Biomedical Engineering Reference
In-Depth Information
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Safety of D
isposable Systems
Out of this nettle, danger, we pluck this flower, safety.
William Shakespeare
Disposable devices from filter housings to the lining of bioreactors make exten-
sive use of plastic materials or elastomer systems. Today, perhaps the most
significant impediment in the wider acceptance of disposable systems is the
controversy surrounding the possibility of contaminating the product from
the chemicals in the plastic film. So, before entering a broad description of the
choices of disposables available, this topic should be examined in detail.
All final containers and closures shall be made of material that will not
hasten the deterioration of the product or otherwise render it less suit-
able for the intended use. All final containers and closures shall be clean
and free of surface solids, leachable
contaminants and other materials
that will hasten the deterioration of the product or otherwise render it
less suitable for the intended use. (Biologics
21CFR600.11(h))
Leachables are chemicals that migrate from disposable processing equip-
ment into various components of the drug product during manufactur-
ing. Extractables are chemical entities (organic and inorganic) that can be
extracted from disposables using common laboratory solvents in controlled
experiments. They represent the worst-case scenario and are used as a tool
to predict the types of leachables that may be encountered during pharma-
ceutical production.
The issue of chemicals leaching from plastic has been the hottest topic not
just for the bioprocess industry but also for many other industries including
the food industry, where issues such as the safety of bisphenol-A (BPA) in
water bottles keep rising. A Google search of the topic results in millions of
hits. How the use of plastic affects bioprocessing is of great interest to the
stainless steel industry.
While regulatory requirements pertain to the toxic effects of leachables, a
risk unique to biological drugs arises in the effect of leachables on the three-
and four-dimensional structure of protein drugs: such changes can render
the drug more immunogenic if not less effective, and these side effects are
thus of greater importance to the bioprocessing industry. The most well-
known problem is the high incidence of pure red cell aplasia (PRCA) reported
in patients using commercial erythropoietin formulations leading to several
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