Figure 1. An example of a polymeric film. The outer layer (1) is made of PET, a clear protective polymer; the PA layer (2)
gives mechanical strength; the EVOH layer (4) reduces gas transmission; and the fluid contact layer (5) is made of medical
grade ULDPE. The four layers are laminated and the adhesion strength between layers is provided by a thermoset polymer layer
(3).
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The film structure can be laminated, co-extruded, or a combination of the two. In laminated films, all film layers are extruded
separately and are bonded together by a thermoset adhesive. In co-extruded films, the film is manufactured in a single-step
operation in which the film layers are bonded together by a tacky thermoplastic polymer. These two manufacturing techniques
can be combined. Figure 1 shows the structure of a sample polymeric film.
Required testing and validation
Testing and validation requirements for films used in disposable equipment should be established by carrying out a risk analysis
for each application. Product specifications, both technical and regulatory, depend on the level of safety required for each
step in which the single-use products will be used. Applications such as final drug packaging obviously need more guarantees
than initial formulation applications, after which further purification and sterilization steps are performed. For every application,
an appropriate level of requirements and testing must be chosen.
Test conditions often are treated as variable parameters in the standards and are left to the convenience of the users. The
choice of testing parameters must be driven by the application. Organizations such as the Bio-Process Systems Alliance (BPSA)
are currently working on publishing a set of guidelines to help define these test conditions.3
Regulatory Requirements
The regulatory requirements that apply to films used in disposable equipment fall into several broad categories:
Biocompatibility requirements.
4–9 The biocompatibility requirements of a material depend on how it will be used within the process (e.g., media kitchen versus
purification) and vicinity to the human body.
Sterility requirements.
10 The sterility requirements of a film clearly depend on the sterility requirements of the application. If a sterilization
step is carried out after the use of a disposable container, that container may not need to be sterile.
Contamination requirements.
11,12 The contamination requirements of a film depend on the cleanliness requirements of the application. If a filtration step
is carried out after the use of a disposable container, the actual particle contamination level in the disposable container
may not need to be that low.
Endotoxins.
13,14 Regardless of the application, endotoxin requirements must be met, although the levels at which the actual limits are set
can vary. It is important to note that the traditional methods for removing pyrogens cannot be performed in disposable equipment,
because the high temperatures required would be detrimental to the polymeric nature of the materials used.
Container requirements.
15–18 Few current standards for disposables address the containers themselves, and those that exist mainly deal with the use of
disposable bags for drug delivery. Only some of the existing standards are relevant for bioprocessing applications, and must
be adapted to the bag configurations (e.g., sizes, tubes, connectors) used in processing. Risk analysis is necessary to identify
the relevant tests, methods, and specifications for any container under study.
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