The test that measures the durability of a film material while in use is called puncture-resistance testing. Puncture-resistance
testing is comparable to tensile toughness because it assesses the strength of a film and its extensible properties. Good
puncture resistant materials are able to absorb a lot of the energy of impact by increasing elongation or resistance to deformation.
Tear resistance is a combination of tests having some properties of an elastic modulus measurement and tensile strength. As
the name implies, tear resistance is the study of how much a film is able to resist tear. There are many ways to evaluate
tear resistance including loading the film materials at small rates. Another way to measure tear resistance would be to find
the amount of force necessary to induce a slit across a piece of material. Though there are other standard methods available,
the latter is the most commonly used method.
Flex durability is tested using the Gelbo flex test. The Gelbo flex test pushes film material horizontally while simultaneously
twisting and crushing the film. This is done several times and failure is marked by observing the amount of pinholes that
were formed in the film material after the procedure. This test is dependent on how the film is to be used in the process
because this determines the number of cycles a film must undergo during testing.
Finally, another important mechanical property that must be considered is the glass transition temperature (Tg) and the brittle
temperature of film material. Tg is defined as the temperature at which a polymer goes from an inflexible, rigid state to
an elastic, flexible state.4 This quality is very important for determining the suitability for a BPC. When BPCs are used as a freezing application,
they must be able to withstand the extreme freeze temperatures that protein drug products must be stored at. Low Tg values
do not necessarily mean good resistance at low temperatures. Because low Tg materials can absorb more energy from impact or
loading forces, they are able to withstand longer and function better. Several films by vendor companies have been established
to have a Tg of –22 °C while others have developed a film with a Tg of –31 °C. Both of these films, despite their different
Tg values, have the same cold crack temperature definition of –80 °C thus making them fit for use in standard biotech freeze-thaw
applications.
Controlled Freezing
Bulk freezing of macromolecules is a method that makes it safe to store and transport a drug product while reducing microbial
contamination. The active pharmaceutical ingredient (API) is an important part of the bulk drug product and must be preserved
for a protein therapeutic to work. The degradation of the API is detrimental to the bulk product and as such the rate at which
the protein is frozen must be closely regulated because it can be both harmful and beneficial to the API.
Because the biological activity of a protein can change with the mere formation of a soluble aggregate, precipitation freezing
must be closely controlled. If the freezing process is too slow, then solutes may form or the pH may shift because of buffer
salt crystallization. The formation of solutes leads the API to become concentrated and the formulation composition changes,
leading to the aggregation or precipitation of the protein product and chemical degradation of the API. If the rate of freezing
is too rapid, small ice crystals may form with large surface areas. This phenomenon leads to a large interfacial area between
the protein and ice crystals that also can lead to aggregation and precipitation of proteins. In either case, the result is
an unstable protein product.
Figure 1. Trends and fluctuations in freezing bulk product in flexible bags, and variation in freezing rates depending on
bag location in the freezer.
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Many freeze studies were conducted at the Oceanside clinical plant to examine this process and to characterize the freezing
process of a product formulation buffer in disposable bioprocess containers. The results of this experiment (Figure 1) not
only proved the fluctuations and trends in freezing bulk in disposable bags, but also showed a variation of freeze rates in
terms of where the product was placed inside the freezer. These freeze studies reinforce the fact that it is necessary to
examine which freeze rates work best for any new system or product being introduced into a facility.
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