Contact times drug products

For protein-based drugs, filtration via a 0.2 pm filter is an effective way to achieve sterilization. Factors that determine the filtration efficiency include integrity of the filter, pressure, temperature, how rate, contact time of material with the filter, pH, and viscosity. Validation of filters should include chemical compatibility of the filter with the product and possibility of contaminant from the filters leaching into the product. 

The complete and assembled component and its parts should meet suitability criteria appropriate for the drug product and the actual use of the component. Safety and functionality are the most common factors to be established for suitability. The length of time that the associated component and the dosage form are in direct contact should also be taken into consideration when assessing the suitability of an associated component. 

Samples should not be submitted to the FDA with the application. The reviewing chemist will contact the applicant and provide the laboratory addresses) where the samples should be sent. The applicant should prepare four representative samples in sufficient quantity to permit the FDA to perform each test described in the application three times to determine whether the drug substance and the drug product meet the specifications given in the application and whether the assay methodologies work in the FDA s hands. The four samples are ... 

In the small intestine, contact time with the absorptive epithelium is limited, and the small intestinel transit time is 3.5-4.5 h [32], The scintographic data show that many prolonged release products, particularly those intended for twice- or once-daily administration, actually release some of their drug contents in the colon where it may be absorbed into the systemic circulation for higher bioavailability. It is anticipated that conditions of dissolution, absorption, and metabolism in the distal portions of the intestine are different than in the proximal regions, due to differences in pH, lumen fluid, mucosal morphology, and motility. 

The investigation was begun after complaints that the pumps became blocked over time. Pumps typically deliver a low pressure, fine droplet-sized mist at a controlled dose rate. Good control of the dose rate and spray pattern requires precision molding of the components and consistent performance of these components when they are in contact with the drug product for extended periods and over a wide range of ambient temperatures. These components are made of thermoplastic, elastomeric, and metallic materials. The pump actuator and its elastomeric check valve are vital components. Their relative position is shown in Figure 10-3. 

If the drug product is in direct contact with the device (no impermeable protection included), is there potential for leachables to migrate into the drug product over time ... 

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