Pharmaceutical stability tests

The topic of Pharmaceutical Stability Testing actually started on June 5-7,1991 during discussions held in parallel with a conference organized by the APV in Darmstadt, Germany on the topic of "Stability Testing, New Trends and Requirements An International Symposium for the EC, Japan and the USA."... 

Lachman L, Cooper J. A comprehensive pharmaceutical stability-testing laboratory. JAPA 1959 XLVlll(4) 226-233. 

In 1959, after much research and based on the best principles then known, Lachman and Cooper (10), Lachman et al. (11) and Lachman et al. (12) published a series of papers detailing their development of a "Comprehensive Pharmaceutical Stability Testing Laboratory" which included photostability testing capabilities. This... 

Lachman L, Gooper J. A comprehensive pharmaceutical stability-testing laboratory. I. Physical layout of laboratory and facilities available for stability testing. J Am Pharm Assoc Am Pharm Assoc (Baltim) 1959 48(4) 226-233. 

This heterogeneity in the kinetics can make a rate constant deceptive since it will change with the extent of reaction. This is just one challenge in making extrapolations of degradation with time a rapid rate due to a reactive API form may not continue once the reactive API form is consumed. Fortunately, the matter is somewhat simplified in pharmaceutical stability testing since only a small amount of degradation determines the shelf-life. 

Baertschi, S. W. Forced degradation and its relation to real time drug product stability. In Pharmaceutical Stability Testing to Support Global Markets, (K. Huyn-ba, ed.), Springeg New York, NY, 2009. 

Code of Federal Regulations, Title 21, Food and Drugs, Part 211, Current good manufacturing practice for finished pharmaceuticals, Subpart I, 211.166 Stability Testing. 

ICH Expert Working Group, Q1A Stability Testing of New Drug Substances and Products, International Conference on Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use, 1994. 

JE Tingstad Physical stability testing of pharmaceuticals. J Pharm Sci 53(8) 955-962, 1964. 

There are three documents that give guidance on the design and conduct of in-use stability tests the EMEA/CVMP/127/95 final (adopted March 1996), CPMP/QWP/2570/98 (a concept paper adopted in November 1998) and CPMP/QWP/2934/99 draft (released for comment in December 1999). The studies undertaken may be discussed in the development pharmaceutics or the stability section of the dossier. 

There are numerous types of TLC testing done in the pharmaceutical industry, which are quantitative in nature. Release testing or purity evaluation, stability testing, and LOD are the three that will be addressed here. 

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... 

Regulatory bodies such as the Food and Drug Administration (FDA) in the United States require the identification of all impurities above the 0.1% level in formulated pharmaceuticals. Once identified, the structure of the impurity is typically confirmed through synthesis to provide absolute structure identification and for use as standards in subsequent quality assurance analyses. Together, LC-MS and LC-NMR play important roles in stability testing. For example, parallel analysis by LC-NMR and LC-MS was used for the rapid structure elucidation of an unknown impurity in 5-aminosalicylic acid, which is marketed for the treatment of acute ulcerative colitis and Chron s disease [57]. In another study, Fukutsu et al. [58] used a combination... 

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

Stability testing of drug compound Stability testing of pharmaceutical formulations and packagings... 

If a method is developed for use in a strictly controlled regulatory environment such as for use during pharmaceutical stability studies or clinical trials then it is a good idea to test at three levels for the increased confidence this provides in the method. 

World Health Organization (WHO) (2006), Stability testing of active substances and pharmaceutical products, Working Document QAS/06.179, WHO, Geneva. 

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