qc2 lec

• 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