Stability of a drug refers to its capacity to remain within specifications of PCMTT (Physical, Chemical, Microbiological, Toxicological, Therapeutic)
Stability studies should test attributes susceptible to change during storage that can influence quality, safety, and efficacy
Validated stability-indicating analytical procedures should be applied
Period of stability is the time from manufacture until chemical or biological activity is not less than 90% of labelled potency, also known as shelf life (t90)
Accelerated stability testing is used to predict product stability within a short period of time using exaggerated storage conditions
Factors that accelerate instability include temperature, light, moisture, agitation, inversion, method of manufacture, and order of mixing
pH influences drug stability, with many drugs stable between pH 4 and 8
Shelf life is the period a drug product is expected to remain within approved specifications from the date of manufacture
Physical stability includes appearance, uniformity, and availability of the drug
Physical instabilities can include crystal formation, loss of volatile substances, loss of water, absorption of water, and change in crystalline form
Chemical stability involves deterioration through oxidation, reduction, hydrolysis, and racemization
Microbiological stability is important to prevent contamination from microorganisms
Overages are used to extend shelf life but should be justified considering safety and efficacy
Formulation involves the study of chemical compounds to form a drug of medicinal use
Types of stability include physical, chemical, microbiological, therapeutic, and toxicological
Official storage conditions range from cold to excessive heat
Stress testing of the drug substance helps identify likely degradation products and establish degradation pathways
Stress testing is carried out on a single batch of the drug substance
Stress testing should include the effect of temperatures, humidity, oxidation, and photolysis on the drug substance
Frequency of testing for long term studies should be sufficient to establish the stability profile of the drug substance
For drug substances with a proposed re-test period of at least 12 months, the frequency of testing at the long term storage condition should be every 3 months over the first year, every 6 months over the second year, and annually thereafter
At the accelerated storage condition, a minimum of three time points from a 6-month study is recommended, including the initial and final time points
Increased testing should be conducted if results from accelerated studies are likely to approach significant change criteria
When testing at the intermediate storage condition is called for, a minimum of four time points from a 12-month study is recommended
Stability testing of the drug product after constitution or dilution should be conducted to provide information for labeling on the preparation, storage condition, and in-use period
Hydrolysis involves adding water to break a larger molecule into smaller molecules
Decarboxylation refers to a reaction of carboxylic acids erasing a carbon atom from a chain of carbons
Epimerization is a chemical process where an epimer is converted to its distereomeric counterpart
Photochemical reactions include photolytic degradation affected chemically by radiation (UV)
Validation of analytical procedures is directed to identification tests, quantitative tests for impurities' content, limit tests for the control of impurities, and quantitative tests of the active moiety
Assay procedures are intended to measure the analyte present in a given sample
Precision expresses the closeness of agreement between a series of measurements obtained from multiple sampling of the same homogeneous sample under prescribed conditions
Repeatability expresses the precision under the same operating conditions over a short interval of time
Intermediate precision expresses within laboratories variations: different days, different analysts, different equipment, etc
Specificity is the ability to assess unequivocally the analyte together with other components that may be expected to be present
Detection limit is the lowest amount of analyte in a sample that can be detected but not necessarily quantitated
Quantitation limit is the lowest amount of analyte in a sample that can be quantitatively determined with suitable precision and accuracy
Linearity is the ability of an analytical procedure to obtain test results directly proportional to the concentration of analyte in the sample
Range is the interval between the upper and lower concentration of analyte in the sample for which the analytical procedure has a suitable level of precision, accuracy, and linearity
Robustness measures the capacity to remain unaffected by small deliberate variation in method parameters