Stability test substance

HHS/FDA International Conference on Harmonisation Stability Testing of New Drug Substances and Products Guideline Availability Notice, Federal Register, September 22, 1994... 

GL3 Stability 1 Stability testing of new drug substances and products... 

Drug substance/drug product purity, potency, and other testing Drug substance/drug product stability testing Method development, validation, and transfer Drug product formulation development... 

This test is based on a preselected amplitude for the applied strain (y) at a constant frequency (f) and a constant temperature (T). The method can be applied to test the stability of substances with temporary physical changes of structure or the course of chemical reactions like gelling at a given temperature. Again the pectin sols are filled into the measuring system... 

A solution to this dilemma is to place soil samples immediately in a freezer located in the field, the temperature of which is continuously monitored, as described previously. Laboratory-prepared storage study samples can then be used to determine test substance stability under freezer storage conditions that match those used in the field and during transportation and final storage. If a valid laboratory storage stability... 

A reference substance can be either the formulated test substance suspended in water or the technical or analytical grade active ingredient of the test substance dissolved in a solvent. The reference substance is normally used to fortify field matrices to develop information on the field storage stability of the active ingredient. Reference substances should be prepared at the analytical facility where the matrix samples are to be analyzed. Methods to prepare reference substances for field use will be discussed later. 

Field fortification (commonly referred to as field spiking) is the procedure used to prepare study sample matrices to which have been added a known amount of the active ingredient of the test product. The purpose for having field fortification samples available in a worker exposure study is to provide some idea of what happens to the test chemical under the exact environmental field conditions which the worker experiences and to determine the field storage stability of the test substance on or in the field matrix materials. Field fortifications do not serve the purpose of making precise decisions about the chemical, which can better be tested in a controlled laboratory environment. The researcher should not assume that a field fortification sample by its nature provides 100% recovery of the active ingredient at all times. For example, a field fortification sample by its very nature may be prone to cross-contamination of the sample from environmental contaminants expected or not expected to be present at the field site. 

Many types of matrices have been used in the past to measure the field stability of the test substance. Cotton gloves, cellulose patches, face wipe handkerchiefs and/or gauze face wipe matrices, long underwear (inner dosimeters), pants, shirts, coveralls (outer dosimeters), sorbent tubes, urine, and other matrices are common matrices that have been used for this purpose. 

The purpose of stability testing is to assess the effects of temperature, humidity, light, and other environmental factors on the quality of a drug substance or product. The data produced are used to establish storage conditions, retest periods, shelf loss, and to justify overages included in products for stability reasons. The most useful equation relating temperature and reaction rate is the Arrhenius equation. This equation (27) may be integrated and rewritten as Eqs. (31) and (32). 

Worker safety studies are not likely to normally include a control substance (i.e., a material used in the study to serve as basis of comparison with the test substance). However, if a control substance is included as a treatment group, then it must (1) be fully characterized as to its identity, purity (or strength), and stability (and solubility, if appropriate) (2) be appropriately tested in mixtures with any carrier used and (3) meet all the other GLP recordkeeping, labeling, and storage requirements, as specified for the test substance. There is some regulatory relief here, however, in that water, by definition, is excluded from being considered a control substance, and vehicles (those substances added to enhance solubilization or dispersion of the test substance) are addressed separately in the FIFRA GLP Standards. 

With respect to worker safety and re-entry studies, reference substances are necessary to assay the test substance (and, if applicable, any control substance) and determine its stability and for the analyses of specimens collected in the study. Specimens may include plant material (dislodgeable residues), adsorbent media (inhalation), or clothing/dosimeter materials collected during a worker safety study to assess exposure. If biomonitoring is involved, blood and/or urine specimens may be analyzed against reference substances of known purity. 

Although laboratory data regarding homogeneity, stability, effects of adjuvants, etc. may be available from the sponsor, this information is frequently not made available at the site of test substance application. A GLP deviation listed in the compliance statement may be the only realistic alternative without resorting to heroic effort however, it must be kept in mind... 

All theoretical calculations and tests performed in earlier stages, as well as the relevant literature, provide the inputs to the determination of the necessary detailed thermal stability testing for the substance, mixture, or reaction mass. 

Example 1 Typical Outputs of Thermal Stability Test Methods As discussed in detail later in Section 2.3, various techniques with different working principles are available to identify the thermal reactivity hazards of individual substances and reaction mixtures. Some examples are presented here. 

Stability testing is another quantitative test that is routinely used in TLC. A drug substance or drug product is placed on stability and pulled at an appropriate time point. These samples are examined for visual changes as well as purity and potency changes. TLC testing can be done... 

Guidance on Nonclinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals Notice Stability testing of new drug substances and products Stability testing Stability testing... 

ICH Guidance for Industry Topic Q 1 A Stability testing of New Drug Substances and Products, 2003. 

A. Guidelines for Stability Testing on Drug Substances and Drug Products... 

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