Stability protocols contents

EXAMPLE 14 CONTENTS OF A PRODUCT-SPECIFIC STABILITY PROTOCOL... 

A device containing a drug substance reservoir or matrix from which drug substance diffuses should be tested for total drug substance content, degradation products, extractables, in vitro drug release rate, and as appropriate, microbial burden or sterility. The stability protocol should include studies at 37° or 40°C over a sufficient period of time to simulate the in vivo use of the drug delivery device. 

Most problems with solid fat content determination arise from inconsistencies in sample preparation. As noted above, the solids content is dependent on the temperature history of the sample, so deviations from the tempering protocols can lead to inaccuracies. The time required to measure a sample is not expected to lead to extensive crystallization or melting, but care should be taken to start the measurement as soon as possible after the oil is removed from the tempering block. Several instruments can be fitted with a thermostatic control for the sample in the coil, and this should be used if it is reliable. It is recommended that the NMR tubes be capped, particularly for the long tempering times required for stabilizing fats. 

The requirements for jet fuels stress a different combination of properties and tests than those required for aviation gasoline (ASTM D-1655). The same basic controls are needed for such properties as storage stability and corrosivity, but the gasoline antiknock tests are replaced by tests directly and indirectly controlling energy content and combustion characteristics. However, as with other petroleum products, application of sampling protocols (ASTM D-3700, ASTM D-4057, ASTM D-4177, ASTM D-4306, ASTM D-5842) is of prime importance. 

Where the same strength and exact container and closure system is used for three or more fill contents, the manufacturer may elect to place only the smallest and largest container size into the stability program (i.e., bracketing). The design of a protocol that incorporates bracketing assumes that the stability of the intermediate condition samples are represented by those at the extremes. In certain cases, data may be needed to demonstrate that all samples are properly represented by data collected for the extremes. 

Another laboratory observed a loss of Cd in the extract after an equilibrium time of 48 h which was, however, not confirmed by the other participants. This laboratory applied a second filtration step with a membrane filter (not included in the protocol), which could explain the losses observed. Losses due to precipitation were considered to be unlikely since the stability of the extracts over a period of 72 h was verified, providing that they were stored at 4°C. These examples demonstrated how essential it was that the extraction protocols be strictly followed, since a slight variation may lead to an incomparability of data. The protocol should state that the analysis be carried out with the samples as received and that the moisture content in the soil intake be corrected for by determining the loss of mass on drying a separate soil sample. 

USP<11> USP Reference Standards To ensure that the Reference Standards maintain the properties determined at the initial evaluation, USP maintains a Continued Suitability for Use Program. Abbreviated protocols use the stability-indicating methodology employed in the initial characterization of the material to confirm the consistency of attributes such as appearance, chromatographic purity, or volatiles content... 

The oils and the biodiesel products of the transesterification procedures are mainly characterized by nuclear magnetic resonance ( H-NMR) and gas chromatography (GC) techniques. The H-NMR technique provides chemical characteristics of the oils, fats, and products and the conversion degrees of the transesterification procedures. GC allows a more accurate characterization of the molecular species involved in the transesterification procedure. Additionally, the Analysis Biodiesel Protocol for the characterization of the methyl or ethyl biodiesel must include information of the following physicochemical techniques kinematic viscosity, density, flash point, cloud point, pour point, cold filter plugging point, free and total glycerol, ethanol residue, sulfur content, acid number, oxidative stability, and refractive index. 

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