Filter validation

The method yielded >99% label claim of the API for the composite tablet assay. Table 3 lists the results of a filter validation study showing the quantitative recovery of the API from most membrane media. 

Although Brevundimonas (Pseudomonas) diminuta (ATCC 19146) is most commonly used for sterilizing-grade filter validation, in certain applications other bacteria are used. For example, when it is necessary to demonstrate removal of mycoplasma in applications involving sera and tissue culture media, membranes having a smaller pore size rating, eg, 0.1 Jim, are frequendy used. For these membranes, Picholeplasma laidlawii may be employed for validation purposes (9). 

Filter validation now includes tests to prove that sterilizing filters do not generate extractable materials when exposed both to water and to the drug product... 

Hydrophobic filters do not come into direct product contact and, therefore, the standard bacterial retention test alone generally is sufficient validation. However, as hydrophilic filters are in direct product contact, additional validation will be necessary for each product type in order to demonstrate that the filters selected for product sterilization do not alter the safety, identity, strength, quality, or purity of the drug product. Qualification of hydrophilic filters will also be necessary in order to demonstrate that the specific product type, in conjunction with a bacterial challenge, does not affect the efficacy of the filter. Validation of filters by means of bacterial retention tests requires specialist equipment and is often arranged between the filter manufacturer and the BFS operator. 

Meltzer, T.H. Jornitz, M.W. Mittelman, M.W. Surrogate solution attributes and use conditions effects on bacterial cell size and surface charges relevant to filter validation studies. PDA J. Sci. Technol. 1998, Jan/Feb, 52 (1). 

If sterile product aseptic fill/Terminal sterilization Filter validation (if aseptic fill)... 

The predominant method of sterilization for BPCs is by membrane filtration. This filtration will require validation in accord with regulatory expectations. Adaptations to the common filter validation methodologies may be required for certain solvents and/or antibiotic solutions. Subsequent to the filtration step, the succeeding unit operations must be carried out using facilities, equipment, and methods designed to prevent the ingress of microorganisms. The remainder of this section reviews considerations relative to sterile BPC preparation under these constraints. 

Effective measures to reduce the number of spurious initiations include on-line signal filtering, validation of parameters, voting on redundant signals and energizing to actuate. 

Validation Considerations. Mechanisms other then size exclusion maybe operative ia the removal of vimses from biological fluids. Thus vims removal must be vaUdated within the parameters set forth for the production process and usiag membrane material representative of the product line of the filter. 

Validation Guidefor the Palltronic FFE03-P Filter Integrity Pest Instrument TRFFE03-P, PaU Corp., East HiUs, N.Y., 1992. 

In addition, vibration data collected with a microprocessor-based analyzer is filtered and conditioned to eliminate non-recurring events and their associated vibration profiles. Anti-aliasing filters are incorporated into the analyzers specifically to remove spurious signals such as impacts. While the intent behind the use of anti-aliasing filters is valid, however, their use can distort a machine s vibration profile. 

Pharmaceuticals for injection must be presented in a sterile form. Sterility may be achieved by filtration through 0.22 pm filters under aseptic conditions, or by steam, dry heat, radiation or gas sterilisation methods, which may be applied to packaged products. Irrespective of the method, the process must be validated and monitored to assure its effectiveness. As discussed in Chapter 2, this is an example of a process that cannot be assured by verification testing because of its destructive nature. 

Ekins S, Berbaum J, Harrison RK. Generation and validation of rapid computational filters for Cyp2D6 and Cyp3A4. Drug Metab Dispos 2003 31 1077-80. 

Inosine 5 -Monophosphate Dehydrogenase. A series of 21 known inosine 5 -monophosphate dehydrogenase (IMPDH) inhibitors was used to validate a virtual screening protocol. By application of a molecular weight filter (80 < MW < 400), 3425 compounds were extracted from an in-house reagent inventory system. Docking of these compounds into a substrate-IMPDH complex 3D structure was performed with the program FlexX three... 

Galland, A. Towards the validation of in silica models and physicochemical filters to identify and characterize new chemical entities, PhD Thesis, University of Lausanne, 2004. 

Before we can apply an adaptive filter, we should define a criterion to judge the validity of the model to describe the measurements. Such a criterion can be based on the innovation defined in Section 41.2. The concept of innovation, /, has been introduced as a measure of how well the filter predicts new observations ... 

There are also RMs which are prepared for a specific application and are used for validation of relevant methods. Cobbaert et al. (1999) made use of Ion Selective Electrode (ISE)-protein-based materials when evaluating a procedure which used an electrode with an enzyme-linked biosensor to determine glucose and lactate in blood. Chance et al. (1999) are involved with the diagnosis of inherited disorders in newborn children and they prepared a series of reference materials consisting of blood spotted onto filter paper and dried, from which amino-acids can be eluted and... 

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