Clinical stability testing

Formulation development, production, and stability testing of clinical dosage form... 

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... 

Those stages after the preclinical discovery and evaluation that involve technical development. These processes include formulation work, stability testing, scaling-up the compound for larger-scale synthesis, and providing analytical support. Clinical trials are not included in this definition. 

Dissolution is one of the most time-consuming tests in stability testing, clinical release, and process support of pharmaceutical dosage... 

To enable a clinical trial to start as soon as possible, stability testing is carried out in parallel with the clinical trial, but is initiated 3 to 6 months earlier. Three-to-six-month accelerated and real-time data, which are used to project or support the expiration dating period for the batch(es) to be used... 

Cl, H003, pH and the potential for many other clinically significant tests. The more pragmatic issues of packaging design and materials of construction are treated in the context of device performance (i.e., analytical efficacy, reliability and stability) for the biological application intended. 

There are three types of stability testing (technical, clinical, and registration) performed during formulation development. Requirements of a stability program increases going from technical to clinical to registration. The major requirements for each of these are summarized in Table 15-7. In addition, the... 

Erythrocyte GSH concentration is diminished in many people who have defects in the hexose monophosphate or GSH synthesis pathways. The GSH stability test, originally devised to permit identification of people susceptible to hemolysis from primaquine (later shown to be the result of G6PD deficiency), still remains a useful "stress test of the intactness of these closely hnked pathways. Because deficiencies of GSH synthetase and y-glutamyl cysteine synthetase are rare disorders, it is not practical for clinical laboratories to contemplate assays for these enzymes unless results of the easily performed GSH stability test are abnormal. 

The product being crystallized was subject to a familiar set of constraints in the pharmaceutical industry. In early clinical trials, it was established that for bioavailability the active drug had to be supplied with a high specific surface area (2.3 -4.0 m /gm). On the other hand, it had to be highly crystalline, since (accelerated) stability testing had shown that partially (or totally) amorphous product, often encountered in the production of small (high surface area) particles, was subject to unacceptable... 

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