Storage Stability Data

OPPTS 860.1000 Background OPPTS 860.1100 Chemical Identity OPPTS 860.1200 Directions for Use OPPTS 860.1300 Nature of Residue - Plants, Livestock OPPTS 860.1340 Residue Analytical Method OPPTS 860.1360 Multiresidue Method OPPTS 860.1380 Storage Stability Data OPPTS 860.1400 Water, Fish, Irrigated Crops OPPTS 860.1460 Food Handling OPPTS 860.1480 Meat/Milk/Poultry/Eggs OPPTS 860.1500 Crop Field Trials OPPTS 860.1520 Processed Food/Feed OPPTS 860.1550 Proposed Tolerances... 

To calculate the efficiency of the candidate inhibitor from the storage stability data, it is necessary to propose a reaction mechanism. The following set of... 

From the resulting reactions a set of coupled differential equations can be derived describing the deactivation of P, L and PI and the reaction rate constants can be derived from storage stability data by the use of parameter estimation methods. The storage stability data give the concentration of P+PI (it is assumed that the inhibitor fully releases the protease during analysis due to fast dynamics and the extensive dilution in the assay) and L as a function of time. 

Materials are prepared with a sound knowledge or experimental evidence of the stability of both the matrix and the analyte chemical in that matrix. This information may be obtained from published storage stability data or from results of a storage stability trial. 

Data grade Laboratory recovery (%) CV for laboratory recovery Field recovery (%) Storage stability (%) Data corrected for ... 

Storage Stability Data. Storage stability characteristics of the formulations were followed at room temperature (i.e., 25 C) using a Gardner-Holdt bubble viscometer (ASTM D154-56) Termination of a sample s catalyzed lifetime (i.e., storage life) was taken to be when the viscosity reached a value of 1,000 cps at 25 C. 

We thank our colleagues at NIBSC, especially Drs Gray, Hubbard, Longstaff, and Bristow, for providing functional assay and storage stability data. 

For studies of more than four weeks in experimental duration, a reserve sample of each batch of the test, reference (analytical reference standard) and control substance must be retained. As this archive sample may be retained by either the sponsor or the contract facility, the responsibility should be addressed in the protocol. Additionally, a sample of the chemical should be collected prior to each application and immediately frozen for possible analysis for "storage stability of the test, reference and control substance at the test site". If the sponsor s storage stability data are inclusive of the storage conditions recorded at the test site, the GLP requirement will have been met and the above storage stability samples will not have to be analyzed (10). It should be noted that all test substance containers must be retained for the duration of the study i.e., until the study director signs the final report. A conditional exception for disposing of the containers may be obtained by writing to the OCM (11). OCM will set forth certain documentation requirements that will be required to account for the test substance containers. 

The final test of stability is, of course, obtained by shelf storage data, by placing the material under the conditions that will be encountered in commercial practice. But there are many problems encountered in the determination of shelf storage stability. 

One of the factors that will affect the stability data is the temperature of storage the higher the temperature, the shorter the time that will elapse before the fat becomes rancid. 

The following data is the result of a series of high temp storage (stability) expts conducted by (Brit) Imp Chem Inds Ltd (Ref 6) on IPN a) A summary for a series of pressure development tests involving a steel vessel of lOOcc capacity, half filled with IPN, and maintained at a given temp for four hours is presented below ... 

The confirmatory procedure should be developed for the same tissues for which the determinative procedure was developed, preferably using the same extraction procedure as used for the determinative portion of the method. Storage and stability data are necessary for dried or liquid sample extracts if MS analyses of the confirmatory samples are to be conducted in a laboratory other than the laboratory of sample preparation. Analytes present in sample extracts must be stable long enough for the samples to be shipped to the MS laboratory and analyzed. 

Primary container-closure system-related data will need to cover storage, transportation, and use. The choice of materials of construction, their description, and the ability of the container-closure system to protect from moisture and/or light will need to be considered. The compatibility of the container-closure and its contents will need to consider sorption, leaching, and safety. The performance of the container-closure system will also need to be considered in terms of dose delivery from any associated device that is to be supplied as part of the product. Container-closure components will require adequate specifications covering description, identification, critical dimensional tolerances, and test methodology (including pharma-copeial and noncompendial methods). More data are likely to be required for liquid or semi-liquid products than for solid dosage forms. In the latter, product stability data and container-closure system specifications may suffice. 

Drug Stability Data to substantiate the stability of the drug for storage and transportation... 

As the stability data can be affected by many factors like formulation, manufacturing, storage conditions, in-process and GMP controls, analytical methods, and process validation, the biggest challenge is to figure out the source of the variability in the stability results. At least three batches of the drug substance or product are required to establish the acceptance criteria for future production batches as a measurement... 

The chemical stability of an amorphous formulation is usually also a function of its storage temperatme relative to Tg. The enhanced molecular mobility achieved near the glass transition translates into an increase in translational diffusion-dependent degradation pathways, such as aggregation in proteins. It should be noted that the reaction kinetics near the Tg do not obey Arrhenius kinetics, and that extrapolation of the accelerated stability data generated near the Tg to stability at the storage temperature should be viewed with extreme caution. Amorphous materials must be stored well below the glass transition (at least 10°C, and typically 40 to 50°C below Tg) to maintain their physical and chemical stability. 

For drug substances, a retest date is generally determined. The period up to the retest date is a period during which the material is known to adhere to its specification, for example, for assay or degradants. The retest date may be assigned on the basis of real-time stability data obtained at the recommended storage conditions or on the basis of accelerated stability data obtained under more stressful conditions. 

CA, the most powerful lacrlmator used in World War I, was discarded In favor of CN because of storage stability problems resulting from its reactivity with steel and Iron containers. A resurgence of Interest during the 1960s led to Its use to clear persons out of tunnels In Vietnam. The LCt50 f°r humans has been estimated at 11,095 mg min/m3 on the basis of animal data. CA Is not a skin irritant or skin sensitizer In animals. 

Figure 11. G-BB storage stability—percent total mass retained vs. time data points, average of two determinations (O) ambient (75-80°F) ( ) refrigerated...

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