Simplifying Validation of Disposable Technologies with Presterilization by Gamma Irradiation - - BioPharm International


Simplifying Validation of Disposable Technologies with Presterilization by Gamma Irradiation

BioPharm International

Burst pressure tests are conducted to ensure that there is a suitable safety margin for the maximum operating pressure and temperature. This test is performed by filling a sealed capsule housing (without the filter) with water and placing the capsule in a 40 °C water bath. A pressure source is connected to the inlet of the capsule and the pressure is gradually increased until the capsule bursts.

Five (20 in.) Kleenpak Nova capsules were tested for burst pressure after pre-treatment with a gamma irradiation dose of approximately 50 kGy. The capsules all had burst pressures over 200 psi at 40 °C, which provides a considerable safety margin over the maximum operating pressure of 40 psi.

A creep rupture test is performed to determine how long a filter can withstand a given pressure before failure occurs. During the test, the capsules were immersed in a water bath held at 40 °C. The capsules were filled with the warm water and connected to a creep-rupture rig designed to maintain set pressures within the inside of the capsule until failure of the capsule occurs.

Figure 3. Creep rupture test results
For the creep rupture test, 20 in. empty filter capsule housings were used. All were pretreated with a gamma irradiation dose of approximately 50 kGy. Creep rupture data were graphed on semilogarithmic plots and average values were used for each point. Figure 3 shows the results for irradiated 20 in. Kleenpak Nova filter capsules and indicates that these capsules will withstand approximately 100 psig (6.9 barg) for 500 hours.

Real-Time Shelf-Life Tests

Real-time shelf-life tests are used to determine the length of time a filter capsule will remain sterile while in storage. Additionally, filters are tested to ensure that an adequate safety margin is maintained for burst pressure of gamma-irradiated capsules following storage at room temperature. In this case, filters were subjected to burst pressure and bacterial challenge tests at 0, 6, 12, 24, and 36 months to establish interim shelf-life claims. The test results led to establishing a three-year shelf-life for these capsule filters.

Biological Safety Tests

Biopharmaceutical companies also must consider the biological safety of the materials with which filter capsules are constructed. For example, single-use filter capsule housings made out of polypropylene need to meet the requirements of the biological reactivity tests in vivo for Class VI Plastics (121 °C) as described in the current United States Pharmacopoeia. (For the Kleenpak Nova capsule example, the filter membrane is validated separately.)

Extractables Tests

The Role of Disposables
Filter capsules should demonstrate low extractables. For example, extractables were measured for an empty 20 in. Kleenpak Nova capsule and were found to be less than one mg in water and less than 15 mg in a 96% ethanol solution. The extractables for the capsule housing can be added to the filter cartridges used in the application for total filter extractables. In turn, the total filter capsule extractables can be added to the extractables for other system components for a total extractables quantity.

Disposables: A Path to Reduced Validation

As the $65 billion disposables industry continues to mature, manufacturers are looking to simplify disposables implementation with plug-and-play systems. They are also paying closer attention to disposable materials and product configurations to minimize revalidation as processes are scaled up. Echoed in the myriad validation guidelines of global regulatory agencies, companies that use these strategies to simplify validation and reduce contamination risks will find themselves at a regulatory advantage as they navigate the course to drug approval.

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