Advisory Committee for Pharmaceutical Science and Clinical Pharmacology April 14, 2010 Mansoor A. Khan, R.Ph., Ph.D.
CDER/OPS/OTR/DPQR
Stability
Drug substance and products could degrade by oxidation, hydrolysis, racemization etc. Factors such as temperature, humidity, light, pH, ionic strength, buffer strength, residual metals could enhance the degradation. It is expected that a well designed formulation and packaging protects the product from degradation
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Stability Testing
Once a product is designed and developed, the stability of a finished product is required to be demonstrated for the shelf-life of a product Shelf life refers to the time for which the drug product retains the quality specifications Depending upon the clinical consequence, the Agency might tighten the potency/strength requirement- e.g. levothyroxine
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Stability
If a product is stable for two years, a sponsor doesnt have to wait for that time to market a product with two years expiration dating. It can do stability studies in exaggerated/accelerated conditions of temperature and humidity (e.g.. 40C/75%RH) and get an ESTIMATE of real time stability The ESTIMATED/TENTATIVE shelf-life is backed by real time stability studies at controlled room temperature
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% Drug Remaining
37 oC 45 oC 55 oC 60 oC
We need Ea values
k1 E a T1 T2 ln = k2 R T1T2
TIME
We may able to use microcalorimetry or other methods for Ea Know the limitations of Ea
Mansoor Khan, FDA ACPS 2010
Ea ln k 25 = LnA RT
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