A Review of the Aging Process and Facilities Topic.

Aging facilities have become a concern in the pharmaceutical and biopharmaceutical manufacturing industry, so much that task forces are formed by trade organizations to address the topic. Too often, examples of aging or obsolete equipment, unit operations, processes, or entire facilities have been encountered. Major contributors to this outcome are the failure to invest in new equipment, disregarding appropriate maintenance activities, and neglecting the implementation of modern technologies. In some cases, a production process is insufficiently modified to manufacture a new product in an existing process that was used to produce a phased-out product. In other instances, manufacturers expanded the facility or processes to fulfill increasing demand and the scaling occurred in a non-uniform manner, which led to non-optimal results. Regulatory hurdles of post-approval changes in the process may thwart companies' efforts to implement new technologies. As an example, some changes have required 4 years to gain global approval. This paper will address cases of aging processes and facilities aside from modernizing options.

The mechanics of removing organisms by filtration: the importance of theory.

Very often, the concept of filtration is only considered in terms of sieve retention, which can sometimes be misleading. In this review of the adsorptive particle-capture mechanism, the authors aim to familiarize the filtration practitioner with the possible optimisation of particle retention by the manipulation of factors such as ionic strength, osmolarity, temperature and the use of polymeric filters.

Filter construction and design.

Sterilizing and pre-filters are manufactured in different formats and designs. The criteria for the specific designs are set by the application and the specifications of the filter user. The optimal filter unit or even system requires evaluation, such as flow rate, throughput, unspecific adsorption, steam sterilizability and chemical compatibility. These parameters are commonly tested within a qualification phase, which ensures that an optimal filter design and combination finds its use. If such design investigations are neglected it could be costly in the process scale.

Integrity testing.

To ensure that sterilizing grade filters in aseptic processing worked as required, such filters are integrity tested. Integrity tests, like the bubble point, diffusive flow or pressure hold test, are non-destructive tests, which are correlated to a destructive bacteria challenge test. This correlation verifies the integrity test limits the filters have to pass. Integrity tests are required by regulatory authorities. The post filtration integrity test is a must, pre filtration integrity testing is recommended. The different tests have specific limitations therefore there is no overall, best integrity test, which can be utilized for every filtration system.

Types of filtration.

There are a multitude of filter designs and mechanisms utilized within the biopharmaceutical industry. Prefilters are commonly pleated or wound filter fleeces manufactured from melt-blown random fiber matrices. These filters are used to remove a high contaminant content within the fluid. Prefilters have a large band of retention ratings and can be optimized to all necessary applications. The most common application for prefilters is to protect membrane filters, which are tighter and more selective than prefilters. Membrane filters are used to polish or sterilize fluids. These filters need to be integrity testable to assess whether or not they meet the performance criteria. Cross-flow filtration can be utilized with micro- or ultrafiltration membranes. The fluid sweeps over the membrane layer and therefore keeps it unblocked. This mode of filtration also allows diafiltration or concentration of fluid streams. Nanofilters are commonly used as viral removal filters. The most common retention rating of these filters is 20 or 50 nm.