of an isolator
constructed of metal sheet is preferable.
The kind of process to be performed also affects the choice for the number of “chambers” of the
isolator. A single box isolator is simpler and cheaper. On the other hand, it is also more “rigid” in
the utilisation because it cannot be opened until it is completely cleaned. If the process requires
frequent exchange of materials a dual chamber isolator is to be adopted. The additional box allows
the insertion or removal of material without cleaning all the isolator. Only the material to be
transferred must be decontaminated.
In order to help transfer operations, some accessories were invented: Rapid Transport Port; special
containers; continuous plastic film; etc…
The cleaning and sterilizing procedures are also critical. These operations often influence the design
of the isolator itself. In fact, each part of the internals must be easily reachable by the
decontaminating agent and stagnation of the liquor has to be avoided. The above mentioned reasons
often require the isolator internals to have rounded edges and polished surfaces. The supply and the
disposal of the cleaning liquids and liquors can be dedicated to each isolator or distributed to the
rest of the plant.
The diffusion of Vaporized Hydrogen Peroxide (VHP) is one of the more utilised system for the
sterilization of the isolator volume. This method also has the advantage to being compatible with
electrical and electronic devices.
The isolator borders a well defined volume. This situation allows also solves another problem. A
nitrogen flow can be guaranteed inside the volume of the isolator, so the oxygen concentration can
be kept below a maximum level. This prevents problems with powders and vapours that are
potentially explosive.
The isolator technology uses many technical solutions and many construction details. It is not
possible to discuss all of them. But I would like to mention the “push through” system for the vent
filters replacement. This allows replacement of an exhausted filter cartridge to be done safely. In
fact, the “dirty” cartridge drops inside the isolator and can be safely handled and disposed off.
As a consequence of my employment in the Italian Safety Institute, I did a deep study on the
regulation of “high containment” technology. Both legal and technical regulation were examined.
About the legal compliance, one of the strongest points of the isolator technology is that the
dangerous agent is caught immediately at its source. The potentially dangerous agents are not
spread in the working environment and operators don’t need protective devices. This complies with
the request of the European Directive for working safety.
In conclusion, most of the above mentioned points were discussed by me during conferences,
congresses, seminaries and university lessons.
Contact information
Giorgio Mari
e-mail: giorgiomari1961@yahoo.it
web: www.giorgiomari.com -------- http://it.linkedin.com/pub/giorgio-mari/9/b00/604
cell. +39 335 180 46 81