Filter validation studies

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. 

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). 

Changes to filtration parameters for aseptic processing (including flow rate, pressure, time, or volume, but not filter materials or pore size rating) that require additional validation studies for the new parameters. 

Adjustments in the air source should be made to obtain a controlled flow of air within the tunnel and across the entrance and exit openings. Air must be particulate-free as it enters the tunnel area therefore, all high efficiency particulate air (HEPA) filters in the tunnel must be integrity tested and certified prior to validation studies. 

The models can be scaled to various sizes to fit the needs of the experiment. For example, a very small-scale nanofiltration system, such as a Planova P-15 hollow-fiber cartridge with O.OOl-m surface area (Asahi Kasei Corporation, Japan), can be used to study virus retention capabilities of a virus reduction step in a biological manufacturing process, whereas a scaled-up version of the same system with a surface area of 0.01 m provides an excellent way to study the nanofiltration process variables. In a nanofiltration validation study, a feed sample is typically spiked with a known quantity of a model virus. The mixture is filtered under the expected process... 

Scale-down studies have been used for a wide variety of process validation studies, including resin lifetimes, in-process stream hold times, buffer stability, virus clearance, harvest criteria, filter extractables, resin leachables, and cell age at harvest [14, 91, 92]. The ease of scale-down differs depending on step and should be considered in selecting those steps to be validated [5]. In fact, certain validation issues can be addressed only via small-scale models (e.g., virus clearance evaluation, nucleic acid and other impurities/additives removal, cleaning and storage procedure evaluation, and column lifetime estimation) because their use increases worker safety, reduces costs, and permits use of higher titer samples for improved... 

Igci Y, Pannala S, Benyahia S, Sundaresan S Validation studies on filtered model equations for gas-particle flows in risers, Ind Eng Chem Res 51 2094—2103, 2012. 

The choice of the system to be used for collecting particulate matter depends on the water volume to be sampled and the expected particle concentration therein. Borosilicate glass microfiber filters proved to be appropriate to separate the suspended material from the aqueous solution for a sample size up to 300 L [14]. A limiting factor may be represented by filter plugging, as demonstrated in a validation study conducted by Uza and coworkers to test the efficiency of an automated preconcentration water sampler (APS) for PCDDs and PCDFs [21]. The APS system is composed of a two-stage particulate filtering unit with coarse and fine filters, and an Amberlite XAD-2 resin column to trap dissolved hydrophobic compoimds. Various filter combinations were tested and, in all runs, filter plugging was observed. 

The first pesticide exposure study was reported by Griffiths et al. (1951). Parathion was trapped on respirator filter discs during application to citrus trees. Batchelor and Walker (1954) expanded exposure monitoring to include the estimation of potential dermal exposure using pads attached to workers clothing. Durham and Wolfe (1962), in their classic review of worker exposure methodologies, also provided some experimental validation for the best available methods. 

The purpose of the present study is to develop and validate a method for sampling and analysing metal fumes. The techniques under examination are several of those presently prescribed by the National Institute for Occupational Safety and Health (NIOSH) they include collection of particles of the substance from the air by filters, the acid digestion of the filters, and measurement of the residue using atomic absorption spectroscopy. The several components of the study are ... 

A universal sampler applicable to the majority of pesticides would be an ideal sampling device. In this study, personal sampling and analytical methods were developed and validated in the laboratory for determining workplace exposure to several pesticides. The major objectives of the study were to standardize on specific sampling media and to develop and validate methods using filter/ sorbent sampling trains. 

The specificity tests depend on the type and purpose of the method. If a specific method is being validated, an interference study should be undertaken. In the case above of the analysis of citric acid and sodium citrate, all other ingredients except microcrystalline cellulose and carboxymethyl cellulose sodium should be chromatographed separately. The known impurities related to memetasone furoate, if available, should be injected as well as the diluting solvent. Interference from filters is required. For nonspecific methods, specificity studies must be determined on a case-by-case basis. For example, the determination of molar ratio of citric acid and sodium citrate by pH in Nasonex should be designed to exclude any other contribution of acidity from other ingredients. 

Clarification steps must be validated to yield product with a given specification (e.g., no viable cells and a defined particulate level, if any). The specifications should enable production of feedstream for the purification steps. Varying amounts of cell fragmentation during processing can lead to out-of-specification material in the next step. A recent FDA form 483 noted that for a 3.0-pm filter used to clarify the fermenter harvest, no study had been conducted to evaluate the effect of operating the filter at the specified maximum pressure limit on cell fragmentation. 

Filters are used for clarification, removal of small molecules, exchange of buffers, and concentration of product, as well as sterilization and virus removal. A recent review of validation of filtration describes the critical validation issues [29], Filter compatibility is tested with process conditions to avoid nonspecific binding of product to the filter or addition of extractables to the process stream. Extractables are defined and limits established based on final product safety studies. Special considerations apply for sterilizing filters and those that are designed for virus removal. These filters are single use, however, which simplifies the validation effort. 

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